Transcription factor and bone marrow stromal cells in osseointegration of dental implants

Directory of Open Access Journals (Sweden)

SG Yan

2018-05-01

Full Text Available Titanium implants are widely used in dental clinics and orthopaedic surgery. However, bone formation surrounding the implant is relatively slow after inserting the implant. The current study assessed the effects of bone marrow stromal cells (BMSCs with forced expression of special AT-rich sequence-binding protein 2 (SATB2 on the osseointegration of titanium implants. To determine whether SATB2 overexpression in BMSCs can enhance the osseointegration of implants, BMSCs were infected with the retrovirus encoding Satb2 (pBABE-Satb2 and were locally applied to bone defects before implanting the titanium implants in the mouse femur. Seven and twenty-one days after implantation, the femora were isolated for immunohistochemical (IHC staining, haematoxylin eosin (H&E staining, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR, and micro-computed tomography (μCT analysis. IHC staining analysis revealed that SATB2-overexpressing BMSCs were intensely distributed in the bone tissue surrounding the implant. Histological analysis showed that SATB2-overexpressing BMSCs significantly enhanced new bone formation and bone-to-implant contact 3 weeks after implantation. Real-time qRT-PCR results showed that the local delivery of SATB2-overexpressing BMSCs enhanced expression levels of potent osteogenic transcription factors and bone matrix proteins in the implantation sites. μCT analysis demonstrated that SATB2-overexpressing BMSCs significantly increased the density of the newly formed bone surrounding the implant 3 weeks post-operatively. These results conclude that local delivery of SATB2-overexpressing BMSCs significantly accelerates osseointegration of titanium implants. These results provide support for future pharmacological and clinical applications of SATB2, which accelerates bone regeneration around titanium implants.

Induction of quiescence (G0) in bone marrow stromal stem cells enhances their stem cell characteristics

DEFF Research Database (Denmark)

Rumman, Mohammad; Majumder, Abhijit; Harkness, Linda

2018-01-01

Several studies have suggested that bone marrow stromal steam cells (BMSC) exist in a quiescent state (G0) within the in vivo niche; however, an explicit analysis of the biology of G0 state-BMSC has not been reported. We hypothesized that induction of G0 in BMSC might enhance their stem cell...... properties. Thus, we induced quiescence in BMSC in vitro by (a) suspension culture in a viscous medium or (b) culture on soft polyacrylamide substrate; and examined their molecular and functional phenotype. Induction of G0 was confirmed by bromo-deoxyuridine (BrdU) labelling and analysis of cell cycle gene...... expression. Upon reactivation and re-entry into cell cycle, G0 state-BMSC exhibited enhanced clonogenic self-renewal, preferential differentiation into osteoblastic rather than adipocytic cells and increased ectopic bone formation when implanted subcutaneously in vivo in immune-deficient mice, compared...

Effect of osteoporosis on fixation of osseointegrated implants in rats.

Science.gov (United States)

Li, Yunfeng; He, Sheng; Hua, Yunwei; Hu, Jing

2017-11-01

The effect of osteoporosis on implant osseointegration has been widely investigated, whereas osteoporosis may also newly occur in patient with previously osseointegrated implant. This study was designed to investigate the effect of osteoporosis on implant fixation in rats after successful osseointegration had been obtained. Seventy female Sprague-Dawley rats were included, and each animal received two titanium implants in the distal metaphysis of femur bilaterally. Eight weeks later, ten rats were sacrificed to confirm the establishment of implant osseointegration. All left rats were randomly subjected to bilateral ovariectomy (OVX) or sham operation. Three, six, and twelve weeks later, implant osseointegration, peri-implant bone tissue, and biomechanical properties of implant were analyzed. Right femurs with implants were used for micro-CT and histological analysis, and left femurs with implants were used for biomechanical test. Micro-CT, histology, and biomechanical test confirmed the destructive effect of OVX on previously osseointegrated implant in rats; when compared to sham-operated rats, peri-implant bone volume, trabecular architecture, bone-to-implant contact ratio, as well as biomechanical parameters decreased progressively within 12 weeks. Results also indicated that the effect of OVX on undisturbed bone (proximal tibiae) was much stronger than that on peri-implant bone. Osteoporosis produced a progressive negative effect on previously osseointegrated implant in distal femora of rats during 12 weeks. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2426-2432, 2017. © 2016 Wiley Periodicals, Inc.

Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells

International Nuclear Information System (INIS)

Tu Qisheng; Valverde, Paloma; Chen, Jake

2006-01-01

Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed in osteoblasts of all endochondral and membranous bones. In Osx null mice osteoblast differentiation is impaired and bone formation is absent. In this study, we hypothesized that overexpression of Osx in murine bone marrow stromal cells (BMSC) would be able to enhance their osteoblastic differentiation and mineralization in vitro. Retroviral transduction of Osx in BMSC cultured in non-differentiating medium did not affect expression of Runx2/Cbfa1, another key transcription factor of osteoblast differentiation, but induced an increase in the expression of other markers associated with the osteoblastic lineage including alkaline phosphatase, bone sialoprotein, osteocalcin, and osteopontin. Retroviral transduction of Osx in BMSC also increased their proliferation, alkaline phosphatase activity, and ability to form bone nodules. These events occurred without significant changes in the expression of α1(II) procollagen or lipoprotein lipase, which are markers of chondrogenic and adipogenic differentiation, respectively

Osseointegration of subperiosteal implants using bovine bone substitute and various membranes

DEFF Research Database (Denmark)

Aaboe, Merete; Schou, S.; Hjørting-Hansen, E.

2000-01-01

Osseointegration, subperiosteal implant, bone substitute, bovine bone, guided bone, regeneration, histology, rabbits......Osseointegration, subperiosteal implant, bone substitute, bovine bone, guided bone, regeneration, histology, rabbits...

CT and scintigraphic evaluation of osseointegration following immediate versus delayed implantation in dogs

International Nuclear Information System (INIS)

Kim, J.H.; Lee, J.Y.; Lee, W.G.; Oh, W.Y.; Kim, S.S.; Choi, S.H.; Kang, S.S.

2004-01-01

Osseointegration involves anchoring dental implants to stable bone rather than to soft-tissue. Clinical osseointegration is currently defined as the process whereby alloplastic material is asymptomatically and rigidly fixed and maintained in bone during functional loading. Full osseointegration is necessary for the success of long-term dental implants. Recent developments in computer assisted measurement of bone formation have improved maxillofacial examination and osseointegration. Computer assisted examination has also proved effective in dental implantology

Strain driven fast osseointegration of implants

Directory of Open Access Journals (Sweden)

Wiesmann Hans-Peter

2005-09-01

Full Text Available Abstract Background Although the bone's capability of dental implant osseointegration has clinically been utilised as early as in the Gallo-Roman population, the specific mechanisms for the emergence and maintenance of peri-implant bone under functional load have not been identified. Here we show that under immediate loading of specially designed dental implants with masticatory loads, osseointegration is rapidly achieved. Methods We examined the bone reaction around non- and immediately loaded dental implants inserted in the mandible of mature minipigs during the presently assumed time for osseointegration. We used threaded conical titanium implants containing a titanium2+ oxide surface, allowing direct bone contact after insertion. The external geometry was designed according to finite element analysis: the calculation showed that physiological amplitudes of strain (500–3,000 ustrain generated through mastication were homogenously distributed in peri-implant bone. The strain-energy density (SED rate under assessment of a 1 Hz loading cycle was 150 Jm-3 s-1, peak dislocations were lower then nm. Results Bone was in direct contact to the implant surface (bone/implant contact rate 90% from day one of implant insertion, as quantified by undecalcified histological sections. This effect was substantiated by ultrastructural analysis of intimate osteoblast attachment and mature collagen mineralisation at the titanium surface. We detected no loss in the intimate bone/implant bond during the experimental period of either control or experimental animals, indicating that immediate load had no adverse effect on bone structure in peri-implant bone. Conclusion In terms of clinical relevance, the load related bone reaction at the implant interface may in combination with substrate effects be responsible for an immediate osseointegration state.

Analysis of the influence of the macro- and microstructure of dental zirconium implants on osseointegration: a minipig study.

Science.gov (United States)

Mueller, Cornelia Katharina; Solcher, Philipp; Peisker, Andrè; Mtsariashvilli, Maia; Schlegel, Karl Andreas; Hildebrand, Gerhard; Rost, Juergen; Liefeith, Klaus; Chen, Jiang; Schultze-Mosgau, Stefan

2013-07-01

It was the aim of this study to analyze the influence of implant design and surface topography on the osseointegration of dental zirconium implants. Six different implant designs were tested in the study. Nine or 10 test implants were inserted in the frontal skull in each of 10 miniature pigs. Biopsies were harvested after 2 and 4 months and subjected to microradiography. No significant differences between titanium and zirconium were found regarding the microradiographically detected bone-implant contact (BIC). Cylindric zirconium implants showed a higher BIC at the 2-month follow-up than conic zirconium implants. Among zirconium implants, those with an intermediate Ra value showed a significantly higher BIC compared with low and high Ra implants 4 months after surgery. Regarding osseointegration, titanium and zirconium showed equal properties. Cylindric implant design and intermediate surface roughness seemed to enhance osseointegration. Copyright © 2013 Elsevier Inc. All rights reserved.

Osseointegration of hydroxyapatite and remodeling-resorption of tricalciumphosphate ceramics.

Science.gov (United States)

Draenert, Miriam; Draenert, Alice; Draenert, Klaus

2013-04-01

Cancellous bone defects surrounded by still intact bone structures never heal. Ceramics offer a solution providing osteoconductive scaffolds. The purpose of the study is to evaluate whether structured β-TCP and HA implants can reconstruct cancellous bone defects, which role micro- and macro-porosity, stiffness and surface area play; finally the indication for both materials based on its resorbability. 10 German Shepard dogs were operated on both tibial heads implanting shell-like fully interconnected ceramic cylinders, using a wet grinding hollow drill coated with diamonds. β-TCP was compared with HA. A polychromatic sequential labelling with 4 different fluorochromes controlled bone formation dynamics. Non-decalcifying histology after perfusion fixation and vessel casting was performed. μ-CT was combined with high resolution microradiography and histology on thin ground crossections. The stages after 6 weeks, 2, 3, 4 months and 15 months were evaluated. In spite of osseointegration of HA and β-TCP, the osseointegration of both materials was completely different. Both shell-like bone void fillers were osseointegrated in a sandwich-like manner. HA yielded primarily a reinforcement of the recipient's cancellous-bone bed and full osseointegration after 4 months, whereas β-TCP-implants were fully osseointegrated after 6 weeks. HA did not show signs of resorption. The resorption of the β-TCP resulted during remodelling. The final stage showed restitution "ad integrum" of the β-TCP defects with a physiological architecture, whereas HA was integrated in the cancellous bone construction providing 600 μm measuring macropores showing osteoinductive properties. Copyright © 2013 Wiley Periodicals, Inc.

Bioelectric analyses of an osseointegrated intelligent implant design system for amputees.

Science.gov (United States)

Isaacson, Brad M; Stinstra, Jeroen G; MacLeod, Rob S; Webster, Joseph B; Beck, James P; Bloebaum, Roy D

2009-07-15

The projected number of American amputees is expected to rise to 3.6 million by 2050. Many of these individuals depend on artificial limbs to perform routine activities, but prosthetic suspensions using traditional socket technology can prove to be cumbersome and uncomfortable for a person with limb loss. Moreover, for those with high proximal amputations, limited residual limb length may prevent exoprosthesis attachment all together. Osseointegrated implant technology is a novel operative procedure which allows firm skeletal attachment between the host bone and an implant. Preliminary results in European amputees with osseointegrated implants have shown improved clinical outcomes by allowing direct transfer of loads to the bone-implant interface. Despite the apparent advantages of osseointegration over socket technology, the current rehabilitation procedures require long periods of restrictive load bearing prior which may be reduced with expedited skeletal attachment via electrical stimulation. The goal of the osseointegrated intelligent implant design (OIID) system is to make the implant part of an electrical system to accelerate skeletal attachment and help prevent periprosthetic infection. To determine optimal electrode size and placement, we initiated proof of concept with computational modeling of the electric fields and current densities that arise during electrical stimulation of amputee residual limbs. In order to provide insure patient safety, subjects with retrospective computed tomography scans were selected and three dimensional reconstructions were created using customized software programs to ensure anatomical accuracy (Seg3D and SCIRun) in an IRB and HIPAA approved study. These software packages supported the development of patient specific models and allowed for interactive manipulation of electrode position and size. Preliminary results indicate that electric fields and current densities can be generated at the implant interface to achieve the

Methods to Improve Osseointegration of Dental Implants in Low Quality (Type-IV Bone: An Overview

Directory of Open Access Journals (Sweden)

Hamdan S. Alghamdi

2018-01-01

Full Text Available Nowadays, dental implants have become more common treatment for replacing missing teeth and aim to improve chewing efficiency, physical health, and esthetics. The favorable clinical performance of dental implants has been attributed to their firm osseointegration, as introduced by Brånemark in 1965. Although the survival rate of dental implants over a 10-year observation has been reported to be higher than 90% in totally edentulous jaws, the clinical outcome of implant treatment is challenged in compromised (bone conditions, as are frequently present in elderly people. The biomechanical characteristics of bone in aged patients do not offer proper stability to implants, being similar to type-IV bone (Lekholm & Zarb classification, in which a decreased clinical fixation of implants has been clearly demonstrated. However, the search for improved osseointegration has continued forward for the new evolution of modern dental implants. This represents a continuum of developments spanning more than 20 years of research on implant related-factors including surgical techniques, implant design, and surface properties. The methods to enhance osseointegration of dental implants in low quality (type-IV bone are described in a general manner in this review.

Methods to Improve Osseointegration of Dental Implants in Low Quality (Type-IV) Bone: An Overview.

Science.gov (United States)

Alghamdi, Hamdan S

2018-01-13

Nowadays, dental implants have become more common treatment for replacing missing teeth and aim to improve chewing efficiency, physical health, and esthetics. The favorable clinical performance of dental implants has been attributed to their firm osseointegration, as introduced by Brånemark in 1965. Although the survival rate of dental implants over a 10-year observation has been reported to be higher than 90% in totally edentulous jaws, the clinical outcome of implant treatment is challenged in compromised (bone) conditions, as are frequently present in elderly people. The biomechanical characteristics of bone in aged patients do not offer proper stability to implants, being similar to type-IV bone (Lekholm & Zarb classification), in which a decreased clinical fixation of implants has been clearly demonstrated. However, the search for improved osseointegration has continued forward for the new evolution of modern dental implants. This represents a continuum of developments spanning more than 20 years of research on implant related-factors including surgical techniques, implant design, and surface properties. The methods to enhance osseointegration of dental implants in low quality (type-IV) bone are described in a general manner in this review.

Layer-by-layer self-assembled multilayers on PEEK implants improve osseointegration in an osteoporosis rabbit model.

Science.gov (United States)

Liu, Xilin; Han, Fei; Zhao, Peng; Lin, Chao; Wen, Xuejun; Ye, Xiaojian

2017-05-01

This study aims to fabricate and deposit nanoscale multilayers on polyetheretherketone (PEEK) to improve cell adhesion and osseointegration. Bio-activated PEEK constructs were designed with prepared surface of different layers of polystyrene sulfonate (PSS) and polyallylamine hydrochloride (PAH) multilayers. Irregular morphology was found on the 5 and 10-layer PEEK surfaces, while "island-like" clusters were observed for 20-layer (20 L) multilayers. Besides, the 20 L PEEK showed more hydrophilic feature than native PEEK, and the surface contact angle reduced from 39.7° to 21.7° as layers increased from 5 to 20. In vitro, modified PEEK allowed excellent adhesion and proliferation of bone marrow stromal cells, and induced higher cell growth rate and alkaline phosphatase level. In vivo, this bio-active PEEK exhibited significantly enhanced integration with bone tissue in an osteoporosis rabbit model. This work highlights layer-by-layer self-assembly as a practical method to construct bio-active PEEK implants for enhanced osseointegration. Copyright © 2017 Elsevier Inc. All rights reserved.

Laser surface modification of Ti implants to improve osseointegration

International Nuclear Information System (INIS)

Marticorena, M; Corti, G; Olmedo, D; Guglielmotti, M B; Duhalde, S

2007-01-01

Commercially Pure Titanium foils, were irradiated using a pulsed Nd:YAG laser under ambient air, in order to produce and characterize a well controlled surface texture (roughness and waviness) that enhances osseointegration. To study the 'peri-implant' reparative process response, the laser treated Ti foils were implanted in the tibia of 10 male Wistar rats. At 14 days post-implantation, the histological analysis showed a tendency to more bone formation compared to the untreated control implants. The formation of a layer of TiN on the surface and the obtained roughness, have been demonstrated to improve bone response

Functional and social results of osseointegrated hearing aids

Directory of Open Access Journals (Sweden)

Inmaculada MORENO-ALARCÓN

2017-06-01

Full Text Available Introduction and objective: Osseointegrated implants are nowadays a good therapeutic option for patients suffering from transmission or mixed hearing loss. The aims of this study are both to assess audiology benefits for patients with osseointegrated implants and quantify the change in their quality of life. Method: The study included 10 patients who were implanted in our hospital between March 2013 and September 2014. The instrument used to quantify their quality of life was the Glasgow Benefit Inventory (GBI and a questionnaire including three questions: use of implant, postoperative pain and whether they would recommend the operation to other patients. Audiology assessment was performed through tone audiometry and free field speech audiometric testing. Results: The average total benefit score with the Glasgow Benefit Inventory was +58, and the general, social and physical scores were +75, +18 and +29, respectively. The improvement with the implant regarding free-field tonal audiometry at the frequencies of 500, 1000 and 2000 Hz was found to be statistically significant, as was the difference between verbal audiometry before and after implantation. Discussion: Improvements in surgical technique for osseointegrated implants, at present minimally invasive, foregrounds the assessment of functional and social aspects as a measure of their effectiveness. Conclusions: The use of the osseointegrated implant is related to an important improvement in the audiological level, especially in patients with conductive or mixed hearing loss, together with a great change in the quality of life of implanted patients.

Osseointegration: a review of the fundamentals for assuring cementless skeletal fixation

Directory of Open Access Journals (Sweden)

Isaacson BM

2014-04-01

Full Text Available Brad M Isaacson,1,2 Sujee Jeyapalina3,4 1Henry M Jackson Foundation for the Advancement of Military Medicine, 2The Center for Rehabilitation Sciences Research, Department of Physical Medicine and Rehabilitation, Uniformed Services University of Health Sciences, Bethesda, MD, USA; 3Department of Orthopedics, 4Orthopedic Research Laboratory, University of Utah, Salt Lake City, UT, USA Abstract: Direct skeletal fixation, termed osseointegration, has expanded in the last century and includes use in total joint replacements, the edentulous mandible and maxilla, and percutaneous osseointegrated prosthetics. Although it is well known that titanium and bone have the ability to form a durable bone–implant interface, new applications have emerged in the field of orthopedics, which requires a more thorough assessment of the literature. This review aims to introduce the basic biological principles for attaining osseointegration and discusses the major factors for assuring successful cementless fixation. Keywords: osseointegration, bone, skeletal attachment, total joint replacements, dental implants, percutaneous

Preparation of well-distributed titania nanopillar arrays on Ti6Al4V surface by induction heating for enhancing osteogenic differentiation of stem cells

Science.gov (United States)

Li, Ning-Bo; Sun, Sheng-Jun; Bai, Han-Ying; Xiao, Gui-Yong; Xu, Wen-Hua; Zhao, Jun-Han; Chen, Xin; Lu, Yu-Peng; Zhang, Yi-Lin

2018-01-01

Great effort has recently been devoted to the preparation of nanoscale surfaces on titanium-based implants to achieve clinically fast osteoinduction and osseointegration, which relies on the unique characteristics of the nanostructure. In this work, we used induction heating treatment (IHT) as a rapid oxidation method to fabricate a porous nanoscale oxide layer on the Ti6Al4V surface for better medical application. Well-distributed vertical nanopillars were yielded by IHT for 20-35 s on the alloy surface. The composition of the oxides contained rutile/anatase TiO2 and a small amount of Al2O3 between the TiO2 grain boundaries (GBs). This technology resulted in a reduction and subsequent increase of surface roughness of 26-32 nm when upregulating the heating time, followed by the successive enhancement of the thickness, wettability and adhesion strength of the oxidation layer to the matrix. The surface hardness also distinctly rose to 554 HV in the IHT-35 s group compared with the 350 HV of bare Ti6Al4V. The massive small-angle GBs in the bare alloy promoted the formation of nanosized oxide crystallites. The grain refinement and deformation texture reduction further improved the mechanical properties of the matrix after IHT. Moreover, in vitro experiments on a mesenchymal stem cell (BMSC) culture derived from human bone marrow for 1-7 days indicated that the nanoscale layers did not cause cytotoxicity, and facilitated cell differentiation in osteoblasts by enhancing the gene and osteogenesis-related protein expressions after 1-3 weeks of culturing. The increase of the IHT time slightly advanced the BMSC proliferation and differentiation, especially during long-term culture. Our findings provide strong evidence that IHT oxidation technology is a novel nanosurface modification technology, which is potentially promising for further clinical development.

Comparison between inflammation-related markers in peri-implant crevicular fluid and clinical parameters during osseointegration in edentulous jaws

DEFF Research Database (Denmark)

Bielemann, Amália Machado; Marcello-Machado, Raissa Micaella; Manzolli Leite, Fabio Renato

2017-01-01

Objectives The aim of this study is to improve the understanding of interleukin mechanisms during osseointegration to enhance the monitoring of implant failure and success. Clinical parameters, implant stability, and cytokine levels in peri-implant crevicular fluid (PICF) during early bone healin...

Osseointegration of KrF laser hydroxylapatite films on Ti6A14V alloy by mini-pigs: loaded osseointegration of dental implants

Science.gov (United States)

Dostalova, Tatjana; Jelinek, Miroslav; Himmlova, Lucia; Grivas, Christos

1999-05-01

Aim of study was to evaluate osseointegration of the KrF laser hydroxyapatite coated titanium alloy Ti6Al4V dental implants. For deposition KrF excimer laser in stainless- steel deposition chamber was used. Thickness of HA films were round 1 μm . Mini-pigs were used in this investigation. Implants were placed vertically into the lower jaw. After 14 weeks unloaded osseointegration the metal ceramic crowns were inserted. the experimental animals were sacrificed (1 year post insertion). The vertical position of implants was controlled with a radiograph. Microscopical sections were cut and ground. Sections were viewed using microscope with CCD camera. 1 year osseointegration in lower jaw confirmed by all implants presence of newly formed bone around the all implants. Laser-deposited coating the layer of fibrous connective tissue was seen only seldom. In the control group (titamium implant without cover) the fibrous connective tissue was seen between implant and newly formed bone.

3D bioprinting of BMSC-laden methacrylamide gelatin scaffolds with CBD-BMP2-collagen microfibers.

Science.gov (United States)

Du, Mingchun; Chen, Bing; Meng, Qingyuan; Liu, Sumei; Zheng, Xiongfei; Zhang, Cheng; Wang, Heran; Li, Hongyi; Wang, Nuo; Dai, Jianwu

2015-12-18

Three-dimensional (3D) bioprinting combines biomaterials, cells and functional components into complex living tissues. Herein, we assembled function-control modules into cell-laden scaffolds using 3D bioprinting. A customized 3D printer was able to tune the microstructure of printed bone mesenchymal stem cell (BMSC)-laden methacrylamide gelatin scaffolds at the micrometer scale. For example, the pore size was adjusted to 282 ± 32 μm and 363 ± 60 μm. To match the requirements of the printing nozzle, collagen microfibers with a length of 22 ± 13 μm were prepared with a high-speed crusher. Collagen microfibers bound bone morphogenetic protein 2 (BMP2) with a collagen binding domain (CBD) as differentiation-control module, from which BMP2 was able to be controllably released. The differentiation behaviors of BMSCs in the printed scaffolds were compared in three microenvironments: samples without CBD-BMP2-collagen microfibers in the growth medium, samples without microfibers in the osteogenic medium and samples with microfibers in the growth medium. The results indicated that BMSCs showed high cell viability (>90%) during printing; CBD-BMP2-collagen microfibers induced BMSC differentiation into osteocytes within 14 days more efficiently than the osteogenic medium. Our studies suggest that these function-control modules are attractive biomaterials and have potential applications in 3D bioprinting.

Computerized axial tomography : the tool in osseointegrated dental implants

International Nuclear Information System (INIS)

Fernandez-Lopez, Otton

2002-01-01

Failure rates in rehabilitations with osseointegrated implants are handled through appropriate radiographic preoperative planning. The appropriate length of the implant without running the risk of a perforation of vital structures, has been determined by a radiographic diagnosis. Computerized and conventional axial tomography have proved to be invaluable elements for pre-surgical evaluation. A radiologic guidance is elaborated to perform a computerized axial tomography (CT) of maxillary bones in totally edentulous patients. Surgical guides are constructed from a wax-up emanated from the information of the CT. The CT has proven to be an radiographic indispensable element to achieve the surgical-prosthetic success in osseointegrated dental implants. The CT has allowed the realization of a precise wax-up for making of surgical guide and a precise temporary prostheses in positioning of osseointegrated implants, with the consequent saving time and money for the rehabilitator and patient [es

Augmenting the osseointegration of endoprostheses using laser-sintered porous collars: an in vivo study.

Science.gov (United States)

Mumith, A; Coathup, M; Chimutengwende-Gordon, M; Aston, W; Briggs, T; Blunn, G

2017-02-01

Massive endoprostheses rely on extra-cortical bone bridging (ECBB) to enhance fixation. The aim of this study was to investigate the role of selective laser sintered (SLS) porous collars in augmenting the osseointegration of these prostheses. The two novel designs of porous SLS collars, one with small pores (Ø700 μm, SP) and one with large pores (Ø1500 μm, LP), were compared in an ovine tibial diaphyseal model. Osseointegration of these collars was compared with that of a clinically used solid, grooved design (G). At six months post-operatively, the ovine tibias were retrieved and underwent radiological and histological analysis. Porous collars provided a significantly greater surface (p direct ingrowth of more bone and are better than current designs which rely on surface ongrowth and ECBB. Cite this article: Bone Joint J 2017;99-B:276-82. ©2017 The British Editorial Society of Bone & Joint Surgery.

A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats

Energy Technology Data Exchange (ETDEWEB)

Tao, Zhou-Shan [Department of Orthopaedic Surgery, Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, Zhejiang 325027 (China); Zhou, Wan-Shu [Endocrine & Metabolic Diseases Unit, Affiliated Hospital of Guizhou Medical University, Guizhou 550001 (China); He, Xing-Wen [Department of Orthopaedic Surgery, Hangzhou Bay Hospital of Ningbo, 315000 (China); Liu, Wei [Department of Orthopaedic Surgery, Jingmen No. 1 People' s Hospital, Jingmen 44800, Hubei (China); Bai, Bing-Li; Zhou, Qiang; Huang, Zheng-Liang; Tu, Kai-kai; Li, Hang; Sun, Tao [Department of Orthopaedic Surgery, Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, Zhejiang 325027 (China); Lv, Yang-Xun [Department of Orthopaedic Surgery, Wenzhou Central Hospital, Wenzhou, Zhejiang 325000 (China); Cui, Wei [Sichuan Provincial Orthopedics Hospital, No. 132 West First Section First Ring Road, Chengdu, Sichuan 610000 (China); Yang, Lei, E-mail: tzs19900327@163.com [Department of Orthopaedic Surgery, Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, Zhejiang 325027 (China)

2016-05-01

growth, and positively affects bone regeneration. • It seems that Zn, Mg, Sr ions enhance bone-implant osseointegration in osteoporotic bone, but concerns still exist on which one is more effective, however, there is still no direct comparative study on these three coatings. • Our current study was designed to compare the effects of Zn, Mg, Sr-substituted hydroxyapatite coatings on bone-implant osseointegration in bone loss rats.

Selective laser melting of titanium alloy enables osseointegration of porous multi-rooted implants in a rabbit model.

Science.gov (United States)

Peng, Wei; Xu, Liangwei; You, Jia; Fang, Lihua; Zhang, Qing

2016-07-21

Osseointegration refers to the direct connection between living bone and the surface of a load-bearing artificial implant. Porous implants with well-controlled porosity and pore size can enhance osseointegration. However, until recently implants were produced by machining solid core titanium rods. The aim of this study was to develop a multi-rooted dental implant (MRI) with a connected porous surface structure to facilitate osseointegration. MRIs manufactured by selective laser melting (SLM) and commercial implants with resorbable blasting media (RBM)-treated surfaces were inserted into the hind limbs of New Zealand white rabbits. Osseointegration was evaluated periodically over 12 weeks by micro-computerized tomography (CT) scanning, histological analysis, mechanical push-out tests, and torque tests. Bone volume densities were consistently higher in the MRI group than in the RBM group throughout the study period, ultimately resulting in a peak value of 48.41 % for the MRI group. Histological analysis revealed denser surrounding bone growth in the MRIs; after 4 and 8 weeks, bone tissue had grown into the pore structures and root bifurcation areas, respectively. Biomechanics tests indicated binding of the porous MRIs to the neobone tissues, as push-out forces strengthened from 294.7 to 446.5 N and maximum mean torque forces improved from 81.15 to 289.57 N (MRI), versus 34.79 to 87.8 N in the RBM group. MRIs manufactured by SLM possess a connected porous surface structure that improves the osteogenic characteristics of the implant surface.

Local Application of Growth Hormone to Enhance Osseointegration in Osteoporotic Bones: A Morphometric and Densitometric Study.

Science.gov (United States)

Martin-Monge, Elena; Tresguerres, Isabel F; Clemente, Celia; Tresguerres, Jesús Af

The aim of this study was to assess the effect of local application of growth hormone on osseointegration of dental implants inserted in osteoporotic bones. Twenty female New Zealand rabbits were used in this study. Ten were ovariectomized and fed a low-calcium diet for 6 weeks, and the others remained intact. A titanium implant was inserted into each tibia, in both groups. In half of the rabbits, 2 IU of growth hormone was placed into the ostectomy prior to the implant insertion. Two weeks after implant surgery, all animals were sacrificed. Tibiae were dissected from soft tissues, and included in methacrylate to be studied under light microscopy. Bone-to-implant contact (BIC) and bone mineral density (BMD) were measured by morphometric and densitometric analysis, respectively. Multifactorial analysis of variance (ANOVA) was used for statistical evaluation. P growth hormone was able to increase the BIC in the ovariectomized group, with statistically significant differences with respect to the control group (P growth hormone at the moment of titanium implant insertion in rabbit tibiae significantly enhanced the BIC around titanium implants 15 days after the implantation in this experimental osteoporotic animal model, without affecting the BMD.

Effect of surface contamination on osseointegration of dental implants surrounded by circumferential bone defects.

LENUS (Irish Health Repository)

Mohamed, Seif

2010-05-01

This study was designed to evaluate the effect of surface contamination on osseointegration of dental implants surrounded by a circumferential bone defect and to compare osseointegration around Osseotite with that around Nanotite implants.

Functional Apparent Moduli (FAMs) as Predictors of Oral Implant Osseointegration Dynamics

OpenAIRE

Chang, Po-Chun; Seol, Yang-Jo; Kikuchi, Noboru; Goldstein, Steven A.; Giannobile, William V.

2010-01-01

At present, limited functional data exists regarding the application and use of biomechanical and imaging technologies for oral implant osseointegration assessment. The objective of this investigation was to determine the functional apparent moduli (FAMs) that could predict the dynamics of oral implant osseointegration. Using an in vivo dental implant osseous healing model, two FAMs, functional bone apparent modulus (FBAM) and composite tissue apparent modulus (FCAM), of the selected peri-imp...

The impact of nicotine on osseointegration. An experimental study in the femur and tibia of rabbits

DEFF Research Database (Denmark)

Balatsouka, Dimitra; Gotfredsen, Klaus; Lindh, Christian H

2005-01-01

OBJECTIVES: The aim of the present study was to analyze the effect of an enhanced systematic dose of nicotine on osseointegration of titanium implants. MATERIAL AND METHODS: Sixteen female rabbits received either nicotine (n=8) or saline (n=8) administered subcutaneously via mini-osmotic pumps...... for 2 months. The pump delivered 6 mug/kg/min of nicotine for the animals in the test group. Blood was withdrawn and plasma cotinine levels were measured weekly. Thirty-two titanium implants were inserted into the femur and tibia of all rabbits after 4 weeks and after 6 weeks of nicotine...... and the peri-implant BD-i showed no significant differences between the test and the control group after 2 or after 4 weeks. CONCLUSION: Nicotine exposure for a short period of time even in a high dose did not have a significant impact on implant osseointegration in rabbits....

Enhanced biocompatibility and osseointegration of calcium titanate coating on titanium screws in rabbit femur.

Science.gov (United States)

Wang, Zi-Li; He, Rong-Zhen; Tu, Bin; Cao, Xu; He, Jin-Shen; Xia, Han-Song; Liang, Chi; Zou, Min; Wu, Song; Wu, Zhen-Jun; Xiong, Kun

2017-06-01

This study aimed to examine the biocompatibility of calcium titanate (CaTiO 3 ) coating prepared by a simplified technique in an attempt to assess the potential of CaTiO 3 coating as an alternative to current implant coating materials. CaTiO 3 -coated titanium screws were implanted with hydroxyapatite (HA)-coated or uncoated titanium screws into medial and lateral femoral condyles of 48 New Zealand white rabbits. Imaging, histomorphometric and biomechanical analyses were employed to evaluate the osseointegration and biocompatibility 12 weeks after the implantation. Histology and scanning electron microscopy revealed that bone tissues surrounding the screws coated with CaTiO 3 were fully regenerated and they were also well integrated with the screws. An interfacial fibrous membrane layer, which was found in the HA coating group, was not noticeable between the bone tissues and CaTiO 3 -coated screws. X-ray imaging analysis showed in the CaTiO 3 coating group, there was a dense and tight binding between implants and the bone tissues; no radiation translucent zone was found surrounding the implants as well as no detachment of the coating and femoral condyle fracture. In contrast, uncoated screws exhibited a fibrous membrane layer, as evidenced by the detection of a radiation translucent zone between the implants and the bone tissues. Additionally, biomechanical testing revealed that the binding strength of CaTiO 3 coating with bone tissues was significantly higher than that of uncoated titanium screws, and was comparable to that of HA coating. The study demonstrated that CaTiO 3 coating in situ to titanium screws possesses great biocompatibility and osseointegration comparable to HA coating.

Effects of type I collagen coating on titanium osseointegration: histomorphometric, cellular and molecular analyses

International Nuclear Information System (INIS)

Sverzut, Alexander Tadeu; Crippa, Grasiele Edilaine; Tambasco de Oliveira, Paulo; Beloti, Marcio Mateus; Rosa, Adalberto Luiz; Morra, Marco

2012-01-01

The investigation of titanium (Ti) surface modifications aiming to increase implant osseointegration is one of the most active research areas in dental implantology. This study was carried out to evaluate the benefits of coating Ti with type I collagen on the osseointegration of dental implants. Acid etched Ti implants (AETi), either untreated or coated with type I collagen (ColTi), were placed in dog mandibles for three and eight weeks for histomorphometric, cellular and molecular evaluations of bone tissue response. While the histological aspects were essentially the same with both implants being surrounded by lamellar bone trabeculae, histomorphometric analysis showed more abundant bone formation in ColTi, mainly at three weeks. Cellular evaluation showed that cells harvested from bone fragments in close contact with ColTi display lower proliferative capacity and higher alkaline phosphatase activity, phenotypic features associated with more differentiated osteoblasts. Confirming these findings, molecular analyses showed that ColTi implants up-regulates the expression of a panel of genes well known as osteoblast markers. Our results present a set of evidences that coating AETi with collagen fastens the osseointegration by stimulating bone formation at the cellular and molecular levels, making this combination of morphological and biochemical modification a promising approach to treat Ti surfaces. (paper)

Radiographic evaluation of bone adaptation adjacent to percutaneous osseointegrated prostheses in a sheep model.

Science.gov (United States)

Jeyapalina, Sujee; Beck, James Peter; Bachus, Kent N; Chalayon, Ornusa; Bloebaum, Roy D

2014-10-01

Percutaneous osseointegrated prostheses (POPs) are being investigated as an alternative to conventional socket suspension and require a radiographic followup in translational studies to confirm that design objectives are being met. In this 12-month animal study, we determined (1) radiographic signs of osseointegration and (2) radiographic signs of periprosthetic bone hypertrophy and resorption (adaptation) and (3) confirmed them with the histologic evidence of host bone osseointegration and adaptation around a novel, distally porous-coated titanium POP with a collar. A POP device was designed to fit the right metacarpal bone of sheep. Amputation and implantation surgeries (n = 14) were performed, and plane-film radiographs were collected quarterly for 12 months. Radiographs were assessed for osseointegration (fixation) and bone adaptation (resorption and hypertrophy). The cortical wall and medullary canal widths were used to compute the cortical index and expressed as a percentage. Based on the cortical index changes and histologic evaluations, bone adaptation was quantified. Radiographic data showed signs of osseointegration including those with incomplete seating against the collar attachment. Cortical index data indicated distal cortical wall thinning if the collar was not seated distally. When implants were bound proximally, bone resorbed distally and the diaphyseal cortex hypertrophied. Histopathologic evidence and cortical index measurements confirmed the radiographic indications of adaptation and osseointegration. Distal bone loading, through collar attachment and porous coating, limited the distal bone resorption. Serial radiographic studies, in either animal models or preclinical trials for new POP devices, will help to determine which designs are likely to be safe over time and avoid implant failures.

Novel hydrophilic nanostructured microtexture on direct metal laser sintered Ti-6Al-4V surfaces enhances osteoblast response in vitro and osseointegration in a rabbit model.

Science.gov (United States)

Hyzy, Sharon L; Cheng, Alice; Cohen, David J; Yatzkaier, Gustavo; Whitehead, Alexander J; Clohessy, Ryan M; Gittens, Rolando A; Boyan, Barbara D; Schwartz, Zvi

2016-08-01

The purpose of this study was to compare the biological effects in vivo of hierarchical surface roughness on laser sintered titanium-aluminum-vanadium (Ti-6Al-4V) implants to those of conventionally machined implants on osteoblast response in vitro and osseointegration. Laser sintered disks were fabricated to have micro-/nano-roughness and wettability. Control disks were computer numerical control (CNC) milled and then polished to be smooth (CNC-M). Laser sintered disks were polished smooth (LST-M), grit blasted (LST-B), or blasted and acid etched (LST-BE). LST-BE implants or implants manufactured by CNC milling and grit blasted (CNC-B) were implanted in the femurs of male New Zealand white rabbits. Most osteoblast differentiation markers and local factors were enhanced on rough LST-B and LST-BE surfaces in comparison to smooth CNC-M or LST-M surfaces for MG63 and normal human osteoblast cells. To determine if LST-BE implants were osteogenic in vivo, we compared them to implant surfaces used clinically. LST-BE implants had a unique surface with combined micro-/nano-roughness and higher wettability than conventional CNC-B implants. Histomorphometric analysis demonstrated a significant improvement in cortical bone-implant contact of LST-BE implants compared to CNC-B implants after 3 and 6 weeks. However, mechanical testing revealed no differences between implant pullout forces at those time points. LST surfaces enhanced osteoblast differentiation and production of local factors in vitro and improved the osseointegration process in vivo. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2086-2098, 2016. © 2016 Wiley Periodicals, Inc.

The impact of glucocorticosteroids administered for systemic diseases on the osseointegration and survival of dental implants placed without bone grafting-A retrospective study in 31 patients.

Science.gov (United States)

Petsinis, Vassilis; Kamperos, Georgios; Alexandridi, Foteini; Alexandridis, Konstantinos

2017-08-01

To evaluate the impact of glucocorticosteroids, administered for the treatment of systemic diseases, on the osseointegration and survival of dental implants placed without bone grafting. A retrospective study was conducted in search of patients treated with dental implants while receiving glucocorticosteroid therapy for various systemic diseases. In these cases, a conventional two-stage surgical protocol was used, without bone regeneration procedures. The osseointegration was clinically and radiographically tested at the uncovering of the implants. The follow-up after loading was set at a minimum of 3 years. A total of 31 patients were included in the study. Of the 105 dental implants placed, 104 were osseointegrated (99%). No bone absorption was radiographically noted at the uncovering of the osseointegrated implants. All of the osseointegrated implants were successfully loaded for the prosthetic restoration. The mean follow-up period after loading was 71 months, with an implant survival rate of 99%. Glucocorticosteroid intake for systemic diseases does not have a significant impact on the osseointegration and the 3-year survival of dental implants placed with a conventional two-stage surgical protocol and without bone grafting. Therefore, it should not be considered a contraindication for dental implant placement. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Chronological Age as Factor Influencing the Dental Implant Osseointegration in the Jaw Bone

Directory of Open Access Journals (Sweden)

Jan Papež

2018-04-01

Full Text Available The objectives of this study were to evaluate osseointegration of dental implant in the jaw bone in the young and elderly population and comparing the results to assess indicators and risk factors as age for the success or failure of dental implants. A retrospective study of 107 implants (Impladent, LASAK, Czech Republic was prepared. The patients at implants surgery were divided in three groups. The patients were followed-up for a 7-year period. We evaluated osseointegration from long term point of view as a change of marginal bone levels close to dental implant. Marginal bone levels were recorded and analysed with regard to different patient- and implant-related factors. An influence of chronological age on change of marginal bone levels during 6-year retrospective study vas evaluated. The study examined 47 patient charts and 107 implants from the Second Faculty of Medicine, Charles University and University Hospital Motol. We proved that young healthy patients with long bridges or Branemarks have the same progression of marginal bone levels changes. The chronological age hasn’t therefore direct influence on the osseointegration from long term point of view. But we found that the length of dental suprastrucure-prosthetic construction negatively influences marginal bone changes, though these results weren’t statistically significant. More extensive dental implant suprastrucure undergoes smaller osseointegration. On the other hand the length of dental suprastrucure (prosthetic construction negatively influences dental osseointegration in both groups of patient.

Osseointegration of zirconia implants: an SEM observation of the bone-implant interface.

Science.gov (United States)

Depprich, Rita; Zipprich, Holger; Ommerborn, Michelle; Mahn, Eduardo; Lammers, Lydia; Handschel, Jörg; Naujoks, Christian; Wiesmann, Hans-Peter; Kübler, Norbert R; Meyer, Ulrich

2008-11-06

The successful use of zirconia ceramics in orthopedic surgery led to a demand for dental zirconium-based implant systems. Because of its excellent biomechanical characteristics, biocompatibility, and bright tooth-like color, zirconia (zirconium dioxide, ZrO2) has the potential to become a substitute for titanium as dental implant material. The present study aimed at investigating the osseointegration of zirconia implants with modified ablative surface at an ultrastructural level. A total of 24 zirconia implants with modified ablative surfaces and 24 titanium implants all of similar shape and surface structure were inserted into the tibia of 12 Göttinger minipigs. Block biopsies were harvested 1 week, 4 weeks or 12 weeks (four animals each) after surgery. Scanning electron microscopy (SEM) analysis was performed at the bone implant interface. Remarkable bone attachment was already seen after 1 week which increased further to intimate bone contact after 4 weeks, observed on both zirconia and titanium implant surfaces. After 12 weeks, osseointegration without interposition of an interfacial layer was detected. At the ultrastructural level, there was no obvious difference between the osseointegration of zirconia implants with modified ablative surfaces and titanium implants with a similar surface topography. The results of this study indicate similar osseointegration of zirconia and titanium implants at the ultrastructural level.

Dental Implant Macro-Design Features Can Impact the Dynamics of Osseointegration.

Science.gov (United States)

Vivan Cardoso, Marcio; Vandamme, Katleen; Chaudhari, Amol; De Rycker, Judith; Van Meerbeek, Bart; Naert, Ignace; Duyck, Joke

2015-08-01

The purpose of this study was to compare the clinical performance of two dental implant types possessing a different macro-design in the in vivo pig model. Titanium Aadva(TM) implants (GC, Tokyo, Japan) were compared with OsseoSpeed(TM) implants (Astra, Mölndal, Sweden), with the Aadva implant displaying significant larger inter-thread dimensions than the OsseoSpeed implant. Implants were installed in the parietal bone of 12 domestic pigs and left for healing for either 1 or 3 months. Implant osseointegration was evaluated by quantitative histology (bone volume relative to the tissue volume [BV/TV]; bone-to-implant contact [BIC]) for distinct implant regions (collar, body, total implant length) with specific implant thread features. The Wilcoxon-Mann-Whitney nonparametric test with α = 0.05 was performed. An inferior amount of bone enveloping the Aadva implant compared with the OsseoSpeed implant was observed, in particular at the implant body part with its considerable inter-thread gaps (p macro-design negatively affected the amount of bone in direct contact with the implant for this specific implant part (p implant osseointegration at the initial healing stage (total implant length; 1-month healing; p implant displayed a clinically acceptable level of osseointegration, the findings demonstrate that implant macro-design features can impact the dynamics of implant osseointegration. Consideration of specific implant macro-design features should be made relative to the biological and mechanical microenvironment. © 2013 Wiley Periodicals, Inc.

Osseointegration of biochemically modified implants in an osteoporosis rodent model

Directory of Open Access Journals (Sweden)

B Stadlinger

2013-07-01

Full Text Available The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX osteoporotic rats (n = 32/group. In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout. Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC, peri-implant bone area (BA, bone volume/tissue volume (BV/TV and bone-mineral density (BMD in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

A study of the effect of low intensity laser therapy on the osseointegration of hydroxyapatite implants

International Nuclear Information System (INIS)

Rajab, A.A.

1999-01-01

Three significant developments over the last decade in the maxillofacial region have been the predictable use of dental implants, the employment of hydroxyapatite as an implant coating, with a potential for more rapid osseointegration, and the introduction of Low Intensity Laser Therapy (LILT) for the enhancement of healing. Implants, although proving a major advance in prosthetics have the disadvantage that loading has to be delayed for a period, which in the case of the mouth needs to be 3 - 6 months after insertion. Hydroxyapatite offers the possibility of a shortened period of delay. Low Intensity Laser Therapy (LILT) has been shown to accelerate the healing of bony fractures, both experimentally and clinically. This thesis sets out to evaluate whether LILT could enhance the process of osseointegration, particularly when used with ceramic hydroxyapatite implants in an animal model. If so, this could provide a future clinical combination which would allow earlier loading of hydroxyapatite coated dental implants and also their counterparts in femoral head replacement. There has been virtually no research work undertaken on this aspect. An animal research study has been undertaken to investigate the effect of LILT on the osseointegration of endosseous implants. HA ceramic implants were inserted in two different anatomical sites, namely the mandible and femur in 40 rabbits. The animals were divided into three groups, comprising a low energy laser group (25 J/cm 2 per treatment), a high energy group (125 J/cm 2 per treatment ) and a control group. Animals were sacrificed at four and twelve weeks, with equivalent numbers of representatives of the three groups. The evolved method of evaluation involved radiographic methods (plain x-ray, radiovisiography RVG and the innovative technique of x-ray microtomography XMT), mechanical push out testing (Instron machine) and histological examination (qualitative and quantitative histomorphometry). The conclusions of the study

The impact of nicotine on bone healing and osseointegration

DEFF Research Database (Denmark)

Balatsouka, Dimitra; Gotfredsen, Klaus; Lindh, Christian H

2005-01-01

OBJECTIVES: To examine the short-term effect of nicotine on bone healing and osseointegration. MATERIAL AND METHODS: Sixteen female rabbits were divided into two groups. The test group was exposed to nicotine tartrate for 8 weeks and the control group was exposed to placebo. Nicotine or placebo...... was administered via a miniosmotic pump and plasma cotinine levels were measured weekly. The pump delivered 15 mg of nicotine/day for the animals in the test group. All rabbits had three tibial bone preparations. In the proximal and distal bone bed, implants were placed after 4 weeks (right tibia) and after 6...... and the control group. CONCLUSION: Nicotine exposure in a short period of time did not have a significant impact on bone healing or implant osseointegration in rabbits....

Effect of insertion torque on titanium implant osseointegration: an animal experimental study.

Science.gov (United States)

Duyck, Joke; Roesems, Rutger; Cardoso, Marcio V; Ogawa, Toru; De Villa Camargos, Germana; Vandamme, Katleen

2015-02-01

To evaluate the effect of implant insertion torque on the peri-implant bone healing and implant osseointegration. Bilaterally in the tibia of five adult New Zealand white rabbits, 20 implants were installed, subdivided into four groups, corresponding to two insertion torque conditions (low, 50 Ncm) and 2 experimental periods (2 weeks vs. 4 weeks of healing). The implant insertion torque was determined by the surgical drill diameter relative to the implant diameter. Implant osseointegration was evaluated by quantitative histology (bone-to-implant contact with host bone [BIC-host], with neoformed bone [BIC-de novo], with both bone types [BIC-total], and peri-implant bone [BA/TA]). Every response was modelled over time using GEE (general estimation equation) with an unstructured variance-covariance matrix to correct for dependency between the measurements from one animal. The statistical significance level of α = 0.05 was applied. Significantly, more BIC-host and BIC-total were recorded for H implants compared with L implants after 2 week of healing (P = 0.010 and P = 0.0001, respectively). However, this result was no longer found for the extended healing period. Furthermore, BIC-total significantly increased over time for L implants (P torque led to an increased BA/TA after 4 week of healing (P torque implants installed in the rabbit tibial bone osseointegrate with considerable de novo bone formation. This bone neoformation enables L implants to catch up, already during the early osseointegration stage, the initial inferior amount BIC contact compared with that of H implants. A negative impact of the created strain environment accompanying H insertion torque implant installation on the biological process of osseointegration could not be observed, at least not at tissue level. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Osseointegration of Plateau Root Form Implants: Unique Healing Pathway Leading to Haversian-Like Long-Term Morphology.

Science.gov (United States)

Coelho, Paulo G; Suzuki, Marcelo; Marin, Charles; Granato, Rodrigo; Gil, Luis F; Tovar, Nick; Jimbo, Ryo; Neiva, Rodrigo; Bonfante, Estevam A

2015-01-01

Endosteal dental implants have been utilized as anchors for dental and orthopedic rehabilitations for decades with one of the highest treatment success rates in medicine. Such success is due to the phenomenon of osseointegration where after the implant surgical placement, bone healing results into an intimate contact between bone and implant surface. While osseointegration is an established phenomenon, the route which osseointegration occurs around endosteal implants is related to various implant design factors including surgical instrumentation and implant macro, micro, and nanometer scale geometry. In an implant system where void spaces (healing chambers) are present between the implant and bone immediately after placement, its inherent bone healing pathway results in unique opportunities to accelerate the osseointegration phenomenon at the short-term and its maintenance on the long-term through a haversian-like bone morphology and mechanical properties.

Osseointegration and biocompatibility of different metal implants - a comparative experimental investigation in sheep

Science.gov (United States)

2012-01-01

Background In the present study, 4 different metallic implant materials, either partly coated or polished, were tested for their osseointegration and biocompatibility in a pelvic implantation model in sheep. Methods Materials to be evaluated were: Cobalt-Chrome (CC), Cobalt-Chrome/Titanium coating (CCTC), Cobalt-Chrome/Zirconium/Titanium coating (CCZTC), Pure Titanium Standard (PTST), Steel, TAN Standard (TANST) and TAN new finish (TANNEW). Surgery was performed on 7 sheep, with 18 implants per sheep, for a total of 63 implants. After 8 weeks, the specimens were harvested and evaluated macroscopically, radiologically, biomechanically (removal torque), histomorphometrically and histologically. Results Cobalt-Chrome screws showed significantly (p = 0.031) lower removal torque values than pure titanium screws and also a tendency towards lower values compared to the other materials, except for steel. Steel screws showed no significant differences, in comparison to cobalt-chrome and TANST, however also a trend towards lower torque values than the remaining materials. The results of the fluorescence sections agreed with those of the biomechanical test. Histomorphometrically, there were no significant differences of bone area between the groups. The BIC (bone-to-implant-contact), used for the assessment of the osseointegration, was significantly lower for cobalt-chrome, compared to steel (p = 0.001). Steel again showed a lower ratio (p = 0.0001) compared to the other materials. Conclusion This study demonstrated that cobalt-chrome and steel show less osseointegration than the other metals and metal-alloys. However, osseointegration of cobalt-chrome was improved by zirconium and/or titanium based coatings (CCTC, TANST, TAN, TANNEW) being similar as pure titanium in their osseointegrative behavior. PMID:22400715

Adenoviral Mediated Expression of BMP2 by Bone Marrow Stromal Cells Cultured in 3D Copolymer Scaffolds Enhances Bone Formation.

Science.gov (United States)

Sharma, Sunita; Sapkota, Dipak; Xue, Ying; Sun, Yang; Finne-Wistrand, Anna; Bruland, Ove; Mustafa, Kamal

2016-01-01

Selection of appropriate osteoinductive growth factors, suitable delivery method and proper supportive scaffold are critical for a successful outcome in bone tissue engineering using bone marrow stromal cells (BMSC). This study examined the molecular and functional effect of a combination of adenoviral mediated expression of bone morphogenetic protein-2 (BMP2) in BMSC and recently developed and characterized, biodegradable Poly(L-lactide-co-є-caprolactone){poly(LLA-co-CL)}scaffolds in osteogenic molecular changes and ectopic bone formation by using in vitro and in vivo approaches. Pathway-focused custom PCR array, validation using TaqMan based quantitative RT-PCR (qRT-PCR) and ALP staining showed significant up-regulation of several osteogenic and angiogenic molecules, including ALPL and RUNX2 in ad-BMP2 BMSC group grown in poly(LLA-co-CL) scaffolds both at 3 and 14 days. Micro CT and histological analyses of the subcutaneously implanted scaffolds in NOD/SCID mice revealed significantly increased radiopaque areas, percentage bone volume and formation of vital bone in ad-BMP2 scaffolds as compared to the control groups both at 2 and 8 weeks. The increased bone formation in the ad-BMP2 group in vivo was paralleled at the molecular level with concomitant over-expression of a number of osteogenic and angiogenic genes including ALPL, RUNX2, SPP1, ANGPT1. The increased bone formation in ad-BMP2 explants was not found to be associated with enhanced endochondral activity as evidenced by qRT-PCR (SOX9 and FGF2) and Safranin O staining. Taken together, combination of adenoviral mediated BMP-2 expression in BMSC grown in the newly developed poly(LLA-co-CL) scaffolds induced expression of osteogenic markers and enhanced bone formation in vivo.

Osseointegrated Supported Prosthesis and Interdisciplinary Approach for Prosthodontic Rehabilitation of a Young Patient with Ectodermal Dysplasia

Directory of Open Access Journals (Sweden)

Karthik M. Sadashiva

2013-01-01

Full Text Available Anhidrotic ectodermal dysplasia is a triad of hypodontia or anodontia, hypotrichosis, and hypohydrosis, associated with other problems that result from the defective development of structures of ectodermal origin (Freire-Maia, Pinheiro (1988. Early and extensive dental treatment is needed keeping in mind the effect on the craniofacial growth. Due to rapid growth of the jaws, the patients are rehabilitated using removable prostheses (Tarjan et al. (2005. Hence for a young patient in this case report, the placement of endosseous osseointegrated implants was delayed till adulthood. Finally a definitive fixed tooth-supported and osseointegrated implant supported fixed partial denture therapy was used to rehabilitate the patient satisfactorily after she had completed her growth (Sweeney et al. (2005. A review of the current literature relevant to several aspects of syndromic hypodontia, patient selection, and implant planning is discussed.

In vivo osseointegration of dental implants with an antimicrobial peptide coating.

Science.gov (United States)

Chen, X; Zhou, X C; Liu, S; Wu, R F; Aparicio, C; Wu, J Y

2017-05-01

This study aimed to evaluate the in vivo osseointegration of implants with hydrophobic antimicrobial GL13K-peptide coating in rabbit femoral condyles by micro-CT and histological analysis. Six male Japanese Rabbits (4 months old and weighing 2.5 kg each) were included in this study. Twelve implants (3.75 mm wide, 7 mm long) were randomly distributed in two groups, with six implants in the experimental group coated with GL13K peptide and six implants in the control group without surface coating. Each implant in the test and the control group was randomly implanted in the left or right side of femoral condyles. On one side randomly-selected of the femur, each rabbit received a drill that was left without implant as control for the natural healing of bone. After 3 weeks of healing radiographic evaluation of the implant sites was taken. After 6 weeks of healing, rabbits were sacrificed for evaluation of the short-term osseointegration of the dental implants using digital radiography, micro-CT and histology analysis. To perform evaluation of osseointegration, implant location and group was double blinded for surgeon and histology/radiology researcher. Two rabbits died of wound infection in sites with non-coated implants 2 weeks after surgery. Thus, at least four rabbits per group survived after 6 weeks of healing. The wounds healed without suppuration and inflammation. No implant was loose after 6 weeks of healing. Radiography observations showed good osseointegration after 3 and 6 weeks postoperatively, which proved that the tissues followed a natural healing process. Micro-CT reconstruction and analysis showed that there was no statistically significant difference (P > 0.05) in volume of bone around the implant between implants coated with GL13K peptide and implants without coating. Histomorphometric analysis also showed that the mineralized bone area was no statistically different (P > 0.05) between implants coated with GL13K peptide and

Kinetics of transfemoral amputees with osseointegrated fixation performing common activities of daily living.

Science.gov (United States)

Lee, Winson C C; Frossard, Laurent A; Hagberg, Kerstin; Haggstrom, Eva; Brånemark, Rickard; Evans, John H; Pearcy, Mark J

2007-07-01

Direct anchorage of a lower-limb prosthesis to the bone through an implanted fixation (osseointegration) has been suggested as an excellent alternative for amputees experiencing complications from use of a conventional socket-type prosthesis. However, an attempt needs to be made to optimize the mechanical design of the fixation and refine the rehabilitation program. Understanding the load applied on the fixation is a crucial step towards this goal. The load applied on the osseointegrated fixation of nine transfemoral amputees was measured using a load transducer, when the amputees performed activities which included straight-line level walking, ascending and descending stairs and a ramp as well as walking around a circle. Force and moment patterns along each gait cycle, magnitudes and time of occurrence of the local extrema of the load, as well as impulses were analysed. Managing a ramp and stairs, and walking around a circle did not produce a significant increase (P>0.05) in load compared to straight-line level walking. The patterns of the moment about the medio-lateral axis were different among the six activities which may reflect the different strategies used in controlling the prosthetic knee joint. This study increases the understanding of biomechanics of bone-anchored osseointegrated prostheses. The loading data provided will be useful in designing the osseointegrated fixation to increase the fatigue life and to refine the rehabilitation protocol.

Influence of bone marrow on osseointegration in long bones: an experimental study in sheep.

Science.gov (United States)

Morelli, Fabrizio; Lang, Niklaus P; Bengazi, Franco; Baffone, Davide; Vila Morales, C Dadonim; Botticelli, Daniele

2015-03-01

To evaluate the influence of yellow bone marrow on osseointegration of titanium oral implants using a long bone model. The two tibiae of eight sheep were used as experimental sites. Two osteotomies for implant installation were prepared in each tibia. At the control sites, no further treatments were performed while, at the test sites, bone marrow was removed from the osteotomy site with a curette to an extent that exceeded the implant dimensions. As a result, the apical portion of the implants at the control sites was in contact with bone marrow while, at the test sites, it was in contact with the blood clot. After 2 months, the same procedures were performed in the contralateral side. After another month, the animal was sacrificed. Ground sections were obtained for histological analysis. After 1 month of healing, no differences between test and control sites were found in the apical extension of osseointegration and the percentage of new bone-to-implant contact. However, after 3 months of healing, a higher percentage of new bone-to-implant contact was found at the test compared to the control sites in the marrow compartment. The apical extension of osseointegration, however, was similar to that found at the 1-month healing period both for test and control sites. Osseointegration appeared to be favored by the presence of a blood clot when compared to the presence of yellow fatty bone marrow. Moreover, the contact with cortical bone appeared to be a prerequisite for the osseointegration process in the long bone model. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fast plasma sintering delivers functional graded materials components with macroporous structures and osseointegration properties.

Science.gov (United States)

Godoy, R F; Coathup, M J; Blunn, G W; Alves, A L; Robotti, P; Goodship, A E

2016-04-13

We explored the osseointegration potential of two macroporous titanium surfaces obtained using fast plasma sintering (FPS): Ti macroporous structures with 400-600 µmØ pores (TiMac400) and 850-1000 µmØ pores (TiMac850). They were compared against two surfaces currently in clinical use: Ti-Growth® and air plasma spray (Ti-Y367). Each surface was tested, once placed over a Ti-alloy and once onto a CoCr bulk substrate. Implants were placed in medial femoral condyles in 24 sheep. Samples were explanted at four and eight weeks after surgery. Push-out loads were measured using a material-testing system. Bone contact and ingrowth were assessed by histomorphometry and SEM and EDX analyses. Histology showed early osseointegration for all the surfaces tested. At 8 weeks, TiMac400, TiMac850 and Ti-Growth® showed deep bone ingrowth and extended colonisation with newly formed bone. The mechanical push-out force was equal in all tested surfaces. Plasma spray surfaces showed greater bone-implant contact and higher level of pores colonisation with new bone than FPS produced surfaces. However, the void pore area in FPS specimens was significantly higher, yet the FPS porous surfaces allowed a deeper osseointegration of bone to implant. FPS manufactured specimens showed similar osseointegration potential to the plasma spray surfaces for orthopaedic implants. FPS is a useful technology for manufacturing macroporous titanium surfaces. Furthermore, its capability to combine two implantable materials, using bulk CoCr with macroporous titanium surfaces, could be of interest as it enables designers to conceive and manufacture innovative components. FPS delivers functional graded materials components with macroporous structures optimised for osseointegration.

CT in dental osseointegration

International Nuclear Information System (INIS)

Witte, D.

1992-01-01

Computerised tomography (CT) plays a key role in the pre-surgical evaluation of the alveolar process for titanium dental implants. The successful replacement of lost teeth by tissue integrated tooth root implants is a major advance in clinical dentistry. The paper will discuss briefly the history of osseointegration and how CT is now involved in helping the edentulous patient. CT is considered as a quick and convenient method of obtaining excellent anatomical information about the maxilla. Conventional tomography is difficult to obtain and does not provide valuable cross-sectional images. Exact height and width calculations can be made as well as screening out patients with advanced bone resorption. 3 refs. 6 figs

Pulsed electromagnetic fields preserve bone architecture and mechanical properties and stimulate porous implant osseointegration by promoting bone anabolism in type 1 diabetic rabbits.

Science.gov (United States)

Cai, J; Li, W; Sun, T; Li, X; Luo, E; Jing, D

2018-05-01

The effects of exogenous pulsed electromagnetic field (PEMF) stimulation on T1DM-associated osteopathy were investigated in alloxan-treated rabbits. We found that PEMF improved bone architecture, mechanical properties, and porous titanium (pTi) osseointegration by promoting bone anabolism through a canonical Wnt/β-catenin signaling-associated mechanism, and revealed the clinical potential of PEMF stimulation for the treatment of T1DM-associated bone complications. Type 1 diabetes mellitus (T1DM) is associated with deteriorated bone architecture and impaired osseous healing potential; nonetheless, effective methods for resisting T1DM-associated osteopenia/osteoporosis and promoting bone defect/fracture healing are still lacking. PEMF, as a safe and noninvasive method, have proven to be effective for promoting osteogenesis, whereas the potential effects of PEMF on T1DM osteopathy remain poorly understood. We herein investigated the effects of PEMF stimulation on bone architecture, mechanical properties, bone turnover, and its potential molecular mechanisms in alloxan-treated diabetic rabbits. We also developed novel nontoxic Ti2448 pTi implants with closer elastic modulus with natural bone and investigated the impacts of PEMF on pTi osseointegration for T1DM bone-defect repair. The deteriorations of cancellous and cortical bone architecture and tissue-level mechanical strength were attenuated by 8-week PEMF stimulation. PEMF also promoted osseointegration and stimulated more adequate bone ingrowths into the pore spaces of pTi in T1DM long-bone defects. Moreover, T1DM-associated reduction of bone formation was significantly attenuated by PEMF, whereas PEMF exerted no impacts on bone resorption. We also found PEMF-induced activation of osteoblastogenesis-related Wnt/β-catenin signaling in T1DM skeletons, but PEMF did not alter osteoclastogenesis-associated RANKL/RANK signaling gene expression. We reveal that PEMF improved bone architecture, mechanical properties, and

Effects of a micro/nano rough strontium-loaded surface on osseointegration

Science.gov (United States)

Li, Yongfeng; Qi, Yaping; Gao, Qi; Niu, Qiang; Shen, Mingming; Fu, Qian; Hu, Kaijin; Kong, Liang

2015-01-01

We developed a hierarchical hybrid micro/nanorough strontium-loaded Ti (MNT-Sr) surface fabricated through hydrofluoric acid etching followed by magnetron sputtering and evaluated the effects of this surface on osseointegration. Samples with a smooth Ti (ST) surface, micro Ti (MT) surface treated with hydrofluoric acid etching, and strontium-loaded nano Ti (NT-Sr) surface treated with SrTiO3 target deposited via magnetron sputtering technique were investigated in parallel for comparison. The results showed that MNT-Sr surfaces were prepared successfully and with high interface bonding strength. Moreover, slow Sr release could be detected when the MNT-Sr and NT-Sr samples were immersed in phosphate-buffered saline. In in vitro experiments, the MNT-Sr surface significantly improved the proliferation and differentiation of osteoblasts compared with the other three groups. Twelve weeks after the four different surface implants were inserted into the distal femurs of 40 rats, the bone–implant contact in the ST, MT, NT-Sr, and MNT-Sr groups were 39.70%±6.00%, 57.60%±7.79%, 46.10%±5.51%, and 70.38%±8.61%, respectively. In terms of the mineral apposition ratio, the MNT-Sr group increased by 129%, 58%, and 25% compared with the values of the ST, MT, and NT-Sr groups, respectively. Moreover, the maximal pullout force in the MNT-Sr group was 1.12-, 0.31-, and 0.69-fold higher than the values of the ST, MT, and NT-Sr groups, respectively. These results suggested that the MNT-Sr surface has a synergistic effect of hierarchical micro/nano-topography and strontium for enhanced osseointegration, and it may be a promising option for clinical use. Compared with the MT surface, the NT-Sr surface significantly improved the differentiation of osteoblasts in vitro. In the in vivo animal experiment, the MT surface significantly enhanced the bone-implant contact and maximal pullout force than the NT-Sr surface. PMID:26213468

Osseointegration in osteoporotic-like condition: A systematic review of preclinical studies.

Science.gov (United States)

Dereka, X; Calciolari, E; Donos, N; Mardas, N

2018-05-30

Osteoporosis is one of the most common skeletal disorders affecting a significant percentage of people worldwide. Research data suggested that systemic diseases such as osteoporosis could act as risk factors for osseointegration, jeopardizing the healing process and thus the predictability of dental implant success on compromised patients. It is well accepted that preclinical studies in animal models reproducing the osteoporotic condition are one of the most important stages in the research of new biomaterials and therapeutic modalities. The aim of this systematic review was to investigate whether osteoporosis compromises dental implant osseointegration in experimental osteoporotic-like conditions. A 3-stage systematic literature research was conducted in MEDLINE via OVID and EMBASE up to and including March 2017. Experimental studies reporting on dental implant osseointegration on different osteoporotic animal models were assessed. The studies had to report on the percentage of bone-to-implant contact (%BIC) as the primary outcome. ARRIVE guidelines for reporting on animal research were applied to evaluate the methodological quality and risk of bias of the studies. Fifty-seven studies met the inclusion criteria and were assessed qualitatively. The most adopted animal model was the rat. A variability of %BIC values was observed, ranging from 30% to 99% and from 26% to 94% for the healthy and osteoporotic group, respectively. The great majority (47) of the included studies concluded that estrogen deficiency significantly affects BIC values, 9 studies stated that it was not possible to observe statistical differences in BIC between ovariectomized and healthy groups and 1 study did not provide a comparison between the healthy and osteoporotic group. Owing to the great heterogeneity in implant surface, study design, observation time-points, site of implant placement and reported outcomes, a meta-analysis could not be performed. An overall high risk of bias was observed

Effect of ultraviolet irradiation on the osseointegration of a titanium alloy with bone

Directory of Open Access Journals (Sweden)

Ashish Yadav

2017-01-01

Full Text Available Introduction: Attempt has been made to analyze the potential of titanium (Ti alloy for osteointegration by the effect of surface photo functionalization in different aspects as follows: in Ringer's solution, in vitro cell growth, and in vivo study on rabbit. The present study was aimed to investigate the influence of ultraviolet (UV light on surface topography, corrosion behavior, and bioactivity of indigenously manufactured samples of Ti alloy mini-implant. Materials and Methods: The study includes surface modification of Ti samples by UV treatment, corrosion testing of the specimens using Potentiostat (GAMRY System, qualitative examination of modified surface topography using scanning electron microscope, and cellular viability test on Ti alloy surface (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide ASSAY. To find the effect of UV light on implant bone integration, biochemical test was performed on the femur of rabbits. Results and Discussion: Corrosion resistance of untreated Ti alloy in Ringer's solution was found to be less, whereas corrosion rate was more. Corrosion resistance of UV-treated samples was found to increase significantly, thereby lowering the corrosion rate. Cell growth in UV-treated specimen was observed to be higher than that in untreated samples. It is important to mention that cell growth was significantly enhanced on samples which were UV treated for longer duration of time. Conclusions: There was a marked improvement in cell growth on UV-treated Ti alloy samples. Hence, it is expected that it would enhance the process of osseointegration of Ti with bone. Another important finding obtained was that the removal torque values of UV-treated implants were higher than that of untreated implants. The overall result reveals that UV treatment of implants does help us in speeding up the osseointegration process.

Enhanced Bioactivity and Bacteriostasis of Surface Fluorinated Polyetheretherketone.

Science.gov (United States)

Chen, Meiling; Ouyang, Liping; Lu, Tao; Wang, Heying; Meng, Fanhao; Yang, Yan; Ning, Congqin; Ma, Jingzhi; Liu, Xuanyong

2017-05-24

Although polyetheretherketone (PEEK) has been considered as a potential orthopedic and dental application material due to its similar elastic modulus as bones, inferior osseointegration and bacteriostasis of PEEK hampers its clinical application. In this work, fluorinated PEEK was constructed via plasma immersion ion implantation (PIII) followed by hydrofluoric acid treatment to ameliorate the osseointegration and antibacterial properties of PEEK. The surface microstructure, composition, and hydrophilicity of all samples were investigated. Rat bone mesenchymal stem cells (rBMSCs) were cultured on their surfaces to estimate bioactivity. The fluorinated PEEK can enhance the cell adhesion, cell spreading, proliferation, and alkaline phosphatase (ALP) activity compared to pristine PEEK. Furthermore, the fluorinated PEEK surface exhibits good bacteriostatic effect against Porphyromonas gingivalis, which is one of the major periodontal pathogens. In summary, we provide an effective route to introduce fluorine and the results reveal that the fluorinated PEEK can enhance the osseointegration and bacteriostasis, which provides a potential candidate for dental implants.

Osteoporotic rat models for evaluation of osseointegration of bone implants

NARCIS (Netherlands)

Alghamdi, H.S.A.; Beucken, J.J.J.P van den; Jansen, J.A.

2014-01-01

Osseointegration of dental and orthopedic bone implants is the important process that leads to mechanical fixation of implants and warrants implant functionality. In view of increasing numbers of osteoporotic patients, bone implant surface optimization strategies with instructive and drug-loading

An in vitro assessment of titanium functionalized with polysaccharides conjugated with vascular endothelial growth factor for enhanced osseointegration and inhibition of bacterial adhesion.

Science.gov (United States)

Hu, Xuefeng; Neoh, Koon-Gee; Shi, Zhilong; Kang, En-Tang; Poh, Chyekhoon; Wang, Wilson

2010-12-01

The long-term success of orthopedic implants may be compromised by defective osseointegration and bacterial infection. An effective approach to minimize implant failure would be to modify the surface of the implant to make it habitable for bone-forming cells and anti-infective at the same time. In this in vitro study, the surfaces of titanium (Ti) substrates were functionalized by first covalently grafting either dopamine followed by carboxymethyl chitosan (CMCS) or hyaluronic acid-catechol (HAC). Vascular endothelial growth factor (VEGF) was then conjugated to the polysaccharide-grafted surface. Antibacterial assay with Staphylococcus aureus (S. aureus) showed that the polysaccharide-modified substrates significantly decrease bacterial adhesion. The CMCS-functionalized Ti demonstrated better antibacterial property than the HAC-functionalized Ti since CMCS is bactericidal while HA only inhibits the adhesion of bacteria without killing them. Osteoblast attachment, as well as alkaline phosphatase (ALP) activity and calcium deposition were enhanced by the immobilized VEGF on the polysaccharide-grafted Ti. Thus, Ti substrates modified with polysaccharides conjugated with VEGF can promote osteoblast functions and concurrently reduce bacterial adhesion. Since VEGF is also known to enhance angiogenesis, the VEGF-polysaccharide functionalized substrates will have promising applications in the orthopedic field. Copyright © 2010 Elsevier Ltd. All rights reserved.

Repositioning Titanium: An In Vitro Evaluation of Laser-Generated Microporous, Microrough Titanium Templates As a Potential Bridging Interface for Enhanced Osseointegration and Durability of Implants

Directory of Open Access Journals (Sweden)

Daniel Tang

2017-12-01

Full Text Available Although titanium alloys remain the preferred biomaterials for the manufacture of biomedical implants today, such devices can fail within 15 years of implantation due to inadequate osseointegration. Furthermore, wear debris toxicity due to alloy metal ion release has been found to cause side-effects including neurotoxicity and chronic inflammation. Titanium, with its known biocompatibility, corrosion resistance, and high elastic modulus, could if harnessed in the form of a superficial scaffold or bridging device, resolve such issues. A novel three-dimensional culture approach was used to investigate the potential osteoinductive and osseointegrative capabilities of a laser-generated microporous, microrough medical grade IV titanium template on human skeletal stem cells (SSCs. Human SSCs seeded on a rough 90-µm pore surface of ethylene oxide-sterilized templates were observed to be strongly adherent, and to display early osteogenic differentiation, despite their inverted culture in basal conditions over 21 days. Limited cellular migration across the template surface highlighted the importance of high surface wettability in maximizing cell adhesion, spreading and cell-biomaterial interaction, while restricted cell ingrowth within the conical-shaped pores underlined the crucial role of pore geometry and size in determining the extent of osseointegration of an implant device. The overall findings indicate that titanium only devices, with appropriate optimizations to porosity and surface wettability, could yet play a major role in improving the long-term efficacy, durability, and safety of future implant technology.

Osseointegration of nanohydroxyapatite- or nano-calcium silicate-incorporated polyetheretherketone bioactive composites in vivo

Directory of Open Access Journals (Sweden)

Ma R

2016-11-01

Full Text Available Rui Ma,1,2 Zhifeng Yu,1 Songchao Tang,3 Yongkang Pan,3 Jie Wei,3 Tingting Tang1 1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Orthopedic Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi Province, People’s Republic of China; 3Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China Abstract: Polyetheretherketone (PEEK exhibits appropriate biomechanical strength as well as good biocompatibility and stable chemical properties but lacks bioactivity and cannot achieve highly efficient osseointegration after implantation. Incorporating bioceramics into the PEEK matrix is a feasible approach for improving its bioactivity. In this study, nanohydroxyapatite (n-HA and nano-calcium silicate (n-CS were separately incorporated into PEEK to prepare n-HA/PEEK and n-CS/PEEK biocomposites, respectively, using a compounding and injection-molding technique, and the in vitro degradation characteristics were evaluated. Discs with a diameter of 8 mm were inserted in 8 mm full-thickness cranial defects in rabbits for 4 and 8 weeks, and implantation of pure PEEK was used as the control. Three-dimensional microcomputed tomography, histological analysis, fluorescence microscopy of new bone formation, and scanning electron microscopy were used to evaluate the osseointegration performance at the bone/implant interface. The results of the in vitro degradation study demonstrated that degradation of n-CS on the surface of n-CS/PEEK could release Ca and Si ions and form a porous structure. In vivo tests revealed that both n-CS/PEEK and n-HA/PEEK promoted osseointegration at the bone/implant interface compared to PEEK

Titanium Implant Osseointegration Problems with Alternate Solutions Using Epoxy/Carbon-Fiber-Reinforced Composite

Directory of Open Access Journals (Sweden)

Richard C. Petersen

2014-12-01

Full Text Available The aim of the article is to present recent developments in material research with bisphenyl-polymer/carbon-fiber-reinforced composite that have produced highly influential results toward improving upon current titanium bone implant clinical osseointegration success. Titanium is now the standard intra-oral tooth root/bone implant material with biocompatible interface relationships that confer potential osseointegration. Titanium produces a TiO2 oxide surface layer reactively that can provide chemical bonding through various electron interactions as a possible explanation for biocompatibility. Nevertheless, titanium alloy implants produce corrosion particles and fail by mechanisms generally related to surface interaction on bone to promote an inflammation with fibrous aseptic loosening or infection that can require implant removal. Further, lowered oxygen concentrations from poor vasculature at a foreign metal surface interface promote a build-up of host-cell-related electrons as free radicals and proton acid that can encourage infection and inflammation to greatly influence implant failure. To provide improved osseointegration many different coating processes and alternate polymer matrix composite (PMC solutions have been considered that supply new designing potential to possibly overcome problems with titanium bone implants. Now for important consideration, PMCs have decisive biofunctional fabrication possibilities while maintaining mechanical properties from addition of high-strengthening varied fiber-reinforcement and complex fillers/additives to include hydroxyapatite or antimicrobial incorporation through thermoset polymers that cure at low temperatures. Topics/issues reviewed in this manuscript include titanium corrosion, implant infection, coatings and the new epoxy/carbon-fiber implant results discussing osseointegration with biocompatibility related to nonpolar molecular attractions with secondary bonding, carbon fiber in vivo

The effect of hierarchical micro/nanosurface titanium implant on osseointegration in ovariectomized sheep.

Science.gov (United States)

Xiao, J; Zhou, H; Zhao, L; Sun, Y; Guan, S; Liu, B; Kong, L

2011-06-01

Hydrofluoric etching and anodized hierarchical micro/nanotextured surface titanium implant was placed in mandibles of ovariectomized sheep for 12 weeks, and it showed improved osseointegration by resonance frequency analysis (RFA), microcomputed tomography (micro-CT) evaluation, histomorphometry, and biomechanical test. This study aimed to investigate the effects of micro/nanotextured titanium implant on osseointegration in ovariectomized (OVX) sheep. The hierarchical micro/nanotextured surface of titanium implant was fabricated by acid in 0.5% (w/v) hydrofluoric (HF) and anodized in HF acid electrolytes with a DC power of 20 V, and the machined surface implants with no treatment served as control group. The implants were placed in mandibles of OVX sheep, respectively. Twelve weeks after implantation, RFA, microcomputed tomography, histomorphometry, and biomechanical tests were applied to detect the osseointegration of the two groups. The implant stability quotient (ISQ) values, the maximum pull-out forces, and the bone-implant contact (BIC) were 65.5 ± 6.3, 490.6 ± 72.7 N, and 58.31 ± 5.79% in the micro/nanogroup and 58.3 ± 8.9, 394.5 ± 54.5 N, and 46.85 ± 5.04% in the control group, respectively. There was no significant difference between the two groups in ISQ values (p > 0.05), but in the micro/nanogroup, the maximal pull-out force and the BIC were increased significantly (p Micro-CT analysis showed that the bone volume ratio and the trabecular number increased significantly (p micro/nanogroup. Implant modification by HF acid etching and anodization to form a hierarchical micro/nanotextured surface could improve titanium implant osseointegration in OVX sheep 12 weeks after implantation.

Effect of 2 Different Drilling Speeds on the Osseointegration of Implants Placed With Flapless Guided Surgery: A Study in Rabbits

DEFF Research Database (Denmark)

Landazuri-Del Barrio, Ricardo Andres; Nunes de Paula, Wagner; Spin-Neto, Rubens

2017-01-01

OBJECTIVE: The aim of this study was to evaluate the influence of the drilling speed on bone healing and the osseointegration of implants placed with a guided flapless surgical technique in rabbit tibias. METHODS: For the evaluation of bone healing, a total of 30 perforations (defects) were made...... in both tibias of 15 rabbits using 2 different drilling speeds (1500 rpm-control group; 50 rpm-test group). The regeneration of bone tissue in the surgical sites was evaluated at 0, 7, and 14 days. For the evaluation of implant osseointegration, another 15 rabbits underwent drilling in both tibias...... with no statistically significant differences in the assessment of the osseointegration between the groups. CONCLUSION: In the experimental models used, the drilling speed does not prejudice the pattern of bone healing and osseointegration of implants placed with guided flapless surgery....

Numerical investigations on the osseointegration of uncemented endoprostheses based on bio-active interface theory

Science.gov (United States)

Lutz, André; Nackenhorst, Udo

2012-09-01

In order to simulate the osseointegration of bone implants, a bio-active interface theory is necessary. The thin bone-implant interface layer is described by the Drucker-Prager plasticity model. The formulation of bone mineral density depends on the local mechanical environment. For the simulation of the osseointegration of bone implants a bio-active interface theory is suggested. A thin bone-implant interface layer is described by a Drucker-Prager plasticity model. An evolution rule for the bone mineral density is formulated in dependency of the local mechanical environment. The time dependent ingrowth is modeled by a hardening rule which modifies the Drucker-Prager yield-surface cone in the principle stress state in dependency of the local bone mineral density. The osseointegration process is limited by the violation of a so called micromotion threshold. This relative motion in the implant-bone interface is computed by dynamic loads of daily motion activity. For parameter studies on detailed 3D models model reduction techniques are introduced. The applicability is demonstrated on a hip-joint prosthesis which is in clinical usage.

[Effect of osseointegration in the posterior area by Shenggu pills].

Science.gov (United States)

Cuifen, Luo; Guoguang, Peng

2017-10-01

This study aimed to investigate the osseointegration condition by measuring the implant stability quotient (ISQ) to study the effect of osseointegration in the posterior area by Shenggu pills. A total of 101 DENTIUM implants were placed in 48 patients. Fifty implants placed in 24 patients were addressed as usual, whereas 51 implants placed in 24 patients were treated with Shenggu pills. ISQ was tested on the day of surgery and consecutively at 4, 8, and 12 weeks. All data were analyzed. The efficacy of the treatment group was no much better than that of control group on the day of surgery and consecutively at 12 weeks with no significant difference (P>0.05). The efficacy of the treatment group was significantly better than that of the control group at 4 and 8 weeks (Ppills could accelerate the implant bone union, improve the implants' ISQ, and ensure the success rate of the operation.

[Endo-exo prostheses : Osseointegrated percutaneously channeled implants for rehabilitation after limb amputation].

Science.gov (United States)

Aschoff, H-H; Juhnke, D-L

2016-05-01

In 1999 the first endo-exo femoral prosthesis (EEFP) was implanted in Germany in a patient who had suffered a traumatic above-knee amputation. This procedure involves a skeletally anchored exoprosthetic device that is inserted into the residual femur. The distal part of the implant protrudes transcutaneously and allows attachment to a prosthetic limb which provides direct force transmission to the external prosthetic components. The technique originated from dental implantology and helps to avoid possible problems resulting from treatment of amputated limbs using socket prostheses. In the meantime, durability times of over 10 years have now helped to invalidate the initially well-founded reservations held against the procedure. What advantages can be achieved by osseointegrated and percutaneously channeled prostheses and which problems had to be overcome for treatment. Critical evaluation of data from patients operated on in Lübeck, Germany from January 2003 to December 2014. With osseointegrated and percutaneously channeled prostheses permanent durability times can be achieved. Infection-associated soft tissue problems at the site of skin protrusion (stoma) can be successfully prevented. The creation of this so-called stoma means acceptance of a possible bacterial portal of entry into the body. Patient satisfaction has so far been high, postoperative rehabilitation is simplified and the technique could possibly lower the costs of medical treatment. Endo-exo prostheses have proved to be successful for more than 15 years. A critical appraisal of the indications as well as a close cooperation between the surgeon, orthopedic technician and the associated rehabilitation facilities with the patient are the basis for the long-term success of this relatively new treatment approach.

Bone cutting capacity and osseointegration of surface-treated orthodontic mini-implants.

Science.gov (United States)

Kim, Ho-Young; Kim, Sang-Cheol

2016-11-01

The objective of the study was to evaluate the practicality and the validity of different surface treatments of self-drilling orthodontic mini-implants (OMIs) by comparing bone cutting capacity and osseointegration. Self-drilling OMIs were surface-treated in three ways: Acid etched (Etched), resorbable blasting media (RBM), partially resorbabla balsting media (Hybrid). We compared the bone cutting capacity by measuring insertion depths into artificial bone (polyurethane foam). To compare osseointegration, OMIs were placed in the tibia of 25 rabbits and the removal torque value was measured at 1, 2, 4, and 8 weeks after placement. The specimens were analyzed by optical microscopy, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS). The bone cutting capacity of the etched and hybrid group was lower than the machined (control) group, and was most inhibited in the RBM group ( p drilling OMIs, without a corresponding reduction in bone cutting capacity.

In vitro osteogenic capacity of bone marrow MSCs from postmenopausal women reflect the osseointegration of their cementless hip stems

Directory of Open Access Journals (Sweden)

Jessica J. Alm

2016-12-01

Full Text Available Age-related dysfunction of mesenchymal stromal cells (MSCs is suggested as a main cause of altered bone repair with aging. We recently showed that in postmenopausal women undergoing cementless total hip arthroplasty (THA aging, low bone mineral density (BMD and age-related geometric changes of the proximal femur are risk factors for increased early migration and delayed osseointegration of the femoral stems. Extending these analyses, we have here explored how the in vitro osteogenic capacity of bone marrow MSCs from these patients reflects implant osseointegration, representing the patient's in vivo bone healing capacity. A total of 19 postmenopausal women with primary hip osteoarthritis (mean age 65 years, range 50–78 and well-defined bone quality underwent successful preoperative in vitro analysis of osteogenic capacity of iliac crest bone marrow MSCs as well as two-year radiostereometric (RSA follow-up of femoral stem migration after cementless THA. In patients with MSCs of low osteogenic capacity, the magnitude of cumulative stem subsidence after the settling period of three months was greater (p = 0.028 and the time point for translational osseointegration was significantly delayed (p = 0.030 compared to patients with MSCs of high osteogenic capacity. This study suggests that patients with MSCs of low in vitro osteogenic capacity may display increased stem subsidence after the settling period of 3 months and thereby delayed osseointegration. Our study presents a novel approach for studying the biological progress of hip implant osseointegration and to verify the impact of decreased MSCs function, especially in patients with age-related dysfunction of MSCs and bone healing capacity. Keywords: Human mesenchymal stromal cells, Osteogenic differentiation, Radiostereometric analysis, Total hip arthroplasty, Osseointegration

Creatine Enhances Transdifferentiation of Bone Marrow Stromal Cell-Derived Neural Stem Cell Into GABAergic Neuron-Like Cells Characterized With Differential Gene Expression.

Science.gov (United States)

Darabi, Shahram; Tiraihi, Taki; Delshad, AliReza; Sadeghizadeh, Majid; Taheri, Taher; Hassoun, Hayder K

2017-04-01

Creatine was reported to induce bone marrow stromal cells (BMSC) into GABAergic neuron-like cells (GNLC). In a previous study, creatine was used as a single inducer for BMSC into GNLC with low yield. In this study, BMSC-derived neurospheres (NS) have been used in generating GABAergic phenotype. The BMSC were isolated from adult rats and used in generating neurospheres and used for producing neural stem cells (NSC). A combination of all-trans-retinoic acid (RA), the ciliary neurotrophic factor (CNTF), and creatine was used in order to improve the yield of GNLC. We also used other protocols for the transdifferentiation including RA alone; RA and creatine; RA and CNTF; and RA, CNTF, and creatine. The BMSC, NSC, and GNLC were characterized by specific markers. The activity of the GNLC was evaluated using FM1-43. The isolated BMSC expressed Oct4, fibronectin, and CD44. The NS were immunoreactive to nestin and SOX2, the NSC were immunoreactive to nestin, NF68 and NF160, while the GNLC were immunoreactive to GAD1/2, VGAT, GABA, and synaptophysin. Oct4 and c-MYC, pluripotency genes, were expressed in the BMSC, while SOX2 and c-MYC were expressed in the NSC. The activity of GNLC indicates that the synaptic vesicles were released upon stimulation. The conclusion is that the combination of RA, CNTF, and creatine induced differentiation of neurosphere-derived NSC into GNLC within 1 week. This protocol gives higher yield than the other protocols used in this study. The mechanism of induction was clearly associated with several differential pluripotent genes.

Hydroxyapatite-lignin composite as a metallic implant-bone tissue osseointegration improver: experimental study in dogs

Directory of Open Access Journals (Sweden)

Fabrício Luciani Valente

2015-01-01

Full Text Available The study aimed to evaluate biocompatibility, osteoconduction and osseointegration of a pasty composite of hydroxyapatite (20% and lignin (80% as a promoter of metal implant and bone tissue integration. An intramedullary Schanz pin was implanted in both tibias of fifteen bitches. In the left tibia, the pin was coated with the biomaterial at the time of surgery. Marrow cavity was also filled with the biomaterial. Right limb did not receive the biomaterial, then constituting the control group. Tibias were harvested from five animals at 8, 60 and 150 days after surgery; three of them were analyzed by histological and biomechanical assessment and the two remaining tibias by X-ray diffraction. Results showed that the biomaterial is biocompatible, with osteoconductivity and osseointegration properties. Histological analysis and diffractograms showed the presence of hydroxyapatite in samples in all periods, although the presence of organic material of low crystallinity was variable. There was no statistical difference in the forces required for removal of the biocompatibility, osteoconductivity and osseointegration, it was not able to promote a better intramedullary pin anchorage.

Osseointegrated Transtibial Implants in Patients with Peripheral Vascular Disease: A Multicenter Case Series of 5 Patients with 1-Year Follow-up

NARCIS (Netherlands)

Atallah, R.; Li, J.J.; Lu, W.; Leijendekkers, R.A.; Frolke, J.P.M.; Muderis, M. Al

2017-01-01

BACKGROUND: Osseointegration is an alternative treatment for amputees who are unable to wear or have difficulty wearing a socket prosthesis. Although the majority of limb amputations are due to vascular disease, such amputations have been perceived as a contraindication to osseointegration surgery.

Intranasal delivery of hypoxia-preconditioned bone marrow-derived mesenchymal stem cells enhanced regenerative effects after intracerebral hemorrhagic stroke in mice.

Science.gov (United States)

Sun, Jinmei; Wei, Zheng Zachory; Gu, Xiaohuan; Zhang, James Ya; Zhang, Yongbo; Li, Jimei; Wei, Ling

2015-10-01

Intracerebral hemorrhagic stroke (ICH) causes high mortality and morbidity with very limited treatment options. Cell-based therapy has emerged as a novel approach to replace damaged brain tissues and promote regenerative processes. In this study we tested the hypothesis that intranasally delivered hypoxia-preconditioned BMSCs could reach the brain, promote tissue repair and improve functional recovery after ICH. Hemorrhagic stroke was induced in adult C57/B6 mice by injection of collagenase IV into the striatum. Animals were randomly divided into three groups: sham group, intranasal BMSC treatment group, and vehicle treatment group. BMSCs were pre-treated with hypoxic preconditioning (HP) and pre-labeled with Hoechst before transplantation. Behavior tests, including the mNSS score, rotarod test, adhesive removal test, and locomotor function evaluation were performed at varying days, up to 21days, after ICH to evaluate the therapeutic effects of BMSC transplantation. Western blots and immunohistochemistry were performed to analyze the neurotrophic effects. Intranasally delivered HP-BMSCs were identified in peri-injury regions. NeuN+/BrdU+ co-labeled cells were markedly increased around the hematoma region, and growth factors, including BDNF, GDNF, and VEGF were significantly upregulated in the ICH brain after BMSC treatment. The BMSC treatment group showed significant improvement in behavioral performance compared with the vehicle group. Our data also showed that intranasally delivered HP-BMSCs migrated to peri-injury regions and provided growth factors to increase neurogenesis after ICH. We conclude that intranasal administration of BMSC is an effective treatment for ICH, and that it enhanced neuroregenerative effects and promoted neurological functional recovery after ICH. Overall, the investigation supports the potential therapeutic strategy for BMSC transplantation therapy against hemorrhagic stroke. Copyright © 2015 Elsevier Inc. All rights reserved.

Cytocompatibility and early osseointegration of nanoTiO{sub 2}-modified Ti-24 Nb-4 Zr-7.9 Sn surfaces

Energy Technology Data Exchange (ETDEWEB)

Liu, X.H. [Department of Prosthodontics, China Medical University School of Stomatology, Shenyang (China); Wu, L., E-mail: wulin13@163.com [Department of Prosthodontics, China Medical University School of Stomatology, Shenyang (China); Ai, H.J. [Department of Prosthodontics, China Medical University School of Stomatology, Shenyang (China); Han, Y. [State Key laboratory for Mechanical Behaviour of Materials, Xi' an Jiaotong University, Xi' an (China); Hu, Y. [Department of Prosthodontics, China Medical University School of Stomatology, Shenyang (China)

2015-03-01

This study aimed to evaluate the cytocompatibility and early osseointegration of Ti-24 Nb-4 Zr-7.9 Sn (Ti-2448) surfaces that were modified with a nanoscale TiO{sub 2} coating. The coating was fabricated using a hydrothermal synthesis method to generate nanoTiO{sub 2}/Ti-2448. The surface characteristics of the samples were evaluated using scanning electron microscopy (SEM), energy dispersive spectrometry (EDS) and X-ray diffraction (XRD). The cytotoxicity of the fabricated nanoTiO{sub 2}/Ti-2448 was determined using MTT assays. The proliferation and alkaline phosphatase (ALP) activity of MC3T3-E1 osteoblasts cultured on nanoTiO{sub 2}/Ti-2448 were compared with those cultured on Ti-2448. Disk-shaped implants were placed in Wistar rats. The histological sections were stained with haematoxylin and eosin (HE), and the histocompatibility was analysed at 4 and 12 weeks post-implantation. Cylindrical implants were embedded in Japanese white rabbits, and the histological sections were stained with HE and anti-TGF-β1 to evaluate the histocompatibility and early osseointegration at 4, 12 and 26 weeks post-implantation. NanoTiO{sub 2}/Ti-2448 exhibited a rougher surface than did Ti-2448. NanoTiO{sub 2}/Ti-2448 was determined to be non-cytotoxic. More osteoblasts and higher ALP activity were observed for nanoTiO{sub 2}/Ti-2448 than Ti-2448 (p < 0.05). Few inflammatory cells were detected around nanoTiO{sub 2}/Ti-2448, and the expression of TGF-β1 on nanoTiO{sub 2}/Ti-2448 peaked at earlier time than that on Ti-2448. The results indicate that the cytocompatibility and early osseointegration were enhanced by the nanoTiO{sub 2} coating. - Highlights: • The cytocompatibility of nanoTiO2/Ti-2448 is first reported in our work. • The early osseointegration of nanoTiO2/Ti-2448 is first reported in our work. • We evaluate the biocompatibility of nanoTiO2/Ti-2448 by in-vitro and in-vivo tests.

Resonance frequency analysis of thermal acid-etched, hydrophilic implants during first 3 months of healing and osseointegration in an early-loading protocol

NARCIS (Netherlands)

van Eekeren, P.; Said, C.; Tahmaseb, A.; Wismeijer, D.

2015-01-01

Purpose: Safe loading of dental implants requires an optimal osseointegration. This osseointegration process during healing could be analyzed by resonance frequency analysis (RFA). The purpose of the study was to evaluate RFA changes during healing in splinted, early-loaded, thermal acid-etched,

Finite element analysis (FEA) of dental implant fixture for mechanical stability and rapid osseointegration

Science.gov (United States)

Tabassum, Shafia; Murtaza, Ahmar; Ali, Hasan; Uddin, Zia Mohy; Zehra, Syedah Sadaf

2017-10-01

For rapid osseointegration of dental implant fixtures, various surface treatments including plasma spraying, hydroxyapatite coating, acid-etching, and surface grooving are used. However undesirable effects such as chemical modifications, loss of mechanical properties, prolonged processing times and post production treatment steps are often associated with these techniques. The osseointegration rate of the dental implants can be promoted by increasing the surface area of the dental implant, thus increasing the bone cells - implant material contact and allow bone tissues to grow rapidly. Additive Manufacturing (AM) techniques can be used to fabricate dental implant fixtures with desirable surface area in a single step manufacturing process. AM allows the use of Computer Aided Designing (CAD) for customised rapid prototyping of components with precise control over geometry. In this study, the dental implant fixture that replaces the tooth root was designed on commercially available software COMSOL. Nickel - titanium alloy was selected as build materials for dental implant. The geometry of the dental fixture was varied by changing the interspacing distance (thread pitch) and number of threads to increase the total surface area. Three different microstructures were introduced on the surface of dental implant. The designed models were used to examine the effect of changing geometries on the total surface area. Finite Element Analysis (FEA) was performed to investigate the effect of changing geometries on the mechanical properties of the dental implant fixtures using stress analysis.

Osseointegration of dental implants in patients with and without radiotherapy

International Nuclear Information System (INIS)

Wagner, W.; Esser, E.; Ostkamp, K.

1998-01-01

Between 1987 and 1997, 275 dental implants were inserted in the mandibles of 63 patients with squamous cell carcinoma of the lower oropharyngeal level following a radical surgical procedure. Thirty-five of these patients had been preirradiated with a complete dose of 60 Gy. In a retrospective analysis we have reviewed the data of these patients for age, sex, localization of the implants, irradiation, interval of implantation and interval of the abutment operation. Thus far, the median follow-up time is 65 months. The 5-year success rate for all implants was 97.9%. We found that radiotherapy, age, sex, localization of implantation or the interval between the end of the tumor therapy and the time of implantation did not have any significant influence on osseointegration or loss of osseointegration. Only the time interval between implantation and the abutment operation was recorded to be of any great significance (p=0.0001). No augmentation in the osteoradionecrosis rate could be recorded after dental implantation (1.6%), which leads us to conclude that radiotherapy (60 Gy) in patients with head and neck cancers should not be regarded as a contraindication for dental implantation. (orig.)

A reductionist approach to extract robust molecular markers from microarray data series - Isolating markers to track osseointegration.

Science.gov (United States)

Barik, Anwesha; Banerjee, Satarupa; Dhara, Santanu; Chakravorty, Nishant

2017-04-01

Complexities in the full genome expression studies hinder the extraction of tracker genes to analyze the course of biological events. In this study, we demonstrate the applications of supervised machine learning methods to reduce the irrelevance in microarray data series and thereby extract robust molecular markers to track biological processes. The methodology has been illustrated by analyzing whole genome expression studies on bone-implant integration (ossointegration). Being a biological process, osseointegration is known to leave a trail of genetic footprint during the course. In spite of existence of enormous amount of raw data in public repositories, researchers still do not have access to a panel of genes that can definitively track osseointegration. The results from our study revealed panels comprising of matrix metalloproteinases and collagen genes were able to track osseointegration on implant surfaces (MMP9 and COL1A2 on micro-textured; MMP12 and COL6A3 on superimposed nano-textured surfaces) with 100% classification accuracy, specificity and sensitivity. Further, our analysis showed the importance of the progression of the duration in establishment of the mechanical connection at bone-implant surface. The findings from this study are expected to be useful to researchers investigating osseointegration of novel implant materials especially at the early stage. The methodology demonstrated can be easily adapted by scientists in different fields to analyze large databases for other biological processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Osseointegration bei dentalen Implantaten : eine Literaturübersicht und -auswertung

OpenAIRE

Bras da Silva, Manuel A.

2003-01-01

Die Osseointegration in der dentalen Implantologie wurde anhand einer Literaturübersicht dargestellt und ausgewertet. Die Literaturübersicht beinhaltet Verlaufsstudien, in vitro und in vivo Studien, die ultrastrukturelle, biomechanische und biochemische Untersuchungen und deren Resultate aufzeigen. Im 1. Kapitel wurden die Kriterien zur Beurteilung des Implantaterfolges dargestellt. Es lässt sich feststellen, dass nicht nur ein Implantatverlust als Misserfolg zu bewerten ist, sondern auch kli...

Selective etching of injection molded zirconia-toughened alumina: Towards osseointegrated and antibacterial ceramic implants.

Science.gov (United States)

Flamant, Quentin; Caravaca, Carlos; Meille, Sylvain; Gremillard, Laurent; Chevalier, Jérôme; Biotteau-Deheuvels, Katia; Kuntz, Meinhard; Chandrawati, Rona; Herrmann, Inge K; Spicer, Christopher D; Stevens, Molly M; Anglada, Marc

2016-12-01

Due to their outstanding mechanical properties and excellent biocompatibility, zirconia-toughened alumina (ZTA) ceramics have become the gold standard in orthopedics for the fabrication of ceramic bearing components over the last decade. However, ZTA is bioinert, which hampers its implantation in direct contact with bone. Furthermore, periprosthetic joint infections are now the leading cause of failure for joint arthroplasty prostheses. To address both issues, an improved surface design is required: a controlled micro- and nano-roughness can promote osseointegration and limit bacterial adhesion whereas surface porosity allows loading and delivery of antibacterial compounds. In this work, we developed an integrated strategy aiming to provide both osseointegrative and antibacterial properties to ZTA surfaces. The micro-topography was controlled by injection molding. Meanwhile a novel process involving the selective dissolution of zirconia (selective etching) was used to produce nano-roughness and interconnected nanoporosity. Potential utilization of the porosity for loading and delivery of antibiotic molecules was demonstrated, and the impact of selective etching on mechanical properties and hydrothermal stability was shown to be limited. The combination of injection molding and selective etching thus appears promising for fabricating a new generation of ZTA components implantable in direct contact with bone. Zirconia-toughened alumina (ZTA) is the current gold standard for the fabrication of orthopedic ceramic components. In the present work, we propose an innovative strategy to provide both osseointegrative and antibacterial properties to ZTA surfaces: we demonstrate that injection molding allows a flexible design of surface micro-topography and can be combined with selective etching, a novel process that induces nano-roughness and surface interconnected porosity without the need for coating, avoiding reliability issues. These surface modifications have the

The effect of osteotomy dimension on osseointegration to resorbable media-treated implants: a study in the sheep.

Science.gov (United States)

Galli, Silvia; Jimbo, Ryo; Tovar, Nick; Yoo, Daniel Y; Anchieta, Rodolfo B; Yamaguchi, Satoshi; Coelho, Paulo G

2015-03-01

The drilling technique and the surface characteristics are known to influence the healing times of oral implants. The influence of osteotomy dimension on osseointegration of microroughned implant surfaces treated with resorbable blasting media was tested in an in vivo model. Ninety-six implants (ø4.5 mm, 8 mm in length) with resorbable blasting media-treated surfaces were placed in the ileum of six sheep. The final osteotomy diameters were 4.6 mm (reamer), 4.1 mm (loose), 3.7 mm (medium), and 3.2 mm (tight). After three and six weeks of healing, the implants were biomechanically tested and histologically evaluated. Statistical analysis was performed using Page L trend test for ordered and paired sample and linear regression, with significance level at p bone with all the implant surfaces and osteoblast lines were visible in all sections. The resorbable blasting media microroughed surfaces achieved successful osseointegration for all the instrumentation procedures tested, with higher osseointegration scores for the high insertion torque group. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Assessment of Atmospheric Pressure Plasma Treatment for Implant Osseointegration

Directory of Open Access Journals (Sweden)

Natalie R. Danna

2015-01-01

Full Text Available This study assessed the osseointegrative effects of atmospheric pressure plasma (APP surface treatment for implants in a canine model. Control surfaces were untreated textured titanium (Ti and calcium phosphate (CaP. Experimental surfaces were their 80-second air-based APP-treated counterparts. Physicochemical characterization was performed to assess topography, surface energy, and chemical composition. One implant from each control and experimental group (four in total was placed in one radius of each of the seven male beagles for three weeks, and one implant from each group was placed in the contralateral radius for six weeks. After sacrifice, bone-to-implant contact (BIC and bone area fraction occupancy (BAFO were assessed. X-ray photoelectron spectroscopy showed decreased surface levels of carbon and increased Ti and oxygen, and calcium and oxygen, posttreatment for Ti and CaP surfaces, respectively. There was a significant (P<0.001 increase in BIC for APP-treated textured Ti surfaces at six weeks but not at three weeks or for CaP surfaces. There were no significant (P=0.57 differences for BAFO between treated and untreated surfaces for either material at either time point. This suggests that air-based APP surface treatment may improve osseointegration of textured Ti surfaces but not CaP surfaces. Studies optimizing APP parameters and applications are warranted.

No positive effect of Acid etching or plasma cleaning on osseointegration of titanium implants in a canine femoral condyle press-fit model

DEFF Research Database (Denmark)

Saksø, Henrik; Jakobsen, Thomas Vestergaard; Mortensen, Mikkel Saksø

2013-01-01

Implant surface treatments that improve early osseointegration may prove useful in long-term survival of uncemented implants. We investigated Acid Etching and Plasma Cleaning on titanium implants.......Implant surface treatments that improve early osseointegration may prove useful in long-term survival of uncemented implants. We investigated Acid Etching and Plasma Cleaning on titanium implants....

Monitoring osseointegration and developing intelligent systems (Conference Presentation)

Science.gov (United States)

Salvino, Liming W.

2017-05-01

Effective monitoring of structural and biological systems is an extremely important research area that enables technology development for future intelligent devices, platforms, and systems. This presentation provides an overview of research efforts funded by the Office of Naval Research (ONR) to establish structural health monitoring (SHM) methodologies in the human domain. Basic science efforts are needed to utilize SHM sensing, data analysis, modeling, and algorithms to obtain the relevant physiological and biological information for human-specific health and performance conditions. This overview of current research efforts is based on the Monitoring Osseointegrated Prosthesis (MOIP) program. MOIP develops implantable and intelligent prosthetics that are directly anchored to the bone of residual limbs. Through real-time monitoring, sensing, and responding to osseointegration of bones and implants as well as interface conditions and environment, our research program aims to obtain individualized actionable information for implant failure identification, load estimation, infection mitigation and treatment, as well as healing assessment. Looking ahead to achieve ultimate goals of SHM, we seek to expand our research areas to cover monitoring human, biological and engineered systems, as well as human-machine interfaces. Examples of such include 1) brainwave monitoring and neurological control, 2) detecting and evaluating brain injuries, 3) monitoring and maximizing human-technological object teaming, and 4) closed-loop setups in which actions can be triggered automatically based on sensors, actuators, and data signatures. Finally, some ongoing and future collaborations across different disciplines for the development of knowledge automation and intelligent systems will be discussed.

Noncontact tomography and a pH-sensitive nanocomposite for monitoring osseointegrated prosthesis interfaces

Science.gov (United States)

Gupta, Sumit; Loh, Kenneth J.

2017-04-01

The main objective of this research is to develop a noncontact and noninvasive method for monitoring infections at the interface of human tissue and osseointegrated prostheses. The technique used here is centered on the theory of a noncontact permittivity imaging technique known as electrical capacitance tomography (ECT). This work is divided into two main parts. First, an ECT electrical permittivity reconstruction software and hardware system was developed. Second, a carbon nanotube-polyaniline nanocomposite thin film was designed and fabricated such that its electrical permittivity is sensitive to pH stimuli. The dielectric properties of this thin film were characterized as it was exposed to different pH buffer solutions. It is envisioned that osseointegrated implants can be pre-coated with the pH-sensitive nanocomposite prior to implant. When infection occurs and alters the local pH of tissue at the human-prosthesis interface, the dielectric property of the film would change accordingly. Then, ECT can interrogate the cross-section of the human limb and reconstruct its permittivity distribution, revealing localized changes in permittivity due to infection. To validate this concept, a prosthesis phantom was coated with the nanocomposite pH sensor and then immersed in different pH buffer solutions. ECT was conducted, and the results showed that the magnitude and location of subsurface, localized, pH changes could be detected. In general, noncontact tomography coupled with stimuliresponsive thin films could pave way for new modalities of noninvasive human body imaging, in particular, for patients with osseointegrated implants and prostheses.

Evaluation of autogenous PRGF+β-TCP with or without a collagen membrane on bone formation and implant osseointegration in large size bone defects. A preclinical in vivo study.

Science.gov (United States)

Batas, Leonidas; Stavropoulos, Andreas; Papadimitriou, Serafim; Nyengaard, Jens R; Konstantinidis, Antonios

2016-08-01

The aim of this study was to evaluate whether the adjunctive use of a collagen membrane enhances bone formation and implant osseointegration in non-contained defects grafted with chair-side prepared autologous platelet-rich growth factor (PRGF) adsorbed on a β-TCP particulate carrier. Large box-type defects (10 × 6 mm; W × D) were prepared in the edentulated and completely healed mandibles of six Beagles dogs. An implant with moderately rough surface was placed in the center of each defect leaving the coronal 6 mm of the implant not covered with bone. The remaining defect space was then filled out with chair-side prepared autologous PRGF adsorbed on β-TCP particles and either covered with a collagen membrane (PRGF/β-TCP+CM) (6 defects) or left without a membrane (PRGF/β-TCP) (5 defects). Histology 4 months post-op showed new lamellar and woven bone formation encompassing almost entirely the defect and limited residual β-TCP particles. Extent of osseointegration of the previously exposed portion of the implants varied, but in general was limited. Within the defect, new mineralized bone (%) averaged 43.2 ± 9.86 vs. 39.9 ± 13.7 in the PRGF/β-TCP+CM and PRGF/β-TCP group (P = 0.22) and relative mineralized bone-to-implant contact (%) averaged 26.2 ± 16.45 vs. 35.91 ± 24.45, respectively (P = 0.5). First, bone-to-implant contact from the implant top was 4.1 ± 1.5 and 3.2 ± 2.3 (P = 0.9), in the PRGF/β-TCP+CM and PRGF/β-TCP group, respectively. Implantation of chair-side prepared autologous PRGF adsorbed on a β-TCP carrier in non-contained peri-implant defects resulted in large amounts of bone regeneration, but osseointegration was limited. Provisions for GBR with a collagen membrane did not significantly enhance bone regeneration or implant osseointegration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cost of placement and complications associated with osseointegrated bone-conducting hearing prostheses: a retrospective analysis of medicare billing data.

Science.gov (United States)

Pross, Seth E; Layton, Andrew; Tong, Kuo; Lustig, Lawrence R

2014-03-01

To report the cost of placement and complications related to osseointegrated bone-conducting hearing prostheses (OBHPs) in a Medicare population. We performed a retrospective analysis of nationwide Medicare claims data for operative and nonoperative complications associated with the placement of percutaneous OBHPs between the first quarter of 2007 and the second quarter of 2009 for which there were 6 subsequent quarters of follow-up. We used Medicare Standard Analytical Files (SAF), which contain a 5% random sample of Medicare fee-for-service beneficiaries, excluding those that also were enrolled in a managed-care organization. We identified 118 patients who had OBHPs placed in the requisite period. Their complication billing data were analyzed for the six-quarters after initial placement. Seventy patients (59%) had no billing codes for complications or repeat procedures after receiving the implant, whereas 48 patients (41%) had such codes. The total adjusted mean cost with repeat/revision operations or complications was $7,812 per patient compared with $6,733 for those without these issues, an increase of $1,079 or 16%. We estimate that complications associated with the implantation of percutaneous OBHPs led to $417,616 in additional costs in the entire Medicare fee-for-service population during the study period and that the total cost of placement of these devices together with the cost of their complications totaled $6,789,248. In conclusion, the Medicare SAF database suggests that complications associated with OBHP increased the overall cost of placement by 16%. Like all surgical procedures, these complications and their associated costs should be taken into account when considering treatment options for patients who experience hearing loss.

Improving osseointegration of dental implants.

Science.gov (United States)

Elias, Carlos Nelson; Meirelles, Luiz

2010-03-01

In the beginning of implantology, the procedures adopted for treating patients were performed in two surgical phases with an interval of 3-6 months. Nowadays, it is possible to insert and load a dental implant in the same surgical procedure. This change is due to several factors, such as improvement of surgical technique, modifications of the implant design, increased quality of implant manufacturing, development of the surgical instruments' quality, careful patient screening and adequate treatment of the implant surface. The clinical results show that adequate treatment of surfaces is crucial for reducing healing time and treating at-risk patients. The surface properties of dental implants can be significantly improved at the manufacturing stage, affecting cells' activity during the healing phase that will ultimately determine the host tissue response, a fundamental requirement for clinical success. This review focuses on different types of dental implant surfaces and the influence of surface characteristics on osseointegration.

A 15-year study of osseointegrated implants in the treatment of the edentulous jaw.

Science.gov (United States)

Adell, R; Lekholm, U; Rockler, B; Brånemark, P I

1981-12-01

Osseointegration implies a firm, direct and lasting connection between vital bone and screw-shaped titanium implants of defined finish and geometry-fixtures. Thus, there is no interposed tissue between fixture and bone. Osseointegration can only be achieved and maintained by a gentle surgical installation technique, a long healing time and a proper stress distribution when in function. During a 15-year period (1965-1980), 2768 fixtures were installed in 410 edentulous jaws of 371 consecutive patients. All patients were provided with facultatively removable bridges and were examined at continuous yearly controls. The surgical and prosthetic technique was developed and evaluated over a pilot period of 5 years. The results of standardized procedures applied on a consecutive clinical material with an observation time of 5-9 years were thought to properly reflect the potential of the method. In this group, 130 jaws were provided with 895 fixtures, and of these 81% of the maxillary and 91% of the mandibular fixtures remained stable, supporting bridges. In 89% of the maxillary and 100% of the mandibular cases, the bridges were continuously stable. During healing and the first year after connection of the bridge, the mean value for marginal bone loss was 1.5 mm. Thereafter only 0.1 mm was lost annually. The clinical results achieved with bridges on osseointegrated fixtures fulfill and exceed the demands set by the 1978 Harvard Conference on successful dental implantation procedures.

Association between in vivo bone formation and ex vivo migratory capacity of human bone marrow stromal cells

DEFF Research Database (Denmark)

Andersen, Rikke K.; Zaher, Walid; Larsen, Kenneth Hauberg

2015-01-01

INTRODUCTION: There is a clinical need for developing systemic transplantation protocols for use of human skeletal stem cells (also known bone marrow stromal stem cells) (hBMSC) in tissue regeneration. In systemic transplantation studies, only a limited number of hBMSC home to injured tissues...... populations derived from telomerized hBMSC (hBMSC-TERT) with variable ability to form heterotopic bone when implanted subcutaneously in immune deficient mice. In vitro transwell migration assay was used and the in vivo homing ability of transplanted hBMSC to bone fractures in mice was visualized...... suggesting that only a subpopulation of hBMSC possesses "homing" capacity. Thus, we tested the hypothesis that a subpopulation of hBMSC defined by ability to form heterotopic bone in vivo, is capable of homing to injured bone. METHODS: We tested ex vivo and in vivo homing capacity of a number of clonal cell...

Effects of a micro/nano rough strontium-loaded surface on osseointegration

Directory of Open Access Journals (Sweden)

Li Y

2015-07-01

-Sr groups, respectively. These results suggested that the MNT-Sr surface has a synergistic effect of hierarchical micro/nano-topography and strontium for enhanced osseointegration, and it may be a promising option for clinical use. Compared with the MT surface, the NT-Sr surface significantly improved the differentiation of osteoblasts in vitro. In the in vivo animal experiment, the MT surface significantly enhanced the bone-implant contact and maximal pullout force than the NT-Sr surface. Keywords: surface modification, micro/nanorough, implant

MicroCT Analysis of Micro-Nano Titanium Implant Surface on the Osseointegration.

Science.gov (United States)

Ban, Jaesam; Kang, Seongsoo; Kim, Jihyun; Lee, Kwangmin; Hyunpil, Lim; Vang, Mongsook; Yang, Hongso; Oh, Gyejeong; Kim, Hyunseung; Hwang, Gabwoon; Jung, Yongho; Lee, Kyungku; Park, Sangwon; Yunl, Kwidug

2015-01-01

This study was to investigate the effects of micro-nano titanium implant surface on the osseointegration. A total of 36 screw-shaped implants were used. The implant surfaces were classified into 3 groups (n = 12): machined surface (M group), nanosurface which is nanotube formation on the machined surface (MA group) and nano-micro surface which is nanotube formation on the RBM surface (RA group). Anodic oxidation was performed at a 20 V for 10 min with 1 M H3PO4 and 1.5 wt% HF solutions. The implants were installed on the humerus on 6 beagles. After 4 and 12 weeks, the morphometric analysis with micro CT (skyscan 1172, SKYSCAN, Antwerpen, Belgium) was done. The data were statistically analyzed with two-way ANOVA. Bone mineral density and bone volume were significantly increased depending on time. RA group showed the highest bone mineral density and bone volume at 4 weeks and 12 weeks significantly. It indicated that nano-micro titanium implant surface showed faster and more mature osseointegration.

Embedded System for Prosthetic Control Using Implanted Neuromuscular Interfaces Accessed Via an Osseointegrated Implant.

Science.gov (United States)

Mastinu, Enzo; Doguet, Pascal; Botquin, Yohan; Hakansson, Bo; Ortiz-Catalan, Max

2017-08-01

Despite the technological progress in robotics achieved in the last decades, prosthetic limbs still lack functionality, reliability, and comfort. Recently, an implanted neuromusculoskeletal interface built upon osseointegration was developed and tested in humans, namely the Osseointegrated Human-Machine Gateway. Here, we present an embedded system to exploit the advantages of this technology. Our artificial limb controller allows for bioelectric signals acquisition, processing, decoding of motor intent, prosthetic control, and sensory feedback. It includes a neurostimulator to provide direct neural feedback based on sensory information. The system was validated using real-time tasks characterization, power consumption evaluation, and myoelectric pattern recognition performance. Functionality was proven in a first pilot patient from whom results of daily usage were obtained. The system was designed to be reliably used in activities of daily living, as well as a research platform to monitor prosthesis usage and training, machine-learning-based control algorithms, and neural stimulation paradigms.

Tissue non-specific alkaline phosphatase production by human dental pulp stromal cells is enhanced by high density cell culture.

Science.gov (United States)

Tomlinson, Matthew J; Dennis, Caitriona; Yang, Xuebin B; Kirkham, Jennifer

2015-08-01

The cell surface hydrolase tissue non-specific alkaline phosphatase (TNAP) (also known as MSCA-1) is used to identify a sub-population of bone marrow stromal cells (BMSCs) with high mineralising potential and is found on subsets of cells within the dental pulp. We aim to determine whether TNAP is co-expressed by human dental pulp stromal cells (hDPSCs) alongside a range of BMSC markers, whether this is an active form of the enzyme and the effects of culture duration and cell density on its expression. Cells from primary dental pulp and culture expanded hDPSCs expressed TNAP. Subsequent analyses revealed persistent TNAP expression and co-expression with BMSC markers such as CD73 and CD90. Flow cytometry and biochemical assays showed that increased culture durations and cell densities enhanced TNAP expression by hDPSCs. Arresting the hDPSC cell cycle also increased TNAP expression. These data confirm that TNAP is co-expressed by hDPSCs together with other BMSC markers and show that cell density affects TNAP expression levels. We conclude that TNAP is a potentially useful marker for hDPSC selection especially for uses in mineralised tissue regenerative therapies.

A novel osseointegrated percutaneous prosthetic system for the treatment of patients with transfemoral amputation: A prospective study of 51 patients.

Science.gov (United States)

Brånemark, R; Berlin, O; Hagberg, K; Bergh, P; Gunterberg, B; Rydevik, B

2014-01-01

Patients with transfemoral amputation (TFA) often experience problems related to the use of socket-suspended prostheses. The clinical development of osseointegrated percutaneous prostheses for patients with a TFA started in 1990, based on the long-term successful results of osseointegrated dental implants. Between 1999 and 2007, 51 patients with 55 TFAs were consecutively enrolled in a prospective, single-centre non-randomised study and followed for two years. The indication for amputation was trauma in 33 patients (65%) and tumour in 12 (24%). A two-stage surgical procedure was used to introduce a percutaneous implant to which an external amputation prosthesis was attached. The assessment of outcome included the use of two self-report questionnaires, the Questionnaire for Persons with a Transfemoral Amputation (Q-TFA) and the Short-Form (SF)-36. The cumulative survival at two years' follow-up was 92%. The Q-TFA showed improved prosthetic use, mobility, global situation and fewer problems (all p reported following treatment with osseointegrated percutaneous prostheses.

Effects of Untreated Periodontitis on Osseointegration of Dental Implants in a Beagle Dog Model.

Science.gov (United States)

Lee, Daehyun; Sohn, Byungjin; Kim, Kyoung Hwa; Kim, Sungtae; Koo, Ki-Tae; Kim, Tae-Il; Seol, Yang-Jo; Lee, Yong-Moo; Rhyu, In-Chul; Ku, Young

2016-10-01

There have been previous studies on the relationship between periodontitis and peri-implantitis, but limited information is available on how periodontitis affects osseointegration and wound healing of newly placed dental implants adjacent to natural teeth. The objective of the present experiment is to evaluate healing around dental implants adjacent to teeth with untreated experimental periodontitis. The study included six male beagle dogs. Scaling and plaque control procedures were performed on three dogs (control group). In the other three dogs (experimental group), retraction cords and ligature wires were placed subgingivally around all premolars and the first molars. Induced experimental periodontitis was confirmed after 3 months. Each control or experimental group was divided into two subgroups depending on the timing of implant placement (immediate/delayed). Twelve dental implants (two implants for each dog) were placed immediately, and the other 12 dental implants (two implants for each dog) were placed 2 months after extraction. The animals were sacrificed 2 months after implant placement. Histologic and histometric analyses were performed. Four implants (three from the immediate placement group and one from the delayed placement group) failed in the experimental group. There were significant differences in the percentage of bone-to-implant contact and marginal bone volume density between the control and experimental groups. Both parameters were significantly lower in the experimental group than in the control group (P implants is associated with a higher failure rate compared with delayed placement. Untreated experimental periodontitis was correlated with compromised osseointegration in the implants with delayed placement.

The Effect of Hierarchical Micro/Nanotextured Titanium Implants on Osseointegration Immediately After Tooth Extraction in Beagle Dogs.

Science.gov (United States)

Fu, Qian; Bellare, Anuj; Cui, Yajun; Cheng, Bingkun; Xu, Shanshan; Kong, Liang

2017-06-01

Owing to simplify the operation and shorten the overall duration of treatment, immediate implantation earned much satisfactory from patients and dentists. The results of immediate implantation determined by osseointegration, we fabricated a micro/nanotextured titanium implants to improve osseointegration immediately after tooth extraction. The aim of this study was to investigate the effect of hierarchical micro/nanotextured titanium implant on osseointegration immediately after tooth extraction. The micro/nanotextured titanium implants were fabricated by etching with 0.5 wt% hydrofluoric (HF) acid followed by anodization in HF electrolytes. Implants with a machined surface as well as implants a microtextured surface prepared by 0.5 wt% HF etching served as control groups. The machined, microtextured, and micro/nanotextured implants were inserted into fresh sockets immediately after tooth extraction in beagle dogs. Twelve weeks after implantation, the animals were sacrificed for micro-CT scanning, histological analysis and biomechanical test. The micro-CT imaging revealed that the bone volume/total volume (BV/TV) and trabecular thickness (Tb.Th) in the micro/nanotextured group was significantly higher than that in the machined group and microtextured group, and the trabecular separation (Tb.Sp) in the micro/nanotextured group was significantly lower than that in the other groups. For the histological analysis, the bone-to-implant contact in the machined, micro and micro/nanotextured groups were 47.13 ± 6.2%, 54.29 ± 4.18%, and 63.38 ± 7.63%, respectively, and the differences significant. The maximum pull-out force in the machined, micro, and micro/nanotextured groups were 216.58 ± 38.71 N, 259.42 ± 28.93 N, and 284.73 ± 47.09 N, respectively. The results indicated that implants with a hierarchical micro/nanotextured can promote osseointegration immediately after tooth extraction. © 2016 Wiley Periodicals, Inc.

A comparative study of zirconium and titanium implants in rat: osseointegration and bone material quality.

Science.gov (United States)

Hoerth, Rebecca M; Katunar, María R; Gomez Sanchez, Andrea; Orellano, Juan C; Ceré, Silvia M; Wagermaier, Wolfgang; Ballarre, Josefina

2014-02-01

Permanent metal implants are widely used in human medical treatments and orthopedics, for example as hip joint replacements. They are commonly made of titanium alloys and beyond the optimization of this established material, it is also essential to explore alternative implant materials in view of improved osseointegration. The aim of our study was to characterize the implant performance of zirconium in comparison to titanium implants. Zirconium implants have been characterized in a previous study concerning material properties and surface characteristics in vitro, such as oxide layer thickness and surface roughness. In the present study, we compare bone material quality around zirconium and titanium implants in terms of osseointegration and therefore characterized bone material properties in a rat model using a multi-method approach. We used light and electron microscopy, micro Raman spectroscopy, micro X-ray fluorescence and X-ray scattering techniques to investigate the osseointegration in terms of compositional and structural properties of the newly formed bone. Regarding the mineralization level, the mineral composition, and the alignment and order of the mineral particles, our results show that the maturity of the newly formed bone after 8 weeks of implantation is already very high. In conclusion, the bone material quality obtained for zirconium implants is at least as good as for titanium. It seems that the zirconium implants can be a good candidate for using as permanent metal prosthesis for orthopedic treatments.

Cellulose acetate membranes functionalized with resveratrol by covalent immobilization for improved osseointegration

Science.gov (United States)

Pandele, A. M.; Neacsu, P.; Cimpean, A.; Staras, A. I.; Miculescu, F.; Iordache, A.; Voicu, S. I.; Thakur, V. K.; Toader, O. D.

2018-04-01

Covalent immobilization of resveratrol onto cellulose acetate polymeric membranes used as coating on a Mg-1Ca-0.2Mn-0.6Zr alloy is presented for potential application in the improvement of osseointegration processes. For this purpose, cellulose acetate membrane is hydrolysed in the presence of potassium hydroxide, followed by covalent immobilization of aminopropyl triethoxy silane. Resveratrol was immobilized onto membranes using glutaraldehyde as linker. The newly synthesised functional membranes were thoroughly characterized for their structural characteristics determination employing X-ray photoelectron spectroscopy (XPS), infrared spectroscopy (FT-IR), Raman spectroscopy, thermogravimetric analysis (TGA/DTG) and scanning electron microscopy (SEM) techniques. Subsequently, in vitro cellular tests were performed for evaluating the cytotoxicity biocompatibility of synthesized materials and also the osseointegration potential of obtained derivatised membrane material. It was demonstrated that both polymeric membranes support viability and proliferation of the pre-osteoblastic MC3T3-E1 cells, thus providing a good protection against the potential harmful effects of the compounds released from coated alloys. Furthermore, cellulose acetate membrane functionalized with resveratrol exhibits a significant increase in alkaline phosphatase activity and extracellular matrix mineralization, suggesting its suitability to function as an implant surface coating for guided bone regeneration.

Establishment of a new pull-out strength testing method to quantify early osseointegration-An experimental pilot study.

Science.gov (United States)

Nonhoff, J; Moest, T; Schmitt, Christian Martin; Weisel, T; Bauer, S; Schlegel, K A

2015-12-01

The animal study aims to evaluate a new experimental model for measuring sole the influence of the surface characteristics independent from implant macro-design on the level of osseointegration by registering the pull-out strength needed for removal of experimental devices with different surfaces from artificial defects. Seventy-two test bodies (36 with the FRIADENT(®) plus surface, 36 with the P15/HAp biofunctionalized surface) were inserted in six adult domestic pigs with artificial calvarial defects. The experimental devices were designed to fit in the defects leaving a gap between the test body and the local bone. After 21 days of healing, the animals were sacrificed and the test bodies were pulled out with a standardised reproducible pull-out device measuring the pull-out strength. The pull-out strength for both groups was compared. Twenty-one days after insertion a mean force of 412 ± 142 N for the P15/HAp group and 183 ± 105 N for the FRIADENT(®) plus group was measured for the removal of the specimens from the calvarial bone. The difference between the groups was statistically significant (p implant surfaces on the early stage of osseointegration. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Enhancement of biodegradation and osseointegration of poly(ε-caprolactone)/calcium phosphate ceramic composite screws for osteofixation using calcium sulfate.

Science.gov (United States)

Wu, Chang-Chin; Hsu, Li-Ho; Tsai, Yuh-Feng; Sumi, Shoichiro; Yang, Kai-Chiang

2016-04-04

Internal fixation devices, which can stabilize and realign fractured bone, are widely used in fracture management. In this paper, a biodegradable composite fixator, composed of poly(ε-caprolactone), calcium phosphate ceramic and calcium sulfate (PCL/CPC/CS), is developed. The composition of CS, which has a high dissolution rate, was expected to create a porous structure to improve osteofixation to the composite fixator. PCL, PCL/CPC, and PCL/CPC/CS samples were prepared and their physical properties were characterized in vitro. In vivo performance of the composite screws was verified in the distal femurs of rabbits. Results showed that the PCL/CPC/CS composite had a higher compressive strength (28.55 ± 3.32 MPa) in comparison with that of PCL (20.64 ± 1.81 MPa) (p < 0.05). A larger amount of apatite was formed on PCL/CPC/CS than on PCL/CPC, while no apatite was found on PCL after simulated body fluid immersion. In addition, PCL/CPC/CS composites also had a faster in vitro degradation rate (13.05 ± 3.42% in weight loss) relative to PCL (1.79 ± 0.23%) and PCL/CPC (4.32 ± 2.18%) (p < 0.001). In animal studies, PCL/CPC/CS screws showed a greater volume loss than that of PCL or PCL/CPC at 24 weeks post-implantation. Under micro-computerized tomography observation, animals with PCL/CPC/CS implants had better osseointegration in terms of the structural parameters of the distal metaphysis, including trabecular number, trabecular spacing, and connectivity density, than the PCL screw. This study reveals that the addition of CS accelerates the biodegradation and enhanced apatite formation of the PCL/CPC composite screw. This osteoconductive PCL/CPC/CS is a good candidate material for internal fixation devices.

Biological Response of Human Bone Marrow-Derived Mesenchymal Stem Cells to Commercial Tantalum Coatings with Microscale and Nanoscale Surface Topographies

Science.gov (United States)

Skoog, Shelby A.; Kumar, Girish; Goering, Peter L.; Williams, Brian; Stiglich, Jack; Narayan, Roger J.

2016-06-01

Tantalum is a promising orthopaedic implant coating material due to its robust mechanical properties, corrosion resistance, and excellent biocompatibility. Previous studies have demonstrated improved biocompatibility and tissue integration of surface-treated tantalum coatings compared to untreated tantalum. Surface modification of tantalum coatings with biologically inspired microscale and nanoscale features may be used to evoke optimal tissue responses. The goal of this study was to evaluate commercial tantalum coatings with nanoscale, sub-microscale, and microscale surface topographies for orthopaedic and dental applications using human bone marrow-derived mesenchymal stem cells (hBMSCs). Tantalum coatings with different microscale and nanoscale surface topographies were fabricated using a diffusion process or chemical vapor deposition. Biological evaluation of the tantalum coatings using hBMSCs showed that tantalum coatings promote cellular adhesion and growth. Furthermore, hBMSC adhesion to the tantalum coatings was dependent on surface feature characteristics, with enhanced cell adhesion on sub-micrometer- and micrometer-sized surface topographies compared to hybrid nano-/microstructures. Nanostructured and microstructured tantalum coatings should be further evaluated to optimize the surface coating features to promote osteogenesis and enhance osseointegration of tantalum-based orthopaedic implants.

Findings from the experience with the punch technique for auditory osseointegrated implants: A retrospective single center comparative study.

Science.gov (United States)

Bonilla, Alfonso; Magri, Carlos; Juan, Eulalia

To compare the punch technique and linear incision with soft tissue reduction for the placement of auditory osseointegrated implants (AOI) and analyze results of osseointegration obtained with the punch technique as measured with the Implant Stability Quotient (ISQ). Case review of 34 patients who received auditory osseointegrated implants between January 2010 and July 2015 and were divided into two groups according to the surgical technique: 18 with the punch technique (PT) and 16 with the linear incision technique (LI). Minimum follow-up was four months (mean: 24 months; range 4-64 months). Included in the analysis were patient profiles and records of the demographic data, surgical indications, surgical technique, implant placement, surgical time, intraoperative complications, as well as postsurgical complications (Holgers classification) and implant stability quotients (ISQ). Use of larger abutments was significantly greater in the PT group (PT, 10mm; LI, 6mm, p<0.001). The PT technique resulted in a shorter procedure than the LI (PT, 20min; LI, 45min, p<0.001). Holgers classification scores identified significantly fewer skin complications one week after surgery for the PT group; however, only small differences were seen between the two groups at the one- and three-month control visits. As shown for our cohort, the punch technique for surgical placement of AOI is faster and presents fewer immediate postoperative complications when compared to the linear incision technique. The clinical application of the ISQ is a useful, easy method to demonstrate the status of osseointegration and, thus, the stability of the device. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Decontamination of titanium implant surface and re-osseointegration to treat peri-implantitis: a literature review

NARCIS (Netherlands)

Subramani, K.; Wismeijer, D.

2012-01-01

PURPOSE: To review the literature on decontamination of titanium implant surfaces following peri-implantitis and the effect of various cleaning methods on re-osseointegration. MATERIALS AND METHODS: An electronic search of the literature at PubMed was conducted on the studies published between 1966

Osteogenesis of Adipose-Derived and Bone Marrow Stem Cells with Polycaprolactone/Tricalcium Phosphate and Three-Dimensional Printing Technology in a Dog Model of Maxillary Bone Defects

Directory of Open Access Journals (Sweden)

Jeong Woo Lee

2017-09-01

Full Text Available Bone graft material should possess sufficient porosity and permeability to allow integration with native tissue and vascular invasion, and must satisfy oxygen and nutrient transport demands. In this study, we have examined the use of three-dimensional (3D-printed polycaprolactone/tricalcium phosphate (PCL/TCP composite material in bone grafting, to estimate the scope of its potential application in bone surgery. Adipose-derived stem cells (ADSCs and bone marrow stem cells (BMSCs are known to enhance osteointegration. We hypothesized that a patient-specific 3D-printed solid scaffold could help preserve seeded ADSCs and BMSCs and enhance osteointegration. Diffuse osteogenic tissue formation was observed by micro-computed tomography with both stem cell types, and the ADSC group displayed similar osteogenesis compared to the BMSC group. In histological assessment, the scaffold pores showed abundant ossification in both groups. Reverse transcription polymerase chain reaction (RT-PCR showed that the BMSC group had higher expression of genes associated with ossification, and this was confirmed by Western blot analysis. The ADSC- and BMSC-seeded 3D-printed PCL/TCP scaffolds displayed promising enhancement of osteogenesis in a dog model of maxillary bone defects.

Osseointegration of three-dimensional designed titanium implants manufactured by selective laser melting.

Science.gov (United States)

Shaoki, Algabri; Xu, Jia-Yun; Sun, Haipeng; Chen, Xian-Shuai; Ouyang, Jianglin; Zhuang, Xiu-Mei; Deng, Fei-Long

2016-10-27

The selective laser melting (SLM) technique is a recent additive manufacturing (AM) technique. Several studies have reported success in the SLM-based production of biocompatible orthopaedic implants and three-dimensional bone defect constructs. In this study, we evaluated the surface properties and biocompatibility of an SLM titanium implant in vitro and compared them with those of a machined (MA) titanium control surface. In addition, we evaluated the osseointegration capability of the SLM implants in vivo and compared it with those of MA and Nobel-speedy (Nobel-S) implants. SLM microtopographical surface analysis revealed porous and high roughness with varied geometry compared with a smooth surface in MA Ti samples but with similar favourable wettability. Osteoblast proliferation and alkaline phosphatase activity were significantly enhanced on the SLM surface. Histological analysis of the bone-implant contact ratio revealed no significant difference among SLM, MA, and Nobel-S implants. Micro-CT assessment indicated that there was no significant difference in bone volume fraction around the implant among SLM implants and other types of surface modification implants. The removal torque value measurement of SLM implants was significantly lower that of than Nobel-S implants P manufacturing technique.

Monitoring the osseointegration process in porous Ti6Al4V implants produced by additive manufacturing: an experimental study in sheep.

Science.gov (United States)

Kayacan, Mehmet C; Baykal, Yakup B; Karaaslan, Tamer; Özsoy, Koray; Alaca, İlker; Duman, Burhan; Delikanlı, Yunus E

2018-04-01

This study investigated the design and osseointegration process of transitive porous implants that can be used in humans and all trabecular and compact bone structure animals. The aim was to find a way of forming a strong and durable tissue bond on the bone-implant interface. Massive and transitive porous implants were produced on a direct metal laser sintering machine, surgically implanted into the skulls of sheep and kept in place for 12 weeks. At the end of the 12-week period, the Massive and porous implants removed from the sheep were investigated by scanning electron microscopy (SEM) to monitor the osseointegration process. In the literature, each study has selected standard sizes for pore diameter in the structures they use. However, none of these involved transitional porous structures. In this study, as opposed to standard pores, there were spherical or elliptical pores at the micro level, development channels and an inner region. Bone cells developed in the inner region. Transitive pores grown gradually in accordance with the natural structure of the bone were modeled in the inner region for cells to develop. Due to this structure, a strong and durable tissue bond could be formed at the bone-implant interface. Osseointegration processes of Massive vs. porous implants were compared. It was observed that cells were concentrated on the surface of Massive implants. Therefore, osseointegration between implant and bone was less than that of porous implants. In transitive porous implants, as opposed to Massive implants, an outer region was formed in the bone-implant interface that allowed tissue development.

Enhancement of osseointegration of polyethylene terephthalate artificial ligament by coating of silk fibroin and depositing of hydroxyapatite

Science.gov (United States)

Jiang, Jia; Wan, Fang; Yang, Jianjun; Hao, Wei; Wang, Yaxian; Yao, Jinrong; Shao, Zhengzhong; Zhang, Peng; Chen, Jun; Zhou, Liang; Chen, Shiyi

2014-01-01

Background Application of artificial ligament in anterior cruciate ligament reconstruction is one of the research focuses of sports medicine but the biological tendon–bone healing still remains a problem. The preliminary study of hydroxyapatite (HAP) coating on the polyethylene terephthalate (PET) surface could effectively induce the osteoblast differentiation, but the tendon–bone healing was still not stable. As a green synthesis process, the biomimetic mineralization can simulate the natural bone growth in vitro and in vivo. Methods HAP crystals were grown under the guide of silk fibroin (SF) PET surface by biomimetic route. Several techniques including scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy were utilized for proving the introduction of both SF and HAP. The viability and osseointegration of bone marrow stromal cells on the surface of three kinds of ligament, including PET group (non-coating group), PET+SF group (SF-coating group), and PET+SF+HAP group (combined HAP- and SF-coating group), were analyzed by CCK-8 assays and alkaline phosphatase (ALP) detection. Seventy-two mature male New Zealand rabbits were randomly divided into three groups. Among them, 36 rabbits were sacrificed for mechanical testing, and histological examination for the others. Results The SF and SF+HAP were successfully coated on the surface of PET fiber. The CCK-8 assay showed that the cell proliferation on PET+SF+HAP group was better than the other two groups from 24 to 120 hours. After 14 days of culture, the cells in the PET+SF+HAP group delivered higher levels of ALP than the other two groups. After 3 days of culture, the expression level of integrin β1 in the PET+SF+HAP group and PET+SF group were higher than in the PET group. The mean load to failure and the stiffness value of the PET+SF+HAP group were both higher than the other two groups. Hematoxylin and

Enhancement of osseointegration of polyethylene terephthalate artificial ligament by coating of silk fibroin and depositing of hydroxyapatite.

Science.gov (United States)

Jiang, Jia; Wan, Fang; Yang, Jianjun; Hao, Wei; Wang, Yaxian; Yao, Jinrong; Shao, Zhengzhong; Zhang, Peng; Chen, Jun; Zhou, Liang; Chen, Shiyi

2014-01-01

Application of artificial ligament in anterior cruciate ligament reconstruction is one of the research focuses of sports medicine but the biological tendon-bone healing still remains a problem. The preliminary study of hydroxyapatite (HAP) coating on the polyethylene terephthalate (PET) surface could effectively induce the osteoblast differentiation, but the tendon-bone healing was still not stable. As a green synthesis process, the biomimetic mineralization can simulate the natural bone growth in vitro and in vivo. HAP crystals were grown under the guide of silk fibroin (SF) PET surface by biomimetic route. Several techniques including scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy were utilized for proving the introduction of both SF and HAP. The viability and osseointegration of bone marrow stromal cells on the surface of three kinds of ligament, including PET group (non-coating group), PET+SF group (SF-coating group), and PET+SF+HAP group (combined HAP- and SF-coating group), were analyzed by CCK-8 assays and alkaline phosphatase (ALP) detection. Seventy-two mature male New Zealand rabbits were randomly divided into three groups. Among them, 36 rabbits were sacrificed for mechanical testing, and histological examination for the others. The SF and SF+HAP were successfully coated on the surface of PET fiber. The CCK-8 assay showed that the cell proliferation on PET+SF+HAP group was better than the other two groups from 24 to 120 hours. After 14 days of culture, the cells in the PET+SF+HAP group delivered higher levels of ALP than the other two groups. After 3 days of culture, the expression level of integrin β1 in the PET+SF+HAP group and PET+SF group were higher than in the PET group. The mean load to failure and the stiffness value of the PET+SF+HAP group were both higher than the other two groups. Hematoxylin and eosin staining showed that new bone

Establishing quiescence in human bone marrow stem cells leads to enhanced osteoblast marker expression

DEFF Research Database (Denmark)

Harkness, Linda; Rumman, Mohammad; Kassem, Moustapha

Human bone marrow stromal (skeletal) stem cells (hBMSC) are cells that retain a multi-lineage differentiation potential and are thus increasingly being investigated for use in clinical applications. In vivo BMSC, which comprise approximately 0.1% of the bone marrow compartment, are thought to mai...

Modulation of Host Osseointegration during Bone Regeneration by Controlling Exogenous Stem Cells Differentiation Using a Material Approach.

Science.gov (United States)

Yu, Xiaohua; Wang, Liping; Xia, Zengmin; Chen, Li; Jiang, Xi; Rowe, David; Wei, Mei

2014-02-01

Stem cell-based tissue engineering for large bone defect healing has attracted enormous attention in regenerative medicine. However, sufficient osseointegration of the grafts combined with exogenous stem cells still remains a major challenge. Here we developed a material approach to modulate the integration of the grafts to the host tissue when exogenous bone marrow stromal cells (BMSCs) were used as donor cells. Distinctive osseointegration of bone grafts was observed as we varied the content of hydroxyapatite (HA) in the tissue scaffolds implanted in a mouse femur model. More than 80% of new bone was formed in the first two weeks of implantation in high HA content scaffold but lack of host integration while only less than 5% of the new bone was formed during this time period in the no HA group but with much stronger host integration. Cell origin analysis leveraging GFP reporter indicates new bone in HA containing groups was mainly derived from donor BMSCs. In comparison, both host and donor cells were found on new bone surface in the no HA groups which led to seamless bridging between host tissue and the scaffold. Most importantly, host integration during bone formation is closely dictated to the content of HA present in the scaffolds. Taken together, we demonstrate a material approach to modulate the osseointegration of bone grafts in the context of exogenous stem cell-based bone healing strategy which might lead to fully functional bone tissue regeneration.

Optimal delivery route of bone marrow stromal cells for rat infarct brain – A study using non-invasive optical imaging

Directory of Open Access Journals (Sweden)

Tamaki N

2010-01-01

Full Text Available BACKGROUND - Recent studies have indicated that bone marrow stromal cells (BMSC have the potential to improve neurological function when transplanted into animal model of central nervous system (CNS disorders. However, there still exist several questions to solved prior to clinical application. In this study, therefore, we aimed to clarify the optimal delivery route of BMSC transplantation over a reasonable time window.MATERIALS AND METHODS - The rats were subjected to permanent middle cerebral artery occlusion. The BMSC were labeled with quantum dot (QD 800. The labeled BMSC were transplanted into the infarct brain directly or intravenously at 7 days after the insult. Motor function was serially assessed. The BMSC were also tracked using near infrared (NIR fluorescence imaging technique every week. The fate of the transplanted BMSC was examined at 5 weeks after transplantation, using Immunohistochemistry. RESULTS - Direct, but not intravenous, transplantation of BMSC significantly enhanced functional recovery. NIR fluorescence imaging could visualize their migration towards cerebral infarct in directly, but not intravenously, injected animals. The findings were supported on histological analysis. Thus, the BMSC were widely engrafted in the infarct brain in the directly injected animals, but few BMSC were observed in the intravenously injected ones. CONCLUSION - This study strongly suggests that direct transplantation of BMSC may be more beneficial in treating patients with ischemic stroke than their intravenous transplantation. Therapeutic time window must be called into account when considering the route of BMSC transplantation.

Effects of orthopedic implants with a polycaprolactone polymer coating containing bone morphogenetic protein-2 on osseointegration in bones of sheep.

Science.gov (United States)

Niehaus, Andrew J; Anderson, David E; Samii, Valerie F; Weisbrode, Steven E; Johnson, Jed K; Noon, Mike S; Tomasko, David L; Lannutti, John J

2009-11-01

To determine elution characteristics of bone morphogenetic protein (BMP)-2 from a polycaprolactone coating applied to orthopedic implants and determine effects of this coating on osseointegration. 6 sheep. An in vitro study was conducted to determine BMP-2 elution from polycaprolactone-coated implants. An in vivo study was conducted to determine the effects on osseointegration when the polycaprolactone with BMP-2 coating was applied to bone screws. Osseointegration was assessed via radiography, measurement of peak removal torque and bone mineral density, and histomorphometric analysis. Physiologic response was assessed by measuring serum bone-specific alkaline phosphatase activity and uptake of bone markers. Mean +/- SD elution on day 1 of the in vitro study was 263 +/- 152 pg/d, which then maintained a plateau at 59.8 +/- 29.1 pg/d. Mean peak removal torque for screws coated with polycalprolactone and BMP-2 (0.91 +/- 0.65 dN x m) and screws coated with polycaprolactone alone (0.97 +/- 1.30 dN.m) did not differ significantly from that for the control screws (2.34 +/- 1.62 dN x m). Mean bone mineral densities were 0.535 +/- 0.060 g/cm(2), 0.596 +/- 0.093 g/cm(2), and 0.524 +/- 0.142 g/cm(2) for the polycaprolactone-BMP-2-coated, polycaprolactone-coated, and control screws, respectively, and did not differ significantly among groups. Histologically, bone was in closer apposition to the implant with the control screws than with either of the coated screws. BMP-2 within the polycaprolactone coating did not stimulate osteogenesis. The polycaprolactone coating appeared to cause a barrier effect that prevented formation of new bone. A longer period or use of another carrier polymer may result in increased osseointegration.

Gallium and silicon synergistically promote osseointegration of dental implant in patients with osteoporosis.

Science.gov (United States)

Liu, Jinsong; Wu, Zuosu; He, Hongli; Cai, Kaiyong; Zhang, Hualin; Xu, Lihua

2017-06-01

Over the last few decades, a wide variety of dental implants have been successfully placed in jaw bones to restore tooth function. But major challenges still remain in patients with osteoporosis involving compromised osseointegration, and the therapeutic methods is far from optimism. Gallium can directly inhibit bone osteolysis, prevent bone calcium release and augment bone mass, which makes Ga unique among the potential antiresorptive drugs. Silicon, as an indispensable modulator in bone formation, presents its bone anabolic effects, while reduces, at least doesn't increase, bone resorption. We hypothesize that the combination of bone anabolic effects of Si and antiresorptive effects of Ga will result in synergistic effects on the improvement of osteointegration under osteoporotic condition. In our strategy, in order to maximize the efficacy while minimize the side effects of ions, a novel titania mesoporous layer fabricated by electrochemical anodization on the surface of titanium implant will be employed as a promising local drug delivery system. The synergistic effects of Ga and Si on improving osseointegration will be verified by animal experiments, and be furthered by clinical trials. Our hypothesis could help to create an option to improve success rate of dental implants in osteoporotic patients. Copyright © 2017. Published by Elsevier Ltd.

Multi-body simulation of various falling scenarios for determining resulting loads at the prosthesis interface of transfemoral amputees with osseointegrated fixation.

Science.gov (United States)

Welke, Bastian; Schwarze, Michael; Hurschler, Christof; Calliess, Tilman; Seehaus, Frank

2013-07-01

Conventionally, transfemoral amputees are treated with a shaft prosthesis fitted over the residual limb. To improve the quality of life of such patients, in particular those with complications relating to conventional attachment (e.g., skin irritation, stump ulcers, and poor motor-control with short stumps), osseointegrated prosthesis fixation implants have been developed and implanted in a limited population of patients. To assess possible damage to the implant/prosthesis during falling scenarios, the loads in high-risk situations were estimated using a multi-body simulation of motion. Five falling scenarios were identified and performed by healthy volunteer wearing safety equipment. Kinematic data and ground reaction forces were captured as input for the inverse-dynamics-based simulations, from which the forces and moments at a typical implant-prosthesis interface location were computed. The estimated peak loads in all five scenarios were of a magnitude that could lead to bone fracture. The largest peak force observed was 3274 ± 519 N, with an associated resultant moment of 176 ± 55 Nm on the prosthesis-implant interface. A typical femur is prone to fracture under this load, thus illustrating the need for a safety-release element in osseointegrated prosthesis fixation. Copyright © 2013 Orthopaedic Research Society.

Osseointegration of loaded dental implant with KrF laser hydroxylapatite films on Ti6Al4V alloy by minipigs

Science.gov (United States)

Dostalova, Tatjana; Himmlova, Lucia; Jelinek, Miroslav; Grivas, Christos

2001-04-01

This study was performed with the objective of evaluating osseointegration of titanium alloy Ti6Al4V dental implants coated with hydroxylapatite (HA) deposited by a KrF laser. For this a KrF excimer laser and stainless-steel deposition chamber were used. The thickness of the HA films was approximately 1 micrometers . IN this investigation experimental animals minipigs were used; the implants were placed vertically into the lower jaw. After 14 weeks of unloaded osseointegration, metal-ceramic crowns were inserted and, at the same time, fluorescent solution was injected into the experimental animals. Six months after insertion of crowns the animals were sacrificed. The vertical position of the implants was checked by a radiograph. Microscopic sections were cut and ground, and the sections were examined under polarized and fluorescent light using a microscope with a charge coupled device camera. The six month long osseointegration in the lower jaw has confirmed the presence of newly formed bone around all the implants. In the experimental group, which had a laser-deposited coating, the layer of fibrous connective tissue was seen only randomly. In the control group (titanium implant without a cover) the fibrous connective tissue between the implant and the newly formed bone was observed more frequently, but this difference was not significant.

Sheep Hip Arthroplasty Model of Failed Implant Osseointegration

DEFF Research Database (Denmark)

Jakobsen, Thomas; Kold, Søren; Baas, Jørgen

2015-01-01

femoral condyles in ten sheep. The micromotion device consists of an anchor bearing a PMMA implant and a PE plug. During each gait cycle the PE plug will make the PMMA implant axially piston 0.5 mm. After 12 weeks of observation the bone specimens were harvested and a post-mortem control implant......Early secure stability of an implant is important for long-term survival. We examined whether micromotion of implants consistently would induce bone resorption and formation of a fibrous membrane and thereby prevent osseointegration. One micromotion implant was inserted into one of the medial...... was inserted into the contra-lateral medial femoral condyle. Histomorphometrical evaluation showed that the surface on the implant observed for 12 weeks was covered by fibrous tissue. The control implants were covered by lamellar bone. No difference was found with respect to the volume fraction of lamellar...

Osseointegration of titanium, titanium alloy and zirconia dental implants: current knowledge and open questions.

Science.gov (United States)

Bosshardt, Dieter D; Chappuis, Vivianne; Buser, Daniel

2017-02-01

Bone healing around dental implants follows the pattern and sequence of intramembraneous osteogenesis with formation of woven bone first of all followed later by formation of parallel-fibered and lamellar bone. Bone apposition onto the implant surface starts earlier in trabecular bone than in compact bone. While the first new bone may be found on the implant surface around 1 week after installation, bone remodeling starts at between 6 and 12 weeks and continues throughout life. Bone remodeling also involves the bone-implant interface, thus transiently exposing portions of the implant surface. Surface modifications creating micro-rough implant surfaces accelerate the osseointegration process of titanium implants, as demonstrated in numerous animal experiments. Sandblasting followed by acid-etching may currently be regarded as the gold standard technique to create micro-rough surfaces. Chemical surface modifications, resulting in higher hydrophilicity, further increase the speed of osseointegration of titanium and titanium-zirconium implants in both animals and humans. Surface modifications of zirconia and alumina-toughened zirconia implants also have an influence on the speed of osseointegration, and some implant types reach high bone-to-implant contact values in animals. Although often discussed independently of each other, surface characteristics, such as topography and chemistry, are virtually inseparable. Contemporary, well-documented implant systems with micro-rough implant surfaces, placed by properly trained and experienced clinicians, demonstrate high long-term survival rates. Nevertheless, implant failures do occur. A low percentage of implants are diagnosed with peri-implantitis after 10 years in function. In addition, a low number of implants seem to be lost for primarily reasons other than biofilm-induced infection. Patient factors, such as medications interfering with the immune system and bone cells, may be an element contributing to continuous bone

Application of high resolution synchrotron micro-CT radiation in dental implant osseointegration.

Science.gov (United States)

Neldam, Camilla Albeck; Lauridsen, Torsten; Rack, Alexander; Lefolii, Tore Tranberg; Jørgensen, Niklas Rye; Feidenhans'l, Robert; Pinholt, Else Marie

2015-06-01

The purpose of this study was to describe a refined method using high-resolution synchrotron radiation microtomography (SRmicro-CT) to evaluate osseointegration and peri-implant bone volume fraction after titanium dental implant insertion. SRmicro-CT is considered gold standard evaluating bone microarchitecture. Its high resolution, high contrast, and excellent high signal-to-noise-ratio all contribute to the highest spatial resolutions achievable today. Using SRmicro-CT at a voxel size of 5 μm in an experimental goat mandible model, the peri-implant bone volume fraction was found to quickly increase to 50% as the radial distance from the implant surface increased, and levelled out to approximately 80% at a distance of 400 μm. This method has been successful in depicting the bone and cavities in three dimensions thereby enabling us to give a more precise answer to the fraction of the bone-to-implant contact compared to previous methods. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Immunohistochemical evaluation: The effects of propolis on osseointegration of dental implants in rabbit′s tibia

Directory of Open Access Journals (Sweden)

Bushra Habeeb Al-Molla

2014-01-01

Full Text Available Background: Dental implant is an artificial tooth root-fixed into the jaws to hold a replacement tooth or bridge. Functional surface modifications by organic material such as propolis coating seem to enhance early peri-implant bone formation, enhancing the initial cell attachment. The aim of the study was to study the expression of osteocalcin (OC and type I collagen (COLL1 as bone formation markers in propolis-coated and -uncoated implant in interval periods (1, 2, 4, and 6 weeks. Materials and Methods: Commercially pure titanium (cpTi implants, coated with propolis protein, were placed in the tibias of 40 New Zealand white rabbits, histological and immunohistochemical tests for detection of expression of OC and COLL1were performed on all the implants of both control and experimental groups for (1, 2, 4, and 6 weeks healing intervals. Results: Histological finding for coated titanium implant with propolis illustrated an early bone formation, mineralization, and maturation in comparison to control. Immunohistochemical finding showed that positive reaction for OC and COLL1 was expressed by osteoblast cells at implants coated with propolis, indicating that bone formation and maturation was accelerated by adding biological materials as a modification modality of implant surface. Conclusion: The present study concludes that coating of implants with propolis showed increment in osseointegration in short interval period.

Biological Strategies for Improved Osseointegration and Osteoinduction of Porous Metal Orthopedic Implants

Science.gov (United States)

Riester, Scott M.; Bonin, Carolina A.; Kremers, Hilal Maradit; Dudakovic, Amel; Kakar, Sanjeev; Cohen, Robert C.; Westendorf, Jennifer J.

2015-01-01

The biological interface between an orthopedic implant and the surrounding host tissue may have a dramatic effect upon clinical outcome. Desired effects include bony ingrowth (osseointegration), stimulation of osteogenesis (osteoinduction), increased vascularization, and improved mechanical stability. Implant loosening, fibrous encapsulation, corrosion, infection, and inflammation, as well as physical mismatch may have deleterious clinical effects. This is particularly true of implants used in the reconstruction of load-bearing synovial joints such as the knee, hip, and the shoulder. The surfaces of orthopedic implants have evolved from solid-smooth to roughened-coarse and most recently, to porous in an effort to create a three-dimensional architecture for bone apposition and osseointegration. Total joint surgeries are increasingly performed in younger individuals with a longer life expectancy, and therefore, the postimplantation lifespan of devices must increase commensurately. This review discusses advancements in biomaterials science and cell-based therapies that may further improve orthopedic success rates. We focus on material and biological properties of orthopedic implants fabricated from porous metal and highlight some relevant developments in stem-cell research. We posit that the ideal primary and revision orthopedic load-bearing metal implants are highly porous and may be chemically modified to induce stem cell growth and osteogenic differentiation, while minimizing inflammation and infection. We conclude that integration of new biological, chemical, and mechanical methods is likely to yield more effective strategies to control and modify the implant–bone interface and thereby improve long-term clinical outcomes. PMID:25348836

Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.

Directory of Open Access Journals (Sweden)

Jing Xia

Full Text Available During retina development, retinal progenitor cell (RPC proliferation and differentiation are regulated by complex inter- and intracellular interactions. Bone marrow mesenchymal stem cells (BMSCs are reported to express a variety of cytokines and neurotrophic factors, which have powerful trophic and protective functions for neural tissue-derived cells. Here, we show that the expanded RPC cultures treated with BMSC-derived conditioned medium (CM which was substantially enriched for bFGF and CNTF, expressed clearly increased levels of nuclear receptor TLX, an essential regulator of neural stem cell (NSC self-renewal, as well as betacellulin (BTC, an EGF-like protein described as supporting NSC expansion. The BMSC CM- or bFGF-treated RPCs also displayed an obviously enhanced proliferation capability, while BMSC CM-derived bFGF knocked down by anti-bFGF, the effect of BMSC CM on enhancing RPC proliferation was partly reversed. Under differentiation conditions, treatment with BMSC CM or CNTF markedly favoured RPC differentiation towards retinal neurons, including Brn3a-positive retinal ganglion cells (RGCs and rhodopsin-positive photoreceptors, and clearly diminished retinal glial cell differentiation. These findings demonstrate that BMSCs supported RPC proliferation and neuronal differentiation which may be partly mediated by BMSC CM-derived bFGF and CNTF, reveal potential limitations of RPC culture systems, and suggest a means for optimizing RPC cell fate determination in vitro.

Application of high resolution synchrotron micro-CT radiation in dental implant osseointegration

DEFF Research Database (Denmark)

Neldam, Camilla Albeck; Lauridsen, Torsten; Rack, Alexander

2015-01-01

The purpose of this study was to describe a refined method using high-resolution synchrotron radiation microtomography (SRmicro-CT) to evaluate osseointegration and peri-implant bone volume fraction after titanium dental implant insertion. SRmicro-CT is considered gold standard evaluating bone...... microarchitecture. Its high resolution, high contrast, and excellent high signal-to-noise-ratio all contribute to the highest spatial resolutions achievable today. Using SRmicro-CT at a voxel size of 5 μm in an experimental goat mandible model, the peri-implant bone volume fraction was found to quickly increase...

Ag-plasma modification enhances bone apposition around titanium dental implants: an animal study in Labrador dogs

Directory of Open Access Journals (Sweden)

Qiao SC

2015-01-01

Full Text Available Shichong Qiao,1,* Huiliang Cao,2,* Xu Zhao,1,* Hueiwen Lo,1 Longfei Zhuang,1 Yingxin Gu,1 Junyu Shi,1 Xuanyong Liu,2 Hongchang Lai1 1Department of Oral and Maxillofacial Implantology, Shanghai Key Laboratory of Stomatology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 2State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Dental implants with proper antibacterial ability as well as ideal osseointegration are being actively pursued. The antimicrobial ability of titanium implants can be significantly enhanced via modification with silver nanoparticles (Ag NPs. However, the high mobility of Ag NPs results in their potential cytotoxicity. The silver plasma immersion ion-implantation (Ag-PIII technique may remedy the defect. Accordingly, Ag-PIII technique was employed in this study in an attempt to reduce the mobility of Ag NPs and enhance osseointegration of sandblasted and acid-etched (SLA dental implants. Briefly, 48 dental implants, divided equally into one control and three test groups (further treated by Ag-PIII technique with three different implantation parameters, were inserted in the mandibles of six Labrador dogs. Scanning electron microscopy, X-ray photoelectron spectroscopy, and inductively coupled plasma optical emission spectrometry were used to investigate the surface topography, chemical states, and silver release of SLA- and Ag-PIII-treated titanium dental implants. The implant stability quotient examination, Microcomputed tomography evaluation, histological observations, and histomorphometric analysis were performed to assess the osseointegration effect in vivo. The results demonstrated that normal soft tissue healing around dental implants was observed in all the groups, whereas the implant stability

Osseointegration improvement by plasma electrolytic oxidation of modified titanium alloys surfaces.

Science.gov (United States)

Echeverry-Rendón, Mónica; Galvis, Oscar; Quintero Giraldo, David; Pavón, Juan; López-Lacomba, José Luis; Jiménez-Piqué, Emilio; Anglada, Marc; Robledo, Sara M; Castaño, Juan G; Echeverría, Félix

2015-02-01

Titanium (Ti) is a material frequently used in orthopedic applications, due to its good mechanical properties and high corrosion resistance. However, formation of a non-adherent fibrous tissue between material and bone drastically could affect the osseointegration process and, therefore, the mechanical stability of the implant. Modifications of topography and configuration of the tissue/material interface is one of the mechanisms to improve that process by manipulating parameters such as morphology and roughness. There are different techniques that can be used to modify the titanium surface; plasma electrolytic oxidation (PEO) is one of those alternatives, which consists of obtaining porous anodic coatings by controlling parameters such as voltage, current, anodizing solution and time of the reaction. From all of the above factors, and based on previous studies that demonstrated that bone cells sense substrates features to grow new tissue, in this work commercially pure Ti (c.p Ti) and Ti6Al4V alloy samples were modified at their surface by PEO in different anodizing solutions composed of H2SO4 and H3PO4 mixtures. Treated surfaces were characterized and used as platforms to grow osteoblasts; subsequently, cell behavior parameters like adhesion, proliferation and differentiation were also studied. Although the results showed no significant differences in proliferation, differentiation and cell biological activity, overall results showed an important influence of topography of the modified surfaces compared with polished untreated surfaces. Finally, this study offers an alternative protocol to modify surfaces of Ti and their alloys in a controlled and reproducible way in which biocompatibility of the material is not compromised and osseointegration would be improved.

Multilineage differentiation of porcine bone marrow stromal cells associated with specific gene expression pattern

DEFF Research Database (Denmark)

Zou, Lijin; Zou, Xuenong; Chen, Li

2007-01-01

There are increasing reports regarding differentiation of bone marrow stromal cells (BMSC) from human and various species of animals including pigs. The phenotype and function of BMSC along a mesenchymal lineage differentiation are well characterized by specific transcription factors and marker g...

Subpopulations of Bone Marrow Mesenchymal Stem Cells Exhibit Differential Effects in Delaying Retinal Degeneration.

Science.gov (United States)

Li, P; Tian, H; Li, Z; Wang, L; Gao, F; Ou, Q; Lian, C; Li, W; Jin, C; Zhang, J; Xu, J-Y; Wang, J; Zhang, J; Wang, F; Lu, L; Xu, G-T

2016-01-01

Bone marrow mesenchymal stem cells (BMSCs) have a therapeutic role in retinal degeneration (RD). However, heterogeneity of BMSCs may be associated with differential therapeutic effects in RD. In order to confirm this hypothesis, two subsets of rat BMSCs, termed rBMSC1 and rBMSC2, were obtained, characterized and functionally evaluated in the treatment of RD of Royal College of Surgeons (RCS) rats. Both subpopulations expressed mesenchymal stem cells (MSC) markers CD29 and CD90, but were negative for hemacyte antigen CD11b and CD45 expression. In comparison with rBMSC2, rBMSC1 showed higher rate of proliferation, stronger colony formation, and increased adipogenic potential, whereas rBMSC2 exhibited higher osteogenic potential. Microarray analysis showed differential gene expression patterns between rBMSC1 and rBMSC2, including functions related to proliferation, differentiation, immunoregulation, stem cell maintenance and division, survival and antiapoptosis. After subretinal transplantation in RCS rats, rBMSC1 showed stronger rescue effect than rBMSC2, including increased b-wave amplitude, restored retinal nuclear layer thickness, and decreased number of apoptotic photoreceptors, whereas the rescue function of rBMSC2 was essentially not better than the control. Histological analysis also demonstrated that rBMSC1 possessed a higher survival rate than rBMSC2 in subretinal space. In addition, treatment of basic fibroblast growth factor, an accompanying event in subretinal injection, triggered more robust increase in secretion of growth factors by rBMSC1 as compared to rBMSC2. Taken together, these results have suggested that the different therapeutic functions of BMSC subpopulations are attributed to their distinct survival capabilities and paracrine functions. The underlying mechanisms responsible for the different functions of BMSC subpopulation may lead to a new strategy for the treatment of RD.

Expansion of Bone Marrow Mesenchymal Stromal Cells in Perfused 3D Ceramic Scaffolds Enhances In Vivo Bone Formation.

Science.gov (United States)

Hoch, Allison I; Duhr, Ralph; Di Maggio, Nunzia; Mehrkens, Arne; Jakob, Marcel; Wendt, David

2017-12-01

Bone marrow-derived mesenchymal stromal cells (BMSC), when expanded directly within 3D ceramic scaffolds in perfusion bioreactors, more reproducibly form bone when implanted in vivo as compared to conventional expansion on 2D polystyrene dishes/flasks. Since the bioreactor-based expansion on 3D ceramic scaffolds encompasses multiple aspects that are inherently different from expansion on 2D polystyrene, we aimed to decouple the effects of specific parameters among these two model systems. We assessed the effects of the: 1) 3D scaffold vs. 2D surface; 2) ceramic vs. polystyrene materials; and 3) BMSC niche established within the ceramic pores during in vitro culture, on subsequent in vivo bone formation. While BMSC expanded on 3D polystyrene scaffolds in the bioreactor could maintain their in vivo osteogenic potential, results were similar as BMSC expanded in monolayer on 2D polystyrene, suggesting little influence of the scaffold 3D environment. Bone formation was most reproducible when BMSC are expanded on 3D ceramic, highlighting the influence of the ceramic substrate. The presence of a pre-formed niche within the scaffold pores had negligible effects on the in vivo bone formation. The results of this study allow a greater understanding of the parameters required for perfusion bioreactor-based manufacturing of osteogenic grafts for clinical applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exosomes secreted from mutant-HIF-1α-modified bone-marrow-derived mesenchymal stem cells attenuate early steroid-induced avascular necrosis of femoral head in rabbit.

Science.gov (United States)

Li, Haile; Liu, Danping; Li, Chen; Zhou, Shanjian; Tian, Dachuan; Xiao, Dawei; Zhang, Huan; Gao, Feng; Huang, Jianhua

2017-12-01

Mesenchymal stem cells (MSCs)-derived exosomes exhibit protective effects on damaged or diseased tissues. Hypoxia-inducible factor 1α (HIF-1α) plays a critical role in bone development. However, HIF-1α is easily biodegradable under normoxic conditions. The bone-marrow-derived mesenchymal stem cells (BMSCs) were transfected with adenovirus carrying triple point-mutations (amino acids 402, 564, and 803) in the HIF-1α coding sequence (CDS). The mutant HIF-1α can efficiently express functional proteins under normoxic conditions. To date, no study has reported the role of exosomes secreted by mutant HIF-1α modified BMSCs in the recovery of the early steroid-induced avascular necrosis of femoral head (SANFH). In this study, we firstly analyzed exosomes derived from BMSCs modified by mutant (BMSC-Exos MU ) or wild-type HIF-1α (BMSC-Exos WT ). In vitro, we investigated the osteogenic differentiation capacity of BMSCs modified by BMSC-Exos MU or BMSC-Exos WT , and the angiogenesis effects of BMSC-Exos MU and BMSC-Exos WT on human umbilical vein endothelial cells (HUVECs). Besides, the healing of the femoral head was also assessed in vivo. We found that the potential of osteogenic differentiation of BMSCs treated with BMSC-Exos MU was higher than the wild-type group in vitro. In addition, BMSC-Exos MU stimulated the proliferation, migration, and tube formation of HUVECs in a dose-dependent manner. Compared with the BMSC-Exos WT or PBS control group, the injection of BMSC-Exos MU into the necrosis region markedly accelerated the bone regeneration and angiogenesis, which were indicated by the increased trabecular reconstruction and microvascular density. Taken together, our data suggest that BMSC-Exos MU facilitates the repair of SANFH by enhancing osteogenesis and angiogenesis. © 2017 International Federation for Cell Biology.

Osseointegration of Implants Surface-Treated with Various Diameters of TiO2 Nanotubes in Rabbit

Directory of Open Access Journals (Sweden)

Cheul-Goo Kang

2015-01-01

Full Text Available The aim of this study was to evaluate the osseointegration of implants which were surface-treated with various diameters of TiO2 nanotubes (30 nm, 70 nm, and 100 nm in rabbit. Resorbable blast media (RBM surfaced implants (Osstem, Busan, Korea 3.5 mm in diameter and 8.5 mm in length were designated as the control group and the implants surface-treated with various diameters of nanotubes (30 nm, 70 nm, and 100 nm with the same shapes were designated as the experimental groups. The implants were maintained unloaded for 4 and 12 weeks. After this period, the animals were sacrificed and micro-CT analysis, histomorphometric analysis (bone to implant contact (BIC, bone volume (BV, and removal torque test were performed. Micro-CT analysis, histomorphometric analysis, and removal torque test results all showed the similar pattern, showing that 70 nm experimental group had the highest value at 4 weeks while 30 nm experimental group had the highest value at 12 weeks. Therefore, on the basis of the results above, it can be concluded that 30 nm and 70 nm TiO2 nanotubes may have positive effects on osteogenesis and osseointegration depending on the healing time.

Administration of BMSCs with muscone in rats with gentamicin-induced AKI improves their therapeutic efficacy.

Directory of Open Access Journals (Sweden)

Pengfei Liu

Full Text Available The therapeutic action of bone marrow-derived mesenchymal stem cells (BMSCs in acute kidney injury (AKI has been reported by several groups. However, recent studies indicated that BMSCs homed to kidney tissues at very low levels after transplantation. The lack of specific homing of exogenously infused cells limited the effective implementation of BMSC-based therapies. In this study, we provided evidence that the administration of BMSCs combined with muscone in rats with gentamicin-induced AKI intravenously, was a feasible strategy to drive BMSCs to damaged tissues and improve the BMSC-based therapeutic effect. The effect of muscone on BMSC bioactivity was analyzed in vitro and in vivo. The results indicated that muscone could promote BMSC migration and proliferation. Some secretory capacity of BMSC still could be improved in some degree. The BMSC-based therapeutic action was ameliorated by promoting the recovery of biochemical variables in urine or blood, as well as the inhibition of cell apoptosis and inflammation. In addition, the up-regulation of CXCR4 and CXCR7 expression in BMSCs could be the possible mechanism of muscone amelioration. Thus, our study indicated that enhancement of BMSCs bioactivities with muscone could increase the BMSC therapeutic potential and further developed a new therapeutic strategy for the treatment of AKI.

The impact of a modified cutting flute implant design on osseointegration.

Science.gov (United States)

Jimbo, R; Tovar, N; Marin, C; Teixeira, H S; Anchieta, R B; Silveira, L M; Janal, M N; Shibli, J A; Coelho, P G

2014-07-01

Information concerning the effects of the implant cutting flute design on initial stability and its influence on osseointegration in vivo is limited. This study evaluated the early effects of implants with a specific cutting flute design placed in the sheep mandible. Forty-eight dental implants with two different macro-geometries (24 with a specific cutting flute design - Blossom group; 24 with a self-tapping design - DT group) were inserted into the mandibular bodies of six sheep; the maximum insertion torque was recorded. Samples were retrieved and processed for histomorphometric analysis after 3 and 6 weeks. The mean insertion torque was lower for Blossom implants (Pimplant contact (BIC) and P=0.52 for bone area fraction occupied (BAFO); at 6 weeks, P=0.55 for BIC and P=0.45 for BAFO. While no histomorphometric differences were observed, ground sections showed different healing patterns between the implants, with better peri-implant bone organization around those with the specific cutting flute design (Blossom group). Implants with the modified cutting flute design had a significantly reduced insertion torque compared to the DT implants with a traditional cutting thread, and resulted in a different healing pattern. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Osseointegration of loaded dental implant with KrF laser hydroxylapatite films on Ti6Al4V alloy by minipigs

Czech Academy of Sciences Publication Activity Database

Dostálová, T.; Jelínek, Miroslav; Grivas, C.

2001-01-01

Roč. 6, č. 2 (2001), s. 239-243 ISSN 1083-3668 Institutional research plan: CEZ:AV0Z1010914 Keywords : osseointegration * titanium alloy * KrF laser Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.292, year: 2001

Targeting eradication of malignant cells derived from human bone marrow mesenchymal stromal cells

Energy Technology Data Exchange (ETDEWEB)

Yang, Yingbin [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); School of Life Science, Southwest University, Chongqing 400715 (China); Cai, Shaoxi, E-mail: sxcai@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Yang, Li [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); College of Pharmacy, Jinan University, Guangzhou 510632 (China); Yu, Shuhui [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Library of Southwest University, Chongqing 400715 (China); Jiang, Jiahuan; Yan, Xiaoqing [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Zhang, Haoxing [School of Life Science, Southwest University, Chongqing 400715 (China); Liu, Lan [Department of Laboratory of Medicine, Children' s Hospital of Chongqin Medical University, Chongqing 400014 (China); Liu, Qun [College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041 (China); Du, Jun [Center of Microbiology, Biochemistry, and Pharmacology, School of Pharmaceutical Science, Sun Yat-Sen University, Guangzhou 510080 (China); Cai, Shaohui [College of Pharmacy, Jinan University, Guangzhou 510632 (China); Sung, K.L. Paul [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Departments of Orthopaedic Surgery and Bioengineering, University of California, SD 0412 (United States)

2010-12-10

Human bone marrow mesenchymal stromal cells (hBMSC) have been shown to participate in malignant transformation. However, hampered by the low frequency of malignant transformation of hBMSC, we do not yet know how to prevent malignant transformation of implanted hBMSC. In this study, in order to establish a model for the eradication of hBMSC-derived malignant cells, a gene fusion consisting of a human telomerase (hTERT) promoter modified with both c-Myc and myeloid zinc finger protein2 (MZF-2) binding elements and followed by the E. coli cytosine deaminase (CD) and luciferase genes was stably transferred into hBMSC via lentiviral transduction; n-phosphonacelyl-L-aspartic acid (PALA) selection was used to generate malignant cell colonies derived from transduced hBMSC after treatment with the carcinogenic reagent BPDE. Cells that were amplified after PALA selection were used for transplantation and 5-FC pro-drug cytotoxicity tests. The results showed that PALA-resistant malignant cells could be generated from hBMSC co-induced with lentiviral transduction and treatment with Benzo(a)pyrene Diol Epoxide (BPDE); the modification of c-Myc and MZF-2 binding elements could remarkably enhance the transcriptional activities of the hTERT promoter in malignant cells, whereas transcriptional activity was depressed in normal hBMSC; malignant cells stably expressing CD under the control of the modified hTERT promoter could be eliminated by 5-FC administration. This study has provided a method for targeted eradication of malignant cells derived from hBMSC.

Targeting eradication of malignant cells derived from human bone marrow mesenchymal stromal cells

International Nuclear Information System (INIS)

Yang, Yingbin; Cai, Shaoxi; Yang, Li; Yu, Shuhui; Jiang, Jiahuan; Yan, Xiaoqing; Zhang, Haoxing; Liu, Lan; Liu, Qun; Du, Jun; Cai, Shaohui; Sung, K.L. Paul

2010-01-01

Human bone marrow mesenchymal stromal cells (hBMSC) have been shown to participate in malignant transformation. However, hampered by the low frequency of malignant transformation of hBMSC, we do not yet know how to prevent malignant transformation of implanted hBMSC. In this study, in order to establish a model for the eradication of hBMSC-derived malignant cells, a gene fusion consisting of a human telomerase (hTERT) promoter modified with both c-Myc and myeloid zinc finger protein2 (MZF-2) binding elements and followed by the E. coli cytosine deaminase (CD) and luciferase genes was stably transferred into hBMSC via lentiviral transduction; n-phosphonacelyl-L-aspartic acid (PALA) selection was used to generate malignant cell colonies derived from transduced hBMSC after treatment with the carcinogenic reagent BPDE. Cells that were amplified after PALA selection were used for transplantation and 5-FC pro-drug cytotoxicity tests. The results showed that PALA-resistant malignant cells could be generated from hBMSC co-induced with lentiviral transduction and treatment with Benzo(a)pyrene Diol Epoxide (BPDE); the modification of c-Myc and MZF-2 binding elements could remarkably enhance the transcriptional activities of the hTERT promoter in malignant cells, whereas transcriptional activity was depressed in normal hBMSC; malignant cells stably expressing CD under the control of the modified hTERT promoter could be eliminated by 5-FC administration. This study has provided a method for targeted eradication of malignant cells derived from hBMSC.

Surface topography of silicon nitride affects antimicrobial and osseointegrative properties of tibial implants in a murine model.

Science.gov (United States)

Ishikawa, Masahiro; de Mesy Bentley, Karen L; McEntire, Bryan J; Bal, B Sonny; Schwarz, Edward M; Xie, Chao

2017-12-01

While silicon nitride (Si 3 N 4 ) is an antimicrobial and osseointegrative orthopaedic biomaterial, the contribution of surface topography to these properties is unknown. Using a methicillin-resistant strain of Staphylococcus aureus (MRSA), this study evaluated Si 3 N 4 implants in vitro utilizing scanning electron microscopy (SEM) with colony forming unit (CFU) assays, and later in an established in vivo murine tibia model of implant-associated osteomyelitis. In vitro, the "as-fired" Si 3 N 4 implants displayed significant reductions in adherent bacteria versus machined Si 3 N 4 (2.6 × 10 4 vs. 8.7 × 10 4 CFU, respectively; p SEM imaging demonstrated that MRSA cannot directly adhere to native as-fired Si 3 N 4 . Subsequently, a cross-sectional study was completed in which sterile or MRSA contaminated as-fired and machined Si 3 N 4 implants were inserted into the tibiae of 8-week old female Balb/c mice, and harvested on day 1, 3, 5, 7, 10, or 14 post-operatively for SEM. The findings demonstrated that the antimicrobial activity of the as-fired implants resulted from macrophage clearance of the bacteria during biofilm formation on day 1, followed by osseointegration through the apparent recruitment of mesenchymal stem cells on days 3-5, which differentiated into osteoblasts on days 7-14. In contrast, the antimicrobial behavior of the machined Si 3 N 4 was due to repulsion of the bacteria, a phenomenon that also limited osteogenesis, as host cells were also unable to adhere to the machined surface. Taken together, these results suggest that the in vivo biological behavior of Si 3 N 4 orthopaedic implants is driven by critical features of their surface nanotopography. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3413-3421, 2017. © 2017 Wiley Periodicals, Inc.

Microarc oxidation coating covered Ti implants with micro-scale gouges formed by a multi-step treatment for improving osseointegration.

Science.gov (United States)

Bai, Yixin; Zhou, Rui; Cao, Jianyun; Wei, Daqing; Du, Qing; Li, Baoqiang; Wang, Yaming; Jia, Dechang; Zhou, Yu

2017-07-01

The sub-microporous microarc oxidation (MAO) coating covered Ti implant with micro-scale gouges has been fabricated via a multi-step MAO process to overcome the compromised bone-implant integration. The as-prepared implant has been further mediated by post-heat treatment to compare the effects of -OH functional group and the nano-scale orange peel-like morphology on osseointegration. The bone regeneration, bone-implant contact interface, and biomechanical push-out force of the modified Ti implant have been discussed thoroughly in this work. The greatly improved push-out force for the MAO coated Ti implants with micro-scale gouges could be attributed to the excellent mechanical interlocking effect between implants and biologically meshed bone tissues. Attributed to the -OH functional group which promotes synostosis between the biologically meshed bone and the gouge surface of implant, the multi-step MAO process could be an effective strategy to improve the osseointegration of Ti implant. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation the success of osseointegrated implants in maxillary sinus grafts

Directory of Open Access Journals (Sweden)

Rubens Eduardo Gigli

2008-01-01

Full Text Available Objective: To analyze implants placed in maxillary sinus grafts with biomaterial of bovine origin and platelet-rich plasma, observing bone neoformation and the clinical and histologic success rate presented.Methods: Analysis of the clinical findings was based on 36 maxillary sinus grafts with 101 implants placed in 30 patients with a mean age of 47 years, and the histologic analysis, based on nine samples of the 36 grafts performed, with a mean interval of 7.5 months time of the graft, the majority of patients being men with a mean age of 42 years. Results: Clinically, 91 implants placed were osseointegrated.Conclusion: Based on the results presented, it was concluded that when implants are placed in the maxillary sinus region grafted with biomaterial, they present a high success rate. ISRCTN24003246

The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs.

Science.gov (United States)

Tan, Naiwen; Liu, Xiangwei; Cai, Yanhui; Zhang, Sijia; Jian, Bo; Zhou, Yuchao; Xu, Xiaoru; Ren, Shuai; Wei, Hongbo; Song, Yingliang

2017-01-01

High failure rates of oral implants have been reported in diabetic patients due to the disruption of osseointegration. The aim of this study was to investigate whether direct laser metal sintering (DLMS) could improve osseointegration in diabetic animal models. Surface characterizations were carried out on two types of implants. Cell morphology and the osteogenic-related gene expression of MG63 cells were observed under conditions of DLMS and microarc oxidation (MAO). A diabetes model in mini-pigs was established by intravenous injection of streptozotocin (150 mg/kg), and a total of 36 implants were inserted into the mandibular region. Micro-computed tomography (micro-CT) and histologic evaluations were performed 3 and 6 months after implantation. The Ra (the average of the absolute height of all points) of MAO surface was 2.3±0.3 µm while the DLMS surface showed the Ra of 27.4±1.1 µm. The cells on DLMS implants spread out more podia than those on MAO implants through cell morphology analysis. Osteogenic-related gene expression was also dramatically increased in the DLMS group. Obvious improvement was observed in the micro-CT and Van Gieson staining analyses of DLMS implants compared with MAO at 3 months, although this difference disappeared by 6 months. DLMS implants showed a higher bone-implant contact percentage (33.2%±11.2%) at 3 months compared with MAO group (18.9%±7.3%) while similar results were showed at 6 months between DLMS group (42.8%±10.1%) and MAO group (38.3%±10.8%). The three-dimensional environment of implant surfaces with highly porous and fully interconnected channel and pore architectures can improve cell spreading and accelerate the progress of osseointegration in diabetic mini-pigs.

An Autologous Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Matrix Scaffold Applied with Bone Marrow Stimulation for Cartilage Repair

Science.gov (United States)

Tang, Cheng; Jin, Chengzhe; Du, Xiaotao; Yan, Chao; Min, Byoung-Hyun; Xu, Yan

2014-01-01

Purpose: It is well known that implanting a bioactive scaffold into a cartilage defect site can enhance cartilage repair after bone marrow stimulation (BMS). However, most of the current scaffolds are derived from xenogenous tissue and/or artificial polymers. The implantation of these scaffolds adds risks of pathogen transmission, undesirable inflammation, and other immunological reactions, as well as ethical issues in clinical practice. The current study was undertaken to evaluate the effectiveness of implanting autologous bone marrow mesenchymal stem cell–derived extracellular matrix (aBMSC-dECM) scaffolds after BMS for cartilage repair. Methods: Full osteochondral defects were performed on the trochlear groove of both knees in 24 rabbits. One group underwent BMS only in the right knee (the BMS group), and the other group was treated by implantation of the aBMSC-dECM scaffold after BMS in the left knee (the aBMSC-dECM scaffold group). Results: Better repair of cartilage defects was observed in the aBMSC-dECM scaffold group than in the BMS group according to gross observation, histological assessments, immunohistochemistry, and chemical assay. The glycosaminoglycan and DNA content, the distribution of proteoglycan, and the distribution and arrangement of type II and I collagen fibers in the repaired tissue in the aBMSC-dECM scaffold group at 12 weeks after surgery were similar to that surrounding normal hyaline cartilage. Conclusions: Implanting aBMSC-dECM scaffolds can enhance the therapeutic effect of BMS on articular cartilage repair, and this combination treatment is a potential method for successful articular cartilage repair. PMID:24666429

Significant improvement of the osseointegration of zirconia dental implants by HS-LEIS analysis

International Nuclear Information System (INIS)

Beekmans, H.; Breitenstein, D.; Brongersma, H.H.; Ridder, M. de; Tromp, Th.J.

2010-01-01

The use of sintered yttria stabilized zirconia dental implants is a recent development. After initial successes with these new implants a pattern of erratic results emerged. Reliable osseointegration would not always occur. High-sensitivity low energy ion scattering (HS-LEIS) is used to investigate both virgin and rejected implants. The surfaces of the implant are found to be covered with both an organic and inorganic contamination layer. Sterilization does not remove this contamination. Using LEIS as analytic tool a new cleaning process has been developed. Since this cleaning process is in use, the failure rate has dropped to a very low value.

Osseointegration of Implants Surface-Treated with Various Diameters of TiO2 Nano tubes in Rabbit

International Nuclear Information System (INIS)

Kang, Ch.G.; Park, Y.B.; Choi, H.; Lee, K.W.; Shim, J.S.; Oh, S.; Choi, S.H.

2014-01-01

The aim of this study was to evaluate the osseointegration of implants which were surface-treated with various diameters of TiO 2 nano tubes (30 nm, 70 nm, and 100 nm) in rabbit. Resorbable blast media (RBM) surfaced implants (Osstem, Busan, Korea) 3.5 mm in diameter and 8.5 mm in length were designated as the control group and the implants surface-treated with various diameters of nano tubes (30 nm, 70 nm, and 100 nm) with the same shapes were designated as the experimental groups. The implants were maintained unloaded for 4 and 12 weeks. After this period, the animals were sacrificed and micro-CT analysis, histomorphometric analysis (bone to implant contact (BIC), bone volume (BV)), and removal torque test were performed. Micro-CT analysis, histomorphometric analysis, and removal torque test results all showed the similar pattern, showing that 70 nm experimental group had the highest value at 4 weeks while 30 nm experimental group had the highest value at 12 weeks. Therefore, on the basis of the results above, it can be concluded that 30 nm and 70 nm TiO 2 nano tubes may have positive effects on osteogenesis and osseointegration depending on the healing time

The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs

Directory of Open Access Journals (Sweden)

Tan NW

2017-07-01

Full Text Available Naiwen Tan,1–3,* Xiangwei Liu,1,2,* Yanhui Cai,4 Sijia Zhang,1,2 Bo Jian,1,2 Yuchao Zhou,1,2 Xiaoru Xu,1,2 Shuai Ren,1,2 Hongbo Wei,1,2 Yingliang Song1,2 1State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Xi’an, Shaanxi, China; 2Department of Implant Dentistry, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, China; 3Department of Stomatology, Hospital 463 of PLA, Xi’an, Shaanxi, China; 4Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, China *These authors contributed equally to this work Background: High failure rates of oral implants have been reported in diabetic patients due to the disruption of osseointegration. The aim of this study was to investigate whether direct laser metal sintering (DLMS could improve osseointegration in diabetic animal models. Methods: Surface characterizations were carried out on two types of implants. Cell morphology and the osteogenic-related gene expression of MG63 cells were observed under conditions of DLMS and microarc oxidation (MAO. A diabetes model in mini-pigs was established by intravenous injection of streptozotocin (150 mg/kg, and a total of 36 implants were inserted into the mandibular region. Micro-computed tomography (micro-CT and histologic evaluations were performed 3 and 6 months after implantation. Results: The Ra (the average of the absolute height of all points of MAO surface was 2.3±0.3 µm while the DLMS surface showed the Ra of 27.4±1.1 µm. The cells on DLMS implants spread out more podia than those on MAO implants through cell morphology analysis. Osteogenic-related gene expression was also dramatically increased in the DLMS group. Obvious improvement was observed in the micro-CT and Van Gieson staining analyses of DLMS implants compared with MAO at 3 months

Micro-arc oxidation of Ti-15Zr-based alloys for osseointegrative implants

International Nuclear Information System (INIS)

Correa, Diego Rafael Nespeque; Rocha, Luis Augusto; Doi, Hisashi; Tsutsumi, Yusuke; Hanawa, Takao

2016-01-01

Full text: Micro-arc oxidation (MAO) is well-known as low-cost coating technique which can produce porous structure in valve metals [1]. Studies have indicated that MAOcoatings are suitable for improve biofunctionalization of Ti-based implants by bioactive ions incorporation in the oxide layer [2]. This work aims to evaluate the characteristics of the MAO-coating in recent developed biomedical Ti-15Zr-based alloys in order to use as osseointegrative implants. Ti-15Zr-xMo (x = 0, 5, 10 and 15 % wt.) alloys were produced by argon arc-melting and molded in a centrifugal casting machine. MAO treatment were performed in disks (ϕ 8 mm x 1.5 mm), at room temperature, with a 304 stainless steel plate as counter electrode. Electrolyte was composed by 0.15 M calcium acetate and 0.10 M calcium glycerophosphate. The electrodes were connected to a DC power supply, and applied a density current of 311 A/m 2 , for 10 min, with voltages of 300, 350 and 400 V. Morphology, thickness, composition and crystal structure of the oxide layer were evaluated by SEM, XRF and XRD techniques. A typical porous layer was produced in all surfaces, being the porosity, porous size and thickness increased with the voltage. The composition of the oxide layer indicated Ca and P incorporation, being the concentration increased with the voltage applied. The XRD patterns do not exhibited peaks from oxides compounds, but only peaks from bulk-Ti phases. The results showed that the bioactive coatings were successfully growth in the Ti-15Zr-based alloys, being suitable for osseointegrative implants. References: [1] Hanawa, T. Japanese dental Science Review 46, 93-101, 2010; [2] Tsutsumi, Y. et al. Metals 6, 76-85, 2016. (author)

Micro-arc oxidation of Ti-15Zr-based alloys for osseointegrative implants

Energy Technology Data Exchange (ETDEWEB)

Correa, Diego Rafael Nespeque; Rocha, Luis Augusto [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Bauru, SP (Brazil); Doi, Hisashi; Tsutsumi, Yusuke; Hanawa, Takao [Tokyo Medical and Dental University (Japan)

2016-07-01

Full text: Micro-arc oxidation (MAO) is well-known as low-cost coating technique which can produce porous structure in valve metals [1]. Studies have indicated that MAOcoatings are suitable for improve biofunctionalization of Ti-based implants by bioactive ions incorporation in the oxide layer [2]. This work aims to evaluate the characteristics of the MAO-coating in recent developed biomedical Ti-15Zr-based alloys in order to use as osseointegrative implants. Ti-15Zr-xMo (x = 0, 5, 10 and 15 % wt.) alloys were produced by argon arc-melting and molded in a centrifugal casting machine. MAO treatment were performed in disks (ϕ 8 mm x 1.5 mm), at room temperature, with a 304 stainless steel plate as counter electrode. Electrolyte was composed by 0.15 M calcium acetate and 0.10 M calcium glycerophosphate. The electrodes were connected to a DC power supply, and applied a density current of 311 A/m{sup 2}, for 10 min, with voltages of 300, 350 and 400 V. Morphology, thickness, composition and crystal structure of the oxide layer were evaluated by SEM, XRF and XRD techniques. A typical porous layer was produced in all surfaces, being the porosity, porous size and thickness increased with the voltage. The composition of the oxide layer indicated Ca and P incorporation, being the concentration increased with the voltage applied. The XRD patterns do not exhibited peaks from oxides compounds, but only peaks from bulk-Ti phases. The results showed that the bioactive coatings were successfully growth in the Ti-15Zr-based alloys, being suitable for osseointegrative implants. References: [1] Hanawa, T. Japanese dental Science Review 46, 93-101, 2010; [2] Tsutsumi, Y. et al. Metals 6, 76-85, 2016. (author)

Enhancing the antibacterial performance of orthopaedic implant materials by fibre laser surface engineering

DEFF Research Database (Denmark)

Chan, Chi-Wai; Carson, Louise; Smith, Graham C.

2017-01-01

to the effort on enhancing osseointegration, wear and corrosion resistance of implant materials. In this study, the effects of laser surface treatment on enhancing the antibacterial properties of commercially pure (CP) Ti (Grade 2), Ti6Al4V (Grade 5) and CoCrMo alloy implant materials were studied and compared...... for the first time. Laser surface treatment was performed by a continuous wave (CW) fibre laser with a near-infrared wavelength of 1064 nm in a nitrogen-containing environment. Staphylococcus aureus, commonly implicated in infection associated with orthopaedic implants, was used to investigate the antibacterial...... properties of the laser-treated surfaces. The surface roughness and topography of the laser-treated materials were analysed by a 2D roughness testing and by AFM. The surface morphologies before and after 24 h of bacterial cell culture were captured by SEM, and bacterial viability was determined using live...

Neutral atom beam technique enhances bioactivity of PEEK

International Nuclear Information System (INIS)

Khoury, Joseph; Kirkpatrick, Sean R.; Maxwell, Melissa; Cherian, Raymond E.; Kirkpatrick, Allen; Svrluga, Richard C.

2013-01-01

Polyetheretherketone (PEEK) is currently gaining popularity in orthopedic and spinal applications but has potential drawbacks in use. PEEK is biocompatible, similar in elasticity to bone, and radiolucent; however, it has been shown to be inert and does not integrate well with bone. Recent efforts have focused on increasing the bioactivity of PEEK by modifying the surface to improve the bone-implant interface. We have employed a novel Accelerated Neutral Atom Beam technique (ANAB) to enhance the bioactivity of PEEK. ANAB employs an intense beam of cluster-like packets of accelerated unbonded neutral argon (Ar) gas atoms. These beams are created by first producing a highly energetic Gas Cluster Ion Beam (GCIB) comprised of van der Waals bonded Ar atoms, then transferring energy to the clusters so as to cause release of most of the interatomic bonds, and finally deflecting away the remaining electrically charged cluster cores of still bonded atoms. We identified that ANAB treatment of PEEK results in nanometer scale surface modifications as well as increased surface hydrophilicity. Human osteoblasts seeded onto the surface of ANAB-treated PEEK exhibited enhanced growth as compared to control PEEK as evidenced by cell proliferation assays and microscopy. This increase in bioactivity resulted in cell proliferation levels comparable to native titanium. An in vivo study using a rat calvarial critical size defect model revealed enhanced osseointegration where bone tissue formation was evident only on the ANAB treated PEEK. Taken together, these data suggest that ANAB treatment of PEEK has the potential to enhance its bioactivity, resulting in bone formation and significantly decreasing osseointegration time of orthopedic and spinal implants

Future of bone pathology, bone grafting, and osseointegration in oral and maxillofacial surgery: how applying optical advancements can help both fields

Science.gov (United States)

Tandon, Rahul; Herford, Alan S.

2013-03-01

Introduction: In recent years, advances in technology are propelling the field of oral and maxillofacial surgery into new realms. With a relatively thin alveolar mucosa overlying the underlying bone, significant diagnostic and therapeutic advantages are present. However, there remains an enormous gap between advancements in physics, in particular optics, and oral and maxillofacial surgery. Bone Pathology: Improvements in diagnosis, classification, and treatment of the various bone pathologies are still being sought after as advancements in technology continue to progress. Combining the clinical, histological, and pathological characteristics with these advancements, patients with debilitating pathologies may have more promising treatment options and prognosis. Bone Grafting: Defects in the facial bones, in particular the jaws, may be due to a number of reasons: pathology, trauma, infections, congenital deformities, or simply due to atrophy. Bone grafting is commonly employed to correct such defects, and allows new bone formation through tissue regeneration. Osseointegration: Growing use of dental implants has focused attention on osseointegration and its process. Osseointegration refers to the actual process of the direct contact between bone and implant, without an intervening soft tissue layer. The theories proposed regarding this process are many, yet there lacks a clear, unified stance on the actual process and its mechanisms. Further investigation using optical probes could provide that unifying answer. Conclusion: The primary goal of this lecture is to introduce pioneers in the field of optics to the field of oral and maxillofacial surgery. With a brief introduction into the procedures and techniques, we are hopeful to bridge the ever-widening gap between the clinical science and the basic sciences.

Bioactivity and Osseointegration of PEEK Are Inferior to Those of Titanium: A Systematic Review.

Science.gov (United States)

Najeeb, Shariq; Bds, Zohaib Khurshid; Bds, Sana Zohaib; Bds, Muhammad Sohail Zafar

2016-12-01

Polyetheretherketone (PEEK) has been suggested as an alternative to replace titanium as a dental implant material. However, PEEK's bioactivity and osseointegration are debatable. This review has systematically analyzed studies that have compared PEEK (or PEEK-based) implants with titanium implants so that its feasibility as a possible replacement for titanium can be determined. The focused question was: "Are the bioactivity and osseointegration of PEEK implants comparable to or better than titanium implants?" Using the key words "dental implant," "implant," "polyetheretherketone," "PEEK," and "titanium" in various combinations, the following databases were searched electronically: PubMED/MEDLINE, Embase, Google Scholar, ISI Web of Knowledge, and Cochrane Database. 5 in vitro and 4 animal studies were included in the review. In 4 out of 5 in vitro studies, titanium exhibited more cellular proliferation, angiogenesis, osteoblast maturation, and osteogenesis compared to PEEK; one in vitro study observed comparable outcomes regardless of the implant material. In all animal studies, uncoated and coated titanium exhibited a more osteogenic behavior than did uncoated PEEK, while comparable bone-implant contact was observed in HA-coated PEEK and coated titanium implants. Unmodified PEEK is less osseoconductive and bioactive than titanium. Furthermore, the majority of studies had multiple sources of bias; hence, in its unmodified form, PEEK is unsuitable to be used as dental implant. Significantly more research and long-term trials must focus on improving the bioactivity of PEEK before it can be used as dental implant. More comparative animal and clinical studies are warranted to ascertain the potential of PEEK as a viable alternative to titanium.

Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury

Directory of Open Access Journals (Sweden)

Jack M. Milwid

2012-01-01

Full Text Available Acute kidney injury is a devastating syndrome that afflicts over 2,000,000 people in the US per year, with an associated mortality of greater than 70% in severe cases. Unfortunately, standard-of-care treatments are not sufficient for modifying the course of disease. Many groups have explored the use of bone marrow stromal cells (BMSCs for the treatment of AKI because BMSCs have been shown to possess unique anti-inflammatory, cytoprotective, and regenerative properties in vitro and in vivo. It is yet unresolved whether the primary mechanisms controlling BMSC therapy in AKI depend on direct cell infusion, or whether BMSC-secreted factors alone are sufficient for mitigating the injury. Here we show that BMSC-secreted factors are capable of providing a survival benefit to rats subjected to cisplatin-induced AKI. We observed that when BMSC-conditioned medium (BMSC-CM is administered intravenously, it prevents tubular apoptosis and necrosis and ameliorates AKI. In addition, we observed that BMSC-CM causes IL-10 upregulation in treated animals, which is important to animal survival and protection of the kidney. In all, these results demonstrate that BMSC-secreted factors are capable of providing support without cell transplantation, and the IL-10 increase seen in BMSC-CM-treated animals correlates with attenuation of severe AKI.

The promotion of osseointegration of titanium surfaces by coating with silk protein sericin.

Science.gov (United States)

Nayak, Sunita; Dey, Tuli; Naskar, Deboki; Kundu, Subhas C

2013-04-01

A promising strategy to influence the osseointegration process around orthopaedic titanium implants is the immobilization of bioactive molecules. This recruits appropriate interaction between the surface and the tissue by directing cells adhesion, proliferation, differentiation and active matrix remodelling. In this study, we aimed to investigate the functionalization of metallic implant titanium with silk protein sericin. Titanium surface was immobilized with non-mulberry Antheraea mylitta sericin using glutaraldehyde as crosslinker. To analyse combinatorial effects the sericin immobilized titanium was further conjugated with integrin binding peptide sequence Arg-Gly-Asp (RGD) using ethyl (dimethylaminopropyl) carbodiimide and N-hydroxysulfosuccinimide as coupling agents. The surface of sericin immobilized titanium was characterized biophysically. Osteoblast-like cells were cultured on sericin and sericin/RGD functionalized titanium and found to be more viable than those on pristine titanium. The enhanced adhesion, proliferation, and differentiation of osteoblast cells were observed. RT-PCR analysis showed that mRNA expressions of bone sialoprotein, osteocalcin and alkaline phosphatase were upregulated in osteoblast cells cultured on sericin and sericin/RGD immobilized titanium substrates. Additionally, no significant amount of pro-inflammatory cytokines TNF-α, IL-1β and nitric oxide production were recorded when macrophages cells and osteoblast-macrophages co culture cells were grown on sericin immobilized titanium. The findings demonstrate that the sericin immobilized titanium surfaces are potentially useful bioactive coated materials for titanium-based medical implants. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rehabilitation with ear prosthesis linked to osseointegrated implants.

Science.gov (United States)

Goiato, Marcelo C; dos Santos, Daniela M; Haddad, Marcela F; Moreno, Amália

2012-06-01

The absence of an ear, which can be the result of a congenital malformation, surgical tumour resection or traumatic injury, is a significant aesthetic problem. Attachment of ear prostheses with adhesives can cause local irritation for the wearer and affect the colour of the prostheses. Use of implants in craniofacial reconstruction can improve the retention and stability of prostheses giving to patient greater comfort and security relative to adhesive attachment. The aim of this report was to present a clinical case of a mutilated patient who was rehabilitated by means of installing an ear prosthesis fixed through osseointegrated implants. The patient had two implants installed in the mastoid region that were linked by a bar, and a clip-type system was used. The ear prosthesis was constructed from medical-use silicone, pigmented to match the patient's skin colour and linked to the retention system. The patient's rehabilitation was satisfactory from both a functional and an aesthetic point of view, making it possible for the patient to return to a normal social life and regain lost self-esteem. © 2012 The Gerodontology Society and John Wiley & Sons A/S.

Chromosome copy number variation in telomerized human bone marrow stromal cells; insights for monitoring safe ex-vivo expansion of adult stem cells.

Science.gov (United States)

Burns, Jorge S; Harkness, Linda; Aldahmash, Abdullah; Gautier, Laurent; Kassem, Moustapha

2017-12-01

Adult human bone marrow stromal cells (hBMSC) cultured for cell therapy require evaluation of potency and stability for safe use. Chromosomal aberrations upsetting genomic integrity in such cells have been contrastingly described as "Limited" or "Significant". Previously reported stepwise acquisition of a spontaneous neoplastic phenotype during three-year continuous culture of telomerized cells (hBMSC-TERT20) didn't alter a diploid karyotype measured by spectral karyotype analysis (SKY). Such screening may not adequately monitor abnormal and potentially tumorigenic hBMSC in clinical scenarios. We here used array comparative genomic hybridization (aCGH) to more stringently compare non-tumorigenic parental hBMSC-TERT strains with their tumorigenic subcloned populations. Confirmation of a known chromosome 9p21 microdeletion at locus CDKN2A/B, showed it also impinged upon the adjacent MTAP gene. Compared to reference diploid human fibroblast genomic DNA, the non-tumorigenic hBMSC-TERT4 cells had a copy number variation (CNV) in at least 14 independent loci. The pre-tumorigenic hBMSC-TERT20 cell strain had further CNV including 1q44 gain enhancing SMYD3 expression and 11q13.1 loss downregulating MUS81 expression. Bioinformatic analysis of gene products reflecting 11p15.5 CNV gain in tumorigenic hBMSC-TERT20 cells highlighted networks implicated in tumorigenic progression involving cell cycle control and mis-match repair. We provide novel biomarkers for prospective risk assessment of expanded stem cell cultures. Copyright © 2017. Published by Elsevier B.V.

Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells

Energy Technology Data Exchange (ETDEWEB)

Liu, Lingling, E-mail: liulingling2012@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Luo, Qing, E-mail: qing.luo@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Sun, Jinghui, E-mail: sunjhemail@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Wang, Aoli, E-mail: leaf13332@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Shi, Yisong, E-mail: shiyis@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Ju, Yang, E-mail: ju@mech.nagoya-u.ac.jp [Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603 (Japan); Morita, Yasuyuki, E-mail: morita@mech.nagoya-u.ac.jp [Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603 (Japan); Song, Guanbin, E-mail: song@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

2017-06-15

Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. - Highlights: • OPN promotes BMSC migration by decreasing nuclear stiffness. • Lamin A/C knockdown decreases, while its overexpression enhances, the nuclear stiffness of BMSCs. • Lamin A/C overexpression and downregulation affect the migration of BMSCs. • OPN diminishes lamin A/C expression and decreases nuclear stiffness through the activation of the FAK-ERK1/2 signaling pathway. • OPN promotes BMSC migration via the FAK-ERK1/2 signaling pathway.

Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells

International Nuclear Information System (INIS)

Liu, Lingling; Luo, Qing; Sun, Jinghui; Wang, Aoli; Shi, Yisong; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

2017-01-01

Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. - Highlights: • OPN promotes BMSC migration by decreasing nuclear stiffness. • Lamin A/C knockdown decreases, while its overexpression enhances, the nuclear stiffness of BMSCs. • Lamin A/C overexpression and downregulation affect the migration of BMSCs. • OPN diminishes lamin A/C expression and decreases nuclear stiffness through the activation of the FAK-ERK1/2 signaling pathway. • OPN promotes BMSC migration via the FAK-ERK1/2 signaling pathway.

Analysis of annealing effects on osseointegration in vitro of TiO{sub 2} coatings formed from Ti ATSM F67 e Ti ATSM F67

Energy Technology Data Exchange (ETDEWEB)

Simon, Anna Paulla; Lima, Amanda Santos de; Sikora, Mariana de Souza, E-mail: anna17simon@gmail.com [Universidade Tecnologica Federal do Parana (UTFPR), PR (Brazil)

2016-07-01

Full text: Amorphous TiO{sub 2} coatings can be converted to crystalline phases submitting the samples to annealing (heat treatment). These crystalline structures improve structural conformation of atoms being significantly efficient in terms of osseointegration. To analyse the annealing treatment effects on osseointegration, Ti ATSM F67 e Ti ATSM F67 were submitted to potentiostatic anodization in organic media containing 0.5 and 0.75 % w/w of NH-4F and 10 % w/w of water, applying 25 V during 90 minutes, using static and stirring methods. The annealing was performed using a temperature ramp of 2 °C/min until it reaches 450 °C, remaining in this condition during 2 hours, with ambient cooling. The samples were examined by SEM and XRD. After the characterization, the synthesized films were subjected to immersion tests in simulated body fluid (SBF) during 1 and 2 weeks in order to qualitatively evaluate the in vitro osseointegration capacity. The results show that TiO{sub 2} porous films can be formed, except for the film grown on Ti ASTM F136 using a NH{sub 4}F concentration of 0.75 % w/w with stirring. This result can be explained by aggressive homogeneous dissolution in the entire surface of the film, once the reaction is no longer limited by diffusion. The films as-formed are amorphous, being necessary the annealing to convert the oxide to its crystalline phases. With the annealing the amorphous oxide was converted to the crystalline anatase phase in all synthesized films, but in different proportions. It was observed that films grown from Ti ASTM F136 have shown lower crystallinity due to phase stabilizers which compose the alloy. So TiO{sub 2} grown from Ti ATSM F67 presents higher quantities of crystalline phase tending to show higher hydrophilic aspects, what contributed to the better osseointegration as observed in this work, qualitatively evaluated by the extent and amount of deposited hydroxyapatite on surface. (author)

Enhancement of osseointegration of polyethylene terephthalate artificial ligament by coating of silk fibroin and depositing of hydroxyapatite

Directory of Open Access Journals (Sweden)

Jiang J

2014-09-01

Full Text Available Jia Jiang,1,2 Fang Wan,1 Jianjun Yang,1 Wei Hao,3 Yaxian Wang,3 Jinrong Yao,3 Zhengzhong Shao,3 Peng Zhang,1 Jun Chen,1 Liang Zhou,4 Shiyi Chen11Fudan University Sports Medicine Center and Department of Sports Medicine and Arthroscopy Surgery, Huashan Hospital, 2State Key Laboratory of Molecular Engineering of Polymers, 3Laboratory of Advanced Materials, National Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, People’s Republic of China; 4Department of Forest Products, Anhui Agricultural University, Hefei Anhui Province, People’s Republic of ChinaBackground: Application of artificial ligament in anterior cruciate ligament reconstruction is one of the research focuses of sports medicine but the biological tendon–bone healing still remains a problem. The preliminary study of hydroxyapatite (HAP coating on the polyethylene terephthalate (PET surface could effectively induce the osteoblast differentiation, but the tendon–bone healing was still not stable. As a green synthesis process, the biomimetic mineralization can simulate the natural bone growth in vitro and in vivo.Methods: HAP crystals were grown under the guide of silk fibroin (SF PET surface by biomimetic route. Several techniques including scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy were utilized for proving the introduction of both SF and HAP. The viability and osseointegration of bone marrow stromal cells on the surface of three kinds of ligament, including PET group (non-coating group, PET+SF group (SF-coating group, and PET+SF+HAP group (combined HAP- and SF-coating group, were analyzed by CCK-8 assays and alkaline phosphatase (ALP detection. Seventy-two mature male New Zealand rabbits were randomly divided into three groups. Among them, 36 rabbits were sacrificed for mechanical testing, and

Peri-implant osseointegration after low-level laser therapy: micro-computed tomography and resonance frequency analysis in an animal model.

Science.gov (United States)

Mayer, Luciano; Gomes, Fernando Vacilotto; de Oliveira, Marília Gerhardt; de Moraes, João Feliz Duarte; Carlsson, Lennart

2016-12-01

The purpose of the present study is to evaluate the effects of low-level laser therapy on the osseointegration process by comparing resonance frequency analysis measurements performed at implant placement and after 30 days and micro-computed tomography images in irradiated vs nonirradiated rabbits. Fourteen male New Zealand rabbits were randomly divided into two groups of seven animals each, one control group (nonirradiated animals) and one experimental group that received low-level laser therapy (Thera Lase®, aluminum-gallium-arsenide laser diode, 10 J per spot, two spots per session, seven sessions, 830 nm, 50 mW, CW, Ø 0.0028 cm 2 ). The mandibular left incisor was surgically extracted in all animals, and one osseointegrated implant was placed immediately afterward (3.25ø × 11.5 mm; NanoTite, BIOMET 3i). Resonance frequency analysis was performed with the Osstell® device at implant placement and at 30 days (immediately before euthanasia). Micro-computed tomography analyses were then conducted using a high-resolution scanner (SkyScan 1172 X-ray Micro-CT) to evaluate the amount of newly formed bone around the implants. Irradiated animals showed significantly higher implant stability quotients at 30 days (64.286 ± 1.596; 95 % confidence interval (CI) 60.808-67.764) than controls (56.357 ± 1.596; 95 %CI 52.879-59.835) (P = .000). The percentage of newly formed bone around the implants was also significantly higher in irradiated animals (75.523 ± 8.510; 95 %CI 61.893-89.155) than in controls (55.012 ± 19.840; 95 %CI 41.380-68.643) (P = .027). Laser therapy, based on the irradiation protocol used in this study, was able to provide greater implant stability and increase the volume of peri-implant newly formed bone, indicating that laser irradiation effected an improvement in the osseointegration process.

Comparison Study of Percutaneous Osseointegrated Bone Conduction Device Complications When Using the 9 mm Abutment Versus 6 mm Abutment at Initial Implantation.

Science.gov (United States)

Wise, Sean R; LaRouere, Jacqueline S; Bojrab, Dennis I; LaRouere, Michael J

2018-04-01

To assess differences in the incidence, type, and management of complications encountered with implantation of percutaneous osseointegrated bone conduction devices when using a 9 mm abutment versus 6 mm abutment at initial implantation. Retrospective cohort study. One hundred thirty consecutive patients between January 2010 and December 2011 underwent single-stage percutaneous osseointegrated bone conduction device implantation using a 9 or 6 mm abutment. Clinical outcomes assessed for the two groups included the incidence, type, and management of postoperative complications. Abutment size, age, sex, indication for surgery, implant device type, duration of follow-up, and patient comorbidities were evaluated as potential factors affecting outcomes. Average duration of follow-up was 16 months (range 6-29 mo). Postoperative complications occurred in 38 (29.2%) patients. Twenty-four (18.4%) patients experienced minor complications requiring simple, local care; eight (6.1%) patients required in-office procedural intervention; and six (4.6%) patients required revision surgery in the operating room. Implant extrusion occurred in three (2.3%) patients. Eleven (8.5%) patients required placement of a longer abutment. Patients receiving the 6 mm abutment at initial surgery were significantly more likely to encounter a complication requiring in-office procedural intervention or revision surgery (p = 0.001). Minor complications after implantation of percutaneous osseointegrated bone conduction devices are common. The vast majority of these complications are due to localized skin reactions, most of which are readily addressed through local care. Patients receiving the 9 mm abutment during initial implantation are significantly less likely to require in-office procedural intervention or revision surgery postoperatively as compared with those receiving the shorter, 6 mm abutment.

Single-stage osseointegrated implants for nasal prosthodontic rehabilitation: A clinical report.

Science.gov (United States)

de Carvalho, Bruna M D F; Freitas-Pontes, Karina M; de Negreiros, Wagner A; Verde, Marcus A R L

2015-08-01

Malignant tumors in the nasal region may be treated by means of invasive surgical procedures, with large facial losses. Nasal prostheses, retained by osseointegrated facial implants, instead of plastic surgery, will, in most patients, offer good biomechanical and cosmetic results. This clinical report describes the prosthetic rehabilitation of a patient with nasal cancer who had the entire nasal vestibule removed in a single-stage surgical procedure in order to shorten the rehabilitation time. The nasal prosthesis was built on a 3-magnet bar and was made of platinum silicone with intrinsic pigmentation, thereby restoring the patient's appearance and self-esteem. The authors concluded that single-stage implants may reduce the rehabilitation time to as little as 1 month, and the correct use of materials and techniques may significantly improve the nasal prosthesis. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Enhancement of osteogenesis on micro/nano-topographical carbon fiber-reinforced polyetheretherketone–nanohydroxyapatite biocomposite

Energy Technology Data Exchange (ETDEWEB)

Xu, Anxiu [College of Stomatology, Chongqing Medical University, Chongqing 401147 (China); Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing 401147 (China); Liu, Xiaochen [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Gao, Xiang; Deng, Feng [College of Stomatology, Chongqing Medical University, Chongqing 401147 (China); Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing 401147 (China); Deng, Yi, E-mail: 18210357357@163.com [College of Stomatology, Chongqing Medical University, Chongqing 401147 (China); Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing 401147 (China); Wei, Shicheng, E-mail: weishicheng99@163.com [College of Stomatology, Chongqing Medical University, Chongqing 401147 (China); Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing 401147 (China)

2015-03-01

As an FDA-approved implantable material, carbon fiber-reinforced polyetheretherketone (CFRPEEK) possesses excellent mechanical properties similar to those of human cortical bone and is a prime candidate to replace conventional metallic implants. The bioinertness and inferior osteogenic properties of CFRPEEK, however, limit its clinical application as orthopedic/dental implants. The present work aimed at developing a novel carbon fiber-reinforced polyetheretherketone–nanohydroxyapatite (PEEK/CF/n-HA) ternary biocomposite with micro/nano-topographical surface for the enhancement of the osteogenesis as a potential bioactive material for bone grafting and bone tissue-engineering applications. The combined modification of oxygen plasma and sand-blasting could improve the hydrophily and generate micro/nano-topographical structures on the surface of the CFRPEEK-based ternary biocomposite. The results clearly showcased that the micro-/nano-topographical PEEK/n-HA/CF ternary biocomposite demonstrated the outstanding ability to promote the proliferation and differentiation of MG-63 cells in vitro as well as to boost the osseointegration between implant and bone in vivo, thereby boding well application to bone tissue engineering. - Highlights: • A novel micro/nano-topographical PEEK/n-HA/CF ternary biocomposite was developed. • The modified PEEK biocomposite promotes proliferation and differentiation of cells. • In vivo osseointegration of the micro/nano-topographical PEEK/n-HA/CF was enhanced.

Enhancement of osteogenesis on micro/nano-topographical carbon fiber-reinforced polyetheretherketone–nanohydroxyapatite biocomposite

International Nuclear Information System (INIS)

Xu, Anxiu; Liu, Xiaochen; Gao, Xiang; Deng, Feng; Deng, Yi; Wei, Shicheng

2015-01-01

As an FDA-approved implantable material, carbon fiber-reinforced polyetheretherketone (CFRPEEK) possesses excellent mechanical properties similar to those of human cortical bone and is a prime candidate to replace conventional metallic implants. The bioinertness and inferior osteogenic properties of CFRPEEK, however, limit its clinical application as orthopedic/dental implants. The present work aimed at developing a novel carbon fiber-reinforced polyetheretherketone–nanohydroxyapatite (PEEK/CF/n-HA) ternary biocomposite with micro/nano-topographical surface for the enhancement of the osteogenesis as a potential bioactive material for bone grafting and bone tissue-engineering applications. The combined modification of oxygen plasma and sand-blasting could improve the hydrophily and generate micro/nano-topographical structures on the surface of the CFRPEEK-based ternary biocomposite. The results clearly showcased that the micro-/nano-topographical PEEK/n-HA/CF ternary biocomposite demonstrated the outstanding ability to promote the proliferation and differentiation of MG-63 cells in vitro as well as to boost the osseointegration between implant and bone in vivo, thereby boding well application to bone tissue engineering. - Highlights: • A novel micro/nano-topographical PEEK/n-HA/CF ternary biocomposite was developed. • The modified PEEK biocomposite promotes proliferation and differentiation of cells. • In vivo osseointegration of the micro/nano-topographical PEEK/n-HA/CF was enhanced

The effects of PRGF on bone regeneration and on titanium implant osseointegration in goats: a histologic and histomorphometric study.

Science.gov (United States)

Anitua, Eduardo; Orive, Gorka; Pla, Rafael; Roman, Pedro; Serrano, Victoriano; Andía, Isabel

2009-10-01

The effect of local application of scaffold-like preparation rich in growth factors (PRGF) on bone regeneration in artificial defects and the potential effect of humidifying titanium dental implants with liquid PRGF on their osseointegration were investigated. The PRGF formulations were obtained from venous blood of three goats and applied either as a 3D fibrin scaffold (scaffold-like PRGF) in the regeneration of artificial defects or as liquid PRGF via humidifying the implants before their insertion. Initially, 12 defects were filled with scaffold-like PRGF and another 12 were used as controls. The histological analysis at 8 weeks revealed mature bone trabeculae when PRGF was used, whereas the control samples showed mainly connective tissue with incipient signs of bone formation. For the second set of experiments, 26 implants (13 humidified with liquid PRGF) were placed in the tibiae of goats. Histological and histomorphometric results demonstrated that application of liquid PRGF increased the percentage of bone-implant contact in 84.7%. The whole surface of the PRGF-treated implants was covered by newly formed bone, whereas only the upper half was surrounded in control implants. In summary, PRGF can accelerate bone regeneration in artificial defects and improve the osseointegration of titanium dental implants.

Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its implication in promoting osseointegration of titanium implant in type 2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Liu X

2017-09-01

Full Text Available Xiangwei Liu,1,* Naiwen Tan,1,* Yuchao Zhou,1 Hongbo Wei,1,* Shuai Ren,1 Fan Yu,2 Hui Chen,3 Chengming Jia,4 Guodong Yang,5 Yingliang Song1 1State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Implant Dentistry, 2Department of Prosthodontics, School of Stomatology, 3Department of Plastic Surgery, Tangdu Hospital, 4Department of Traditional Chinese Medicine, Xijing Hospital, 5Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, China *These authors contributed equally to this work Abstract: Impaired osseointegration of the implant remains the big hurdle for dental implant therapy in diabetic patients. In this study, the authors first identified that miR204 was strikingly highly expressed in the bone mesenchymal stem cells (BMSCs of diabetic rats. Forced expression of miR204 repressed the osteogenic potential of BMSCs, while inhibition of miR204 significantly increased the osteogenic capacity. Moreover, the miR204 inhibitor was conjugated with gold nanoparticles (AuNP-antagomiR204 and dispersed them in the poly(lactic-co-glycolic acid (PLGA solution. The AuNP-antagomiR204 containing PLGA solution was applied for coating the surface of titanium implant. Electron microscope revealed that an ultrathin sheet was formed on the surface of the implant, and the AuNPs were evenly dispersed in the coated PLGA sheet. Cellular experiments revealed that these encapsulated AuNP-antagomiR204 were able to be released from the PLGA sheet and uptaken by adherent BMSCs. In vivo animal study further confirmed that the AuNP-antagomiR204 released from PLGA sheet promoted osseointegration, as revealed by microcomputerized tomography (microCT reconstruction and histological assay. Taken together, this study established that miR204 misexpression accounted for the deficient

Combination of low-energy shock-wave therapy and bone marrow mesenchymal stem cell transplantation to improve the erectile function of diabetic rats.

Science.gov (United States)

Shan, Hai-Tao; Zhang, Hai-Bo; Chen, Wen-Tao; Chen, Feng-Zhi; Wang, Tao; Luo, Jin-Tai; Yue, Min; Lin, Ji-Hong; Wei, An-Yang

2017-01-01

Stem cell transplantation and low-energy shock-wave therapy (LESWT) have emerged as potential and effective treatment protocols for diabetic erectile dysfunction. During the tracking of transplanted stem cells in diabetic erectile dysfunction models, the number of visible stem cells was rather low and decreased quickly. LESWT could recruit endogenous stem cells to the cavernous body and improve the microenvironment in diabetic cavernous tissue. Thus, we deduced that LESWT might benefit transplanted stem cell survival and improve the effects of stem cell transplantation. In this research, 42 streptozotocin-induced diabetic rats were randomized into four groups: the diabetic group (n = 6), the LESWT group (n = 6), the bone marrow-derived mesenchymal stem cell (BMSC) transplantation group (n = 15), and the combination of LESWT and BMSC transplantation group (n = 15). One and three days after BMSC transplantation, three rats were randomly chosen to observe the survival numbers of BMSCs in the cavernous body. Four weeks after BMSC transplantation, the following parameters were assessed: the surviving number of transplanted BMSCs in the cavernous tissue, erectile function, real-time polymerase chain reaction, and penile immunohistochemical assessment. Our research found that LESWT favored the survival of transplanted BMSCs in the cavernous body, which might be related to increased stromal cell-derived factor-1 expression and the enhancement of angiogenesis in the diabetic cavernous tissue. The combination of LESWT and BMSC transplantation could improve the erectile function of diabetic erectile function rats more effectively than LESWT or BMSC transplantation performed alone.

Composite coating of 58S bioglass and hydroxyapatite on a poly (ethylene terepthalate) artificial ligament graft for the graft osseointegration in a bone tunnel

Energy Technology Data Exchange (ETDEWEB)

Li Hong; Wu Yang; Ge Yunsheng; Jiang Jia; Gao Kai [Department of Sports Medicine, Huashan Hospital, Shanghai (China); Zhang Pengyun; Wu Lingxiang [Shanghai Research Center of Biomedical Engineering, Shanghai (China); Chen Shiyi, E-mail: cshiyi@163.com [Department of Sports Medicine, Huashan Hospital, Shanghai (China)

2011-09-01

The purpose of this study was to determine the effect of the combination of hydroxyapatite (HA) and bioglass (BG) on polyethylene terephthalate (PET) artificial ligament graft osseointegration within the bone tunnel. The results of in vitro culturing of MC3T3-E1 mouse osteoblastic cells proved that this HA/BG composite coating can promote the cell compatibility of grafts. A rabbit extraarticular tendon-to-bone healing model was used to evaluate the effect of this composite coating on PET artificial ligaments in vivo. The final results demonstrated that HA/BG coating improved new bone formation at the graft-bone interface and increased the load-to-failure property of graft in bone tunnel compared to the control group at early time. The study has shown that HA/BG composite coating on the PET artificial ligament surface has a positive effect in the induction of artificial ligament osseointegration within the bone tunnel.

Composite coating of 58S bioglass and hydroxyapatite on a poly (ethylene terepthalate) artificial ligament graft for the graft osseointegration in a bone tunnel

International Nuclear Information System (INIS)

Li Hong; Wu Yang; Ge Yunsheng; Jiang Jia; Gao Kai; Zhang Pengyun; Wu Lingxiang; Chen Shiyi

2011-01-01

The purpose of this study was to determine the effect of the combination of hydroxyapatite (HA) and bioglass (BG) on polyethylene terephthalate (PET) artificial ligament graft osseointegration within the bone tunnel. The results of in vitro culturing of MC3T3-E1 mouse osteoblastic cells proved that this HA/BG composite coating can promote the cell compatibility of grafts. A rabbit extraarticular tendon-to-bone healing model was used to evaluate the effect of this composite coating on PET artificial ligaments in vivo. The final results demonstrated that HA/BG coating improved new bone formation at the graft-bone interface and increased the load-to-failure property of graft in bone tunnel compared to the control group at early time. The study has shown that HA/BG composite coating on the PET artificial ligament surface has a positive effect in the induction of artificial ligament osseointegration within the bone tunnel.

Osseointegration of implants with dendrimers surface characteristics installed conventionally or with Piezosurgery®. A comparative study in the dog.

Science.gov (United States)

Bengazi, Franco; Lang, Niklaus P; Canciani, Elena; Viganò, Paolo; Velez, Joaquin Urbizo; Botticelli, Daniele

2014-01-01

The first aim of the present experiment was to compare bone healing at implants installed in recipient sites prepared with conventional drills or a piezoelectric device. The second aim was to compare implant osseointegration onto surfaces with and without dendrimers coatings. Six Beagles dogs were used in this study. Five implants with two different surfaces, three with a ZirTi(®) surface (zirconia sand blasted, acid etched), and two with a ZirTi(®)-modified surface with dendrimers of phosphoserine and polylysine were installed in the right side of the mandible. In the most anterior region (P2, P3), two recipient sites were prepared with drills, and one implant ZirTi(®) surface and one coated with dendrimers implants were installed at random. In the posterior region (P4 and M1), three recipient sites were randomly prepared: two sites with a Piezosurgery(®) instrument and one site with drill and two ZirTi(®) surface and one coated with dendrimers implants installed. Three months after the surgery, the animals were sacrificed for histological analysis. No complications occurred during the healing period. Three implants were found not integrated and were excluded from analysis. However, n = 6 was obtained. The distance IS-B at the buccal aspect was 2.2 ± 0.8 and 1.8 ± 0.5 mm, while IS-C was 1.5 ± 0.9 and 1.4 ± 0.6 mm at the Piezosurgery(®) and drill groups, respectively. Similar values were obtained between the dendrimers-coated and ZirTi(®) surface implants. The BIC% values were higher at the drill (72%) compared to the Piezosurgery(®) (67%) sites. The BIC% were also found to be higher at the ZirTi(®) (74%) compared to the dendrimers-coated (65%) implants, the difference being statistically significant. This study has revealed that oral implants may osseointegrate equally well irrespective of whether their bed was prepared utilizing conventional drills with abundant cooling or Piezosurgery(®). Moreover, the surface coating of implants with dendrimers

Osseointegration of layer-by-layer polyelectrolyte multilayers loaded with IGF1 and coated on titanium implant under osteoporotic condition

Directory of Open Access Journals (Sweden)

Xing H

2017-10-01

Full Text Available Helin Xing,1,* Xing Wang,2,* Saisong Xiao,3,* Guilan Zhang,1 Meng Li,1 Peihuan Wang,1 Quan Shi,1 Pengyan Qiao,1 Lingling E,1 Hongchen Liu1 1Institute of Stomatology, Chinese PLA General Hospital, Beijing, 2Hospital of Stomatology, Shanxi Medical University, Taiyuan, 3Department of Anesthesia, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China *These authors contributed equally to this work Purpose: Titanium implant is a widely used method for dental prosthesis restoration. Nevertheless, in patients with systemic diseases, including osteoporosis, diabetes, and cancer, the success rate of the implant is greatly reduced. This study investigates a new implant material loaded with insulin-like growth factor 1 (IGF1, which could potentially improve the implant success rate, accelerate the occurrence of osseointegration, and provide a new strategy for implant treatment in osteoporotic patients. Materials and methods: Biofunctionalized polyelectrolyte multilayers (PEMs with polyethylenimine as the excitation layer and gelatin/chitosan loaded with IGF1 were prepared on the surface of titanium implant by layer-by-layer self-assembly technique. The physical and chemical properties of the biofunctionalized PEMs, the biological characteristics of bone marrow mesenchymal stem cells (BMMSCs, and bone implant contact correlation test indexes were detected and analyzed in vitro and in vivo using osteoporosis rat model. Results: PEMs coatings loaded with IGF1 (TNS-PEM-IGF1-100 implant promoted the early stage of BMMSCs adhesion. Under the action of body fluids, the active coating showed sustained release of growth factors, which in turn promoted the proliferation and differentiation of BMMSCs and the extracellular matrix. At 8 weeks from implant surgery, the new bone around the implants was examined using micro-CT and acid fuchsin/methylene blue staining. The new bone formation increased with time in each group, while the TNS-PEM-IGF1

Osseointegration of dental implants in 3D-printed synthetic onlay grafts customized according to bone metabolic activity in recipient site.

Science.gov (United States)

Tamimi, Faleh; Torres, Jesus; Al-Abedalla, Khadijeh; Lopez-Cabarcos, Enrique; Alkhraisat, Mohammad H; Bassett, David C; Gbureck, Uwe; Barralet, Jake E

2014-07-01

Onlay grafts made of monolithic microporous monetite bioresorbable bioceramics have the capacity to conduct bone augmentation. However, there is heterogeneity in the graft behaviour in vivo that seems to correlate with the host anatomy. In this study, we sought to investigate the metabolic activity of the regenerated bone in monolithic monetite onlays by using positron emission tomography-computed tomography (PET-CT) in rats. This information was used to optimize the design of monetite onlays with different macroporous architecture that were then fabricated using a 3D-printing technique. In vivo, bone augmentation was attempted with these customized onlays in rabbits. PET-CT findings demonstrated that bone metabolism in the calvarial bone showed higher activity in the inferior and lateral areas of the onlays. Histological observations revealed higher bone volume (up to 47%), less heterogeneity and more implant osseointegration (up to 38%) in the augmented bone with the customized monetite onlays. Our results demonstrated for the first time that it is possible to achieve osseointegration of dental implants in bone augmented with 3D-printed synthetic onlays. It was also observed that designing the macropore geometry according to the bone metabolic activity was a key parameter in increasing the volume of bone augmented within monetite onlays. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effects of subcutaneous injection of nicotine on osseointegration of machined and anodized implants in rabbits.

Science.gov (United States)

Linden, Maria Salete Sandini; Bittencourt, Marcos Eugênio de; Carli, João Paulo De; Miyagaki, Daniela Cristina; Santos, Pâmela Letícia Dos; Paranhos, Luiz Renato; Groppo, Francisco Carlos; Ramacciato, Juliana Cama

2018-01-01

To evaluate the influence of subcutaneous injection nicotine in osseointegration process on different implant surfaces. Twenty-two male rabbits were distributed into two groups according to the subcutaneous injections: (1) nicotine 3 mg/day/kg and (2) 0.9 % NaCI 3 mL/day/kg, three times a day; subgroups were then designated-machined and anodized implants were placed in the right and left tibia bones, respectively. The animals were submitted euthanasia after periods of eight weeks to determine nicotine and cotinine levels, alkaline phosphatase and biomechanical analysis. The plasmatic levels of nicotine and cotinine were 0.5 ± 0.28 ng/mL and 9.5 ± 6.51 ng/mL, respectively. The alkaline phosphatase analyses in blood levels in control group were observed 40.8 ± 11.88 UI/L and 40.75 ± 12.46 UI/L, for the surfaces machined and anodized, respectively. In the test group was observed levels 37.9 ± 4.84 UI/L, for both implant surfaces. No significant differences were observed between control and test groups and between the implant surfaces regarding alkaline phosphatase blood levels. For biomechanics, no significant differences were observed in control group between the machined (25±8.46 Ncm) or anodized (31.2 ± 6.76 Ncm) implants. However, the treatment with nicotine induced higher torque than control in both machined (38.3 ± 13.52 Ncm) and anodized (35.5 ± 14.17 Ncm) implants, with p = 0.0024 and p = 0.0121, respectively. Subcutaneous injection of nicotine following implant insertion didn't have effect on osseointegration, independently from the implant surface.

New sol-gel bioactive glass and titania composites with enhanced physico-chemical and biological properties.

Science.gov (United States)

Pawlik, Justyna; Widziołek, Magdalena; Cholewa-Kowalska, Katarzyna; Łączka, Maria; Osyczka, Anna Maria

2014-07-01

We developed TiO2 matrix composites modified by sol-gel bioactive glasses (SBG) of either high CaO content (A2) or high SiO2 content (S2). The latter were mixed with titanium dioxide (TiO2) at 75:25, 50:50, and 25:75 weight ratios and sintered at 1250°C for 2 h. We examined the effects of various types (A2 or S2) and compositional TiO2 :SBG ratios on the mechanical properties of resulting composites, their bioactivity and human bone marrow mesenchymal stem cells (MSC) response. The chemistry of SBGs influenced the phase composition, mechanical and biological properties of the composites. Rutile and titanite prevailed in A2-TiO2 composites, and rutile and crystobalite in S2-TiO2 composites. Compressive strength increased significantly for 25A2-TiO2 composites (140 MPa) compared to matrix TiO2 (58 MPa). Composites containing 50-75 wt % of either SBG displayed bioactive properties as determined by simulated body fluid test. Compared to TiO2, human bone marrow stromal cell (BMSC) viability was enhanced on the composites containing 25 wt % of either SBG, whereas the composites modified by 25 wt % of S2 enhanced alkaline phosphatase activity and mineralization in cultures treated with osteogenic inducers-dexamethasone (Dex) or bone morphogenetic protein. Increasing amounts of A2 in TiO2 matrix decreased cell viability but increased collagen deposition and mineralized matrix production by BMSC. Considering the physico-chemical and biological properties of the presented composites, the modification of TiO2 with SBG may prove useful strategy in several bone tissue related regeneration strategies. © 2013 Wiley Periodicals, Inc.

Emotional Arousal Does Not Enhance Association-Memory

Science.gov (United States)

Madan, Christopher R.; Caplan, Jeremy B.; Lau, Christine S. M.; Fujiwara, Esther

2012-01-01

Emotionally arousing information is remembered better than neutral information. This enhancement effect has been shown for memory for items. In contrast, studies of association-memory have found both impairments and enhancements of association-memory by arousal. We aimed to resolve these conflicting results by using a cued-recall paradigm combined…

Laser-Modified Surface Enhances Osseointegration and Biomechanical Anchorage of Commercially Pure Titanium Implants for Bone-Anchored Hearing Systems

Science.gov (United States)

Omar, Omar; Simonsson, Hanna; Palmquist, Anders; Thomsen, Peter

2016-01-01

Osseointegrated implants inserted in the temporal bone are a vital component of bone-anchored hearing systems (BAHS). Despite low implant failure levels, early loading protocols and simplified procedures necessitate the application of implants which promote bone formation, bone bonding and biomechanical stability. Here, screw-shaped, commercially pure titanium implants were selectively laser ablated within the thread valley using an Nd:YAG laser to produce a microtopography with a superimposed nanotexture and a thickened surface oxide layer. State-of-the-art machined implants served as controls. After eight weeks’ implantation in rabbit tibiae, resonance frequency analysis (RFA) values increased from insertion to retrieval for both implant types, while removal torque (RTQ) measurements showed 153% higher biomechanical anchorage of the laser-modified implants. Comparably high bone area (BA) and bone-implant contact (BIC) were recorded for both implant types but with distinctly different failure patterns following biomechanical testing. Fracture lines appeared within the bone ~30–50 μm from the laser-modified surface, while separation occurred at the bone-implant interface for the machined surface. Strong correlations were found between RTQ and BIC and between RFA at retrieval and BA. In the endosteal threads, where all the bone had formed de novo, the extracellular matrix composition, the mineralised bone area and osteocyte densities were comparable for the two types of implant. Using resin cast etching, osteocyte canaliculi were observed directly approaching the laser-modified implant surface. Transmission electron microscopy showed canaliculi in close proximity to the laser-modified surface, in addition to a highly ordered arrangement of collagen fibrils aligned parallel to the implant surface contour. It is concluded that the physico-chemical surface properties of laser-modified surfaces (thicker oxide, micro- and nanoscale texture) promote bone bonding

Computational biomechanics of bone's responses to dental prostheses - osseointegration, remodeling and resorption

International Nuclear Information System (INIS)

Li Wei; Rungsiyakull, Chaiy; Field, Clarice; Lin, Daniel; Zhang Leo; Li Qing; Swain, Michael

2010-01-01

Clinical and experimental studies showed that human bone has the ability to remodel itself to better adapt to its biomechanical environment by changing both its material properties and geometry. As a consequence of the rapid development and extensive applications of major dental restorations such as implantation and fixed partial denture (FPD), the effect of bone remodeling on the success of a dental restorative surgery is becoming critical for prosthetic design and pre-surgical assessment. This paper aims to provide a computational biomechanics framework to address dental bone's responses as a result of dental restoration. It explored three important issues of resorption, apposition and osseointegration in terms of remodeling simulation. The published remodeling data in long bones were regulated to drive the computational remodeling prediction for the dental bones by correlating the results to clinical data. It is anticipated that the study will provide a more predictive model of dental bone response and help develop a new design methodology for patient-specific dental prosthetic restoration.

Acid etching and plasma sterilization fail to improve osseointegration of grit blasted titanium implants

DEFF Research Database (Denmark)

Mortensen, Mikkel Saksø; Jakobsen, Stig Storgaard; Saksø, Henrik

2012-01-01

Interaction between implant surface and surrounding bone influences implant fixation. We attempted to improve the bone-implant interaction by 1) adding surface micro scale topography by acid etching, and 2) removing surface-adherent pro-inflammatory agents by plasma cleaning. Implant fixation...... was evaluated by implant osseointegration and biomechanical fixation.The study consisted of two paired animal sub-studies where 10 skeletally mature Labrador dogs were used. Grit blasted titanium alloy implants were inserted press fit in each proximal tibia. In the first study grit blasted implants were...... compared with acid etched grit blasted implants. In the second study grit blasted implants were compared with acid etched grit blasted implants that were further treated with plasma sterilization. Implant performance was evaluated by histomorphometrical investigation (tissue-to-implant contact, peri-implant...

Oral and masticatory rehabilitation using osseointegrated dental implants after resective treatment of multicystic ameloblastoma in the lower jaw with a fibula graft

Directory of Open Access Journals (Sweden)

João Ricardo Almeida Grossi

2018-01-01

Full Text Available Ameloblastoma is an aggressive odontogenic tumor which typically occurs between third and fourth decade of life that often needs resective approach. Immediate reconstruction may show better results. The treatment of multicystic ameloblastoma in the mandible being a rare case that occurred in the late second decade of life, which was surgically removed along with the affected teeth with safety margins, and the region was immediately reconstructed using a vascularized graft, removed from the fibula. Its integration, in combination with osseointegrated dental implants and fixed implant-supported prostheses, restored chewing function and esthetics. After 6 years from fibular graft and 24 months of dental implants, an excellent outcome was observed, with oral health and normal functions properly restored, and the immediate reconstruction of the mandible in resective cases, associated with oral rehabilitation with dental implants, may be considered a suitable treatment option.

Influence of two barrier membranes on staged guided bone regeneration and osseointegration of titanium implants in dogs: part 1. Augmentation using bone graft substitutes and autogenous bone.

Science.gov (United States)

Schwarz, Frank; Mihatovic, Ilja; Golubovic, Vladimir; Hegewald, Andrea; Becker, Jürgen

2012-01-01

To assess the influence of two barrier membranes and two bone graft substitutes mixed with autogenous bone (AB) on staged guided bone regeneration and osseointegration of titanium implants in dogs. Four saddle-type defects each were prepared in the upper jaw of six fox hounds and randomly filled with a natural bone mineral (NBM)+AB and a biphasic calcium phosphate (SBC)+AB and allocated to either an in situ gelling polyethylene glycol (PEG) or a collagen membrane (CM). At 8 weeks, modSLA titanium implants were inserted and left to heal in a submerged position. At 8+2 weeks, dissected blocks were processed for histomorphometrical analysis (e.g., treated area [TA], bone-to-implant contact [BIC]). The mean TA values (mm(2) ) and BIC values (%) tended to be higher in the PEG groups(TA: NBM+AB [10.4 ± 2.5]; SBC+AB [10.4 ± 5.8]/BIC: NBM+AB [86.4 ± 20.1]; SBC+AB [80.1 ± 21.5]) when compared with the corresponding CM groups (TA: NBM+AB [9.7 ± 4.8]; SBC+AB [7.8 ± 4.3]/BIC: NBM+AB [71.3 ± 20.8]; SBC+AB [72.4 ± 20.3]). A significant difference was observed for the mean TA values in the SBC+AB groups. It was concluded that all augmentation procedures investigated supported bone regeneration and staged osseointegration of modSLA titanium implants. However, the application of PEG may be associated with increased TA values. © 2011 John Wiley & Sons A/S.

Evaluation of the effects of different sand particles that used in dental implant roughened for osseointegration.

Science.gov (United States)

Yurttutan, Mehmet Emre; Keskin, Ahmet

2018-03-20

Successful dental implant treatment is directly related to osseointegration. In achieving osseointegration, the surface property of the implant is of great importance. Sandblasting is the most commonly used basic method for modifying the surface. Many companies use different sand particles for surface roughening and claim their sand is the best. This leads clinicians to mix their minds in product selection. In this study, we tried to find the appropriate sand material by working objectively without praising any brand. We believe that the results of the study will help clinicians choose the right dental implant. In this study, machined-surfaced implants and implants sandblasted with Aluminum oxide (Al 2 O 3 ), Titanium dioxide (TiO 2 ) and Silicon dioxide (SiO 2 ) were compared via biomechanical testing. For the study, four 2 year-old sheep, weighing 45 kilograms (kg), were used. Eight implants (Al 2 O 3 , TiO 2 , and SiO 2 sandblasted implants and machined-surfaced implants), each with different surface characteristics, were inserted into the bilateral tibia of each sheep under general anesthesia. Results of the initial Resonance Frequency Analysis (RFA) were recorded just after implant insertion. The sheep were then randomly divided into two groups, each with 2 sheep, to undergo either a 1-month or a 3-month assessment. At the end of the designated evaluation period, RFA and removal torque tests were performed. Although there were no statistically significant differences between the groups, the implants sandblasted with Al 2 O 3 showed a higher Implant Stability Quotient (ISQ) and removal torque value at the end of the 1st and 3rd month. In short, the results of the study demonstrate that Aluminum oxide is superior to other sand particles.

Magnetically actuated mechanical stimuli on Fe3O4/mineralized collagen coatings to enhance osteogenic differentiation of the MC3T3-E1 cells.

Science.gov (United States)

Zhuang, Junjun; Lin, Suya; Dong, Lingqing; Cheng, Kui; Weng, Wenjian

2018-04-15

, and the IOP-MC coatings with outer distributed IOPs (O-IOPs-MC) shows the maximized mechanical stimuli to cells with enhanced osteogenic differentiation under static magnetic field. The upregulated expression of the associated genes reveals that the enabled mechanotransduction signaling pathway is responsible for the promoted cellular osteogenic differentiation. This work therefore provides a promising strategy for implementing mechanical stimuli to activate mechanotransduction on the bone-implant interface to promote osseointegration. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Does longstanding nicotine exposure impair bone healing and osseointegration? An experimental study in rabbits

DEFF Research Database (Denmark)

Gotfredsen, Klaus; Lindh, Christian H; Berglundh, Tord

2009-01-01

OBJECTIVES: The aim of this study was to analyze the effect of longstanding nicotine exposure on bone healing and osseointegration of titanium implants. MATERIALS AND METHODS: 20 female rabbits received either nicotine (n = 10) or saline (n = 10) administered subcutaneously via mini-osmotic pumps...... for 32 weeks. The pump delivered 6 microg/kg/min of nicotine for the animals in the test group. Blood samples were collected and plasma cotinine levels were measured monthly. Six months after the commencement of nicotine or saline administration three osteotomy preparations, one in right, femoral condyle...... increase in RMT between 2 and 4 weeks within each group. The histomorphometric analysis of bone-to-implant contact and bone density in the bone defects revealed no differences between the test and the control group after 2 or 4 weeks of healing. CONCLUSION: Longstanding (6 months) nicotine exposure did...

Mesenchymal stem cell-derived extracellular matrix enhances chondrogenic phenotype of and cartilage formation by encapsulated chondrocytes in vitro and in vivo.

Science.gov (United States)

Yang, Yuanheng; Lin, Hang; Shen, He; Wang, Bing; Lei, Guanghua; Tuan, Rocky S

2018-03-15

Mesenchymal stem cell derived extracellular matrix (MSC-ECM) is a natural biomaterial with robust bioactivity and good biocompatibility, and has been studied as a scaffold for tissue engineering. In this investigation, we tested the applicability of using decellularized human bone marrow derived MSC-ECM (hBMSC-ECM) as a culture substrate for chondrocyte expansion in vitro, as well as a scaffold for chondrocyte-based cartilage repair. hBMSC-ECM deposited by hBMSCs cultured on tissue culture plastic (TCP) was harvested, and then subjected to a decellularization process to remove hBMSCs. Compared with chondrocytes grown on TCP, chondrocytes seeded onto hBMSC-ECM exhibited significantly increased proliferation rate, and maintained better chondrocytic phenotype than TCP group. After being expanded to the same cell number and placed in high-density micromass cultures, chondrocytes from the ECM group showed better chondrogenic differentiation profile than those from the TCP group. To test cartilage formation ability, composites of hBMSC-ECM impregnated with chondrocytes were subjected to brief trypsin treatment to allow cell-mediated contraction, and folded to form 3-dimensional chondrocyte-impregnated hBMSC-ECM (Cell/ECM constructs). Upon culture in vitro in chondrogenic medium for 21 days, robust cartilage formation was observed in the Cell/ECM constructs. Similarly prepared Cell/ECM constructs were tested in vivo by subcutaneous implantation into SCID mice. Prominent cartilage formation was observed in the implanted Cell/ECM constructs 14 days post-implantation, with higher sGAG deposition compared to controls consisting of chondrocyte cell sheets. Taken together, these findings demonstrate that hBMSC-ECM is a superior culture substrate for chondrocyte expansion and a bioactive matrix potentially applicable for cartilage regeneration in vivo. Current cell-based treatments for focal cartilage defects face challenges, including chondrocyte dedifferentiation, need for

Incorporation of sol–gel bioactive glass into PLGA improves mechanical properties and bioactivity of composite scaffolds and results in their osteoinductive properties

International Nuclear Information System (INIS)

Filipowska, J; Tylko, G; Osyczka, A M; Pawlik, J; Cholewa-Kowalska, K; Laczka, M; Pamula, E; Niedzwiedzki, L; Szuta, M

2014-01-01

In this study, 3D porous bioactive composite scaffolds were produced and evaluated for their physico-chemical and biological properties. Polymer poly-L-lactide-co-glycolide (PLGA) matrix scaffolds were modified with sol–gel-derived bioactive glasses (SBGs) of CaO–SiO 2 –P 2 O 5 systems. We hypothesized that SBG incorporation into PLGA matrix would improve the chemical and biological activity of composite materials as well as their mechanical properties. We applied two bioactive glasses, designated as S2 or A2, differing in the content of SiO 2 and CaO (i.e. 80 mol% SiO 2 , 16 mol% CaO for S2 and 40 mol% SiO 2 , 52 mol% CaO for A2). The composites were characterized for their porosity, bioactivity, microstructure and mechanical properties. The osteoinductive properties of these composites were evaluated in human bone marrow stromal cell (hBMSC) cultures grown in either standard growth medium or treated with recombinant human bone morphogenetic protein-2 (rhBMP-2) or dexamethasone (Dex). After incubation in simulated body fluid, calcium phosphate precipitates formed inside the pores of both A2-PLGA and S2-PLGA scaffolds. The compressive strength of the latter was increased slightly compared to PLGA. Both composites promoted superior hBMSC attachment to the material surface and stimulated the expression of several osteogenic markers in hBMSC compared to cells grown on unmodified PLGA. There were also marked differences in the response of hBMSC to composite scaffolds, depending on chemical compositions of the scaffolds and culture treatments. Compared to silica-rich S2-PLGA, hBMSC grown on calcium-rich A2-PLGA were overall less responsive to rhBMP-2 or Dex and the osteoinductive properties of these A2-PLGA scaffolds seemed partially dependent on their ability to induce BMP signaling in untreated hBMSC. Thus, beyond the ability of currently studied composites to enhance hBMSC osteogenesis, it may become possible to modulate the osteogenic response of hBMSC

Osseointegration of titanium implants functionalised with phosphoserine-tethered poly(epsilon-lysine) dendrons: a comparative study with traditional surface treatments in sheep.

Science.gov (United States)

Stübinger, Stefan; Nuss, Katja; Bürki, Alexander; Mosch, Isabel; le Sidler, Miché; Meikle, Steve T; von Rechenberg, Brigitte; Santin, Matteo

2015-02-01

The aim of this study was to analyse the osseointegrative potential of phosphoserine-tethered dendrons when applied as surface functionalisation molecules on titanium implants in a sheep model after 2 and 8 weeks of implantation. Uncoated and dendron-coated implants were implanted in six sheep. Sandblasted and etched (SE) or porous additive manufactured (AM) implants with and without additional dendron functionalisation (SE-PSD; AM-PSD) were placed in the pelvic bone. Three implants per group were examined histologically and six implants were tested biomechanically. After 2 and 8 weeks the bone-to-implant contact (BIC) total values of SE implants (43.7±12.2; 53.3±9.0%) and SE-PSD (46.7±4.5; 61.7±4.9%) as well as AM implants (20.49±5.1; 43.9±9.7%) and AM-PSD implants (19.7±3.5; 48.3±15.6%) showed no statistically significant differences. For SE-PSD and AM-PSD a separate analysis of only the cancellous BIC demonstrated a statistically significant difference after 2 and 8 weeks. Biomechanical findings proved the overall increased stability of the porous implants after 8 weeks. Overall, the great effect of implant macro design on osseointegration was further supported by additional phosphoserine-tethered dendrons for SE and AM implants.

Damping Factor as a Diagnostic Parameter for Assessment of Osseointegration during the Dental Implant Healing Process: An Experimental Study in Rabbits.

Science.gov (United States)

Feng, Sheng-Wei; Ho, Kuo-Ning; Chan, Ya-Hui; Chang, Kai-Jung; Lai, Wei-Yi; Huang, Haw-Ming

2016-12-01

The purpose of this study was to evaluate the possibility of using damping factor (DF) analysis to provide additional information on osseointegration of dental implants during the healing period. A total of 30 dental implants were installed in the bilateral femoral condyles of 15 rabbits. A DF analyzer detected with an impulse-forced vibration method and a commercialized dental implant stability analyzer based on resonance frequency (RF) analysis were used to measure the implant stability immediately after implant placement and 1, 2, 4, and 8 weeks post-surgically. Results of DF and RF analyses at different time points were compared with the corresponding osseointegration performance of dental implants via micro-computed tomography (micro-CT), histological and histomorphometrical analysis. The DF values revealed a decrease with time and reached 0.062 ± 0.007 at 8 weeks after implantation, which is almost 50% lower than the initial value. Moreover, highly significant correlations between DF values and bone volume densities (R 2  = 0.9797) and percentages of bone-to-implant contact measured at trabecular bone area (R 2  = 0.9773) were also observed. These results suggested that DF analysis combined with RF analysis results in a more sensitive assessment of changes in the dental implant/bone complex during the healing period than RF analysis alone.

Enhancement of chondrogenic differentiation of rabbit mesenchymal stem cells by oriented nanofiber yarn-collagen type I/hyaluronate hybrid

International Nuclear Information System (INIS)

Zheng, Xianyou; Wang, Wei; Liu, Shen; Wu, Jinglei; Li, Fengfeng; Cao, Lei; Liu, Xu-dong; Mo, Xiumei; Fan, Cunyi

2016-01-01

Cartilage defects cause joint pain and loss of mobility. It is crucial to induce the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by both biological and structural signals in cartilage tissue engineering. Sponge-like scaffolds fabricated using native cartilage extracellular matrix components can induce the BMSC differentiation by biological signals and limited structural signals. In this study, an oriented poly(L-lactic acid)-co-poly(ε-caprolactone) P(LLA-CL)/collagen type I (Col-I) nanofiber yarn mesh, fabricated by dynamic liquid electrospinning served as a skeleton for a freeze-dried Col-I/hyaluronate (HA) chondral phase (SPONGE) containing both structural and biological signals to guide BMSC chondrogenic differentiation. In vitro results show that the Yarn Col-I/HA hybrid scaffold (Yarn-CH) promotes orientation, adhesion and proliferation of BMSCs better than SPONGE. Furthermore, BMSCs seeded on the Yarn-CH scaffold demonstrated a large increase in the glycosaminoglycan content and expression of collagen type II following a 21-day culture. - Highlights: • An oriented yarn was used as the skeleton of the sponge-like scaffold. • Both structural and biological signals were given for BMSC chondrogenic differentiation. • Yarn-CH promotes orientation and chondrogenesis differentiation of BMSCs. • Yarn-CH reproduces the superficial zone of the cartilage.

Bone Marrow Derived Mesenchymal Stromal Cells Harness Purinergenic Signaling to Tolerize Human Th1 Cells In Vivo

Science.gov (United States)

Amarnath, Shoba; Foley, Jason E.; Farthing, Don E.; Gress, Ronald E.; Laurence, Arian; Eckhaus, Michael A.; Métais, Jean-Yves; Rose, Jeremy J.; Hakim, Frances T.; Felizardo, Tania C.; Cheng, Austin V.; Robey, Pamela G.; Stroncek, David E.; Sabatino, Marianna; Battiwalla, Minoo; Ito, Sawa; Fowler, Daniel H.; Barrett, Austin J.

2014-01-01

The use of bone marrow derived mesenchymal stromal cells (BMSC) in the treatment of alloimmune and autoimmune conditions has generated much interest, yet an understanding of the therapeutic mechanism remains elusive. We therefore explored immune modulation by a clinical-grade BMSC product in a model of human-into-mouse xenogeneic GVHD (x-GVHD) mediated by human CD4+ Th1 cells. BMSC reversed established, lethal x-GVHD through marked inhibition of Th1 cell effector function. Gene marking studies indicated BMSC engraftment was limited to the lung; further, there was no increase in regulatory T cells, thereby suggesting a paracrine mechanism of BMSC action. BMSC recipients had increased serum CD73 expressing exosomes that promoted adenosine accumulation ex vivo. Importantly, immune modulation mediated by BMSC was fully abrogated by pharmacologic therapy with an adenosine A2A receptor antagonist. To investigate the potential clinical relevance of these mechanistic findings, patient serum samples collected pre- and post-BMSC treatment were studied for exosome content: CD73 expressing exosomes promoting adenosine accumulation were detected in post-BMSC samples. In conclusion, BMSC effectively modulate experimental GVHD through a paracrine mechanism that promotes adenosine-based immune suppression. PMID:25532725

Guided tissue regeneration ensures osseointegration of dental implants placed into extraction sockets. An experimental study in monkeys

DEFF Research Database (Denmark)

Warrer, L; Gotfredsen, K; Hjørting-Hansen, E

1991-01-01

on the buccal and palatal aspects of the maxillary molars in both sides of the jaw. The second molars were then extracted and self tapping titanium implants of the screw type (Astra Dental Implants) were inserted into the sockets of the largest roots. In the coronal portion of the sockets, a void was always...... present between the implant and the socket walls. In one side of the jaw, a membrane (Gore-Tex Augmentation Material) was adjusted to cover the implant. The implant in the other side of the jaw served as control and was only covered by the tissue flaps. Microscopic analysis after 3 months of healing...... technique can secure complete osseointegration of implants inserted immediately into extraction sockets....

Chronic alcohol abuse and endosseous implants: Linkage of in vitro osteoblast dysfunction to titanium osseointegration rate

International Nuclear Information System (INIS)

Torricelli, Paola; Fini, Milena; Giavaresi, Gianluca; Rimondini, Lia; Tschon, Matilde; Rimondini, Roberto; Carrassi, Antonio; Giardino, Roberto

2008-01-01

Chronic alcohol consumption is associated with pathological effects on bone, and it is correlated with the increasing risk of osteoporosis and fractures. The negative effects of alcohol intake also influence bone repair processes and the osseointegration of implants. The aim of the present in vitro study was to investigate the proliferation and synthetic activity of osteoblasts isolated from the trabecular bone of rats previously exposed to 7-week intermittent exposure to ethanol vapour (EE-OB), and sham-aged rats (SA-OB), when cultured on standard commercially pure Ti (cpTi). Osteoblast proliferation (WST-1), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I (CICP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and transforming growth factor-β1 (TGF-β1) were measured at 1, 7, and 14 days of culture. Our results showed a decrease in the cell viability and synthetic activity of osteoblasts exposed to ethanol when cultured on cpTi. Moreover, the release of local regulatory factors from osteoblasts was imbalanced: TGF-β1 production was reduced and TNF-α and IL-6 were up-regulated. These in vitro data suggest that alcohol abuse affects bone repair and decreases the ability to form bone around standard cpTi. Innovative surfaces and adjuvant therapies could be useful when implants are required in alcoholics

Identification of the critical level of implantation of an osseointegrated prosthesis for above-knee amputees.

Science.gov (United States)

Andrango Castro, Elder Michael; Konvickova, Svatava; Daniel, Matej; Horak, Zdenek

2017-11-01

The aim of our study was to identify potential critical levels of implantation of an osseointegrated prosthesis for above-knee amputees. The implant used was the OPRA system. It was inserted in the femur at four different amputation heights, characterized by their residual limb ratios (0.299, 0.44, 0.58 and 0.73). The stress and strain distribution was evaluated in the bone-implant system during walking, considering a body mass of 100 kg. Considerably high stimulus (11,489 με) in the tissue near the tip was found at the highest implantation level. All models presented small non-physiologic stress values in the tissue around the implant. The results revealed that the implantation level has a decisive effect on bone-implant performance. Mainly, the analysis indicates adverse biomechanical conditions for implantations in very short residual limbs.

Cytokine-primed bone marrow stem cells vs. peripheral blood stem cells for autologous transplantation: a randomized comparison of GM-CSF vs. G-CSF.

Science.gov (United States)

Weisdorf, D; Miller, J; Verfaillie, C; Burns, L; Wagner, J; Blazar, B; Davies, S; Miller, W; Hannan, P; Steinbuch, M; Ramsay, N; McGlave, P

1997-10-01

Autologous transplantation for non-Hodgkins lymphoma and Hodgkin's disease is widely used as standard therapy for those with high-risk or relapsed tumor. Peripheral blood stem cell (PBSC) collections have nearly completely replaced bone marrow stem cell (BMSC) harvests because of the perceived advantages of more rapid engraftment, less tumor contamination in the inoculum, and better survival after therapy. The advantage of PBSC, however, may derive from the hematopoietic stimulating cytokines used for PBSC mobilization. Therefore, we tested a randomized comparison of GM-CSF vs. G-CSF used to prime either BMSC or PBSC before collection for use in autologous transplantation. Sixty-two patients receiving transplants (31 PBSC; 31 BMSC) for non-Hodgkin's lymphoma (n = 51) or Hodgkin's disease (n = 11) were treated. All patients received 6 days of randomly assigned cytokine. Those with cellular marrow in morphologic remission underwent BMSC harvest, while those with hypocellular marrow or microscopic marrow tumor involvement had PBSC collected. Neutrophil recovery was similarly rapid in all groups (median 14 days; range 10-23 days), though two patients had delayed neutrophil recovery using GM-CSF primed PBSC (p = 0.01). Red cell and platelet recovery were significantly quicker after BMSC mobilized with GM-CSF or PBSC mobilized with G-CSF. This speedier hematologic recovery resulted in earlier hospital discharge as well. However, in multivariate analysis, neither the stem cell source nor randomly assigned G-CSF vs. GM-CSF was independently associated with earlier multilineage hematologic recovery or shorter hospital stay. Relapse-free survival was not independently affected by either the assigned stem cell source or the randomly assigned priming cytokine, though malignant relapse was more frequent in those assigned to PBSC (RR of relapse 3.15, p = 0.03). These data document that BMSC, when collected following cytokine priming, can yield a similarly rapid hematologic

Mesenchymal stem cell and derived exosome as small RNA carrier and Immunomodulator to improve islet transplantation.

Science.gov (United States)

Wen, Di; Peng, Yang; Liu, Di; Weizmann, Yossi; Mahato, Ram I

2016-09-28

Human bone marrow mesenchymal stem cells (hBMSCs) and their exosomes can suppress immune reaction and deliver small RNAs. Thus, they may improve islet transplantation by delivering small RNAs for promoting islet function and inhibiting immune rejection. Here, we proposed an hBMSC and its exosome-based therapy to overcome immune rejection and poor islet function, both of which hinder the success of islet transplantation. We found overexpressed siFas and anti-miR-375 in plasmid encoding shFas and anti-miR-375 transfected hBMSC-derived exosomes, which silenced Fas and miR-375 of human islets and improved their viability and function against inflammatory cytokines. This plasmid transfected hBMSCs downregulated Fas and miR-375 of human islets in a humanized NOD scid gamma (NSG) mouse model, whose immune reaction was inhibited by injecting hBMSC and peripheral blood mononuclear cell (PBMC) co-cultured exosomes. These exosomes suppressed immune reaction by inhibiting PBMC proliferation and enhancing regulatory T cell (Treg) function. Collectively, our studies elucidated the mechanisms of RNA delivery from hBMSCs to human islets and the immunosuppressive effect of hBMSC and peripheral blood mononuclear cell co-cultured exosomes for improving islet transplantation. Copyright © 2016 Elsevier B.V. All rights reserved.

Trophic effects of adipose-tissue-derived and bone-marrow-derived mesenchymal stem cells enhance cartilage generation by chondrocytes in co-culture.

Science.gov (United States)

Pleumeekers, M M; Nimeskern, L; Koevoet, J L M; Karperien, M; Stok, K S; van Osch, G J V M

2018-01-01

Combining mesenchymal stem cells (MSCs) and chondrocytes has great potential for cell-based cartilage repair. However, there is much debate regarding the mechanisms behind this concept. We aimed to clarify the mechanisms that lead to chondrogenesis (chondrocyte driven MSC-differentiation versus MSC driven chondroinduction) and whether their effect was dependent on MSC-origin. Therefore, chondrogenesis of human adipose-tissue-derived MSCs (hAMSCs) and bone-marrow-derived MSCs (hBMSCs) combined with bovine articular chondrocytes (bACs) was compared. hAMSCs or hBMSCs were combined with bACs in alginate and cultured in vitro or implanted subcutaneously in mice. Cartilage formation was evaluated with biochemical, histological and biomechanical analyses. To further investigate the interactions between bACs and hMSCs, (1) co-culture, (2) pellet, (3) Transwell® and (4) conditioned media studies were conducted. The presence of hMSCs-either hAMSCs or hBMSCs-increased chondrogenesis in culture; deposition of GAG was most evidently enhanced in hBMSC/bACs. This effect was similar when hMSCs and bAC were combined in pellet culture, in alginate culture or when conditioned media of hMSCs were used on bAC. Species-specific gene-expression analyses demonstrated that aggrecan was expressed by bACs only, indicating a predominantly trophic role for hMSCs. Collagen-10-gene expression of bACs was not affected by hBMSCs, but slightly enhanced by hAMSCs. After in-vivo implantation, hAMSC/bACs and hBMSC/bACs had similar cartilage matrix production, both appeared stable and did not calcify. This study demonstrates that replacing 80% of bACs by either hAMSCs or hBMSCs does not influence cartilage matrix production or stability. The remaining chondrocytes produce more matrix due to trophic factors produced by hMSCs.

Sr-doped nanowire modification of Ca-Si-based coatings for improved osteogenic activities and reduced inflammatory reactions

Science.gov (United States)

Li, Kai; Hu, Dandan; Xie, Youtao; Huang, Liping; Zheng, Xuebin

2018-02-01

Biomedical coatings for orthopedic implants should facilitate osseointegration and mitigate implant-induced inflammatory reactions. In our study, Ca-Si coatings with Sr-containing nanowire-like structures (NW-Sr-CS) were achieved via hydrothermal treatment. In order to identify the effect of nanowire-like topography and Sr dopant on the biological properties of Ca-Si-based coatings, the original Ca-Si coating, Ca-Si coatings modified with nanoplate (NP-CS) and similar nanowire-like structure (NW-CS) were fabricated as the control. Surface morphology, phase composition, surface area, zeta potential and ion release of these coatings were characterized. The in vitro osteogenic activities and immunomodulatory properties were evaluated with bone marrow stromal cells (BMSCs) and RAW 264.7 cells, a mouse macrophage cell line. Compared with the CS and NP-CS coatings, the NW-CS coating possessed a larger surface area and pore volume, beneficial protein adsorption, up-regulated the expression levels of integrin β1, Vinculin and focal adhesion kinase and promoted cell spreading. Furthermore, the NW-CS coating significantly enhanced the osteogenic differentiation and mineralization as indicated by the up-regulation of ALP activity, mineralized nodule formation and osteoblastogenesis-related gene expression. With the introduction of Sr, the NW-Sr-CS coatings exerted a greater effect on the BMSC proliferation rate, calcium sensitive receptor gene expression as well as PKC and ERK1/2 phosphorylation. In addition, the Sr-doped coatings significantly up-regulated the ratio of OPG/RANKL in the BMSCs. The NW-Sr-CS coatings could modulate the polarization of macrophages towards the wound-healing M2 phenotype, reduce the mRNA expression levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and enhance anti-inflammatory cytokines (IL-1ra, IL-10). The Sr-doped nanowire modification may be a valuable approach to enhance osteogenic activities and reduce inflammatory reactions.

Influence of postoperative low-level laser therapy on the osseointegration of self-tapping implants in the posterior maxilla: A 6-week split-mouth clinical study

OpenAIRE

Mandić Borka; Lazić Zoran; Marković Aleksa; Mandić Bojan; Mandić Miška; Đinić Ana; Miličić Biljana

2015-01-01

Background/Aim. Low-level laser therapy (LLLT) has been proven to stimulate bone repair, affecting cellular proliferation, differentiation and adhesion, and has shown a potential to reduce the healing time following implant placement. The aim of this clinical study was to investigate the influence of postoperative LLLT osseointegration and early success of self-tapping implants placed into low-density bone. Methods. Following the split-mouth design, self-ta...

In vivo evaluation of biofunctionalized implant surfaces with a synthetic peptide (P-15) and its impact on osseointegration. A preclinical animal study.

Science.gov (United States)

Schmitt, Christian M; Koepple, Markus; Moest, Tobias; Neumann, Konrad; Weisel, Tamara; Schlegel, Karl Andreas

2016-11-01

The overall aim of the study was to investigate a biofunctionalized implant surface with electrochemically deposition of hydroxyapatite and the synthetic peptide (P-15) and its effect on osseointegration. Three modified implant types of ANKYLOS ® C/X implants were used; (1) machined implants used as negative control (M, n = 20), (2) implants with the FRIADENT ® plus surface (grit blasted and acid-etched) used as positive control (P, n = 20), and (3) implants with a biomimetic surface consisting of hydroxyapatite and the synthetic 15 aminoacids containing peptide P-15 (BP, n = 40). The implants were randomly inserted in the mandibles of 10 beagle dogs following 4 months after tooth extraction (P1-P4). Three animals were sacrificed 2 and 7 days after implant insertion, respectively, and four animals were sacrificed 6 months post implant insertion. Bone-to-implant contacts (BICs) were analyzed via histomorphometrical analyses at five different region of interests (ROIs); two at the middle part on either side of the implant (ROI 1/4), two at the apical part of the implant at each side (ROI 2/3), and one at the tip of the implant (ROI 5). All implant surfaces showed a high level of osseointegration and osteoconductivity. The cumulative implant survival rate (CSR) was 93.8%, 100% in the M, 85% in the P, and 95% in the BP group. No statistical difference in BICs at ROI 1/4, 2/3, and 5 could be shown between implant types following 2 and 7 days of healing. BIC values increased in all groups over time. After 6 months of healing the BP group showed superiority in BIC in ROI 2/3 (73.2 ± 15.6%) compared to the P (48.3 ± 10.6%) and M group (66.3 ± 30.2%) with a significant difference between BP and P (P = 0.002). It is hypothesized, that the surface biofunctionalization improves peri-implant bone formation and remodeling, leading to an increased bone-to implant contact. However, within the limitations of the study set-up no benefit in the early phase of

Harnessing Nanotopography to Enhance Osseointegration of Clinical Orthopedic Titanium Implants—An in Vitro and in Vivo Analysis

Directory of Open Access Journals (Sweden)

Vitali Goriainov

2018-04-01

Full Text Available Despite technological advancements, further innovations in the field of orthopedics and bone regeneration are essential to meet the rising demands of an increasing aging population and associated issues of disease, injury and trauma. Nanotopography provides new opportunities for novel implant surface modifications and promises to deliver further improvements in implant performance. However, the technical complexities of nanotopography fabrication and surface analysis have precluded identification of the optimal surface features to trigger osteogenesis. We herein detail the osteoinductive potential of discrete nanodot and nanowire nanotopographies. We have examined the ability of modified titanium and titanium alloy (Ti64 surfaces to induce bone-specific gene activation and extracellular matrix protein expression in human skeletal stem cells (SSCs in vitro, and de novo osteogenic response within a murine calvarial model in vivo. This study provides evidence of enhanced osteogenic response to nanowires 300 surface modifications, with important implications for clinical orthopedic application.

Computer-assisted navigational surgery enhances safety in dental implantology.

Science.gov (United States)

Ng, F C; Ho, K H; Wexler, A

2005-06-01

Dental implants are increasingly used to restore missing dentition. These titanium implants are surgically installed in the edentulous alveolar ridge and allowed to osteointegrate with the bone during the healing phase. After osseo-integration, the implant is loaded with a prosthesis to replace the missing tooth. Conventional implant treatment planning uses study models, wax-ups and panoramic x-rays to prefabricate surgical stent to guide the preparation of the implant site. The drilling into the alveolar ridge is invariably a "blind" procedure as the part of the drill in bone is not visible. Stereotactic systems were first introduced into neurosurgery in 1986. Since then, computer-assisted navigational technology has brought major advances to neuro-, midface and orthopaedic surgeries, and more recently, to implant placement. This paper illustrates the use of real-time computer-guided navigational technology in enhancing safety in implant surgical procedures. Real-time computer-guided navigational technology enhances accuracy and precision of the surgical procedure, minimises complications and facilitates surgery in challenging anatomical locations.

Osseointegration properties of titanium dental implants modified with a nanostructured coating based on ordered porous silica and bioactive glass nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Covarrubias, Cristian, E-mail: ccovarrubias@odontologia.uchile.cl [Laboratory of Nanobiomaterials, Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Santiago (Chile); Mattmann, Matías [Laboratory of Nanobiomaterials, Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Santiago (Chile); Von Marttens, Alfredo [Department of Prosthesis, Faculty of Dentistry, University of Chile, Santiago (Chile); Caviedes, Pablo; Arriagada, Cristián [Laboratory of Cell Therapy, ICBM, Faculty of Medicine, University of Chile (Chile); Valenzuela, Francisco [Laboratory of Nanobiomaterials, Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Santiago (Chile); Rodríguez, Juan Pablo [Laboratory of Cell Biology, INTA, University of Chile, Santiago (Chile); Corral, Camila [Department of Restorative Dentistry, Faculty of Dentistry, University of Chile, Santiago (Chile)

2016-02-15

Graphical abstract: - Highlights: • The fabrication of a coating for osseointegration of titanium implant is presented. • The coating consists of nanoporous silica loaded with bioactive glass nanoparticles. • Coating accelerates the in vitro formation of apatite in simulated body fluid. • Coating promotes the osteogenic differentiation of stem cells. • Coating accelerates the formation of bone tissue in the periphery of the implant. - Abstract: The fabrication of a nanoporous silica coating loaded with bioactive glass nanoparticles (nBG/NSC) on titanium dental implant surface and its in vitro and in vivo evaluation is presented. The coating was produced by a combined sol–gel and evaporation induced self-assembly process. In vitro bioactivity was assessed in simulated body fluid (SBF) and investigating the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). A rat tibial model was employed to analyze the bone response to nBG/NSC-modified titanium implant surface in vivo. The nBG/NSC coating was confirmed at nano level to be constituted by a highly ordered nanoporous silica structure. The coating nanotopography in conjunction with the bioactivity of the BG particles accelerate the in vitro apatite formation and promote the osteogenic differentiation of hBMSCs in absence of osteogenic supplements. These properties accelerate the formation of bone tissue in the periphery of the implant after 3 weeks of implantation. Backscattered scanning electron microscopy images revealed the presence of gaps and soft tissue in the unmodified implant after 6 weeks, whereas the nBG/NSC-modified implant showed mature bone in intimate contact with the implant surface. The nBG/NSC coating appears promising for accelerating the osseointegration of dental implants.

Osseointegration properties of titanium dental implants modified with a nanostructured coating based on ordered porous silica and bioactive glass nanoparticles

International Nuclear Information System (INIS)

Covarrubias, Cristian; Mattmann, Matías; Von Marttens, Alfredo; Caviedes, Pablo; Arriagada, Cristián; Valenzuela, Francisco; Rodríguez, Juan Pablo; Corral, Camila

2016-01-01

Graphical abstract: - Highlights: • The fabrication of a coating for osseointegration of titanium implant is presented. • The coating consists of nanoporous silica loaded with bioactive glass nanoparticles. • Coating accelerates the in vitro formation of apatite in simulated body fluid. • Coating promotes the osteogenic differentiation of stem cells. • Coating accelerates the formation of bone tissue in the periphery of the implant. - Abstract: The fabrication of a nanoporous silica coating loaded with bioactive glass nanoparticles (nBG/NSC) on titanium dental implant surface and its in vitro and in vivo evaluation is presented. The coating was produced by a combined sol–gel and evaporation induced self-assembly process. In vitro bioactivity was assessed in simulated body fluid (SBF) and investigating the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). A rat tibial model was employed to analyze the bone response to nBG/NSC-modified titanium implant surface in vivo. The nBG/NSC coating was confirmed at nano level to be constituted by a highly ordered nanoporous silica structure. The coating nanotopography in conjunction with the bioactivity of the BG particles accelerate the in vitro apatite formation and promote the osteogenic differentiation of hBMSCs in absence of osteogenic supplements. These properties accelerate the formation of bone tissue in the periphery of the implant after 3 weeks of implantation. Backscattered scanning electron microscopy images revealed the presence of gaps and soft tissue in the unmodified implant after 6 weeks, whereas the nBG/NSC-modified implant showed mature bone in intimate contact with the implant surface. The nBG/NSC coating appears promising for accelerating the osseointegration of dental implants.

Influence of two barrier membranes on staged guided bone regeneration and osseointegration of titanium implants in dogs. Part 2: augmentation using bone graft substitutes.

Science.gov (United States)

Mihatovic, Ilja; Becker, Jürgen; Golubovic, Vladimir; Hegewald, Andrea; Schwarz, Frank

2012-03-01

To assess the influence of two barrier membranes and two bone graft substitutes on staged guided bone regeneration and osseointegration of titanium implants in dogs. Saddle-type defects were prepared in the lower jaws of 6 fox hounds and randomly filled with a natural bone mineral (NBM) and a biphasic calcium phosphate (SBC) and allocated to either an in situ gelling polyethylene glycol (PEG) or a collagen membrane (CM). At 8 weeks, modSLA titanium implants were inserted and left to heal in a submerged position. At 8+2 weeks, respectively, dissected blocks were processed for histomorphometrical analysis (e.g., mineralized tissue [MT], bone-to-implant contact [BIC]). The mean MT values (mm2) and BIC values (%) tended to be higher in the PEG groups (MT: NBM [3.4±1.7]; SBC [4.2±2]/BIC: NBM [67.7±16.9]; SBC [66.9±17.8]) when compared with the corresponding CM groups (MT: NBM [2.5±0.8]; SBC [2.3±1.6]/BIC: NBM [54.1±22.6]; SBC [61±8.7]). These differences, however, did not reach statistical significance. It was concluded that all augmentation procedures investigated supported bone regeneration and staged osseointegration of modSLA titanium implants. © 2011 John Wiley & Sons A/S.

The Experimental Study Of Effects Of Irradiation On Osseointegration

Energy Technology Data Exchange (ETDEWEB)

Park, Kwan Soo; Lee, Sang Rae; Hwang, Eui Hwan [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Kyunghee University, Seoul (Korea, Republic of)

1999-02-15

The purpose of this study was to investigate the effects of the Co-60 gamma irradiation on the osseointegration. 2.0 mm titanium alloy screw implants were placed in the tibial metaphysics of the rabbits, bilaterally. The mean length of the implants was 6.0 mm. The right tibia was irradiated with a single dose of 15 Gy from 6{sup 0C}o teletherapic machine at 5th postoperative day. The experimental group was irradiated tibia. The control group was non-irradiated tibia. To observe the phase of bone formation, the bone labeling by intramuscular injection of 20 mg/Kg of Tetracycline, Calcein, Alizarin red S, was performed. The rabbits were sacrificed on the 1st, 2nd, 4th, 6th, 8th week and the tibia including implants were taken, and then the specimens were examined by the microradiography, light microscopy, and fluorescent microscopy.The obtained results were as follows; 1. There were connective tissue between bone and titanium at 1st week, in both group. Especially, the many empty lacunae without nucleus and obscure cytoplasm in experimental group, were observed. 2. The osteons were observed at 4th week in control group, and at 6th week in experimental group. The bone formation in experimental group was retarded as compared to the control group. 3. In fluorescent microscopy, bone labelling band was observed as linear, arc or concentric shape. Occasionary interrupted labelling band was observed, which is demonstrated bone remodeling. 4. In microradiographic examination, the radiolucent image was found between bone and implant with widening of bone marrow spaces as compared to the control group.

Bone Marrow-Derived Mesenchymal Stromal Cells Enhanced by Platelet-Rich Plasma Maintain Adhesion to Scaffolds in Arthroscopic Simulation.

Science.gov (United States)

Hoberman, Alexander R; Cirino, Carl; McCarthy, Mary Beth; Cote, Mark P; Pauzenberger, Leo; Beitzel, Knut; Mazzocca, Augustus D; Dyrna, Felix

2018-03-01

To assess the response of bone marrow-derived mesenchymal stromal cells (bMSCs) enhanced by platelet-rich plasma (PRP) in the setting of a normal human tendon (NHT), a demineralized bone matrix (DBM), and a fibrin scaffold (FS) with simulated arthroscopic mechanical washout stress. Bone marrow was aspirated from the humeral head and concentrated. BMSCs were counted, plated, and grown to confluence. Cells were seeded onto 3 different scaffolds: (1) NHT, (2) DBM, and (3) FS. Each scaffold was treated with a combination of (+)/(-) PRP and (+)/(-) arthroscopic washout simulation. A period of 60 minutes was allotted before arthroscopic washout. Adhesion, proliferation, and differentiation assays were performed to assess cellular activity in each condition. Significant differences were seen in mesenchymal stromal cell adhesion, proliferation, and differentiation among the scaffolds. DBM and FS showed superior results to NHT for cell adhesion, proliferation, and differentiation. PRP significantly enhanced cellular adhesion, proliferation, and differentiation. Arthroscopic simulation did not significantly decrease bMSC adhesion. We found that the type of scaffold impacts bMSCs' behavior. Both scaffolds (DBM and FS) were superior to NHT. The use of an arthroscopic simulator did not significantly decrease the adhesion of bMSCs to the scaffolds nor did it decrease their biologic differentiation potential. In addition, PRP enhanced cellular adhesion, proliferation, and differentiation. Improved healing after tendon repair can lead to better clinical outcomes. BMSCs are attractive for enhancing healing given their accessibility and regenerative potential. Application of bMSCs using scaffolds as cell carriers relies on arthroscopic feasibility. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

A multifunctional bioactive material that stimulates osteogenesis and promotes the vascularization bone marrow stem cells and their resistance to bacterial infection.

Directory of Open Access Journals (Sweden)

Chuang Ma

Full Text Available The main limitation of tissue engineering lies in the inability to stimulate osteogenesis, angiogenesis of stem cells and broad-spectrum antimicrobial activity. However, the development of multifunctional bioactive materials with these capabilities remains a great challenge. In this study, we prepared mesoporous silica nanoparticles encapsulated with silver nanocrystals (AG-MSN with uniform sphere size and mesopores. Platelet-derived growth factor BB (PDGF-BB was effectively loaded in the AG-MSN mesopores (P-AG-MSN. The silicon ions (Si released by P-AG-MSN stimulate osteogenic differentiation of bone marrow stromal cells (BMSC by activating the alkaline phosphatase (ALP activity of bone-related genes and increasing protein (OCN, RUNX2 and OPN expression. Ag+ ions could be slowly released from the interior of the shell, highlighting their durable antibacterial activity. The sustained release of PDGF-BB from P-AG-MSN stimulated the angiogenic differentiation of BMSC, as indicated by the enhanced secretion of vascular endothelial growth factor (VEGF, HIF-1α, HGF and ANG-1 and protein expression. Our results show that P-AG-MSN can clearly promote BMSC osteostimulation and vascularization. This research serves as a preliminary study of the utilization of this multifunctional mixture to fabricate a new active biological scaffold that integrates BMSC osteostimulation, vascularization and bactericidal effects by 3D printing technology.

Skeletal stem cell and bone implant interactions are enhanced by LASER titanium modification

Energy Technology Data Exchange (ETDEWEB)

Sisti, Karin E., E-mail: karinellensisti@gmail.com [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom); Biomaterials Group, Institute of Chemistry, São Paulo State University (UNESP), Box 355, Araraquara (Brazil); Federal University of Mato Grosso do Sul (UFMS), Campo Grande (Brazil); Andrés, María C. de; Johnston, David [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom); Almeida-Filho, Edson; Guastaldi, Antonio C. [Biomaterials Group, Institute of Chemistry, São Paulo State University (UNESP), Box 355, Araraquara (Brazil); Oreffo, Richard O.C. [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom)

2016-05-06

morphology and cytoskeleton structure were affected. The current studies show Ti LASER modification can enhance the osseointegration between Ti and skeletal cells, with important implications for orthopaedic application. - Highlights: • Bone stem cells on LASER Ti surface display enhanced cell growth and viability. • Bone stem cells on LASER Ti surface exhibit marked biocompatibility. • Human bone stem cells on LASER Ti surface exhibit altered morphology. • LASER Ti enhance osteogenic differentiation of human bone skeletal stem cells. • LASER Ti provides a unique approach to enhance osseointegration with the material.

Substance P Promotes the Proliferation, but Inhibits Differentiation and Mineralization of Osteoblasts from Rats with Spinal Cord Injury via RANKL/OPG System.

Directory of Open Access Journals (Sweden)

Hai-Juan Liu

Full Text Available Spinal cord injury (SCI causes a significant amount of bone loss, which results in osteoporosis (OP. The neuropeptide substance P (SP and SP receptors may play important roles in the pathogenesis of OP after SCI. To identify the roles of SP in the bone marrow mesenchymal stem cell derived osteoblasts (BMSC-OB in SCI rats, we investigated the expression of neurokinin-1 receptors (NK1R in BMSC-OB and the effects of SP on bone formation by development of BMSC-OB cultures. Sixty young male Sprague-Dawley rats were randomized into two groups: SHAM and SCI. The expression of NK1R protein in BMSC-OB was observed using immunohistochemistry and Western blot analysis. The dose- and time-dependent effects of SP on the proliferation, differentiation and mineralization of BMSC-OB and the expression of osteoblastic markers by in vitro experiments. The expression of NK1R in BMSC-OB was observed on plasma membranes and in cytoplasm. One week after osteogenic differentiation, the expression of NK1R was significantly increased after SCI at mRNA and protein levels. However, this difference was gradually attenuated at 2 or 3 weeks later. SP have the function to enhance cell proliferation, inhibite cell differentiation and mineralization at a proper concentration and incubation time, and this effect would be inhibited by adding SP or NK1R antagonist. The expression of RANKL/OPG was significantly increased in tibiae after SCI. Similarly, the RANKL/OPG expression in SCI rats was significantly increased when treating with 10-8 M SP. SP plays a very important role in the pathogenesis of OP after SCI. The direct effect of SP may lead to increased bone resorption through the RANKL/OPG axis after SCI. In addition, high expression of SP also results in the suppression of osteogenesis in SCI rats. Then, the balance between bone resorption and bone formation was broken and finally osteoporosis occurred.

Therapeutic effects of radix dipsaci, pyrola herb, and cynomorium songaricum on bone metabolism of ovariectomized rats

Directory of Open Access Journals (Sweden)

Liu Meijie

2012-05-01

Full Text Available Abstract Background The objective of this study was to evaluate the effects of herbal medicines, such as Radix Dipsaci (RDD, Pyrola Herb (PHD, and Cynomorium songaricum decoction (CSD, on osteoporotic rats induced by ovariectomy (OVX. Methods OVX or sham operations were performed on 69 virgin Wistar rats that were divided into six groups: sham (sham, n = 12, OVX control group (OVX, n = 12, and OVX rats with treatments (diethylstilbestrol, E2, n = 12; RDD, n = 11, PHD, n = 11, and CSD, n = 11. Non-surgical rats served as normal control (NC, n = 12. The treatments began four weeks after surgery and lasted for 12 weeks. Bone mass and bone turnover were analyzed by histomorphometry. Levels of protein expression and mRNA of OPG and RANKL in osteoblasts (OB and bone marrow stromal cells (bMSC were evaluated by immunohistochemistry and in situ hybridization. Results Compared to NC and sham rats, trabecular bone formation was significantly reduced in OVX rats, but restored in E2-treated rats. Treatment with either RDD or PHD enhanced trabecular bone formation remarkably. No significant change of bone formation was observed in CSD-treated rats. OPG expression of protein and mRNA was reduced significantly in OB and bMSC of OVX control rats. RANKL expression of protein and mRNA was increased significantly in OB and bMSC of OVX control rats. These effects were substantially reversed (increased in OPG and decreased in RANKL by treatment with E2, RDD, or PHD in OB and bMSC of OVX rats. No significant changes in either OPG or RANKL expression were observed in OB and bMSC of OVX rats treated with CSD. Conclusions Our study showed that RDD and PHD increased bone formation by stimulating overexpression of OPG and downregulation of RANKL in OB and bMSC. This suggests that RDD and PHD may be used as alternative therapeutic agents for postmenopausal osteoporosis.

[Alternation of proteins in brain of Parkinson's disease model rats after the transplantation of TH-NTN gene modified bone marrow mesenchymal stem cells].

Science.gov (United States)

Huang, Yue; Chang, Cheng; Zhang, Jie-wen; Gao, Xiao-qun

2012-09-04

To explore the effects of tyrosine hydroxylase-neurturin (TH-NTN) gene modified bone marrow mesenchymal stem cell (BMSC) transplantation in Parkinson's disease (PD) model rats and the alternations of correlated proteins. The PD rat model was established by the 2-point injection of 6-hydroxydopamine (6-OHDA) into unilateral (right) striatum. Successful modeling rats were separated into PD, BMSC and TH-NTN-BMSC groups. BMSC and TH-NTN-BMSC groups were transplanted into BMSCs and TH-NTN gene modified BMSC cells separately into right striatum. After transplantation, ethology detection in all groups was made with an intraperitoneal injection of apomorphine (APO). Dopamine (DA) and Dihydroxyphenylacetic Acid (DOPAC) in striatum were detected by high performance liquid electrochemical analysis. TH and NTN proteins in right striatum were also analyzed by immunohistochemistry and Western blot. Finally the density of dopamine receptors in post synaptic density of dopaminergic synapses of corpus striatum were compared between each group by post-embedding immunogold electron microscopy. After an injection of APO, rotation frequency decreased in TH-NTN-BMSC group, i.e. (5.7 ± 1.3) circles/min versus (10.8 ± 2.2), (9.9 ± 1.2) circles/min in PD and BMSC groups (P TH-NTN-BMSC group versus (923 ± 132)/µm(2) in PD and (860 ± 116)/µm(2) in BMSC groups was also found. The combined therapy of TH and NTN genes increases the synthesis of DA and also protects the dopaminergic neurons to achieve double therapeutic effects. It may provide potential innovations of PD genetic therapy.

Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN-induced migration of bone marrow-derived mesenchymal stem cells.

Science.gov (United States)

Liu, Lingling; Luo, Qing; Sun, Jinghui; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

2018-03-01

Osteopontin (OPN) is a chemokine-like extracellular matrix-associated protein involved in the migration of bone marrow-derived mesenchymal stem cells (BMSCs). An increasing number of studies have found that chromatin organization may affect cellular migration. However, whether OPN regulates chromatin organization is not understood, nor are the underlying molecular mechanisms. In this study, we investigated the link between chromatin organization and BMSC migration and demonstrated that OPN-mediated BMSC migration leads to elevated levels of heterochromatin marker histone H3 lysine 27 trimethylation (H3K27me3) through the methyltransferase EZH2. The expression of EZH2 reorganizes the chromatin structure of BMSCs. Pharmacological inhibition or depletion of EZH2 blocks BMSC migration. Moreover, using an atomic force microscope (AFM), we found that chromatin decondensation alters the mechanical properties of the nucleus. In addition, inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) signals represses OPN-promoted chromatin condensation and cell migration. Thus, our results identify a mechanism by which ERK1/2 signalling drives specific chromatin modifications in BMSCs, which alters chromatin organization and thereby enables OPN-mediated BMSC migration. Copyright © 2018 Elsevier Ltd. All rights reserved.

Laminin-521 Promotes Rat Bone Marrow Mesenchymal Stem Cell Sheet Formation on Light-Induced Cell Sheet Technology

Directory of Open Access Journals (Sweden)

Zhiwei Jiang

2017-01-01

Full Text Available Rat bone marrow mesenchymal stem cell sheets (rBMSC sheets are attractive for cell-based tissue engineering. However, methods of culturing rBMSC sheets are critically limited. In order to obtain intact rBMSC sheets, a light-induced cell sheet method was used in this study. TiO2 nanodot films were coated with (TL or without (TN laminin-521. We investigated the effects of laminin-521 on rBMSCs during cell sheet culturing. The fabricated rBMSC sheets were subsequently assessed to study cell sheet viability, reattachment ability, cell sheet thickness, collagen type I deposition, and multilineage potential. The results showed that laminin-521 could promote the formation of rBMSC sheets with good viability under hyperconfluent conditions. Cell sheet thickness increased from an initial 26.7 ± 1.5 μm (day 5 up to 47.7 ± 3.0 μm (day 10. Moreover, rBMSC sheets maintained their potential of osteogenic, adipogenic, and chondrogenic differentiation. This study provides a new strategy to obtain rBMSC sheets using light-induced cell sheet technology.

Effects of autologous bone marrow stem cell transplantation on beta-adrenoceptor density and electrical activation pattern in a rabbit model of non-ischemic heart failure

Directory of Open Access Journals (Sweden)

Ullmann Cris

2006-06-01

Full Text Available Abstract Background Since only little is known on stem cell therapy in non-ischemic heart failure we wanted to know whether a long-term improvement of cardiac function in non-ischemic heart failure can be achieved by stem cell transplantation. Methods White male New Zealand rabbits were treated with doxorubicine (3 mg/kg/week; 6 weeks to induce dilative non-ischemic cardiomyopathy. Thereafter, we obtained autologous bone marrow stem cells (BMSC and injected 1.5–2.0 Mio cells in 1 ml medium by infiltrating the myocardium via a left anterolateral thoracotomy in comparison to sham-operated rabbits. 4 weeks later intracardiac contractility was determined in-vivo using a Millar catheter. Thereafter, the heart was excised and processed for radioligand binding assays to detect β1- and β2-adrenoceptor density. In addition, catecholamine plasma levels were determined via HPLC. In a subgroup we investigated cardiac electrophysiology by use of 256 channel mapping. Results In doxorubicine-treated animals β-adrenoceptor density was significantly down-regulated in left ventricle and septum, but not in right ventricle, thereby indicating a typical left ventricular heart failure. Sham-operated rabbits exhibited the same down-regulation. In contrast, BMSC transplantation led to significantly less β-adrenoceptor down-regulation in septum and left ventricle. Cardiac contractility was significantly decreased in heart failure and sham-operated rabbits, but was significantly higher in BMSC-transplanted hearts. Norepinephrine and epinephrine plasma levels were enhanced in heart failure and sham-operated animals, while these were not different from normal in BMSC-transplanted animals. Electrophysiological mapping revealed unaltered electrophysiology and did not show signs of arrhythmogeneity. Conclusion BMSC transplantation improves sympathoadrenal dysregualtion in non-ischemic heart failure.

Knockdown of SVCT2 impairs in-vitro cell attachment, migration and wound healing in bone marrow stromal cells

Directory of Open Access Journals (Sweden)

Rajnikumar Sangani

2014-03-01

Full Text Available Bone marrow stromal cell (BMSC adhesion and migration are fundamental to a number of pathophysiologic processes, including fracture and wound healing. Vitamin C is beneficial for bone formation, fracture repair and wound healing. However, the role of the vitamin C transporter in BMSC adhesion, migration and wound healing is not known. In this study, we knocked-down the sodium-dependent vitamin C transporter, SVCT2, the only known transporter of vitamin C in BMSCs, and performed cell adhesion, migration, in-vitro scratch wound healing and F-actin re-arrangement studies. We also investigated the role of oxidative stress on the above processes. Our results demonstrate that both oxidative stress and down-regulation of SVCT2 decreased cell attachment and spreading. A trans-well cell migration assay showed that vitamin C helped in BMSC migration and that knockdown of SVCT2 decreased cell migration. In the in-vitro scratch wound healing studies, we established that oxidative stress dose-dependently impairs wound healing. Furthermore, the supplementation of vitamin C significantly rescued the BMSCs from oxidative stress and increased wound closing. The knockdown of SVCT2 in BMSCs strikingly decreased wound healing, and supplementing with vitamin C failed to rescue cells efficiently. The knockdown of SVCT2 and induction of oxidative stress in cells produced an alteration in cytoskeletal dynamics. Signaling studies showed that oxidative stress phosphorylated members of the MAP kinase family (p38 and that vitamin C inhibited their phosphorylation. Taken together, these results indicate that both the SVCT2 transporter and oxidative stress play a vital role in BMSC attachment, migration and cytoskeletal re-arrangement. BMSC-based cell therapy and modulation of SVCT2 could lead to a novel therapeutic approach that enhances bone remodeling, fracture repair and wound healing in chronic disease conditions.

Laser-Sintered Constructs with Bio-inspired Porosity and Surface Micro/Nano-Roughness Enhance Mesenchymal Stem Cell Differentiation and Matrix Mineralization In Vitro.

Science.gov (United States)

Cheng, Alice; Cohen, David J; Boyan, Barbara D; Schwartz, Zvi

2016-12-01

Direct metal laser sintering can produce porous Ti-6Al-4V orthopedic and dental implants. The process requires reduced resources and time and can provide greater structural control than machine manufacturing. Implants in bone are colonized by mesenchymal stem cells (MSCs), which can differentiate into osteoblasts and contribute to osseointegration. This study examined osteoblast differentiation and matrix mineralization of human MSCs cultured on laser-sintered Ti-6Al-4V constructs with varying porosity and at different time scales. 2D solid disks and low, medium and high porosity (LP, MP, and HP) 3D constructs based on a human trabecular bone template were laser sintered from Ti-6Al-4V powder and further processed to have micro- and nanoscale roughness. hMSCs exhibited greater osteoblastic differentiation and local factor production on all 3D porous constructs compared to 2D surfaces, which was sustained for 9 days without use of exogenous factors. hMSCs cultured for 8 weeks on MP constructs in osteogenic medium (OM), OM supplemented with BMP2 or collagen-coated MP constructs in OM exhibited bone-like extracellular matrix mineralization. Use of bio-inspired porosity for the 3D architecture of additively manufactured Ti-6Al-4V enhanced osteogenic differentiation of hMSCs beyond surface roughness alone. This study suggests that a 3D architecture may enhance the osseointegration of orthopedic and dental implants in vivo.

Cytoskeletal Configuration Modulates Mechanically Induced Changes in Mesenchymal Stem Cell Osteogenesis, Morphology, and Stiffness

Science.gov (United States)

Pongkitwitoon, Suphannee; Uzer, Gunes; Rubin, Janet; Judex, Stefan

2016-10-01

Mesenchymal stem cells (MSC) responding to mechanical cues generated by physical activity is critical for skeletal development and remodeling. Here, we utilized low intensity vibrations (LIV) as a physiologically relevant mechanical signal and hypothesized that the confined cytoskeletal configuration imposed by 2D culture will enable human bone marrow MSCs (hBMSC) to respond more robustly when LIV is applied in-plane (horizontal-LIV) rather than out-of-plane (vertical-LIV). All LIV signals enhanced hBMSC proliferation, osteogenic differentiation, and upregulated genes associated with cytoskeletal structure. The cellular response was more pronounced at higher frequencies (100 Hz vs 30 Hz) and when applied in the horizontal plane. Horizontal but not vertical LIV realigned the cell cytoskeleton, culminating in increased cell stiffness. Our results show that applying very small oscillatory motions within the primary cell attachment plane, rather than perpendicular to it, amplifies the cell’s response to LIV, ostensibly facilitating a more effective transfer of intracellular forces. Transcriptional and structural changes in particular with horizontal LIV, together with the strong frequency dependency of the signal, emphasize the importance of intracellular cytoskeletal configuration in sensing and responding to high-frequency mechanical signals at low intensities.

Engineered Protein Coatings to Improve the Osseointegration of Dental and Orthopaedic Implants

Science.gov (United States)

Raphel, Jordan; Karlsson, Johan; Galli, Silvia; Wennerberg, Ann; Lindsay, Christopher; Haugh, Matthew; Pajarinen, Jukka; Goodman, Stuart B.; Jimbo, Ryo; Andersson, Martin; Heilshorn, Sarah C.

2016-01-01

Here we present the design of an engineered, elastin-like protein (ELP) that is chemically modified to enable stable coatings on the surfaces of titanium-based dental and orthopaedic implants by novel photocrosslinking and solution processing steps. The ELP includes an extended RGD sequence to confer bio-signaling and an elastin-like sequence for mechanical stability. ELP thin films were fabricated on cp-Ti and Ti6Al4V surfaces using scalable spin and dip coating processes with photoactive covalent crosslinking through a carbene insertion mechanism. The coatings withstood procedures mimicking dental screw and hip replacement stem implantations, a key metric for clinical translation. They promoted rapid adhesion of MG63 osteoblast-like cells, with over 80% adhesion after 24 hours, compared to 38% adhesion on uncoated Ti6Al4V. MG63 cells produced significantly more mineralization on ELP coatings compared to uncoated Ti6Al4V. Human bone marrow mesenchymal stem cells (hMSCs) had an earlier increase in alkaline phosphatase activity, indicating more rapid osteogenic differentiation and mineral deposition on adhesive ELP coatings. Rat tibia and femur in vivo studies demonstrated that cell-adhesive ELP-coated implants increased bone-implant contact area and interfacial strength after one week. These results suggest that ELP coatings withstand surgical implantation and promote rapid osseointegration, enabling earlier implant loading and potentially preventing micromotion that leads to aseptic loosening and premature implant failure. PMID:26790146

Autologous Bone Marrow Stromal Cell Transplantation for Central Nervous System Disorders – Recent Progress and Perspective for Clinical Application

Directory of Open Access Journals (Sweden)

Kuroda S

2011-01-01

Full Text Available There is increasing evidence that the transplanted BMSC significantly promote functional recovery after CNS damage in the animal models of various kinds of CNS disorders, including cerebral infarct, traumatic brain injury and spinal cord injury. However, there are several shortages of information when considering clinical application of BMSC transplantation for patients with CNS disorders. In this review, therefore, we discuss what we should clarify to establish cell transplantation therapy as the scientifically proven entity in clinical situation and describe our recent works for this purpose. The BMSC have the ability to alter their gene expression profile and phenotype in response to the surrounding circumstances and to protect the neurons by producing some neurotrophic factors. They also promote neurite extension and rebuild the neural circuits in the injured CNS. The BMSC can be expanded in vitro using the animal serum-free medium. Pharmacological modulation may accelerate the in vitro proliferation of the BMSC. Using in vivo optical imaging technique, the transplanted BMSC can non-invasively be tracked in the living animals for at least 8 weeks after transplantation. It is urgent issues to develop clinical imaging technique to track the transplanted cells in the CNS and evaluate the therapeutic significance of BMSC transplantation in order to establish it as a definite therapeutic strategy in clinical situation in the future.

Marrow signal changes observed in follow-up whole-body MRI studies in children and young adults with neurofibromatosis type 1 treated with imatinib mesylate (Gleevec) for plexiform neurofibromas

Energy Technology Data Exchange (ETDEWEB)

Karmazyn, Boaz; Cohen, Mervyn D. [Riley Hospital for Children, Indiana University Health, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN (United States); Jennings, Samuel Gregory [Indiana University School of Medicine, Department of Radiology and Imaging Sciences, Indianapolis, IN (United States); Robertson, Kent A. [Riley Hospital for Children, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN (United States)

2012-10-15

We observed bone marrow signal changes (BMSC) in patients with plexiform neurofibromas after treatment with imatinib mesylate (Gleevec). To evaluate the pattern and natural history of BMSC. The data were obtained from a pilot study of imatinib mesylate in patients with plexiform neurofibromas. All patients underwent baseline and sequential whole-body STIR 1.5-T MRI after treatment. The bone marrow signal on MRI was evaluated for abnormalities, location and pattern, and any change on follow-up studies. The study group included 16 patients (8 males) with a median age of 14 years (range 4 to 25 years). The mean whole-body MRI follow-up duration was 1.9 years. Of the 16 patients, 14 (88%) developed BMSC. The signal change was asymmetrical in 9 of the 14 patients (64%). The appendicular skeleton was involved in all 14 patients and the axial skeleton in 3 patients (21%). BMSC was followed in 13 patients and decreased signal was seen in 9 patients (69%) after a mean duration of 1.3 years of treatment (range 0.6 to 2.9 years); no complications were observed. BMSC appeared in most patients with neurofibromatosis type 1 following treatment with imatinib mesylate. BMSC was unusually asymmetrical and involved the lower extremities. On follow-up, BMSC often showed a decrease without complications. (orig.)

E.A.O. guidelines for the use of diagnostic imaging in implant dentistry 2011. A consensus workshop organized by the European Association for Osseointegration at the Medical University of Warsaw.

LENUS (Irish Health Repository)

Harris, David

2012-11-01

Diagnostics imaging is an essential component of patient selection and treatment planning in oral rehabilitation by means of osseointegrated implants. In 2002, the EAO produced and published guidelines on the use of diagnostic imaging in implant dentistry. Since that time, there have been significant developments in both the application of cone beam computed tomography as well as in the range of surgical and prosthetic applications that can potentially benefit from its use. However, medical exposure to ionizing radiation must always be justified and result in a net benefit to the patient. The as low a dose as is reasonably achievable principle must also be applied taking into account any alternative techniques that might achieve the same objectives. This paper reports on current EAO recommendations arising from a consensus meeting held at the Medical University of Warsaw (2011) to update these guidelines. Radiological considerations are detailed, including justification and optimization, with a special emphasis on the obligations that arise for those who prescribe or undertake such investigations. The paper pays special attention to clinical indications and radiographic diagnostic considerations as well as to future developments and trends.

Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells

Directory of Open Access Journals (Sweden)

Fanglong Song

2017-02-01

Full Text Available Background/Aims: This study investigated the effect of mechanical stress on tendon-bone healing in a rabbit anterior cruciate ligament (ACL reconstruction model as well as cell proliferation and matrix formation in co-culture of bone-marrow mesenchymal stem cells (BMSCs and tendon cells (TCs. Methods: The effect of continuous passive motion (CPM therapy on tendon-bone healing in a rabbit ACL reconstruction model was evaluated by histological analysis, biomechanical testing and gene expressions at the tendon-bone interface. Furthermore, the effect of mechanical stretch on cell proliferation and matrix synthesis in BMSC/TC co-culture was also examined. Results: Postoperative CPM therapy significantly enhanced tendon-bone healing, as evidenced by increased amount of fibrocartilage, elevated ultimate load to failure levels, and up-regulated gene expressions of Collagen I, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin at the tendon-bone junction. In addition, BMSC/TC co-culture treated with mechanical stretch showed a higher rate of cell proliferation and enhanced expressions of Collagen I, Collagen III, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin than that of controls. Conclusion: These results demonstrated that proliferation and differentiation of local precursor cells could be enhanced by mechanical stimulation, which results in enhanced regenerative potential of BMSCs and TCs in tendon-bone healing.

Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities

International Nuclear Information System (INIS)

Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta; Ikeda, Osamu; Okabe, Kanako; Kitai, Yuichi; Kon, Shigeyuki; Oritani, Kenji; Matsuda, Tadashi

2015-01-01

Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activated GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR

Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities

Energy Technology Data Exchange (ETDEWEB)

Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta; Ikeda, Osamu; Okabe, Kanako; Kitai, Yuichi; Kon, Shigeyuki [Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812 (Japan); Oritani, Kenji [Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Matsuda, Tadashi, E-mail: tmatsuda@pharm.hokudai.ac.jp [Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812 (Japan)

2015-07-31

Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activated GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR.

Dual expression of hTERT and VEGF prolongs life span and enhances angiogenic ability of aged BMSCs

Energy Technology Data Exchange (ETDEWEB)

Tang, Hao [Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou (China); Department of Neurosurgery, Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA, Beijing (China); Xiang, Yongsheng [Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou (China); Department of Neurosurgery, First Affiliated Hospital of Jinan University, Guangzhou (China); Jiang, Xiaodan; Ke, Yiquan; Xiao, Zongyu; Guo, Yang; Wang, Qiujing; Du, Mouxuan; Qin, Linsha; Zou, Yuxi; Cai, Yingqian [Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou (China); Chen, Zhenzhou, E-mail: czz1020@163.com [Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou (China); Xu, Ruxiang, E-mail: zjxuruxiang@163.com [Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou (China); Department of Neurosurgery, Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA, Beijing (China)

2013-11-01

Highlights: •Expression of hTERT and VEGF changed the lifespan and morphology of hBMSCs. •The expression of VEGF and hTRET promoted angiogenesis in vitro and in vivo. •The expression of VEGF and hTRET in hBMSCs had few effects on tumorigenicity. -- Abstract: Previous studies have confirmed the therapeutic effects of bone marrow stromal cells (BMSCs) transplantation on cerebral ischemia. However, the proliferative, differentiative, and homing capacity of BMSC from the elderly are significantly reduced, especially after several passages expansion in vitro. In this study, by introducing lentivirus-mediated hTERT and VEGF genes to modify human BMSCs from aged donors, we observed extended lifespan, promoted angiogenic capacity while less enhanced tumorigenicity of the genetically engineering BMSCs. These results therefore suggest that the modification of aged BMSCs by dual expression of hTERT and VEGF may be used for autologous cell replacement for ischemic cerebrovascular disease in elderly patients.

Dual expression of hTERT and VEGF prolongs life span and enhances angiogenic ability of aged BMSCs

International Nuclear Information System (INIS)

Tang, Hao; Xiang, Yongsheng; Jiang, Xiaodan; Ke, Yiquan; Xiao, Zongyu; Guo, Yang; Wang, Qiujing; Du, Mouxuan; Qin, Linsha; Zou, Yuxi; Cai, Yingqian; Chen, Zhenzhou; Xu, Ruxiang

2013-01-01

Highlights: •Expression of hTERT and VEGF changed the lifespan and morphology of hBMSCs. •The expression of VEGF and hTRET promoted angiogenesis in vitro and in vivo. •The expression of VEGF and hTRET in hBMSCs had few effects on tumorigenicity. -- Abstract: Previous studies have confirmed the therapeutic effects of bone marrow stromal cells (BMSCs) transplantation on cerebral ischemia. However, the proliferative, differentiative, and homing capacity of BMSC from the elderly are significantly reduced, especially after several passages expansion in vitro. In this study, by introducing lentivirus-mediated hTERT and VEGF genes to modify human BMSCs from aged donors, we observed extended lifespan, promoted angiogenic capacity while less enhanced tumorigenicity of the genetically engineering BMSCs. These results therefore suggest that the modification of aged BMSCs by dual expression of hTERT and VEGF may be used for autologous cell replacement for ischemic cerebrovascular disease in elderly patients

Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential

Directory of Open Access Journals (Sweden)

Tom J. Burdon

2011-01-01

Full Text Available During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.

A paradigm for the development and evaluation of novel implant topologies for bone fixation: in vivo evaluation.

Science.gov (United States)

Long, Jason P; Hollister, Scott J; Goldstein, Steven A

2012-10-11

While contemporary prosthetic devices restore some function to individuals who have lost a limb, there are efforts to develop bio-integrated prostheses to improve functionality. A critical step in advancing this technology will be to securely attach the device to remnant bone. To investigate mechanisms for establishing robust implant fixation in bone while undergoing loading, we previously used a topology optimization scheme to develop optimized orthopedic implants and then fabricated selected designs from titanium (Ti)-alloy with selective laser sintering (SLS) technology. In the present study, we examined how implant architecture and mechanical stimulation influence osseointegration within an in vivo environment. To do this, we evaluated three implant designs (two optimized and one non-optimized) using a unique in vivo model that applied cyclic, tension/compression loads to the implants. Eighteen (six per implant design) adult male canines had implants surgically placed in their proximal, tibial metaphyses. Experimental duration was 12 weeks; daily loading (peak load of ±22 N for 1000 cycles) was applied to one of each animal's bilateral implants for the latter six weeks. Following harvest, osseointegration was assessed by non-destructive mechanical testing, micro-computed tomography (microCT) and back-scatter scanning electron microscopy (SEM). Data revealed that implant loading enhanced osseointegration by significantly increasing construct stiffness, peri-implant trabecular morphology, and percentages of interface connectivity and bone ingrowth. While this experiment did not demonstrate a clear advantage associated with the optimized implant designs, osseointegration was found to be significantly influenced by aspects of implant architecture. Copyright © 2012 Elsevier Ltd. All rights reserved.

New Coating Technique of Ceramic Implants with Different Glass Solder Matrices for Improved Osseointegration-Mechanical Investigations.

Science.gov (United States)

Mick, Enrico; Markhoff, Jana; Mitrovic, Aurica; Jonitz, Anika; Bader, Rainer

2013-09-11

Ceramics are a very popular material in dental implant technology due to their tribological properties, their biocompatibility and their esthetic appearance. However, their natural surface structure lacks the ability of proper osseointegration, which constitutes a crucial process for the stability and, thus, the functionality of a bone implant. We investigated the application of a glass solder matrix in three configurations-consisting mainly of SiO₂, Al₂O₃, K₂O and Na₂O to TZP-A ceramic specimens. The corresponding adhesive strength and surface roughness of the coatings on ceramic specimens have been analyzed. Thereby, high adhesive strength (70.3 ± 7.9 MPa) was found for the three different coatings. The obtained roughness (R z ) amounted to 18.24 ± 2.48 µm in average, with significant differences between the glass solder configurations. Furthermore, one configuration was also tested after additional etching which did not lead to significant increase of surface roughness (19.37 ± 1.04 µm) or adhesive strength (57.2 ± 5.8 MPa). In conclusion, coating with glass solder matrix seems to be a promising surface modification technique that may enable direct insertion of ceramic implants in dental and orthopaedic surgery.

Nef enhances HIV-1 infectivity via association with the virus assembly complex

International Nuclear Information System (INIS)

Qi Mingli; Aiken, Christopher

2008-01-01

The HIV-1 accessory protein Nef enhances virus infectivity by facilitating an early post-entry step of infection. Nef acts in the virus producer cell, leading to a beneficial modification to HIV-1 particles. Nef itself is incorporated into HIV-1 particles, where it is cleaved by the viral protease during virion maturation. To probe the role of virion-associated Nef in HIV-1 infection, we generated a fusion protein consisting of the host protein cyclophilin A (CypA) linked to the amino terminus of Nef. The resulting CypA-Nef protein enhanced the infectivity of Nef-defective HIV-1 particles and was specifically incorporated into the virions via association with Gag during particle assembly. Pharmacologic or genetic inhibition of CypA-Nef binding to Gag prevented incorporation of CypA-Nef into virions and inhibited infectivity enhancement. Our results indicate that infectivity enhancement by Nef requires its association with a component of the assembling HIV-1 particle

Discrete deposition of hydroxyapatite nanoparticles on a titanium implant with predisposing substrate microtopography accelerated osseointegration

International Nuclear Information System (INIS)

Nishimura, Ichiro; Huang Yuhong; Butz, Frank; Ogawa, Takahiro; Lin, Audrey; Wang, Chiachien Jake

2007-01-01

We report here a new versatile method to deposit discrete hydroxyapatite (HA) nanoparticles on a titanium (Ti) implant with predisposing substrate microtopography, which exhibited an unexpectedly robust biological effect. Commercially pure Ti substrates were treated with 3-aminopropyltriethoxysilane, on which HA nanoparticles (20 nm) were deposited and chemically bonded to TiO 2 . The HA deposition rate was linearly related to the treatment time and HA nanoparticles were deposited on up to 50% of the substrate surface. As a result, the discrete deposition of HA nanoparticles generated novel 20-40 nm nanotopography on the Ti substrate with microtopography that was smooth (turned) or roughened by double acid etching (DAE). The experimental implants with or without HA nanoparticles were surgically placed in rat femur and an implant push-in test was performed after two weeks of healing. The deposition of HA nanoparticles on the DAE surface increased the mechanical withstanding load by 129% and 782% as compared to the control DAE and turned implants, respectively. Micro-computed tomography-based 3D bone morphometry revealed equivalent bone volumes around the DAE implant with or without HA nanoparticles. These data suggest that the discrete deposition of HA nanoparticles accelerates the early osseointegration process, likely through increased shear bonding strengths

Discrete deposition of hydroxyapatite nanoparticles on a titanium implant with predisposing substrate microtopography accelerated osseointegration

Energy Technology Data Exchange (ETDEWEB)

Nishimura, Ichiro [UCLA School of Dentistry, Weintraub Center for Reconstructive Biotechnology and Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, Los Angeles, CA (United States); Huang Yuhong [Chemat Technology, Incorporated, Northridge, CA (United States); Butz, Frank [UCLA School of Dentistry, Weintraub Center for Reconstructive Biotechnology and Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, Los Angeles, CA (United States); Ogawa, Takahiro [UCLA School of Dentistry, Weintraub Center for Reconstructive Biotechnology and Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, Los Angeles, CA (United States); Lin, Audrey [UCLA School of Dentistry, Weintraub Center for Reconstructive Biotechnology and Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, Los Angeles, CA (United States); Wang, Chiachien Jake [UCLA School of Dentistry, Weintraub Center for Reconstructive Biotechnology and Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, Los Angeles, CA (United States)

2007-06-20

We report here a new versatile method to deposit discrete hydroxyapatite (HA) nanoparticles on a titanium (Ti) implant with predisposing substrate microtopography, which exhibited an unexpectedly robust biological effect. Commercially pure Ti substrates were treated with 3-aminopropyltriethoxysilane, on which HA nanoparticles (20 nm) were deposited and chemically bonded to TiO{sub 2}. The HA deposition rate was linearly related to the treatment time and HA nanoparticles were deposited on up to 50% of the substrate surface. As a result, the discrete deposition of HA nanoparticles generated novel 20-40 nm nanotopography on the Ti substrate with microtopography that was smooth (turned) or roughened by double acid etching (DAE). The experimental implants with or without HA nanoparticles were surgically placed in rat femur and an implant push-in test was performed after two weeks of healing. The deposition of HA nanoparticles on the DAE surface increased the mechanical withstanding load by 129% and 782% as compared to the control DAE and turned implants, respectively. Micro-computed tomography-based 3D bone morphometry revealed equivalent bone volumes around the DAE implant with or without HA nanoparticles. These data suggest that the discrete deposition of HA nanoparticles accelerates the early osseointegration process, likely through increased shear bonding strengths.

TGF-β1 is Involved in Vitamin D-Induced Chondrogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells by Regulating the ERK/JNK Pathway

Directory of Open Access Journals (Sweden)

Xiaorui Jiang

2017-08-01

Full Text Available Background/Aims: Osteoarthritis (OA is characterized by degradation of cartilage, sole cell type of which is chondrocytes. Bone marrow-derived mesenchymal stem cells (BMSCs possess multipotency and can be directionally differentiated into chondrocytes under stimulation. This study was aimed to explore the possible roles of vitamin D and transforming growth factor-β1 (TGF-β1 in the chondrogenic differentiation of BMSCs. Methods: BMSCs were isolated from femurs and tibias of rats and characterized by flow cytometry. After stimulation with vitamin D, BMSC proliferation and migration were measured by Cell Counting Kit-8 (CCK-8 and Transwell assays, respectively. Chondrogenic differentiation was estimated through expression levels of specific markers by qRT-PCR and Western blot analysis. After stable transfection, the effects of aberrantly expressed TGF-β1 on vitamin D-induced alterations, including BMSC viability, migration and chondrogenic differentiation, were all evaluated utilizing CCK-8 assay, Transwell assay, qRT-PCR and Western blot analysis. Finally, the phosphorylation levels of key kinases in the extracellular signal-regulated kinase (ERK and c-Jun N-terminal kinase (JNK pathways were determined by Western blot analysis. Results: Vitamin D remarkably promoted BMSC viability, migration and chondrogenic differentiation. These alterations of BMSCs induced by vitamin D were reinforced by TGF-β1 overexpression while were reversed by TGF-β1 silencing. Additionally, the phosphorylation levels of ERK, JNK and c-Jun were enhanced by TGF-β1 overexpression but were reduced by TGF-β1 knockdown. Conclusion: Vitamin D promoted BMSC proliferation, migration and chondrogenic differentiation. TGF-β1 might be implicated in the vitamin D-induced alterations of BMSCs through regulating ERK/JNK pathway.

Changes in left ventricular filling patterns after repeated injection of autologous bone marrow cells in heart failure patients

DEFF Research Database (Denmark)

Diederichsen, Axel Cosmus Pyndt; Møller, Jacob E; Thayssen, Per

2010-01-01

Abstract Objectives. We have previously shown that repeated intracoronary infusion of bone marrow cells (BMSC) did not improve left ventricular (LV) ejection fraction in patients with chronic ischemic heart failure. However, the impact of BMSC therapy on LV diastolic filling has remained uncertain....... Conclusion. In this non-randomised study repeated intracoronary BMSC infusions had a beneficial effect on LV filling in patients with chronic ischemic heart failure. Randomised studies are warranted....

Polyethylene glycol enhances lipoplex-cell association and lipofection.

Science.gov (United States)

Ross, P C; Hui, S W

1999-10-15

The association between liposome-DNA complexes (lipoplexes) and targeted cell membranes is a limiting step of cationic liposome-mediated transfection. A novel technique was developed where lipoplex-cell membrane association is enhanced by the addition of 2-6% polyethylene glycol (PEG) to the transfection media. Lipoplex-cell association was found to increase up to 100 times in the presence of PEG. Transfection increased correspondingly in the presence of PEG. This increase was found in several cell lines. These results show that lipoplex adsorption to cell membranes is a critical step in liposome-mediated transfection. This step can be facilitated by PEG-induced particle aggregation.

In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model.

Science.gov (United States)

Lovati, A B; Lopa, S; Recordati, C; Talò, G; Turrisi, C; Bottagisio, M; Losa, M; Scanziani, E; Moretti, M

2016-08-01

Large bone defects still represent a major burden in orthopedics, requiring bone-graft implantation to promote the bone repair. Along with autografts that currently represent the gold standard for complicated fracture repair, the bone tissue engineering offers a promising alternative strategy combining bone-graft substitutes with osteoprogenitor cells able to support the bone tissue ingrowth within the implant. Hence, the optimization of cell loading and distribution within osteoconductive scaffolds is mandatory to support a successful bone formation within the scaffold pores. With this purpose, we engineered constructs by seeding and culturing autologous, osteodifferentiated bone marrow mesenchymal stem cells within hydroxyapatite (HA)-based grafts by means of a perfusion bioreactor to enhance the in vivo implant-bone osseointegration in an ovine model. Specifically, we compared the engineered constructs in two different anatomical bone sites, tibia, and femur, compared with cell-free or static cell-loaded scaffolds. After 2 and 4 months, the bone formation and the scaffold osseointegration were assessed by micro-CT and histological analyses. The results demonstrated the capability of the acellular HA-based grafts to determine an implant-bone osseointegration similar to that of statically or dynamically cultured grafts. Our study demonstrated that the tibia is characterized by a lower bone repair capability compared to femur, in which the contribution of transplanted cells is not crucial to enhance the bone-implant osseointegration. Indeed, only in tibia, the dynamic cell-loaded implants performed slightly better than the cell-free or static cell-loaded grafts, indicating that this is a valid approach to sustain the bone deposition and osseointegration in disadvantaged anatomical sites.

Culture conditions for equine bone marrow mesenchymal stem cells and expression of key transcription factors during their differentiation into osteoblasts

Science.gov (United States)

2013-01-01

Background The use of equine bone marrow mesenchymal stem cells (BMSC) is a novel method to improve fracture healing in horses. However, additional research is needed to identify optimal culture conditions and to determine the mechanisms involved in regulating BMSC differentiation into osteoblasts. The objectives of the experiments were to determine: 1) if autologous or commercial serum is better for proliferation and differentiation of equine BMSC into osteoblasts, and 2) the expression of key transcription factors during the differentiation of equine BMSC into osteoblasts. Equine BMSC were isolated from the sterna of 3 horses, treated with purchased fetal bovine serum (FBS) or autologous horse serum (HS), and cell proliferation determined. To induce osteoblast differentiation, cells were incubated with L-ascorbic acid-2-phosphate and glycerol-2-phosphate in the presence or absence of human bone morphogenetic protein2 (BMP2), dexamethasone (DEX), or combination of the two. Alkaline phosphatase (ALP) activity, a marker of osteoblast differentiation, was determined by ELISA. Total RNA was isolated from differentiating BMSC between d 0 to 18 to determine expression of runt-related transcription factor2 (Runx2), osterix (Osx), and T-box3 (Tbx3). Data were analyzed by ANOVA. Results Relative to control, FBS and HS increased cell number (133 ± 5 and 116 ± 5%, respectively; P  0.8). Runt-related transcription factor2 expression increased 3-fold (P equine BMSC into osteoblasts. In addition, expression of Runx2 and osterix increased and expression of Tbx3 is reduced during differentiation. PMID:24169030

Distributed hippocampal patterns that discriminate reward context are associated with enhanced associative binding.

Science.gov (United States)

Wolosin, Sasha M; Zeithamova, Dagmar; Preston, Alison R

2013-11-01

Recent research indicates that reward-based motivation impacts medial temporal lobe (MTL) encoding processes, leading to enhanced memory for rewarded events. In particular, previous functional magnetic resonance imaging (fMRI) studies of motivated learning have shown that MTL activation is greater for highly rewarded events, with the degree of reward-related activation enhancement tracking the corresponding behavioral memory advantage. These studies, however, do not directly address leading theoretical perspectives that propose such reward-based enhancements in MTL encoding activation reflect enhanced discrimination of the motivational context of specific events. In this study, a high-value or low-value monetary cue preceded a pair of objects, indicating the future reward for successfully remembering the pair. Using representational similarity analysis and high-resolution fMRI, we show that MTL activation patterns are more similar for encoding trials preceded by the same versus different reward cues, indicating a distributed code in this region that distinguishes between motivational contexts. Moreover, we show that activation patterns in hippocampus and parahippocampal cortex (PHc) that differentiate reward conditions during anticipatory cues and object pairs relate to successful associative memory. Additionally, the degree to which patterns differentiate reward contexts in dentate gyrus/CA2,3 and PHc is related to individual differences in reward modulation of memory. Collectively, these findings suggest that distributed activation patterns in the human hippocampus and PHc reflect the rewards associated with individual events. Furthermore, we show that these activation patterns-which discriminate between reward conditions--may influence memory through the incorporation of information about motivational contexts into stored memory representations. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Influence of postoperative low-level laser therapy on the osseointegration of self-tapping implants in the posterior maxilla: a 6-week split-mouth clinical study.

Science.gov (United States)

Mandić, Borka; Lazić, Zoran; Marković, Aleksa; Mandić, Bojan; Mandić, Miška; Djinić, Ana; Miličić, Biljana

2015-03-01

Low-level laser therapy (LLLT) has been proven to stimulate bone repair, affecting cellular proliferation, differentiation and adhesion, and has shown a potential to reduce the healing time following implant placement. The aim of this clinical study was to investigate the influence of postoperative LLLT osseointegration and early success of self-tapping implants placed into low-density bone. Following the split-mouth design, self-tapping implants n = 44) were inserted in the posterior maxilla of 12 patients. One jaw side randomly received LLLT (test group), while the other side was placebo (control group). For LLLT, a 637 nm gallium-aluminum-arsenide (GaAlAs) laser (Medicolaser 637, Technoline, Belgrade, Serbia) with an output power of 40 mW and continuous wave was used. Low-level laser treatment was performed immediately after the surgery and then repeated every day in the following 7 days. The total irradiation dose per treatment was 6.26 J/cm2 per implant. The study outcomes were: implant stability, alkaline-phosphatase (ALP) activity and early implant success rate. The follow-up took 6 weeks. Irradiated implants achieved a higher stability compared with controls during the entire follow-up and the difference reached significance in the 5th postoperative week (paired t-test, p = 0.030). The difference in ALP activity between the groups was insignificant in any observation point (paired t-test, p > 0.05). The early implant success rate was 100%, regardless of LLLT usage. LLLT applied daily during the first postoperative week expressed no significant influence on the osseointegration of self-tapping implants placed into low density bone of the posterior maxilla. Placement of self-tapping macro-designed implants into low density bone could be a predictable therapeutic procedure with a high early success rate regardless of LLLT usage.

Influence of postoperative low-level laser therapy on the osseointegration of self-tapping implants in the posterior maxilla: A 6-week split-mouth clinical study

Directory of Open Access Journals (Sweden)

Mandić Borka

2015-01-01

Full Text Available Background/Aim. Low-level laser therapy (LLLT has been proven to stimulate bone repair, affecting cellular proliferation, differentiation and adhesion, and has shown a potential to reduce the healing time following implant placement. The aim of this clinical study was to investigate the influence of postoperative LLLT osseointegration and early success of self-tapping implants placed into low-density bone. Methods. Following the split-mouth design, self-tapping implants (n = 44 were inserted in the posterior maxilla of 12 patients. One jaw side randomly received LLLT (test group, while the other side was placebo (control group. For LLLT, a 637 nm gallium-aluminum-arsenide (GaAlAs laser (Medicolaser 637, Technoline, Belgrade, Serbia with an output power of 40 mW and continuous wave was used. Low-level laser treatment was performed immediately after the surgery and then repeated every day in the following 7 days. The total irradiation dose per treatment was 6.26 J/cm² per implant. The study outcomes were: implant stability, alkaline-phosphatase (ALP activity and early implant success rate. The follow-up took 6 weeks. Results. Irradiated implants achieved a higher stability compared with controls during the entire follow-up and the difference reached significance in the 5th postoperative week (paired t-test, p = 0.030. The difference in ALP activity between the groups was insignificant in any observation point (paired t-test, p > 0.05. The early implant success rate was 100%, regardless of LLLT usage. Conclusion. LLLT applied daily during the first postoperative week expressed no significant influence on the osseointegration of selftapping implants placed into low density bone of the posterior maxilla. Placement of self-tapping macro-designed implants into low density bone could be a predictable therapeutic procedure with a high early success rate regardless of LLLT usage.

Surface modifications of dental ceramic implants with different glass solder matrices: in vitro analyses with human primary osteoblasts and epithelial cells.

Science.gov (United States)

Markhoff, Jana; Mick, Enrico; Mitrovic, Aurica; Pasold, Juliane; Wegner, Katharina; Bader, Rainer

2014-01-01

Ceramic materials show excellent esthetic behavior, along with an absence of hypersensitivity, making them a possible alternative implant material in dental surgery. However, their surface properties enable only limited osseointegration compared to titanium implants. Within this study, a novel surface coating technique for enhanced osseointegration was investigated biologically and mechanically. Specimens of tetragonal zirconia polycrystal (TZP) and aluminum toughened zirconia (ATZ) were modified with glass solder matrices in two configurations which mainly consisted of SiO2, Al2O3, K2O, and Na2O. The influence on human osteoblastic and epithelial cell viability was examined by means of a WST-1 assay as well as live/dead staining. A C1CP-ELISA was carried out to verify procollagen type I production. Uncoated/sandblasted ceramic specimens and sandblasted titanium surfaces were investigated as a reference. Furthermore, mechanical investigations of bilaterally coated pellets were conducted with respect to surface roughness and adhesive strength of the different coatings. These tests could demonstrate a mechanically stable implant coating with glass solder matrices. The coated ceramic specimens show enhanced osteoblastic and partly epithelial viability and matrix production compared to the titanium control. Hence, the new glass solder matrix coating could improve bone cell growth as a prerequisite for enhanced osseointegration of ceramic implants.

Surface Modifications of Dental Ceramic Implants with Different Glass Solder Matrices: In Vitro Analyses with Human Primary Osteoblasts and Epithelial Cells

Science.gov (United States)

Mick, Enrico

2014-01-01

Ceramic materials show excellent esthetic behavior, along with an absence of hypersensitivity, making them a possible alternative implant material in dental surgery. However, their surface properties enable only limited osseointegration compared to titanium implants. Within this study, a novel surface coating technique for enhanced osseointegration was investigated biologically and mechanically. Specimens of tetragonal zirconia polycrystal (TZP) and aluminum toughened zirconia (ATZ) were modified with glass solder matrices in two configurations which mainly consisted of SiO2, Al2O3, K2O, and Na2O. The influence on human osteoblastic and epithelial cell viability was examined by means of a WST-1 assay as well as live/dead staining. A C1CP-ELISA was carried out to verify procollagen type I production. Uncoated/sandblasted ceramic specimens and sandblasted titanium surfaces were investigated as a reference. Furthermore, mechanical investigations of bilaterally coated pellets were conducted with respect to surface roughness and adhesive strength of the different coatings. These tests could demonstrate a mechanically stable implant coating with glass solder matrices. The coated ceramic specimens show enhanced osteoblastic and partly epithelial viability and matrix production compared to the titanium control. Hence, the new glass solder matrix coating could improve bone cell growth as a prerequisite for enhanced osseointegration of ceramic implants. PMID:25295270

Application of cell sheet technology to bone marrow stromal cell transplantation for rat brain infarct.

Science.gov (United States)

Ito, Masaki; Shichinohe, Hideo; Houkin, Kiyohiro; Kuroda, Satoshi

2017-02-01

Bone marrow stromal cells (BMSC) transplantation enhances functional recovery after cerebral infarct, but the optimal delivery route is undetermined. This study was aimed to assess whether a novel cell-sheet technology non-invasively serves therapeutic benefits to ischemic stroke. First, the monolayered cell sheet was engineered by culturing rat BMSCs on a temperature-responsive dish. The cell sheet was analysed histologically and then transplanted onto the ipsilateral neocortex of rats subjected to permanent middle cerebral artery occlusion at 7 days after the insult. Their behaviours and histology were compared with those in the animals treated with direct injection of BMSCs or vehicle over 4 weeks post-transplantation. The cell sheet was 27.9 ± 8.0 μm thick and was composed of 9.8 ± 2.4 × 10 5 cells. Cell sheet transplantation significantly improved motor function when compared with the vehicle-injected animals. Histological analysis revealed that the BMSCs were densely distributed to the neocortex adjacent to the cerebral infarct and expressed neuronal phenotype in the cell sheet-transplanted animals. These findings were almost equal to those for the animals treated with direct BMSC injection. The attachment of the BMSC sheet to the brain surface did not induce reactive astrocytes in the adjacent neocortex, although direct injection of BMSCs profoundly induced reactive astrocytes around the injection site. These findings suggest that the BMSCs in cell sheets preserve their biological capacity of migration and neural differentiation. Cell-sheet technology may enhance functional recovery after ischaemic stroke, using a less invasive method. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

New Coating Technique of Ceramic Implants with Different Glass Solder Matrices for Improved Osseointegration-Mechanical Investigations

Directory of Open Access Journals (Sweden)

Rainer Bader

2013-09-01

Full Text Available Ceramics are a very popular material in dental implant technology due to their tribological properties, their biocompatibility and their esthetic appearance. However, their natural surface structure lacks the ability of proper osseointegration, which constitutes a crucial process for the stability and, thus, the functionality of a bone implant. We investigated the application of a glass solder matrix in three configurations—consisting mainly of SiO2, Al2O3, K2O and Na2O to TZP-A ceramic specimens. The corresponding adhesive strength and surface roughness of the coatings on ceramic specimens have been analyzed. Thereby, high adhesive strength (70.3 ± 7.9 MPa was found for the three different coatings. The obtained roughness (Rz amounted to 18.24 ± 2.48 µm in average, with significant differences between the glass solder configurations. Furthermore, one configuration was also tested after additional etching which did not lead to significant increase of surface roughness (19.37 ± 1.04 µm or adhesive strength (57.2 ± 5.8 MPa. In conclusion, coating with glass solder matrix seems to be a promising surface modification technique that may enable direct insertion of ceramic implants in dental and orthopaedic surgery.

Biocompatible cephalosporin-hydroxyapatite-poly(lactic-co-glycolic acid)-coatings fabricated by MAPLE technique for the prevention of bone implant associated infections

Energy Technology Data Exchange (ETDEWEB)

Rădulescu, Dragoş [Bucharest University Hospital, Department of Orthopedics and Traumatology, Bucharest (Romania); Grumezescu, Valentina [Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest (Romania); Lasers Department, National Institute for Lasers, Plasma & Radiation Physics, Magurele, Bucharest (Romania); Andronescu, Ecaterina [Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest (Romania); Holban, Alina Maria [Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest (Romania); Microbiology Immunology Department, Faculty of Biology, University of Bucharest, 1–3 Portocalelor Lane, Sector 5, 77206 Bucharest (Romania); Research Institute of the University of Bucharest –ICUB, 91-95 Splaiul Independentei, 050095 Bucharest (Romania); Grumezescu, Alexandru Mihai, E-mail: grumezescu@yahoo.com [Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest (Romania); Socol, Gabriel [Lasers Department, National Institute for Lasers, Plasma & Radiation Physics, Magurele, Bucharest (Romania); Oprea, Alexandra Elena [Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest (Romania); Rădulescu, Marius [Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 1–7 Polizu Street, 011061 Bucharest (Romania); and others

2016-06-30

Graphical abstract: - Highlights: • HAp/PLGA thin coatings by Matrix Assisted Pulsed Laser Evaporation. • Anti-adherent coating on medical surfaces against S. aureus and P. aeruginosa colonization. • Coatings with potential applications in implant osseointegration. - Abstract: In this study we aimed to obtain functionalized thin films based on hydroxyapatite/poly(lactic-co-glycolic acid) (HAp/PLGA) containing ceftriaxone/cefuroxime antibiotics (ATBs) deposited by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The prepared thin films were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-Ray diffraction (XRD), selected area electron diffraction (SAED), and infra red (IR) analysis. HAp/PLGA/ATBs thin films sustained the growth of human osteoblasts, proving their good biocompatibility. The microscopic evaluation and the culture-based quantitative assay of the E. coli biofilm development showed that the thin films inhibited the initial step of microbial attachment as well as the subsequent colonization and biofilm development on the respective surfaces. This study demonstrates that MAPLE technique could represent an appealing technique for the fabrication of antibiotics-containing polymeric implant coatings. The bioevaluation results recommend this type of surfaces for the prevention of bone implant microbial contamination and for the enhanced stimulation of the implant osseointegration process.

Glyoxal Crosslinking of Cell-Seeded Chitosan/Collagen Hydrogels for Bone Regeneration

Science.gov (United States)

Wang, Limin; Stegemann, Jan P.

2011-01-01

Chitosan and collagen are natural biomaterials that have been used extensively in tissue engineering, both separately and as composite materials. Most methods to fabricate chitosan/collagen composites use freeze drying and chemical crosslinking to create stable porous scaffolds, which subsequently can be seeded with cells. In this study, we directly embedded human bone marrow stem cells (hBMSC) in chitosan/collagen materials by initiating gelation using β-glycerophosphate at physiological temperature and pH. We further examined the use of glyoxal, a dialdehyde with relatively low toxicity, to crosslink these materials and characterized the resulting changes in matrix and cell properties. The cytocompatibility of glyoxal and the crosslinked gels were investigated in terms of hBMSC metabolic activity, viability, proliferation, and osteogenic differentiation. These studies revealed that glyoxal was cytocompatible at concentrations below about 1 mM for periods of exposure up to 15 h, though the degree of cell spreading and proliferation were dependent on matrix composition. Glyoxal-crosslinked matrices were stiffer and compacted less than uncrosslinked controls. It was further demonstrated that hBMSC can attach and proliferate in 3D matrices composed of 50/50 chitosan/collagen, and that these materials supported osteogenic differentiation in response to stimulation. Such glyoxal-crosslinked chitosan/collagen composite materials may find utility as cell delivery vehicles for enhancing the repair of bone defects. PMID:21345389

Development and application of biomimetic electrospun nanofibers in total joint replacement

Science.gov (United States)

Song, Wei

Failure of osseointegration (direct anchorage of an implant by bone formation at the bone-implant surface) and implant infection (such as that caused by Staphylococcus aureus, S. aureus) are the two main causes of implant failure and loosening. There is a critical need for orthopedic implants that promote rapid osseointegration and prevent bacterial colonization, particularly when placed in bone compromised by disease or physiology of the patients. A better understanding of the key factors that influence cell fate decisions at the bone-implant interface is required. Our study is to develop a class of "bone-like" nanofibers (NFs) that promote osseointegration while preventing bacterial colonization and subsequent infections. This research goal is supported by our preliminary data on the preparation of coaxial electrospun NFs composed of polycaprolactone (PCL) and polyvinyl alcohol (PVA) polymers arranged in a core-sheath shape. The PCL/PVA NFs are biocompatible and biodegradable with appropriate fiber diameter, pore size and mechanical strength, leading to enhanced cell adhesion, proliferation and differentiation of osteoblast precursor cells. The objective is to develop functionalized "bone-like" PCL/PVA NFs matrix embedded with antibiotics (doxycycline (Doxy), bactericidal and anti-osteoclastic) on prosthesis surface. Through a rat tibia implantation model, the Doxy incorporated coaxial NFs has demonstrated excellent in promoting osseointegration and bacteria inhibitory efficacy. NFs coatings significantly enhanced the bonding between implant and bone remodeling within 8 weeks. The SA-induced osteomyelitis was prevented by the sustained release of Doxy from NFs. The capability of embedding numerous bio-components including proteins, growth factors, drugs, etc. enables NFs an effective solution to overcome the current challenged issue in Total joint replacement. In summary, we proposed PCL/PVA electrospun nanofibers as promising biomaterials that can be applied on

Induced seismicity associated with enhanced geothermal system

Energy Technology Data Exchange (ETDEWEB)

Majer, Ernest; Majer, Ernest L.; Baria, Roy; Stark, Mitch; Oates, Stephen; Bommer, Julian; Smith, Bill; Asanuma, Hiroshi

2006-09-26

Enhanced Geothermal Systems (EGS) offer the potential to significantly add to the world energy inventory. As with any development of new technology, some aspects of the technology has been accepted by the general public, but some have not yet been accepted and await further clarification before such acceptance is possible. One of the issues associated with EGS is the role of microseismicity during the creation of the underground reservoir and the subsequent extraction of the energy. The primary objectives of this white paper are to present an up-to-date review of the state of knowledge about induced seismicity during the creation and operation of enhanced geothermal systems, and to point out the gaps in knowledge that if addressed will allow an improved understanding of the mechanisms generating the events as well as serve as a basis to develop successful protocols for monitoring and addressing community issues associated with such induced seismicity. The information was collected though literature searches as well as convening three workshops to gather information from a wide audience. Although microseismicity has been associated with the development of production and injection operations in a variety of geothermal regions, there have been no or few adverse physical effects on the operations or on surrounding communities. Still, there is public concern over the possible amount and magnitude of the seismicity associated with current and future EGS operations. It is pointed out that microseismicity has been successfully dealt with in a variety of non-geothermal as well as geothermal environments. Several case histories are also presented to illustrate a variety of technical and public acceptance issues. It is concluded that EGS Induced seismicity need not pose any threat to the development of geothermal resources if community issues are properly handled. In fact, induced seismicity provides benefits because it can be used as a monitoring tool to understand the

Nanotubular topography enhances the bioactivity of titanium implants.

Science.gov (United States)

Huang, Jingyan; Zhang, Xinchun; Yan, Wangxiang; Chen, Zhipei; Shuai, Xintao; Wang, Anxun; Wang, Yan

2017-08-01

Surface modification on titanium implants plays an important role in promoting mesenchymal stem cell (MSC) response to enhance osseointegration persistently. In this study, nano-scale TiO 2 nanotube topography (TNT), micro-scale sand blasted-acid etched topography (SLA), and hybrid sand blasted-acid etched/nanotube topography (SLA/TNT) were fabricated on the surfaces of titanium implants. Although the initial cell adherence at 60 min among TNT, SLA and TNT/SLA was not different, SLA and SLA/TNT presented to be rougher and suppressed the proliferation of MSC. TNT showed hydrophilic surface and balanced promotion of cellular functions. After being implanted in rabbit femur models, TNT displayed the best osteogenesis inducing ability as well as strong bonding strength to the substrate. These results indicate that nano-scale TNT provides favorable surface topography for improving the clinical performance of endosseous implants compared with micro and hybrid micro/nano surfaces, suggesting a promising and reliable surface modification strategy of titanium implants for clinical application. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization and evaluation of femtosecond laser-induced sub-micron periodic structures generated on titanium to improve osseointegration of implants

Science.gov (United States)

Lee, Bryan E. J.; Exir, Hourieh; Weck, Arnaud; Grandfield, Kathryn

2018-05-01

Reproducible and controllable methods of modifying titanium surfaces for dental and orthopaedic applications are of interest to prevent poor implant outcomes by improving osseointegration. This study made use of a femtosecond laser to generate laser-induced periodic surface structures with periodicities of 300, 620 and 760 nm on titanium substrates. The reproducible rippled patterns showed consistent submicron scale roughness and relatively hydrophobic surfaces as measured by atomic force microscopy and contact angle, respectively. Transmission electron microscopy and Auger electron spectroscopy identified a thicker oxide layer on ablated surfaces compared to controls. In vitro testing was conducted using osteosarcoma Saos-2 cells. Cell metabolism on the laser-ablated surfaces was comparable to controls and alkaline phosphatase activity was notably increased at late time points for the 620 and 760 nm surfaces compared to controls. Cells showed a more elongated shape on laser-ablated surfaces compared to controls and showed perpendicular alignment to the periodic structures. This work has demonstrated the feasibility of generating submicron features on an implant material with the ability to influence cell response and improve implant outcomes.

Effects of Artificial Ligaments with Different Porous Structures on the Migration of BMSCs

Directory of Open Access Journals (Sweden)

Chun-Hui Wang

2015-01-01

Full Text Available Polyethylene terephthalate- (PET- based artificial ligaments (PET-ALs are commonly used in anterior cruciate ligament (ACL reconstruction surgery. The effects of different porous structures on the migration of bone marrow mesenchymal stem cells (BMSCs on artificial ligaments and the underlying mechanisms are unclear. In this study, a cell migration model was utilized to observe the migration of BMSCs on PET-ALs with different porous structures. A rabbit extra-articular graft-to-bone healing model was applied to investigate the in vivo effects of four types of PET-ALs, and a mechanical test and histological observation were performed at 4 weeks and 12 weeks. The BMSC migration area of the 5A group was significantly larger than that of the other three groups. The migration of BMSCs in the 5A group was abolished by blocking the RhoA/ROCK signaling pathway with Y27632. The in vivo study demonstrated that implantation of 5A significantly improved osseointegration. Our study explicitly demonstrates that the migration ability of BMSCs can be regulated by varying the porous structures of the artificial ligaments and suggests that this regulation is related to the RhoA/ROCK signaling pathway. Artificial ligaments prepared using a proper knitting method and line density may exhibit improved biocompatibility and clinical performance.

Continuity resection of the mandible after ameloblastoma - feasibility of oral rehabilitation with rhBMP-2 associated to bovine xenograft followed by implant installation.

Science.gov (United States)

Lustosa, Romulo Maciel; Macedo, Diogo de Vasconcelos; Iwaki, Lilian Cristina Vessoni; Tolentino, Elen de Souza; Hasse, Paulo Norberto; Marson, Giordano Bruno de Oliveira; Iwaki Filho, Liogi

2015-10-01

Recombinant human morphogenetic protein (rhBMP) is a graft alternative for extensive mandibular reconstruction after tumor resections. However, the feasibility of rhBMP-2 to receive osseointegrated implants and prosthetic rehabilitation has been rarely reported. This study reports on a case of an extensive solid ameloblastoma along the mandibular body. The treatment consisted of resection followed by off-label use of rhBMP type 2 associated with bovine bone xenograft. Eleven months postoperatively, the patient was prosthetically rehabilitated with dental implants, without evidence of resorption or complications. The literature on mandibular reconstructions using rhBMP and their feasibility for future osseointegrated implant placement was also reviewed. Based on the presented case, the association between rhBMP-2 and a bovine bone xenograft could be considered a feasible option for the reconstruction and rehabilitation of large mandibular defects after tumor resection. According to the literature, the use of rhBMP as a graft material is encouraging, with good clinical outcome. However, there are no long-term studies demonstrating success and survival rates of implants placed in these grafts. Future investigations will be required to ascertain the long-term survival of implants in areas grafted with rhBMP. Also, there is a lack of information regarding the prosthetic rehabilitation of these patients. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

The establishment of a bank of stored clinical bone marrow stromal cell products

Directory of Open Access Journals (Sweden)

Sabatino Marianna

2012-02-01

Full Text Available Abstract Background Bone marrow stromal cells (BMSCs are being used to treat a variety of conditions. For many applications a supply of cryopreserved products that can be used for acute therapy is needed. The establishment of a bank of BMSC products from healthy third party donors is described. Methods The recruitment of healthy subjects willing to donate marrow for BMSC production and the Good Manufacturing Practices (GMP used for assessing potential donors, collecting marrow, culturing BMSCs and BMSC cryopreservation are described. Results Seventeen subjects were enrolled in our marrow collection protocol for BMSC production. Six of the 17 subjects were found to be ineligible during the donor screening process and one became ill and their donation was cancelled. Approximately 12 ml of marrow was aspirated from one posterior iliac crest of 10 donors; one donor donated twice. The BMSCs were initially cultured in T-75 flasks and then expanded for three passages in multilayer cell factories. The final BMSC product was packaged into units of 100 × 106 viable cells, cryopreserved and stored in a vapor phase liquid nitrogen tank under continuous monitoring. BMSC products meeting all lot release criteria were obtained from 8 of the 11 marrow collections. The rate of growth of the primary cultures was similar for all products except those generated from the two oldest donors. One lot did not meet the criteria for final release; its CD34 antigen expression was greater than the cut off set at 5%. The mean number of BMSC units obtained from each donor was 17 and ranged from 3 to 40. Conclusions The production of large numbers of BMSCs from bone marrow aspirates of healthy donors is feasible, but is limited by the high number of donors that did not meet eligibility criteria and products that did not meet lot release criteria.

Feasibility of autologous bone marrow mesenchymal stem cell-derived extracellular matrix scaffold for cartilage tissue engineering.

Science.gov (United States)

Tang, Cheng; Xu, Yan; Jin, Chengzhe; Min, Byoung-Hyun; Li, Zhiyong; Pei, Xuan; Wang, Liming

2013-12-01

Extracellular matrix (ECM) materials are widely used in cartilage tissue engineering. However, the current ECM materials are unsatisfactory for clinical practice as most of them are derived from allogenous or xenogenous tissue. This study was designed to develop a novel autologous ECM scaffold for cartilage tissue engineering. The autologous bone marrow mesenchymal stem cell-derived ECM (aBMSC-dECM) membrane was collected and fabricated into a three-dimensional porous scaffold via cross-linking and freeze-drying techniques. Articular chondrocytes were seeded into the aBMSC-dECM scaffold and atelocollagen scaffold, respectively. An in vitro culture and an in vivo implantation in nude mice model were performed to evaluate the influence on engineered cartilage. The current results showed that the aBMSC-dECM scaffold had a good microstructure and biocompatibility. After 4 weeks in vitro culture, the engineered cartilage in the aBMSC-dECM scaffold group formed thicker cartilage tissue with more homogeneous structure and higher expressions of cartilaginous gene and protein compared with the atelocollagen scaffold group. Furthermore, the engineered cartilage based on the aBMSC-dECM scaffold showed better cartilage formation in terms of volume and homogeneity, cartilage matrix content, and compressive modulus after 3 weeks in vivo implantation. These results indicated that the aBMSC-dECM scaffold could be a successful novel candidate scaffold for cartilage tissue engineering. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

Enhancing the antibacterial performance of orthopaedic implant materials by fibre laser surface engineering

Science.gov (United States)

Chan, Chi-Wai; Carson, Louise; Smith, Graham C.; Morelli, Alessio; Lee, Seunghwan

2017-05-01

Implant failure caused by bacterial infection is extremely difficult to treat and usually requires the removal of the infected components. Despite the severe consequence of bacterial infection, research into bacterial infection of orthopaedic implants is still at an early stage compared to the effort on enhancing osseointegration, wear and corrosion resistance of implant materials. In this study, the effects of laser surface treatment on enhancing the antibacterial properties of commercially pure (CP) Ti (Grade 2), Ti6Al4V (Grade 5) and CoCrMo alloy implant materials were studied and compared for the first time. Laser surface treatment was performed by a continuous wave (CW) fibre laser with a near-infrared wavelength of 1064 nm in a nitrogen-containing environment. Staphylococcus aureus, commonly implicated in infection associated with orthopaedic implants, was used to investigate the antibacterial properties of the laser-treated surfaces. The surface roughness and topography of the laser-treated materials were analysed by a 2D roughness testing and by AFM. The surface morphologies before and after 24 h of bacterial cell culture were captured by SEM, and bacterial viability was determined using live/dead staining. Surface chemistry was analysed by XPS and surface wettability was measured using the sessile drop method. The findings of this study indicated that the laser-treated CP Ti and Ti6Al4V surfaces exhibited a noticeable reduction in bacterial adhesion and possessed a bactericidal effect. Such properties were attributable to the combined effects of reduced hydrophobicity, thicker and stable oxide films and presence of laser-induced nano-features. No similar antibacterial effect was observed in the laser-treated CoCrMo.

CELLULAR MECHANISMS OF BONE REMODELING DUE TO EXTERNAL OVERLOAD AND UNDER CONDITIONS OF TITAN IMPLANT OSSEOINTEGRATION

Directory of Open Access Journals (Sweden)

Gaifullin N.M.

2016-04-01

Full Text Available The goal of article concludes to describe the remodeling of the femur, caused by two processes: the increased strain on supporting tissue as a result of anterior cruciate ligament transection and stimulation by installation of endosseous titanium implants with a porous bioactive coating. The process is traced through 4, 8 and 12 weeks in 28 adult Wistar rats. To characterize the bone remodeling the classical methods of histology and morphometry as well as immune histochemistry to reveal osteonectin, tartrate-resistant acid phosphatase, endothelial marker СD31, matrix metalloproteinases MMP-2, MMP-9, and its tissue inhibitor TIMP-1, were used with necessary morphometrics. The study showed for bone remodelling caused by implants with a porous bioactive coating, to be superior to a similar process under conditions of overload on the bone after transection of the anterior cruciate ligament by its intensity and dynamics. This indicates a high osteoinductive effect of bioactive coating that allows not only to achieve full osseointegration, but also to stimulate a process of intensive remodeling of adjacent cancellous bone. The cooperative participation of cell populations as osteoblasts/osteocytes, osteoclasts, and endothelial cells with characteristic parallel intensive expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitor TIMP-1, used to be main characteristics of bone remodeling in these conditions.

Surface Modifications of Dental Ceramic Implants with Different Glass Solder Matrices: In Vitro Analyses with Human Primary Osteoblasts and Epithelial Cells

Directory of Open Access Journals (Sweden)

Jana Markhoff

2014-01-01

Full Text Available Ceramic materials show excellent esthetic behavior, along with an absence of hypersensitivity, making them a possible alternative implant material in dental surgery. However, their surface properties enable only limited osseointegration compared to titanium implants. Within this study, a novel surface coating technique for enhanced osseointegration was investigated biologically and mechanically. Specimens of tetragonal zirconia polycrystal (TZP and aluminum toughened zirconia (ATZ were modified with glass solder matrices in two configurations which mainly consisted of SiO2, Al2O3, K2O, and Na2O. The influence on human osteoblastic and epithelial cell viability was examined by means of a WST-1 assay as well as live/dead staining. A C1CP-ELISA was carried out to verify procollagen type I production. Uncoated/sandblasted ceramic specimens and sandblasted titanium surfaces were investigated as a reference. Furthermore, mechanical investigations of bilaterally coated pellets were conducted with respect to surface roughness and adhesive strength of the different coatings. These tests could demonstrate a mechanically stable implant coating with glass solder matrices. The coated ceramic specimens show enhanced osteoblastic and partly epithelial viability and matrix production compared to the titanium control. Hence, the new glass solder matrix coating could improve bone cell growth as a prerequisite for enhanced osseointegration of ceramic implants.

Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation: Review of Preclinical and Clinical Studies.

Science.gov (United States)

Yamasaki, Shinya; Mera, Hisashi; Itokazu, Maki; Hashimoto, Yusuke; Wakitani, Shigeyuki

2014-10-01

Clinical trials of various procedures, including bone marrow stimulation, mosaicplasty, and autologous chondrocyte implantation, have been explored to treat articular cartilage defects. However, all of them have some demerits. We focused on autologous culture-expanded bone marrow mesenchymal stem cells (BMSC), which can proliferate without losing their capacity for differentiation. First, we transplanted BMSC into the defective articular cartilage of rabbit and succeeded in regenerating osteochondral tissue. We then applied this transplantation in humans. Our previous reports showed that treatment with BMSC relieves the clinical symptoms of chondral defects in the knee and elbow joint. We investigated the efficacy of BMSC for osteoarthritic knee treated with high tibial osteotomy, by comparing 12 BMSC-transplanted patients with 12 cell-free patients. At 16-month follow-up, although the difference in clinical improvement between both groups was not significant, the arthroscopic and histological grading score was better in the cell-transplanted group. At the over 10-year follow-up, Hospital for Special Surgery knee scores improved to 76 and 73 in the BMSC-transplanted and cell-free groups, respectively, which were better than preoperative scores. Additionally, neither tumors nor infections were observed in all patients, and in the clinical study, we have never observed hypertrophy of repaired tissue, thereby guaranteeing the clinical safety of this therapy. Although we have never observed calcification above the tidemark in rabbit model and human histologically, the repair cartilage was not completely hyaline cartilage. To elucidate the optimum conditions for cell therapy, other stem cells, culture conditions, growth factors, and gene transfection methods should be explored.

Two Measures for Enhancing Data Association Performance in SLAM

Directory of Open Access Journals (Sweden)

Wu Zhou

2014-01-01

Full Text Available Data association is one of the key problems in the SLAM community. Several data association failures may cause the SLAM results to be divergent. Data association performance in SLAM is affected by both data association methods and sensor information. Two measures of handling sensor information are introduced herein to enhance data association performance in SLAM. For the first measure, truncating strategy of limited features, instead of all matched features, is used for observation update. These features are selected according to an information variable. This truncating strategy is used to lower the effect of false matched features. For the other measure, a special rejecting mechanism is designed to reject suspected observations. When the predicted robot pose is obviously different from the updated robot pose, all observed sensor information at this moment is discarded. The rejecting mechanism aims at eliminating accidental sensor information. Experimental results indicate that the introduced measures perform well in improving the stability of data association in SLAM. These measures are of extraordinary value for real SLAM applications.

Human Recombinant Peptide Sponge Enables Novel, Less Invasive Cell Therapy for Ischemic Stroke

Directory of Open Access Journals (Sweden)

Michiyuki Miyamoto

2018-01-01

Full Text Available Bone marrow stromal cell (BMSC transplantation has the therapeutic potential for ischemic stroke. However, it is unclear which delivery routes would yield both safety and maximal therapeutic benefits. We assessed whether a novel recombinant peptide (RCP sponge, that resembles human collagen, could act as a less invasive and beneficial scaffold in cell therapy for ischemic stroke. BMSCs from green fluorescent protein-transgenic rats were cultured and Sprague–Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAo. A BMSC-RCP sponge construct was transplanted onto the ipsilateral intact neocortex 7 days after MCAo. A BMSC suspension or vehicle was transplanted into the ipsilateral striatum. Rat motor function was serially evaluated and histological analysis was performed 5 weeks after transplantation. The results showed that BMSCs could proliferate well in the RCP sponge and the BMSC-RCP sponge significantly promoted functional recovery, compared with the vehicle group. Histological analysis revealed that the RCP sponge provoked few inflammatory reactions in the host brain. Moreover, some BMSCs migrated to the peri-infarct area and differentiated into neurons in the BMSC-RCP sponge group. These findings suggest that the RCP sponge may be a promising candidate for animal protein-free scaffolds in cell therapy for ischemic stroke in humans.

Selecting odorant compounds to enhance sweet flavor perception by gas chromatography/olfactometry-associated taste (GC/O-AT).

Science.gov (United States)

Barba, Carmen; Beno, Noelle; Guichard, Elisabeth; Thomas-Danguin, Thierry

2018-08-15

Gas chromatography/olfactometry-associated taste (GC/O-AT) analysis combined with mass spectrometry allowed identification of odorant compounds associated with taste attributes (sweet, salty, bitter and sour) in a multi-fruit juice. Nine compounds were selected for their odor-associated sweetness enhancement in a multi-fruit juice odor context using Olfactoscan and for their odor-induced sweet taste enhancement in sucrose solution and sugar-reduced fruit juice through sensory tests. Sweetness of the fruit juice odor was significantly enhanced by methyl 2-methylbutanoate, ethyl butanoate, ethyl 2-methylbutanoate and linalool; sweet perception was significantly enhanced in 7% sucrose solution by ethyl 2-methylbutanoate, furaneol and γ-decalactone, and in 32% sugar-reduced fruit juice by ethyl 2-methylbutanoate. GC/O-AT analysis is a novel, efficient approach to select odorants associated with a given taste. The further screening of taste-associated odorants by Olfactoscan helps to identify the most efficient odorants to enhance a target taste perception and may be used to find new ways to modulate taste perception in foods and beverages. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Enforcing osseointegration of dental implantates spray-coated by bioceramics with the help of hyaluronic acid and hydroxyapatite gel in experimental conditions].

Science.gov (United States)

Kulakov, A A; Volozhin, A I; Tkachenko, V M; Doktorov, A A; Salim, Ibrakhim Samir

2007-01-01

Influence of HAP-gel (2 g of 2% solution of hyaluronic acid mixed with 0,5 g of hydroxyapatite and 0,1 ml of colloidal silver) upon osseointegration in case of delayed introduction of titanium implantates in dog jaw. By scanning electron microscopy it was shown that solely use either of HAP-gel or of ceramic spraying increased direct contact area between bone and implantates in the 6 and 9 months time period. Combination of spray-coated ceramic with HAP-gel was effective in 3 months after implantation, when solely the HAP-gel or the ceramic spraying were little effective. In the following terms of experiment (6 and 9 months) significant differences between groups 3 and 4 (implantate with ceramic spraying but without HAP-gel in the alveolus and implantate with ceramic spraying and with HAP-gel in the alveolus) were not found. The area of implantate integration with jaw bone (cortical part of it was excluded) was equal to 80% and was maximal for the given conditions of the experiment.

Early passage bone marrow stromal cells express genes involved in nervous system development supporting their relevance for neural repair

NARCIS (Netherlands)

Nandoe Tewarie, R.D.S.; Bossers, K.; Ritfeld, G.J.; Blits, B.; Grotenhuis, J.A.; Verhaagen, J.; Oudega, M.

2011-01-01

PURPOSE: The assessment of the capacity of bone marrow stromal cells (BMSC) to repair the nervous system using gene expression profiling. The evaluation of effects of long-term culturing on the gene expression profile of BMSC. METHODS: Fourty four k whole genome rat microarrays were used to study

Bone marrow stromal cells elicit tissue sparing after acute but not delayed transplantation into the contused adult rat thoracic spinal cord.

NARCIS (Netherlands)

Tewarie, R.D.; Hurtado, A.; Ritfeld, G.J.; Rahiem, S.T.; Wendell, D.F.; Barroso, M.M.; Grotenhuis, J.A.; Oudega, M.

2009-01-01

Bone marrow stromal cells (BMSC) transplanted into the contused spinal cord may support repair by improving tissue sparing. We injected allogeneic BMSC into the moderately contused adult rat thoracic spinal cord at 15 min (acute) and at 3, 7, and 21 days (delayed) post-injury and quantified tissue

Microwave assisted coating of bioactive amorphous magnesium phosphate (AMP) on polyetheretherketone (PEEK).

Science.gov (United States)

Ren, Yufu; Sikder, Prabaha; Lin, Boren; Bhaduri, Sarit B

2018-04-01

Polyetheretherketone (PEEK) with great thermal and chemical stability, desirable mechanical properties and promising biocompatibility is being widely used as orthopedic and dental implant materials. However, the bioinert surface of PEEK can hinder direct osseointegration between the host tissue and PEEK based implants. The important signatures of this paper are as follows. First, we report for the formation of osseointegrable amorphous magnesium phosphate (AMP) coating on PEEK surface using microwave energy. Second, coatings consist of nano-sized AMP particles with a stacked thickness of 800nm. Third, coatings enhance bioactivity in-vitro and induce significantly high amount of bone-like apatite coating, when soaked in simulated body fluid (SBF). Fourth, the as-deposited AMP coatings present no cytotoxicity effects and are beneficial for cell adhesion at early stage. Finally, the high levels of expression of osteocalcin (OCN) in cells cultured on AMP coated PEEK samples indicate that AMP coatings can promote new bone formation and hence osseointegration. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors

Science.gov (United States)

2016-10-01

development of the principal discipline(s) of the project? • We have learned that the drug PEGPH20, which degrades a component of connective tissue called...AWARD NUMBER: W81XWH-15-1-0114 TITLE: Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors PRINCIPAL INVESTIGATOR...14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER NF140089 Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors 5b

Dual-Functionalized Graphene Oxide Based siRNA Delivery System for Implant Surface Biomodification with Enhanced Osteogenesis.

Science.gov (United States)

Zhang, Li; Zhou, Qing; Song, Wen; Wu, Kaimin; Zhang, Yumei; Zhao, Yimin

2017-10-11

Surface functionalization by small interfering RNA (siRNA) is a novel strategy for improved implant osseointegration. A gene delivery system with safety and high transfection activity is a crucial factor for an siRNA-functionalized implant to exert its biological function. To this end, polyethylene glycol (PEG) and polyethylenimine (PEI) dual-functionalized graphene oxide (GO; nGO-PEG-PEI) may present a promising siRNA vector. In this study, nanosized nGO-PEG-PEI was prepared and optimized for siRNA delivery. Titania nanotubes (NTs) fabricated by anodic oxidation were biomodified with nGO-PEG-PEI/siRNA by cathodic electrodeposition, designated as NT-GPP/siRNA. NT-GPP/siRNA possessed benign cytocompatibility, as evaluated by cell adhesion and proliferation. Cellular uptake and knockdown efficiency of the NT-GPP/siRNA were assessed by MC3T3-E1 cells, which exhibited high siRNA delivery efficiency and sustained target gene silencing. Casein kinase-2 interacting protein-1 (Ckip-1) is a negative regulator of bone formation. siRNA-targeting Ckip-1 (siCkip-1) was introduced to the implant, and a series of in vitro and in vivo experiments were carried out to evaluate the osteogenic capacity of NT-GPP/siCkip-1. NT-GPP/siCkip-1 dramatically improved the in vitro osteogenic differentiation of MC3T3-E1 cells in terms of improved osteogenesis-related gene expression, and increased alkaline phosphatase (ALP) production, collagen secretion, and extracellular matrix (ECM) mineralization. Moreover, NT-GPP/siCkip-1 led to apparently enhanced in vivo osseointegration, as indicated by histological staining and EDX line scanning. Collectively, these findings suggest that NT-GPP/siRNA represents a practicable and promising approach for implant functionalization, showing clinical potential for dental and orthopedic applications.

Long-term osseointegration of 3D printed CoCr constructs with an interconnected open-pore architecture prepared by electron beam melting.

Science.gov (United States)

Shah, Furqan A; Omar, Omar; Suska, Felicia; Snis, Anders; Matic, Aleksandar; Emanuelsson, Lena; Norlindh, Birgitta; Lausmaa, Jukka; Thomsen, Peter; Palmquist, Anders

2016-05-01

In orthopaedic surgery, cobalt chromium (CoCr) based alloys are used extensively for their high strength and wear properties, but with concerns over stress shielding and bone resorption due to the high stiffness of CoCr. The structural stiffness, principally related to the bulk and the elastic modulus of the material, may be lowered by appropriate design modifications, to reduce the stiffness mismatch between metal/alloy implants and the adjacent bone. Here, 3D printed CoCr and Ti6Al4V implants of similar macro-geometry and interconnected open-pore architecture prepared by electron beam melting (EBM) were evaluated following 26week implantation in adult sheep femora. Despite higher total bone-implant contact for Ti6Al4V (39±4%) than CoCr (27±4%), bone formation patterns were similar, e.g., densification around the implant, and gradual ingrowth into the porous network, with more bone in the outer half (periphery) than the inner half (centre). Raman spectroscopy revealed no major differences in mineral crystallinity, the apatite-to-collagen ratio, or the carbonate-to-phosphate ratio. Energy dispersive X-ray spectroscopy showed similar Ca/P ratio of the interfacial tissue adjacent to both materials. Osteocytes made direct contact with CoCr and Ti6Al4V. While osteocyte density and distribution in the new-formed bone were largely similar for the two alloys, higher osteocyte density was observed at the periphery of the porous network for CoCr, attributable to slower remodelling and a different biomechanical environment. The results demonstrate the possibility to achieve bone ingrowth into open-pore CoCr constructs, and attest to the potential for fabricating customised osseointegrated CoCr implants for load-bearing applications. Although cobalt chromium (CoCr) based alloys are used extensively in orthopaedic surgery, stress shielding due to the high stiffness of CoCr is of concern. To reduce the stiffness mismatch between CoCr and bone, CoCr and Ti6Al4V implants having

In vitro differentiation of bone marrow stromal cells into neurons and glial cells and differential protein expression in a two-compartment bone marrow stromal cell/neuron co-culture system.

Science.gov (United States)

Qi, Xu; Shao, Ming; Peng, Haisheng; Bi, Zhenggang; Su, Zhiqiang; Li, Hulun

2010-07-01

This study was performed to establish a bone marrow stromal cell (BMSC)/neuron two-compartment co-culture model in which differentiation of BMSCs into neurons could occur without direct contact between the two cell types, and to investigate protein expression changes during differentiation of this entirely BMSC-derived population. Cultured BMSCs isolated from Wistar rats were divided into three groups: BMSC culture, BMSC/neuron co-culture and BMSC/neuron two-compartment co-culture. Cells were examined for neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) expression. The electrophysiological behavior of the BMSCs was examined using patch clamping. Proteins that had significantly different expression levels in BMSCs cultured alone and co-cultured with neurons were studied using a protein chip-mass spectroscopy technique. Expression of NSE and GFAP were significantly higher in co-culture cells than in two-compartment co-culture cells, and significantly higher in both co-culture groups than in BMSCs cultured alone. Five proteins showed significant changes in expression during differentiation: TIP39_RAT and CALC_RAT underwent increases, and INSL6_RAT, PNOC_RAT and PCSK1_RAT underwent decreases in expression. We conclude that BMSCs can differentiate into neurons during both contact co-culture with neurons and two-compartment co-culture with neurons. The rate at which BMSCs differentiated into neurons was higher in contact co-culture than in non-contact co-culture.

Integrin-mediated adhesion of human mesenchymal stem cells to extracellular matrix proteins adsorbed to polymer surfaces

International Nuclear Information System (INIS)

Dånmark, S; Mustafa, K; Finne-Wistrand, A; Albertsson, A-C; Patarroyo, M

2012-01-01

In vitro, degradable aliphatic polyesters are widely used as cell carriers for bone tissue engineering, despite their lack of biological cues. Their biological active surface is rather determined by an adsorbed layer of proteins from the surrounding media. Initial cell fate, including adhesion and proliferation, which are key properties for efficient cell carriers, is determined by the adsorbed layer of proteins. Herein we have investigated the ability of human bone marrow derived stem cells (hBMSC) to adhere to extracellular matrix (ECM) proteins, including fibronectin and vitronectin which are present in plasma and serum. hBMSC expressed integrins for collagens, laminins, fibronectin and vitronectin. Accordingly, hBMSC strongly adhered to these purified ECM proteins by using the corresponding integrins. Although purified fibronectin and vitronectin adsorbed to aliphatic polyesters to a lower extent than to cell culture polystyrene, these low levels were sufficient to mediate adhesion of hBMSC. It was found that plasma- and serum-coated polystyrene adsorbed significant levels of both fibronectin and vitronectin, and fibronectin was identified as the major adhesive component of plasma for hBMSC; however, aliphatic polyesters adsorbed minimal levels of fibronectin under similar conditions resulting in impaired cell adhesion. Altogether, the results suggest that the efficiency of aliphatic polyesters cell carriers could be improved by increasing their ability to adsorb fibronectin. (paper)

Pyogenic granuloma associated with mandibular odontoma.

Directory of Open Access Journals (Sweden)

Karla Ocampo

2014-08-01

Full Text Available Background: pyogenic granuloma is a kind of inflammatory hyperplasia of multifactorial origin, which is usually related to trauma or constant irritation, drug use, hormonal factors, among others. Meanwhile the odontoma is a benign tumor odontogenic composed of epithelial and mesenchymal cells, their development is usually associated with trauma, infections, inherited disorders or hyperactivity odontoblast. Objectives: The objective is to present the clinical case of a patient that presented a case of pyogenic granuloma related to the presence of a mandibular odontoma, and therapeutic management and postoperative results. Case report: The case shows a female patient of 32 years old with a history of multinodular goiter and hypothyroidism, developing a mandibular odontoma of the left side associated with pyogenic granuloma in the same area, which was treated with surgical excision and reconstructed affected tissues with lyophilized bone and collagen membrane. Favorable outcome after surgery without evidence of recurrence, with proper osseointegration of alloplastic materials and soft tissues. Conclusions: The irritant effect of the presence of a tumor (odontoma in developing confirmed pyogenic granuloma.

Local processing enhancements associated with superior observational drawing are due to enhanced perceptual functioning, not weak central coherence.

Science.gov (United States)

Chamberlain, Rebecca; McManus, I C; Riley, Howard; Rankin, Qona; Brunswick, Nicola

2013-01-01

Individuals with drawing talent have previously been shown to exhibit enhanced local visual processing ability. The aim of the current study was to assess whether local processing biases associated with drawing ability result from a reduced ability to cohere local stimuli into global forms, or an increased ability to disregard global aspects of an image. Local and global visual processing ability was assessed in art students and controls using the Group Embedded Figures Task, Navon shape stimuli, the Block Design Task and the Autism Spectrum Quotient, whilst controlling for nonverbal IQ and artistic ability. Local processing biases associated with drawing appear to arise from an enhancement of local processing alongside successful filtering of global information, rather than a reduction in global processing. The relationship between local processing and drawing ability is independent of individual differences in nonverbal IQ and artistic ability. These findings have implications for bottom-up and attentional theories of observational drawing, as well as explanations of special skills in autism.

Enhanced human bone marrow mesenchymal stem cell functions on cathodic arc plasma-treated titanium

Directory of Open Access Journals (Sweden)

Zhu W

2015-12-01

Full Text Available Wei Zhu,1 George Teel,1 Christopher M O’Brien,1 Taisen Zhuang,1 Michael Keidar,1 Lijie Grace Zhang1–3 1Department of Mechanical and Aerospace Engineering, 2Department of Biomedical Engineering, 3Department of Medicine, The George Washington University, Washington, DC, USA Abstract: Surface modification of titanium for use in orthopedics has been explored for years; however, an ideal method of integrating titanium with native bone is still required to this day. Since human bone cells directly interact with nanostructured extracellular matrices, one of the most promising methods of improving titanium’s osseointegration involves inducing biomimetic nanotopography to enhance cell–implant interaction. In this regard, we explored an approach to functionalize the surface of titanium by depositing a thin film of textured titanium nanoparticles via a cathodic arc discharge plasma. The aim is to improve human bone marrow mesenchymal stem cell (MSC attachment and differentiation and to reduce deleterious effects of more complex surface modification methods. Surface functionalization was analyzed by scanning electron microscopy, atomic force microscopy, contact angle testing, and specific protein adsorption. Scanning electron microscopy and atomic force microscopy examination demonstrate the deposition of titanium nanoparticles and the surface roughness change after coating. The specific fibronectin adsorption was enhanced on the modified titanium surface that associates with the improved hydrophilicity. MSC adhesion and proliferation were significantly promoted on the nanocoated surface. More importantly, compared to bare titanium, greater production of total protein, deposition of calcium mineral, and synthesis of alkaline phosphatase were observed from MSCs on nanocoated titanium after 21 days. The method described herein presents a promising alternative method for inducing more cell favorable nanosurface for improved orthopedic applications

Enhancing gene delivery of adeno-associated viruses by cell-permeable peptides

Directory of Open Access Journals (Sweden)

Yarong Liu

2014-01-01

Full Text Available Adeno-associated virus type 2 (AAV2 is considered a promising gene delivery vector and has been extensively applied in several disease models; however, inefficient transduction in various cells and tissues has limited its widespread application in many areas of gene therapy. In this study, we have developed a general, but efficient, strategy to enhance viral transduction, both in vitro and in vivo, by incubating viral particles with cell-permeable peptides (CPPs. We show that CPPs increase internalization of viral particles into cells by facilitating both energy-independent and energy-dependent endocytosis. Moreover, CPPs can significantly enhance the endosomal escape process of viral particles, thus enhancing viral transduction to those cells that have exhibited very low permissiveness to AAV2 infection as a result of impaired intracellular viral processing. We also demonstrated that this approach could be applicable to other AAV serotypes. Thus, the membrane-penetrating ability of CPPs enables us to generate an efficient method for enhanced gene delivery of AAV vectors, potentially facilitating its applicability to human gene therapy.

Contrast enhanced MR findings of lesions associated with radial scar: correlation with histopathology

Energy Technology Data Exchange (ETDEWEB)

Chung, Jee Woo; Cha, Eun Suk; Choi, Hyun Joo; Seo, Young Jin [College of Medicine, The Catholic University of Korea, Suwon (Korea, Republic of)

2007-01-15

To evaluate the contrast-enhanced MR findings of lesions associated with a radial scar and to compare the MR findings with the histopathology results. From Mar. 2001 to Sep. 2005, 8 patients with a surgically proven radial scar who had undergone MRI, mammography, and ultrasonography were enrolled in this study. The morphological findings and dynamic enhancement pattern of the time-intensity curve were retrospectively reviewed using noncontrast and contrast-enhanced MRI. Mammography and ultrasonography were also analyzed according to the BI-RADS category and correlated with the histopathological diagnosis. The age of the patients ranged from 42 to 53 years (mean, 47 years). Five patients presented with a left breast lesion and the others presented with a right breast lesion. The histopathological diagnosis associated with the radial scar were fibrocystic changes (n = 1) adenosis (n = 2), atypical ductal hyperplasia (n = 2), lobular carcinoma in situ (n = 1), ductal carcinoma in situ (n = 1), and invasive ductal carcinoma (n = 1). In all patients, architectural distortion without microcalcification was observed with mammography. Irregular shaped hypoechoic lesions with an indistinct, spiculated, or angular margin was observed in all patients with ultrasonography. Posterior shadowing was observed in 4 cases. MR enhancement revealed two cases with foci enhancement (adenosis and fibrocystic change), five cases with non-mass-like focal enhancement (fibrocystic change, atypical ductal hyperplasia, lobular carcinoma in situ, ductal carcinoma in situ, invasive ductal carcinoma), and one irregular homogeneous mass enhancement (atypical ducal hyperplasia). The time-signal intensity curves are as follows: persistent type (n = 2), adenosis, and fibrocystic changes, respectively; plateu type (n = 4) one adenosis, two atypical ductal hyperplasia, and one ductal carcinoma in situ; and washout type (n = 2), lobular carcinoma in situ, and invasive ductal carcinoma, respectively

Contrast enhanced MR findings of lesions associated with radial scar: correlation with histopathology

International Nuclear Information System (INIS)

Chung, Jee Woo; Cha, Eun Suk; Choi, Hyun Joo; Seo, Young Jin

2007-01-01

To evaluate the contrast-enhanced MR findings of lesions associated with a radial scar and to compare the MR findings with the histopathology results. From Mar. 2001 to Sep. 2005, 8 patients with a surgically proven radial scar who had undergone MRI, mammography, and ultrasonography were enrolled in this study. The morphological findings and dynamic enhancement pattern of the time-intensity curve were retrospectively reviewed using noncontrast and contrast-enhanced MRI. Mammography and ultrasonography were also analyzed according to the BI-RADS category and correlated with the histopathological diagnosis. The age of the patients ranged from 42 to 53 years (mean, 47 years). Five patients presented with a left breast lesion and the others presented with a right breast lesion. The histopathological diagnosis associated with the radial scar were fibrocystic changes (n = 1) adenosis (n = 2), atypical ductal hyperplasia (n = 2), lobular carcinoma in situ (n = 1), ductal carcinoma in situ (n = 1), and invasive ductal carcinoma (n = 1). In all patients, architectural distortion without microcalcification was observed with mammography. Irregular shaped hypoechoic lesions with an indistinct, spiculated, or angular margin was observed in all patients with ultrasonography. Posterior shadowing was observed in 4 cases. MR enhancement revealed two cases with foci enhancement (adenosis and fibrocystic change), five cases with non-mass-like focal enhancement (fibrocystic change, atypical ductal hyperplasia, lobular carcinoma in situ, ductal carcinoma in situ, invasive ductal carcinoma), and one irregular homogeneous mass enhancement (atypical ducal hyperplasia). The time-signal intensity curves are as follows: persistent type (n = 2), adenosis, and fibrocystic changes, respectively; plateu type (n = 4) one adenosis, two atypical ductal hyperplasia, and one ductal carcinoma in situ; and washout type (n = 2), lobular carcinoma in situ, and invasive ductal carcinoma, respectively

The Influence of 1α.25-Dihydroxyvitamin D3 Coating on Implant Osseointegration in the Rabbit Tibia

Directory of Open Access Journals (Sweden)

Yoshihito

2014-10-01

Full Text Available Objectives: This study aims to evaluate bone response to an implant surface modified by 1α,25-dihydroxyvitamin D3 [1.25-(OH2D3] in vivo and the potential link between 1.25-(OH 2D3 surface concentration and bone response. Material and Methods: Twenty-eight implants were divided into 4 groups (1 uncoated control, 3 groups coated with 1.25-(OH2D3 in concentrations of 10-8, 10-7 and 10-6 M respectively, placed in the rabbit tibia for 6 weeks. Topographical analyses were carried out on coated and uncoated discs using interferometer and atomic-force-microscope (AFM. Twenty-eight implants were histologically observed (bone-to-implant-contact [BIC] and new-bone-area [NBA]. Results: The results showed that the 1.25-(OH2D3 coated implants presented a tendency to osseointegrate better than the non-coated surfaces, the differences were not significant (P > 0.05. Conclusions: The effect of 1.25-(OH2D3 coating to implants suggested possible dose dependent effects, however no statistical differences could be found. It is thought that the base substrate topography (turned could not sustain sufficient amount of 1.25-(OH2D3 enough to present significant biologic responses. Thus, development a base substrate that can sustain 1.25-(OH2D3 for a long period is necessary in future studies.

Peri-implant evaluation of osseointegrated implants subjected to orthodontic forces: results after three years of functional loading

Directory of Open Access Journals (Sweden)

Bruna de Rezende Marins

2016-04-01

Full Text Available ABSTRACT Objective: The objective of this study was to clinically and radiographically assess the peri-implant conditions of implants used as orthodontic anchorage. Methods: Two groups were studied: 1 a test group in which osseointegrated implants were used as orthodontic anchorage, with the application of 200-cN force; and 2 a control group in which implants were not subjected to orthodontic force, but supported a screw-retained prosthesis. Clinical evaluations were performed three, six and nine months after prosthesis installation and 1- and 3-year follow-up examinations. Intraoral periapical radiographs were obtained 30 days after surgical implant placement, at the time of prosthesis installation, and one, two and three years thereafter. The results were compared by Kruskal-Wallis test. Results: There was no statistically significant difference in clinical probing depth (p = 0.1078 or mesial and distal crestal bone resorption (p = 0.1832 during the study period. After three years of follow-up, the mean probing depth was 2.21 mm for the control group and 2.39 mm for the test group. The implants of the control group showed a mean distance between the bone crest and implant shoulder of 2.39 mm, whereas the implants used as orthodontic anchorage showed a mean distance of 2.58 mm at the distal site. Conclusion: Results suggest that the use of stable intraoral orthodontic anchorage did not compromise the health of peri-implant tissues or the longevity of the implant.

Characterization of Cellular and Molecular Heterogeneity of Bone Marrow Stromal Cells

DEFF Research Database (Denmark)

Elsafadi, Mona; Manikandan, Muthurangan; Atteya, Muhammad

2016-01-01

and osteoblast differentiation genes which included several homeobox genes: TBX15, HOXA2 and HOXA10, and IGF1, FGFR3, BMP6, MCAM, ITGA10, IGFBP5, and ALP. siRNA-based downregulation of the ALP gene in CL1 impaired osteoblastic and adipocytic differentiation. Our studies demonstrate the existence of molecular......Human bone marrow-derived stromal stem cells (hBMSC) exhibit multiple functions, including differentiation into skeletal cells (progenitor function), hematopoiesis support, and immune regulation (nonprogenitor function). We have previously demonstrated the presence of morphological and functional...... and functional heterogeneity in cultured hBMSC. ALP can be employed to identify osteoblastic and adipocytic progenitor cells in the heterogeneous hBMSC cultures...

Pleiotrophin commits human bone marrow mesenchymal stromal cells towards hypertrophy during chondrogenesis.

Science.gov (United States)

Bouderlique, Thibault; Henault, Emilie; Lebouvier, Angelique; Frescaline, Guilhem; Bierling, Phillipe; Rouard, Helene; Courty, José; Albanese, Patricia; Chevallier, Nathalie

2014-01-01

Pleiotrophin (PTN) is a growth factor present in the extracellular matrix of the growth plate during bone development and in the callus during bone healing. Bone healing is a complicated process that recapitulates endochondral bone development and involves many cell types. Among those cells, mesenchymal stromal cells (MSC) are able to differentiate toward chondrogenic and osteoblastic lineages. We aimed to determine PTN effects on differentiation properties of human bone marrow stromal cells (hBMSC) under chondrogenic induction using histological analysis and quantitative reverse transcription polymerase chain reaction. PTN dramatically potentiated chondrogenic differentiation as indicated by a strong increase of collagen 2 protein, and cartilage-related gene expression. Moreover, PTN increased transcription of hypertrophic chondrocyte markers such as MMP13, collagen 10 and alkaline phosphatase and enhanced calcification and the content of collagen 10 protein. These effects are dependent on PTN receptors signaling and PI3 K pathway activation. These data suggest a new role of PTN in bone regeneration as an inducer of hypertrophy during chondrogenic differentiation of hBMSC.

Pleiotrophin commits human bone marrow mesenchymal stromal cells towards hypertrophy during chondrogenesis.

Directory of Open Access Journals (Sweden)

Thibault Bouderlique

Full Text Available Pleiotrophin (PTN is a growth factor present in the extracellular matrix of the growth plate during bone development and in the callus during bone healing. Bone healing is a complicated process that recapitulates endochondral bone development and involves many cell types. Among those cells, mesenchymal stromal cells (MSC are able to differentiate toward chondrogenic and osteoblastic lineages. We aimed to determine PTN effects on differentiation properties of human bone marrow stromal cells (hBMSC under chondrogenic induction using histological analysis and quantitative reverse transcription polymerase chain reaction. PTN dramatically potentiated chondrogenic differentiation as indicated by a strong increase of collagen 2 protein, and cartilage-related gene expression. Moreover, PTN increased transcription of hypertrophic chondrocyte markers such as MMP13, collagen 10 and alkaline phosphatase and enhanced calcification and the content of collagen 10 protein. These effects are dependent on PTN receptors signaling and PI3 K pathway activation. These data suggest a new role of PTN in bone regeneration as an inducer of hypertrophy during chondrogenic differentiation of hBMSC.

Bone marrow stem cells assuage radiation-induced damage in a murine model of distraction osteogenesis: A histomorphometric evaluation.

Science.gov (United States)

Zheutlin, Alexander R; Deshpande, Sagar S; Nelson, Noah S; Kang, Stephen Y; Gallagher, Kathleen K; Polyatskaya, Yekaterina; Rodriguez, Jose J; Donneys, Alexis; Ranganathan, Kavitha; Buchman, Steven R

2016-05-01

The purpose of this study is to determine if intraoperatively placed bone marrow stem cells (BMSCs) will permit successful osteocyte and mature bone regeneration in an isogenic murine model of distraction osteogenesis (DO) following radiation therapy (XRT). Lewis rats were split into three groups, DO only (Control), XRT followed by DO (xDO) and XRT followed by DO with intraoperatively placed BMSCs (xDO-BMSC). Coronal sections from the distraction site were obtained, stained and analyzed via statistical analysis with analysis of variance (ANOVA) and subsequent Tukey or Games-Howell post-hoc tests. Comparison of the xDO-BMSC and xDO groups demonstrated significantly improved osteocyte count (87.15 ± 10.19 vs. 67.88 ± 15.38, P = 0.00), and empty lacunae number (2.18 ± 0.79 vs 12.34 ± 6.61, P = 0.00). Quantitative analysis revealed a significant decrease in immature osteoid volume relative to total volume (P = 0.00) and improved the ratio of mature woven bone to immature osteoid (P = 0.02) in the xDO-BMSC compared with the xDO group. No significant differences were found between the Control and xDO-BMSC groups. In an isogenic murine model of DO, BMSC therapy assuaged XRT-induced cellular depletion, resulting in a significant improvement in histological and histomorphometric outcomes. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

In vitro induction of alkaline phosphatase levels predicts in vivo bone forming capacity of human bone marrow stromal cells

Directory of Open Access Journals (Sweden)

Henk-Jan Prins

2014-03-01

Full Text Available One of the applications of bone marrow stromal cells (BMSCs that are produced by ex vivo expansion is for use in in vivo bone tissue engineering. Cultured stromal cells are a mixture of cells at different stages of commitment and expansion capability, leading to a heterogeneous cell population that each time can differ in the potential to form in vivo bone. A parameter that predicts for in vivo bone forming capacity is thus far lacking. We employed single colony-derived BMSC cultures to identify such predictive parameters. Using limiting dilution, we have produced sixteen single CFU-F derived BMSC cultures from human bone marrow and found that only five of these formed bone in vivo. The single colony-derived BMSC strains were tested for proliferation, osteogenic-, adipogenic- and chondrogenic differentiation capacity and the expression of a variety of associated markers. The only robust predictors of in vivo bone forming capacity were the induction of alkaline phosphatase, (ALP mRNA levels and ALP activity during in vitro osteogenic differentiation. The predictive value of in vitro ALP induction was confirmed by analyzing “bulk-cultured” BMSCs from various bone marrow biopsies. Our findings show that in BMSCs, the additional increase in ALP levels over basal levels during in vitro osteogenic differentiation is predictive of in vivo performance.

Incorporating simvastatin/poloxamer 407 hydrogel into 3D-printed porous Ti6Al4V scaffolds for the promotion of angiogenesis, osseointegration and bone ingrowth.

Science.gov (United States)

Liu, Hao; Li, Wei; Liu, Can; Tan, Jie; Wang, Hong; Hai, Bao; Cai, Hong; Leng, Hui-Jie; Liu, Zhong-Jun; Song, Chun-Li

2016-10-27

Three-dimensional porous titanium alloys printed via electron beam melting have low stiffness similar to that of cortical bone and are promising scaffolds for orthopedic applications. However, the bio-inert nature of titanium alloy is poorly compatible with bone ingrowth. We previously observed that simvastatin/poloxamer 407 thermosensitive hydrogel induces endogenous angiogenic/osteogenic growth factors and promotes angiogenesis and osteogenesis, but the mechanical properties of this hydrogel are poor. The purpose of this study was to construct 3D-printed porous titanium scaffolds (pTi scaffolds) filled with simvastatin/hydrogel and evaluate the effects of this composite on osseointegration, bone ingrowth and neovascularization using a tibial defect rabbit model. Four and eight weeks after implantation, the bone volume, bone mineral density, mineral apposition rate, and push-in maximum force of the pTi scaffolds filled with simvastatin/hydrogel were significantly higher than those without simvastatin (p bone and neovascularization (p bone ingrowth.

Osseointegration properties of titanium dental implants modified with a nanostructured coating based on ordered porous silica and bioactive glass nanoparticles

Science.gov (United States)

Covarrubias, Cristian; Mattmann, Matías; Von Marttens, Alfredo; Caviedes, Pablo; Arriagada, Cristián; Valenzuela, Francisco; Rodríguez, Juan Pablo; Corral, Camila

2016-02-01

The fabrication of a nanoporous silica coating loaded with bioactive glass nanoparticles (nBG/NSC) on titanium dental implant surface and its in vitro and in vivo evaluation is presented. The coating was produced by a combined sol-gel and evaporation induced self-assembly process. In vitro bioactivity was assessed in simulated body fluid (SBF) and investigating the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). A rat tibial model was employed to analyze the bone response to nBG/NSC-modified titanium implant surface in vivo. The nBG/NSC coating was confirmed at nano level to be constituted by a highly ordered nanoporous silica structure. The coating nanotopography in conjunction with the bioactivity of the BG particles accelerate the in vitro apatite formation and promote the osteogenic differentiation of hBMSCs in absence of osteogenic supplements. These properties accelerate the formation of bone tissue in the periphery of the implant after 3 weeks of implantation. Backscattered scanning electron microscopy images revealed the presence of gaps and soft tissue in the unmodified implant after 6 weeks, whereas the nBG/NSC-modified implant showed mature bone in intimate contact with the implant surface. The nBG/NSC coating appears promising for accelerating the osseointegration of dental implants.

An increase in tobacco craving is associated with enhanced medial prefrontal cortex network coupling.

Directory of Open Access Journals (Sweden)

Amy C Janes

Full Text Available Craving is a key aspect of drug dependence that is thought to motivate continued drug use. Numerous brain regions have been associated with craving, suggesting that craving is mediated by a distributed brain network. Whether an increase in subjective craving is associated with enhanced interactions among brain regions was evaluated using resting state functional magnetic imaging (fMRI in nicotine dependent participants. We focused on craving-related changes in the orbital and medial prefrontal cortex (OMPFC network, which also included the subgenual anterior cingulate cortex (sgACC extending into the ventral striatum. Brain regions in the OMPFC network are not only implicated in addiction and reward, but, due to their rich anatomic interconnections, may serve as the site of integration across craving-related brain regions. Subjective craving and resting state fMRI were evaluated twice with an ∼1 hour delay between the scans. Cigarette craving was significantly increased at the end, relative to the beginning of the scan session. Enhanced craving was associated with heightened coupling between the OMPFC network and other cortical, limbic, striatal, and visceromotor brain regions that are both anatomically interconnected with the OMPFC, and have been implicated in addiction and craving. This is the first demonstration confirming that an increase in craving is associated with enhanced brain region interactions, which may play a role in the experience of craving.

Transplantation of osteoporotic bone marrow stromal cells rejuvenated by the overexpression of SATB2 prevents alveolar bone loss in ovariectomized rats.

Science.gov (United States)

Xu, Rongyao; Fu, Zongyun; Liu, Xue; Xiao, Tao; Zhang, Ping; Du, Yifei; Yuan, Hua; Cheng, Jie; Jiang, Hongbing

2016-11-01

Estrogen-deficient osteoporosis is an aging-related disease with high morbidity that not only significantly increases a woman's risk of fragility fracture but is also associated with tooth and bone loss in the supporting alveolar bone of the jaw. Emerging evidence suggests that the aging of bone marrow stromal cells (BMSCs) contributes to the development of osteoporosis. In this study, we aimed to investigate the role of the special AT-rich sequence-binding protein 2 (SATB2), a stemness and senescence regulator of craniofacial BMSCs, in rat ovariectomy-induced alveolar osteoporosis. We also sought to determine whether transplantation of SATB2-modified BMSCs could ameliorate estrogen deficient alveolar bone loss. Our data revealed that BMSCs from ovariectomy-induced alveolar bone exhibited typical senescence phenotypes such as diminished stemness and osteogenic capacity, increased expression of senescence or osteoclastic markers and enhanced adipogenic potential. These phenotypic changes are a result of SATB2-mediated senescence dysregulation as evidenced by nuclear γH2AX foci formation. Moreover, overexpression of SATB2 significantly alleviated the senescence of osteoporotic BMSCs in vitro. Importantly, transplantation of SATB2-modified BMSCs significantly attenuated ovariectomy-induced alveolar bone loss in vivo. Together, our results revealed that SATB2 is a critical regulator of alveolar BMSC senescence, and its overexpression decreases these senescent changes both in vitro and in vivo. SATB2-modified BMSC delivery could be a viable and promising therapeutic strategy for alveolar bone loss induced by estrogen-deficient osteoporosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Electrical Polarization of Titanium Surfaces for the Enhancement of Osteoblast Differentiation

Science.gov (United States)

Gittens, Rolando A.; Olivares-Navarrete, Rene; Rettew, Robert; Butera, Robert J.; Alamgir, Faisal M.; Boyan, Barbara D.; Schwartz, Zvi

2014-01-01

Electrical stimulation has been used clinically to promote bone regeneration in cases of fractures with delayed union or nonunion, with several in vitro and in vivo reports suggesting its beneficial effects on bone formation. However, the use of electrical stimulation of titanium (Ti) implants to enhance osseointegration is less understood, in part because of the few in vitro models that attempt to represent the in vivo environment. In this article, the design of a new in vitro system that allows direct electrical stimulation of osteoblasts through their Ti substrates without the flow of exogenous currents through the media is presented, and the effect of applied electrical polarization on osteoblast differentiation and local factor production was evaluated. A custom-made polycarbonate tissue culture plate was designed to allow electrical connections directly underneath Ti disks placed inside the wells, which were supplied with electrical polarization ranging from 100 to 500 mV to stimulate MG63 osteoblasts. Our results show that electrical polarization applied directly through Ti substrates on which the cells are growing in the absence of applied electrical currents may increase osteoblast differentiation and local factor production in a voltage-dependent manner. PMID:23996899

Arbuscular mycorrhizal association enhances drought tolerance potential of promising bioenergy grass (Saccharum arundinaceum retz.).

Science.gov (United States)

Mirshad, P P; Puthur, Jos T

2016-07-01

The influence of arbuscular mycorrhizal fungi (AMF) (Glomus spp.) on some physiological and biochemical characteristics of bioenergy grass Saccharum arundinaceum subjected to drought stress was studied. The symbiotic association of Glomus spp. was established with S. arundinaceum, a potential bioenergy grass as evident from the increase in percentage of root infection and distribution frequency of vesicles when compared with non-arbuscular mycorrhizal plants. AMF-treated plants exhibited an enhanced accumulation of osmolytes such as sugars and proline and also increased protein content under drought. AMF association significantly increased the accumulation of non-enzymatic antioxidants like phenols, ascorbate and glutathione as well as enhanced the activities of antioxidant enzymes such as SOD (superoxide dismutase), APX (ascorbate peroxidase) and GPX (guaiacol peroxidase) resulting in reduced lipid peroxidation in S. arundinaceum. AMF symbiosis also ameliorated the drought-induced reduction of total chlorophyll content and activities of photosystem I and II. The maximum quantum efficiency of PS II (F v/F m) and potential photochemical efficiency (F v/F o) were higher in AMF plants as compared to non-AMF plants under drought stress. These results indicate that AMF association alleviate drought stress in S. arundinaceum by the accumulation of osmolytes and non-enzymatic antioxidants and enhanced activities of antioxidant enzymes, and hence, the photosynthetic efficiency is improved resulting in increased biomass production. AMF association with energy grasses also improves the acclimatization of S. arundinaceum for growing in marginal lands of drought-affected soils.

Endogenously produced Indian Hedgehog regulates TGFβ-driven chondrogenesis of human bone marrow stromal/stem cells.

Science.gov (United States)

Handorf, Andrew M; Chamberlain, Connie S; Li, Wan-Ju

2015-04-15

Human bone marrow stromal/stem cells (hBMSCs) have an inherent tendency to undergo hypertrophy when induced into the chondrogenic lineage using transforming growth factor-beta 1 (TGFβ) in vitro, reminiscent of what occurs during endochondral ossification. Surprisingly, Indian Hedgehog (IHH) has received little attention for its role during hBMSC chondrogenesis despite being considered a master regulator of endochondral ossification. In this study, we investigated the role that endogenously produced IHH plays during hBMSC chondrogenesis. We began by analyzing the expression of IHH throughout differentiation using quantitative polymerase chain reaction and found that IHH expression was upregulated dramatically upon chondrogenic induction and peaked from days 9 to 12 of differentiation, which coincided with a concomitant increase in the expression of chondrogenesis- and hypertrophy-related markers, suggesting a potential role for endogenously produced IHH in driving hBMSC chondrogenesis. More importantly, pharmacological inhibition of Hedgehog signaling with cyclopamine or knockdown of IHH almost completely blocked TGFβ1-induced chondrogenesis in hBMSCs, demonstrating that endogenously produced IHH is necessary for hBMSC chondrogenesis. Furthermore, overexpression of IHH was sufficient to drive chondrogenic differentiation, even when TGFβ signaling was inhibited. Finally, stimulation with TGFβ1 induced a significant and sustained upregulation of IHH expression within 3 h that preceded an upregulation in all cartilage-related genes analyzed, and knockdown of IHH blocked the effects of TGFβ1 entirely, suggesting that the effects of TGFβ1 are being mediated through endogenously produced IHH. Together, our findings demonstrate that endogenously produced IHH is playing a critical role in regulating hBMSC chondrogenesis.

Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Vainshtein, Jeffrey M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Kabarriti, Rafi; Mehta, Keyur J. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Roy-Chowdhury, Jayanta [Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Department of Genetics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Guha, Chandan, E-mail: cguhamd@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

2014-07-15

Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local disease control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the

Multifunctions of dual Zn/Mg ion co-implanted titanium on osteogenesis, angiogenesis and bacteria inhibition for dental implants.

Science.gov (United States)

Yu, Yiqiang; Jin, Guodong; Xue, Yang; Wang, Donghui; Liu, Xuanyong; Sun, Jiao

2017-02-01

In order to improve the osseointegration and long-term survival of dental implants, it is urgent to develop a multifunctional titanium surface which would simultaneously have osteogeneic, angiogeneic and antibacterial properties. In this study, a potential dental implant material-dual Zn/Mg ion co-implanted titanium (Zn/Mg-PIII) was developed via plasma immersion ion implantation (PIII). The Zn/Mg-PIII surfaces were found to promote initial adhesion and spreading of rat bone marrow mesenchymal stem cells (rBMSCs) via the upregulation of the gene expression of integrin α1 and integrin β1. More importantly, it was revealed that Zn/Mg-PIII could increase Zn 2+ and Mg 2+ concentrations in rBMSCs by promoting the influx of Zn 2+ and Mg 2+ and inhibiting the outflow of Zn 2+ , and then could enhance the transcription of Runx2 and the expression of ALP and OCN. Meanwhile, Mg 2+ ions from Zn/Mg-PIII increased Mg 2+ influx by upregulating the expression of MagT1 transporter in human umbilical vein endothelial cells (HUVECs), and then stimulated the transcription of VEGF and KDR via activation of hypoxia inducing factor (HIF)-1α, thus inducing angiogenesis. In addition to this, it was discovered that zinc in Zn/Mg-PIII had certain inhibitory effects on oral anaerobic bacteria (Pg, Fn and Sm). Finally, the Zn/Mg-PIII implants were implanted in rabbit femurs for 4 and 12weeks with Zn-PIII, Mg-PIII and pure titanium as controls. Micro-CT evaluation, sequential fluorescent labeling, histological analysis and push-out test consistently demonstrated that Zn/Mg-PIII implants exhibit superior capacities for enhancing bone formation, angiogenesis and osseointegration, while consequently increasing the bonding strength at bone-implant interfaces. All these results suggest that due to the multiple functions co-produced by zinc and magnesium, rapid osseointegration and sustained biomechanical stability are enhanced by the novel Zn/Mg-PIII implants, which have the potential

Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression.

Science.gov (United States)

Peeters, Janneke G C; Vervoort, Stephin J; Tan, Sander C; Mijnheer, Gerdien; de Roock, Sytze; Vastert, Sebastiaan J; Nieuwenhuis, Edward E S; van Wijk, Femke; Prakken, Berent J; Creyghton, Menno P; Coffer, Paul J; Mokry, Michal; van Loosdregt, Jorg

2015-09-29

The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA) is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in JIA patient synovial-fluid-derived CD4(+) memory/effector T cells. RNA sequencing of autoinflammatory site-derived patient T cells revealed that BET inhibition, utilizing JQ1, inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Altogether, these results demonstrate the potential use of enhancer profiling to identify disease mediators and provide evidence for BET inhibition as a possible therapeutic approach for the treatment of autoimmune diseases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression

Directory of Open Access Journals (Sweden)

Janneke G.C. Peeters

2015-09-01

Full Text Available The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in JIA patient synovial-fluid-derived CD4+ memory/effector T cells. RNA sequencing of autoinflammatory site-derived patient T cells revealed that BET inhibition, utilizing JQ1, inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Altogether, these results demonstrate the potential use of enhancer profiling to identify disease mediators and provide evidence for BET inhibition as a possible therapeutic approach for the treatment of autoimmune diseases.

Bone-anchored titanium implants for auricular rehabilitation: case report and review of literature.

Science.gov (United States)

Gumieiro, Emne Hammoud; Dib, Luciano Lauria; Jahn, Ricardo Schmitutz; Santos Junior, João Ferreira dos; Nannmark, Ulf; Granström, Gösta; Abrahão, Márcio

2009-01-01

Osseointegrated implants have acquired an important role in the prosthetic rehabilitation of patients with craniofacial defects. The main indications are lack of local tissue for autogenous reconstruction, previous reconstruction failure and selection of this technique by the patient. This paper presents a clinical case and discusses indications and advantages of the osseointegrated implant technique for retention of auricular prostheses. Case report, Universidade Federal de São Paulo (UNIFESP). A female patient received three auricular implants after surgical resection of a hemangioma in her left ear. The time taken for osseointegration of the temporal bone was three months. After fabrication of the implant-retained auricular prosthesis, the patient was monitored for 12 months. The clinical parameters evaluated showed good postoperative healing, healthy peri-implant tissue, good hygiene and no loss of implants. Good hygiene combined with thin and immobile peri-implant soft tissues resulted in minimal complications. Craniofacial implant integration appears to be site-dependent; increasing age affects osseointegration in the temporal bone. The frequency of adverse skin reactions in peri-implant tissues is generally low. The surgical technique for rehabilitation using implant-retained auricular prostheses seems to be simple. It is associated with low rates of adverse skin reactions and long-term complications. Prostheses anchored by osseointegrated implants seem to provide better retention than do prostheses supported on spectacle frames, less risk of discoloration through the use of adhesives and better esthetic results than do prostheses anchored in the surgical cavity.

Wedelolactone enhances osteoblastogenesis by regulating Wnt/β-catenin signaling pathway but suppresses osteoclastogenesis by NF-κB/c-fos/NFATc1 pathway.

Science.gov (United States)

Liu, Yan-Qiu; Hong, Zhi-Lai; Zhan, Li-Bin; Chu, Hui-Ying; Zhang, Xiao-Zhe; Li, Guo-Hui

2016-08-25

Bone homeostasis is maintained by formation and destruction of bone, which are two processes tightly coupled and controlled. Targeting both stimulation on bone formation and suppression on bone resorption becomes a promising strategy for treating osteoporosis. In this study, we examined the effect of wedelolactone, a natural product from Ecliptae herba, on osteoblastogenesis as well as osteoclastogenesis. In mouse bone marrow mesenchymal stem cells (BMSC), wedelolactone stimulated osteoblast differentiation and bone mineralization. At the molecular level, wedelolactone directly inhibited GSK3β activity and enhanced the phosphorylation of GSK3β, thereafter stimulated the nuclear translocation of β-catenin and runx2. The expression of osteoblastogenesis-related marker gene including osteorix, osteocalcin and runx2 increased. At the same concentration range, wedelolactone inhibited RANKL-induced preosteoclastic RAW264.7 actin-ring formation and bone resorption pits. Further, wedelolactone blocked NF-kB/p65 phosphorylation and abrogated the NFATc1 nuclear translocation. As a result, osteoclastogenesis-related marker gene expression decreased, including c-src, c-fos, and cathepsin K. In ovariectomized mice, administration of wedelolactone prevented ovariectomy-induced bone loss by enhancing osteoblast activity and inhibiting osteoclast activity. Together, these data demonstrated that wedelolactone facilitated osteoblastogenesis through Wnt/GSK3β/β-catenin signaling pathway and suppressed RANKL-induced osteoclastogenesis through NF-κB/c-fos/NFATc1 pathway. These results suggested that wedelolacone could be a novel dual functional therapeutic agent for osteoporosis.

Effects of bone marrow stromal cell transplantation through CSF on the subacute and chronic spinal cord injury in rats.

Directory of Open Access Journals (Sweden)

Norihiko Nakano

Full Text Available It has been demonstrated that the infusion of bone marrow stromal cells (BMSCs through the cerebrospinal fluid (CSF has beneficial effects on acute spinal cord injury (SCI in rats. The present study examined whether BMSC infusion into the CSF is effective for subacute (1- and 2-week post-injury, and/or chronic (4-week post-injury SCI in rats. The spinal cord was contused by dropping a weight at the thoracic 8-9 levels. BMSCs cultured from GFP-transgenic rats of the same strain were injected three times (once weekly into the CSF through the fourth ventricle, beginning at 1, 2 and 4 weeks post-injury. At 4 weeks after initial injection, the average BBB score for locomotor assessment increased from 1.0-3.5 points before injection to 9.0-10.9 points in the BMSC-injection subgroups, while, in the PBS (vehicle-injection subgroups, it increased only from 0.5-4.0 points before injection to 3.0-5.1 points. Numerous axons associated with Schwann cells extended longitudinally through the connective tissue matrices in the astrocyte-devoid lesion without being blocked at either the rostral or the caudal borders in the BMSC-injection subgroups. A small number of BMSCs were found to survive within the spinal cord lesion in SCI of the 1-week post-injury at 2 days of injection, but none at 7 days. No BMSCs were found in the spinal cord lesion at 2 days or at 7 days in the SCI of the 2-week and the 4-week post-injury groups. In an in vitro experiment, BMSC-injected CSF promoted the survival and the neurite extension of cultured neurons more effectively than did the PBS-injected CSF. These results indicate that BMSCs had beneficial effects on locomotor improvement as well as on axonal regeneration in both subacute and chronic SCI rats, and the results also suggest that BMSCs might function as neurotrophic sources via the CSF.

Effects of Bone Marrow Stromal Cell Transplantation through CSF on the Subacute and Chronic Spinal Cord Injury in Rats

Science.gov (United States)

Nakano, Norihiko; Nakai, Yoshiyasu; Seo, Tae-Beom; Homma, Tamami; Yamada, Yoshihiro; Ohta, Masayoshi; Suzuki, Yoshihisa; Nakatani, Toshio; Fukushima, Masanori; Hayashibe, Miki; Ide, Chizuka

2013-01-01

It has been demonstrated that the infusion of bone marrow stromal cells (BMSCs) through the cerebrospinal fluid (CSF) has beneficial effects on acute spinal cord injury (SCI) in rats. The present study examined whether BMSC infusion into the CSF is effective for subacute (1- and 2-week post-injury), and/or chronic (4-week post-injury) SCI in rats. The spinal cord was contused by dropping a weight at the thoracic 8-9 levels. BMSCs cultured from GFP-transgenic rats of the same strain were injected three times (once weekly) into the CSF through the fourth ventricle, beginning at 1, 2 and 4 weeks post-injury. At 4 weeks after initial injection, the average BBB score for locomotor assessment increased from 1.0–3.5 points before injection to 9.0-10.9 points in the BMSC-injection subgroups, while, in the PBS (vehicle)-injection subgroups, it increased only from 0.5–4.0 points before injection to 3.0-5.1 points. Numerous axons associated with Schwann cells extended longitudinally through the connective tissue matrices in the astrocyte-devoid lesion without being blocked at either the rostral or the caudal borders in the BMSC-injection subgroups. A small number of BMSCs were found to survive within the spinal cord lesion in SCI of the 1-week post-injury at 2 days of injection, but none at 7 days. No BMSCs were found in the spinal cord lesion at 2 days or at 7 days in the SCI of the 2-week and the 4-week post-injury groups. In an in vitro experiment, BMSC-injected CSF promoted the survival and the neurite extension of cultured neurons more effectively than did the PBS-injected CSF. These results indicate that BMSCs had beneficial effects on locomotor improvement as well as on axonal regeneration in both subacute and chronic SCI rats, and the results also suggest that BMSCs might function as neurotrophic sources via the CSF. PMID:24039961

Long-Term Engraftment of Primary Bone Marrow Stromal Cells Repairs Niche Damage and Improves Hematopoietic Stem Cell Transplantation.

Science.gov (United States)

Abbuehl, Jean-Paul; Tatarova, Zuzana; Held, Werner; Huelsken, Joerg

2017-08-03

Hematopoietic stem cell (HSC) transplantation represents a curative treatment for various hematological disorders. However, delayed reconstitution of innate and adaptive immunity often causes fatal complications. HSC maintenance and lineage differentiation are supported by stromal niches, and we now find that bone marrow stroma cells (BMSCs) are severely and permanently damaged by the pre-conditioning irradiation required for efficient HSC transplantation. Using mouse models, we show that stromal insufficiency limits the number of donor-derived HSCs and B lymphopoiesis. Intra-bone transplantation of primary, but not cultured, BMSCs quantitatively reconstitutes stroma function in vivo, which is mediated by a multipotent NT5E + (CD73) + ENG - (CD105) - LY6A + (SCA1) + BMSC subpopulation. BMSC co-transplantation doubles the number of functional, donor-derived HSCs and significantly reduces clinically relevant side effects associated with HSC transplantation including neutropenia and humoral immunodeficiency. These data demonstrate the potential of stroma recovery to improve HSC transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

GENOMIC ANALYSIS OF PLANT-ASSOCIATED BACTERIA AND THEIR POTENTIAL IN ENHANCING PHYTOREMEDIATION EFFICIENCY

Directory of Open Access Journals (Sweden)

Artur Piński

2017-07-01

Full Text Available Phytoremediation is an emerging technology that uses plants in order to cleanup pollutants including xenobiotics and heavy metals from soil, water and air. Inoculation of plants with plant growth promoting endophytic and rhizospheric bacteria can enhance efficiency of phytoremediation. Genomic analysis of four plant-associated strains belonging to the Stenotrophomonas maltophilia species revealed the presence of genes encoding proteins involved in plant growth promotion, biocontrol of phytopathogens, biodegradation of xenobiotics, heavy metals resistance and plant-bacteria-environment interaction. The results of this analysis suggest great potential of bacteria belonging to Stenotrophomonas maltophilia species in enhancing phytoremediation efficiency.

Study of TiO2 nanotubes as an implant application

International Nuclear Information System (INIS)

Hazan, Roshasnorlyza; Sreekantan, Srimala; Mydin, Rabiatul Basria S. M. N.; Mat, Ishak; Abdullah, Yusof

2016-01-01

Vertically aligned TiO 2 nanotubes have become the primary candidates for implant materials that can provide direct control of cell behaviors. In this work, 65 nm inner diameters of TiO 2 nanotubes were successfully prepared by anodization method. The interaction of bone marrow stromal cells (BMSC) in term of cell adhesion and cell morphology on bare titanium and TiO 2 nanotubes is reported. Field emission scanning electron microscopy (FESEM) analysis proved interaction of BMSC on TiO 2 nanotubes structure was better than flat titanium (Ti) surface. Also, significant cell adhesion on TiO 2 nanotubes surface during in vitro study revealed that BMSC prone to attach on TiO 2 nanotubes. From the result, it can be conclude that TiO 2 nanotubes are biocompatible to biological environment and become a new generation for advanced implant materials

Nanorod diameter modulated osteogenic activity of hierarchical micropore/nanorod-patterned coatings via a Wnt/β-catenin pathway.

Science.gov (United States)

Zhou, Jianhong; Zhao, Lingzhou; Li, Bo; Han, Yong

2018-04-14

Hierarchical micropore/nanorod-patterned strontium doped hydroxyapatite (Ca 9 Sr 1 (PO 4 ) 6 (OH) 2 , Sr 1 -HA) structures (MNRs) with different nanorod diameters of about 30, 70 and 150 nm were coated on titanium, to investigate the effect of nanorod diameter on osteogenesis and the involved mechanism. Compared to micropore/nanogranule-patterned Sr 1 -HA coating (MNG), MNRs gave rise to dramatically enhanced in vitro mesenchymal stem cell functions including osteogenic differentiation in the absence of osteogenic supplements and in vivo osseointegration related to the nanorod diameter with about 70 nm displaying the best effects. MNRs activated the cellular Wnt/β-catenin pathway by increasing the expression of Wnt3a and LRP6 and decreasing the expression of Wnt/β-catenin pathway antagonists (sFRP1, sFRP2, Dkk1 and Dkk2). The exogenous Wnt3a significantly enhanced the β-catenin signaling activation and cell differentiation on MNG, and the exogenous Dkk1 attenuated the enhancing effect of MNRs on them. The data demonstrate that MNRs favor osseointegration via a Wnt/β-catenin pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

Particle acceleration and wave emissions associated with the formation of auroral cavities and enhancements

International Nuclear Information System (INIS)

Winglee, R.M.; Pritchett, P.L.; Dusenbery, P.B.

1988-01-01

Observations from DE 1 and electrostatic particle simulations are combined in an effort to provide a unified model for (nightside) auroral particle acceleration and wave emissions and their association with plasma cavities and enhancements. The observations show that enhanced electron precipitation during inverted-V events is associated with broadband electrostatic bursts (BEB), increased upward field-aligned currents, and density enhancements. These regions are flanked by return current regions where the density is depleted (i.e., by plasma cavities). Perpendicular acceleration of ambient plasma ions can occur in both upward and return current regions. It is shown through the simulations that these processes are integrally related and are not independent of each other. The free energy for the auroral particle acceleration can be provided by energetic ion beams in the plasma sheet boundary layer with nonzero perpendicular energy. The perpendicular energy allows charge separation between the beam ions and costreaming electrons to occur. The resultant space charge fields accelerate electrons on the same field lines as the costreaming electrons downward toward the ionosphere, without the beam ions actually propagating down to auroral altitudes. Ambient plasma electrons on adjacent field lines are accelerated upward, forming a return current

Osseointegration of dental implants in extraction sockets preserved with porous titanium granules - an experimental study.

Science.gov (United States)

Verket, Anders; Lyngstadaas, Ståle P; Rønold, Hans J; Wohlfahrt, Johan C

2014-02-01

This study investigated osseointegration of dental implants inserted in healed extraction sockets preserved with porous titanium granules (PTG). Three adult female minipigs (Gøttingen minipig; Ellegaard A/S, Dalmose, Denmark) had the mandibular teeth P2, P3 and P4 extracted. The extraction sockets were preserved with metallic PTG (Tigran PTG; Tigran Technologies AB, Malmö, Sweden) n = 12, heat oxidized white porous titanium granules (WPTG) (Tigran PTG White) n = 12 or left empty (sham) n = 6. All sites were covered with collagen membranes (Bio-Gide; Geistlich Pharma, Wolhausen, Switzerland) and allowed 11 weeks of healing before implants (Straumann Bone Level; Straumann, Basel, Switzerland) were inserted. The temperature was measured during preparation of the osteotomies. Resonance frequency analysis (RFA, Osstell; Osstell AB, Gothenburg, Sweden) was performed at implant insertion and at termination. After 6 weeks of submerged implant healing, the pigs were euthanized and jaw segments were excised for microCT and histological analyses. In the temperature and RFA analyses no significant differences were recorded between the test groups. The microCT analysis demonstrated an average bone volume of 61.7% for the PTG group compared to 50.3% for the WPTG group (P = 0.03) and 57.1% for the sham group. Histomorphometry demonstrated an average bone-to-implant contact of 68.2% for the PTG group compared to 36.6% for the WPTG group and 60.9% for the sham group (n.s). Eight out of ten implants demonstrated apical osseous defects in the WPTG group, but similar defects were observed in all groups. PTG preserved extraction sockets demonstrate a similar outcome as the sham control group for all analyses suggesting that this material potentially can be used for extraction socket preservation prior to implant installment. Apical osseous defects were however observed in all groups including the sham group, and a single cause could not be determined. © 2012 John Wiley & Sons A/S.

Enhanced vulnerability of human proteins towards disease-associated inactivation through divergent evolution.

Science.gov (United States)

Medina-Carmona, Encarnación; Fuchs, Julian E; Gavira, Jose A; Mesa-Torres, Noel; Neira, Jose L; Salido, Eduardo; Palomino-Morales, Rogelio; Burgos, Miguel; Timson, David J; Pey, Angel L

2017-09-15

Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine:glyoxylate aminotransferase, mutated in primary hyperoxaluria type I. We demonstrate that a single consensus mutation (H80R) acts as a disease suppressor on the most common cancer-associated polymorphism in NQO1 (P187S). The H80R mutation reactivates P187S by enhancing FAD binding affinity through local and dynamic stabilization of its binding site. Furthermore, we show how a second suppressor mutation (E247Q) cooperates with H80R in protecting the P187S polymorphism towards inactivation through long-range allosteric communication within the structural ensemble of the protein. Our results support that recent divergence of consensus amino acids may have occurred with neutral effects on many functional and regulatory traits of wild-type human proteins. However, divergence at certain sites may have increased the propensity of some human proteins towards inactivation due to disease-associated mutations and polymorphisms. Consensus mutations also emerge as a potential strategy to identify structural hot-spots in proteins as targets for pharmacological rescue in loss-of-function genetic diseases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please

Enhancement of Orthodontic Anchor Screw Stability Under Immediate Loading by Ultraviolet Photofunctionalization Technology.

Science.gov (United States)

Takahashi, Maiko; Motoyoshi, Mitsuru; Inaba, Mizuki; Hagiwara, Yoshiyuki; Shimizu, Noriyoshi

Ultraviolet (UV)-mediated photofunctionalization technology is intended to enhance the osseointegration capability of titanium implants. There are concerns about orthodontic anchor screws loosening under immediate loading protocols in adolescent orthodontic treatment. The purpose of this in vivo study was to evaluate the effects of photofunctionalization on the intrabony stability of orthodontic titanium anchor screws and bone-anchor screw contact under immediate loading in growing rats. Custom-made titanium anchor screws (1.4 mm in diameter and 4.0 mm in length) with or without photofunctionalization pretreatment were placed on the proximal epiphysis of the tibial bone in 6-week-old male Sprague-Dawley rats and were loaded immediately after placement. After 2 weeks of loading, the stability of the anchor screws was evaluated using a Periotest device, and the bone-anchor screw contact ratio (BSC) was assessed by a histomorphometric analysis using field-emission scanning electron microscopy. In the unloaded group, Periotest values (PTVs) were ~25 for UV-untreated screws and 13 for UVtreated screws (P < .01), while in the immediate-loading group, PTVs were 28 for UV-untreated screws and 16 for UV-treated screws (P < .05). Significantly less screw mobility was observed in both UV-treated groups regardless of the loading protocol. The BSC was increased ~1.8 fold for UV-treated screws, compared with UV-untreated screws, regardless of the loading protocol. Photofunctionalization enhanced the intrabony stability of orthodontic anchor screws under immediate loading in growing rats by increasing bone-anchor screw contact.

Curcumin-functionalized silk materials for enhancing adipogenic differentiation of bone marrow-derived human mesenchymal stem cells

Science.gov (United States)

Li, Chunmei; Luo, Tingting; Zheng, Zhaozhu; Murphy, Amanda R.; Wang, Xiaoqin; Kaplan, David L.

2014-01-01

Curcumin, a natural phenolic compound derived from the plant Curcuma longa, was physically entrapped and stabilized in silk hydrogel films and its influence on human bone marrow-derived mesenchymal stem cells (hBMSCs) was assessed related to adipogenic differentiation. The presence of curcumin significantly reduced silk gelation time and changed the porous morphology of gel matrix, but did not change the formation of silk beta-sheet structure. Based on spectrofluorimetric analysis, curcumin likely interacted with hydrophobic residues in silk, interacting with the beta-sheet domains formed in the hydrogels. The antioxidant activity of silk film-associated curcumin remained functional over at least one month in both the dry and hydrated state. Negligible curcumin was released from silk hydrogel films over 48 hours incubation in aqueous solution. For hBMSCs cultured on silk films containing more than 0.25 mg/mL curcumin, cell proliferation was inhibited while adipogenesis was significantly promoted based on transcripts as well as oil red O staining. When hBMSCs were cultured in media containing free curcumin, both proliferation and adipogenesis of hBMSCs were inhibited when curcumin concentrations exceeded 5 μM, which is more than 1,000-times higher than the level of curcumin released from the films in aqueous solution. Thus, silk film-associated curcumin exhibited different effects on hBMSC proliferation and differentiation when compared to curcumin in solution. PMID:25132274

Factors Associated with Enhanced Gross Motor Progress in Children with Cerebral Palsy: A Register-Based Study.

Science.gov (United States)

Størvold, Gunfrid V; Jahnsen, Reidun B; Evensen, Kari Anne I; Romild, Ulla K; Bratberg, Grete H

2018-05-01

To examine associations between interventions and child characteristics; and enhanced gross motor progress in children with cerebral palsy (CP). Prospective cohort study based on 2048 assessments of 442 children (256 boys, 186 girls) aged 2-12 years registered in the Cerebral Palsy Follow-up Program and the Cerebral Palsy Register of Norway. Gross motor progress estimates were based on repeated measures of reference percentiles for the Gross Motor Function Measure (GMFM-66) in a linear mixed model. Mean follow-up time: 2.9 years. Intensive training was the only intervention factor associated with enhanced gross motor progress (mean 3.3 percentiles, 95% CI: 1.0, 5.5 per period of ≥3 sessions per week and/or participation in an intensive program). Gross motor function was on average 24.2 percentiles (95% CI: 15.2, 33.2) lower in children with intellectual disability compared with others. Except for eating problems (-10.5 percentiles 95% CI: -18.5, -2.4) and ankle contractures by age (-1.9 percentiles 95% CI: -3.6, -0.2) no other factors examined were associated with long-term gross motor progress. Intensive training was associated with enhanced gross motor progress over an average of 2.9 years in children with CP. Intellectual disability was a strong negative prognostic factor. Preventing ankle contractures appears important for gross motor progress.

Hydroxyapatite-coated double network hydrogel directly bondable to the bone: Biological and biomechanical evaluations of the bonding property in an osteochondral defect.

Science.gov (United States)

Wada, Susumu; Kitamura, Nobuto; Nonoyama, Takayuki; Kiyama, Ryuji; Kurokawa, Takayuki; Gong, Jian Ping; Yasuda, Kazunori

2016-10-15

We have developed a novel hydroxyapatite (HAp)-coated double-network (DN) hydrogel (HAp/DN gel). The purpose of this study was to determine details of the cell and tissue responses around the implanted HAp/DN gel and to determine how quickly and strongly the HAp/DN gel bonds to the bone in a rabbit osteochondral defect model. Immature osteoid tissue was formed in the space between the HAp/DN gel and the bone at 2weeks, and the osteoid tissue was mineralized at 4weeks. The push-out load of the HAp/DN gel averaged 37.54N and 42.15N at 4 and 12weeks, respectively, while the push-out load of the DN gel averaged less than 5N. The bonding area of the HAp/DN gel to the bone was above 80% by 4weeks, and above 90% at 12weeks. This study demonstrated that the HAp/DN gel enhanced osseointegration at an early stage after implantation. The presence of nanoscale structures in addition to osseointegration of HAp promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Recent studies have reported the development of various hydrogels that are sufficiently tough for application as soft supporting tissues. However, fixation of hydrogels on bone surfaces with appropriate strength is a great challenge. We have developed a novel, tough hydrogel hybridizing hydroxyapatite (HAp/DN gel), which is directly bondable to the bone. The present study demonstrated that the HAp/DN gel enhanced osseointegration in the early stage after implantation. The presence of nanoscale structures in addition to the osseointegration ability of hydroxyapatite promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

Science.gov (United States)

2016-09-01

analysis of tumor necrosis factor - alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype...AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor - Associated...Cancer and Impairs Tumor -Associated Angiogenesis 5b. GRANT NUMBER W81XWH-15-1-0296 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

Prostacyclin Suppresses Twist Expression in the Presence of Indomethacin in Bone Marrow-Derived Mesenchymal Stromal Cells

Science.gov (United States)

Kemper, Oliver; Herten, Monika; Fischer, Johannes; Haversath, Marcel; Beck, Sascha; Classen, Tim; Warwas, Sebastian; Tassemeier, Tjark; Landgraeber, Stefan; Lensing-Höhn, Sabine; Krauspe, Rüdiger; Jäger, Marcus

2014-01-01

Background Iloprost, a stable prostacyclin I2 analogue, seems to have an osteoblast-protective potential, whereas indomethacin suppresses new bone formation. The aim of this study was to investigate human bone marrow stromal cell (BMSC) proliferation and differentiation towards the osteoblastic lineage by administration of indomethacin and/or iloprost. Material/Methods Human bone marrow cells were obtained from 3 different donors (A=26 yrs/m; B=25 yrs/f, C=35 yrs/m) via vacuum aspiration of the iliac crest followed by density gradient centrifugation and flow cytometry with defined antigens (CD105+/73+/45−/14−). The cells were seeded and incubated as follows: without additives (Group 0; donor A/B/C), with 10−7 M iloprost only (Group 0+ilo; A/B), with indomethacin only in concentrations of 10−6 M (Group 1, A), 10−5 M (Group 2, B), 10−4 M (Group 3, A/B), and together with 10−7 M iloprost (Groups 4–6, A/B/C). On Day 10 and 28, UV/Vis spectrometric and immunocytochemical assays (4 samples per group and donor) were performed to investigate cell proliferation (cell count measurement) and differentiation towards the osteoblastic lineage (CD34−, CD45−, CD105+, type 1 collagen (Col1), osteocalcin (OC), alkaline phosphatase (ALP), Runx2, Twist, specific ALP-activity). Results Indomethacin alone suppressed BMSC differentiation towards the osteoblastic lineage by downregulation of Runx2, Col1, and ALP. In combination with indomethacin, iloprost increased cell proliferation and differentiation and it completely suppressed Twist expression at Day 10 and 28. Iloprost alone did not promote cell proliferation, but moderately enhanced Runx2 and Twist expression. However, the proliferative effects and the specific ALP-activity varied donor-dependently. Conclusions Iloprost partially antagonized the suppressing effects of indomethacin on BMSC differentiation towards the osteoblast lineage. It enhanced the expression of Runx2 and, only in the presence of indomethacin

Zirconium, calcium, and strontium contents in magnesium based biodegradable alloys modulate the efficiency of implant-induced osseointegration

Directory of Open Access Journals (Sweden)

Mushahary D

2013-08-01

Full Text Available Dolly Mushahary,1,2 Ragamouni Sravanthi,2 Yuncang Li,2 Mahesh J Kumar,1 Nemani Harishankar,4 Peter D Hodgson,1 Cuie Wen,3 Gopal Pande2 1Institute for Frontier Materials, Deakin University, Geelong, Australia; 2CSIR- Centre for Cellular and Molecular Biology, Hyderabad, India; 3Faculty of Engineering and Industrial Sciences, Swinburne University of Technology, Hawthorn, Australia; 4National Institute of Nutrition (ICMR, Tarnaka, Hyderabad, India Abstract: Development of new biodegradable implants and devices is necessary to meet the increasing needs of regenerative orthopedic procedures. An important consideration while formulating new implant materials is that they should physicochemically and biologically mimic bone-like properties. In earlier studies, we have developed and characterized magnesium based biodegradable alloys, in particular magnesium-zirconium (Mg-Zr alloys. Here we have reported the biological properties of four Mg-Zr alloys containing different quantities of strontium or calcium. The alloys were implanted in small cavities made in femur bones of New Zealand White rabbits, and the quantitative and qualitative assessments of newly induced bone tissue were carried out. A total of 30 experimental animals, three for each implant type, were studied, and bone induction was assessed by histological, immunohistochemical and radiological methods; cavities in the femurs with no implants and observed for the same period of time were kept as controls. Our results showed that Mg-Zr alloys containing appropriate quantities of strontium were more efficient in inducing good quality mineralized bone than other alloys. Our results have been discussed in the context of physicochemical and biological properties of the alloys, and they could be very useful in determining the nature of future generations of biodegradable orthopedic implants. Keywords: osteoblasts, bone mineralization, corrosion, osseointegration, surface energy, peri-implant

The Differentiation Balance of Bone Marrow Mesenchymal Stem Cells Is Crucial to Hematopoiesis

Directory of Open Access Journals (Sweden)

Jiang Wu

2018-01-01

Full Text Available Bone marrow mesenchymal stem cells (BMSCs, the important component and regulator of bone marrow microenvironment, give rise to hematopoietic-supporting stromal cells and form hematopoietic niches for hematopoietic stem cells (HSCs. However, how BMSC differentiation affects hematopoiesis is poorly understood. In this review, we focus on the role of BMSC differentiation in hematopoiesis. We discussed the role of BMSCs and their progeny in hematopoiesis. We also examine the mechanisms that cause differentiation bias of BMSCs in stress conditions including aging, irradiation, and chemotherapy. Moreover, the differentiation balance of BMSCs is crucial to hematopoiesis. We highlight the negative effects of differentiation bias of BMSCs on hematopoietic recovery after bone marrow transplantation. Keeping the differentiation balance of BMSCs is critical for hematopoietic recovery. This review summarises current understanding about how BMSC differentiation affects hematopoiesis and its potential application in improving hematopoietic recovery after bone marrow transplantation.

Study of TiO{sub 2} nanotubes as an implant application

Energy Technology Data Exchange (ETDEWEB)

Hazan, Roshasnorlyza, E-mail: roshasnorlyza@nm.gov.my; Sreekantan, Srimala [School of Materials and Mineral Resources Engineering, Universiti Sains Malaysia, 14300, Nibong Tebal, Pulau Pinang (Malaysia); Mydin, Rabiatul Basria S. M. N.; Mat, Ishak [Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200, Kepala Batas, Pulau Pinang (Malaysia); Abdullah, Yusof [Materials Technology Group, Industrial Technology Division, Nuclear Malaysia Agency, Bangi, 43000, Kajang, Selangor. Malaysia (Malaysia)

2016-01-22

Vertically aligned TiO{sub 2} nanotubes have become the primary candidates for implant materials that can provide direct control of cell behaviors. In this work, 65 nm inner diameters of TiO{sub 2} nanotubes were successfully prepared by anodization method. The interaction of bone marrow stromal cells (BMSC) in term of cell adhesion and cell morphology on bare titanium and TiO{sub 2} nanotubes is reported. Field emission scanning electron microscopy (FESEM) analysis proved interaction of BMSC on TiO{sub 2} nanotubes structure was better than flat titanium (Ti) surface. Also, significant cell adhesion on TiO{sub 2} nanotubes surface during in vitro study revealed that BMSC prone to attach on TiO{sub 2} nanotubes. From the result, it can be conclude that TiO{sub 2} nanotubes are biocompatible to biological environment and become a new generation for advanced implant materials.

Bone-anchored titanium implants for auricular rehabilitation: case report and review of literature

Directory of Open Access Journals (Sweden)

Emne Hammoud Gumieiro

Full Text Available CONTEXT AND OBJECTIVE: Osseointegrated implants have acquired an important role in the prosthetic rehabilitation of patients with craniofacial defects. The main indications are lack of local tissue for autogenous reconstruction, previous reconstruction failure and selection of this technique by the patient. This paper presents a clinical case and discusses indications and advantages of the osseointegrated implant technique for retention of auricular prostheses. TYPE OF STUDY: Case report, Universidade Federal de São Paulo (UNIFESP. METHODS: A female patient received three auricular implants after surgical resection of a hemangioma in her left ear. The time taken for osseointegration of the temporal bone was three months. After fabrication of the implant-retained auricular prosthesis, the patient was monitored for 12 months. RESULTS: The clinical parameters evaluated showed good postoperative healing, healthy peri-implant tissue, good hygiene and no loss of implants. Good hygiene combined with thin and immobile peri-implant soft tissues resulted in minimal complications. Craniofacial implant integration appears to be site-dependent; increasing age affects osseointegration in the temporal bone. The frequency of adverse skin reactions in peri-implant tissues is generally low. CONCLUSION: The surgical technique for rehabilitation using implant-retained auricular prostheses seems to be simple. It is associated with low rates of adverse skin reactions and long-term complications. Prostheses anchored by osseointegrated implants seem to provide better retention than do prostheses supported on spectacle frames, less risk of discoloration through the use of adhesives and better esthetic results than do prostheses anchored in the surgical cavity

A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration.

Science.gov (United States)

Yassin, Mohammed A; Mustafa, Kamal; Xing, Zhe; Sun, Yang; Fasmer, Kristine Eldevik; Waag, Thilo; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Leknes, Knut N

2017-06-01

Functionalizing polymer scaffolds with nanodiamond particles (nDPs) has pronounced effect on the surface properties, such as improved wettability, an increased active area and binding sites for cellular attachment and adhesion, and increased ability to immobilize biomolecules by physical adsorption. This study aims to evaluate the effect of poly(l-lactide-co-ε-caprolactone) (poly(LLA-co-CL)) scaffolds, functionalized with nDPs, on bone regeneration in a rat calvarial critical size defect. Poly(LLA-co-CL) scaffolds functionalized with nDPs are also compared with pristine scaffolds with reference to albumin adsorption and seeding efficiency of bone marrow stromal cells (BMSCs). Compared with pristine scaffolds, the experimental scaffolds exhibit a reduction in albumin adsorption and a significant increase in the seeding efficiency of BMSCs (p = 0.027). In the calvarial defects implanted with BMSC-seeded poly(LLA-co-CL)/nDPs scaffolds, live imaging at 12 weeks discloses a significant increase in osteogenic metabolic activity (p = 0.016). Microcomputed tomography, confirmed by histological data, reveals a substantial increase in bone volume (p = 0.021). The results show that compared with conventional poly(LLA-co-CL) scaffolds those functionalized with nDPs promote osteogenic metabolic activity and mineralization capacity. It is concluded that poly(LLA-co-CL) composite matrices functionalized with nDPs enhance osteoconductivity and therefore warrant further study as potential scaffolding material for bone tissue engineering. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In Vitro and In Vivo Osteogenic Activity of Titanium Implants Coated by Pulsed Laser Deposition with a Thin Film of Fluoridated Hydroxyapatite

Directory of Open Access Journals (Sweden)

Luyuan Chen

2018-04-01

Full Text Available To enhance biocompatibility, osteogenesis, and osseointegration, we coated titanium implants, by krypton fluoride (KrF pulsed laser deposition, with a thin film of fluoridated hydroxyapatite (FHA. Coating was confirmed by scanning electron microscopy (SEM and scanning probe microscopy (SPM, while physicochemical properties were evaluated by attenuated reflectance Fourier transform infrared spectroscopy (ATR-FTIR. Calcium deposition, osteocalcin production, and expression of osteoblast genes were significantly higher in rat bone marrow mesenchymal stem cells seeded on FHA-coated titanium than in cells seeded on uncoated titanium. Implantation into rat femurs also showed that the FHA-coated material had superior osteoinductive and osseointegration activity in comparison with that of traditional implants, as assessed by microcomputed tomography and histology. Thus, titanium coated with FHA holds promise as a dental implant material.

In Vivo Response of Laser Processed Porous Titanium Implants for Load-Bearing Implants.

Science.gov (United States)

Bandyopadhyay, Amit; Shivaram, Anish; Tarafder, Solaiman; Sahasrabudhe, Himanshu; Banerjee, Dishary; Bose, Susmita

2017-01-01

Applications of porous metallic implants to enhance osseointegration of load-bearing implants are increasing. In this work, porous titanium implants, with 25 vol.% porosity, were manufactured using Laser Engineered Net Shaping (LENS™) to measure the influence of porosity towards bone tissue integration in vivo. Surfaces of the LENS™ processed porous Ti implants were further modified with TiO 2 nanotubes to improve cytocompatibility of these implants. We hypothesized that interconnected porosity created via additive manufacturing will enhance bone tissue integration in vivo. To test our hypothesis, in vivo experiments using a distal femur model of male Sprague-Dawley rats were performed for a period of 4 and 10 weeks. In vivo samples were characterized via micro-computed tomography (CT), histological imaging, scanning electron microscopy, and mechanical push-out tests. Our results indicate that porosity played an important role to establish early stage osseointegration forming strong interfacial bonding between the porous implants and the surrounding tissue, with or without surface modification, compared to dense Ti implants used as a control.

In vivo response of laser processed porous titanium implants for load-bearing implants

Science.gov (United States)

Bandyopadhyay, Amit; Shivaram, Anish; Tarafder, Solaiman; Sahasrabudhe, Himanshu; Banerjee, Dishary; Bose, Susmita

2016-01-01

Applications of porous metallic implants to enhance osseointegration of load-bearing implants are increasing. In this work, porous titanium implants, with 25 volume% porosity, were manufactured using Laser Engineered Net Shaping (LENS™) to measure the influence of porosity towards bone tissue integration in vivo. Surfaces of the LENS™ processed porous Ti implants were further modified with TiO2 nanotubes to improve cytocompatibility of these implants. We hypothesized that interconnected porosity created via additive manufacturing will enhance bone tissue integration in vivo. To test our hypothesis, in vivo experiments using a distal femur model of male Sprague-Dawley rats were performed for a period of 4 and 10 weeks. In vivo samples were characterized via micro-computed tomography (CT), histological imaging, scanning electron microscopy, and mechanical push-out tests. Our results indicate that porosity played an important role to establish early stage osseointegration forming strong interfacial bonding between the porous implants and the surrounding tissue, with or without surface modification, compared to dense Ti implants used as a control. PMID:27307009

Enhancement of synchronized activity between hippocampal CA1 neurons during initial storage of associative fear memory.

Science.gov (United States)

Liu, Yu-Zhang; Wang, Yao; Shen, Weida; Wang, Zhiru

2017-08-01

Learning and memory storage requires neuronal plasticity induced in the hippocampus and other related brain areas, and this process is thought to rely on synchronized activity in neural networks. We used paired whole-cell recording in vivo to examine the synchronized activity that was induced in hippocampal CA1 neurons by associative fear learning. We found that both membrane potential synchronization and spike synchronization of CA1 neurons could be transiently enhanced after task learning, as observed on day 1 but not day 5. On day 1 after learning, CA1 neurons showed a decrease in firing threshold and rise times of suprathreshold membrane potential changes as well as an increase in spontaneous firing rates, possibly contributing to the enhancement of spike synchronization. The transient enhancement of CA1 neuronal synchronization may play important roles in the induction of neuronal plasticity for initial storage and consolidation of associative memory. The hippocampus is critical for memory acquisition and consolidation. This function requires activity- and experience-induced neuronal plasticity. It is known that neuronal plasticity is largely dependent on synchronized activity. As has been well characterized, repetitive correlated activity of presynaptic and postsynaptic neurons can lead to long-term modifications at their synapses. Studies on network activity have also suggested that memory processing in the hippocampus may involve learning-induced changes of neuronal synchronization, as observed in vivo between hippocampal CA3 and CA1 networks as well as between the rhinal cortex and the hippocampus. However, further investigation of learning-induced synchronized activity in the hippocampus is needed for a full understanding of hippocampal memory processing. In this study, by performing paired whole-cell recording in vivo on CA1 pyramidal cells (PCs) in anaesthetized adult rats, we examined CA1 neuronal synchronization before and after associative fear

Osteoblast response on co-modified titanium surfaces via anodization and electrospinning

Energy Technology Data Exchange (ETDEWEB)

Bayram, Cem [Nanotechnology and Nanomedicine Division, Hacettepe University, Ankara, Beytepe, 06800 (Turkey); Chemistry Department, Aksaray University, Aksaray, 68100 (Turkey); Demirbilek, Murat; Yalçın, Eda [Nanotechnology and Nanomedicine Division, Hacettepe University, Ankara, Beytepe, 06800 (Turkey); Bozkurt, Murat; Doğan, Metin [Orthopaedics and Traumatology Division, Yıldırım Beyazıt University, School of Medicine, Cankaya, 06550 (Turkey); Denkbaş, Emir Baki, E-mail: denkbas@hacettepe.edu.tr [Chemistry Department, Hacettepe University, Ankara, Beytepe, 06800 (Turkey)

2014-01-01

Topography plays a key role in osseointegration and surface modifications at the subcellular level, increasing initial cell attachment in the early period. In the past decade, nanosized texture on metal like a nanotube layer and also more recently extracellular matrix like surface modifications – such as polymeric nanofibrils – have been proposed for a better osseointegration in the literature. Here, we investigate two types of nanoscaled modifications alone and together for the first time. We characterized different types of surface modifications morphologically and investigated how they affected osteoblast cells in vitro, in terms of cell adhesion, proliferation, alkaline phosphatase activity and calcium content. We anodized titanium samples with a thickness of 0.127 mm to obtain a nanotubular titania layer and the silk fibroin (SF), as a biocompatible polymeric material, was electrospun onto both anodized and unanodized samples to acquire 4 sample groups. We analyzed the resulting samples morphologically by scanning electron microscopy (SEM). Cell adhesion, proliferation, alkaline phosphatase (ALP) activity and calcium content were evaluated at 3, 7 and 14 days. We found that cell proliferation increased by 70% on the groups having two modifications respect to unmodified titanium and after 7 days, ALP activity and calcium content were 110% and 150%, respectively, higher on surfaces having both surface treatments than that of unmodified group. In conclusion, a nanotube layer and SF nanofibers on a titanium surface enhanced cell attachment and proliferation most. Comodification of titanium surfaces by anodization and SF electrospinning may be useful to enhance osseointegration but it requires in vivo confirmation.

Human bone marrow stem cell-encapsulating calcium phosphate scaffolds for bone repair

Science.gov (United States)

Weir, Michael D.; Xu, Hockin H.K.

2010-01-01

Due to its injectability and excellent osteoconductivity, calcium phosphate cement (CPC) is highly promising for orthopedic applications. However, a literature search revealed no report on human bone marrow mesenchymal stem cell (hBMSC) encapsulation in CPC for bone tissue engineering. The aim of this study was to encapsulate hBMSCs in alginate hydrogel beads and then incorporate them into CPC, CPC–chitosan and CPC–chitosan–fiber scaffolds. Chitosan and degradable fibers were used to mechanically reinforce the scaffolds. After 21 days, that the percentage of live cells and the cell density of hBMSCs inside CPC-based constructs matched those in alginate without CPC, indicating that the CPC setting reaction did not harm the hBMSCs. Alkaline phosphate activity increased by 8-fold after 14 days. Mineral staining, scanning electron microscopy and X-ray diffraction confirmed that apatitic mineral was deposited by the cells. The amount of hBMSC-synthesized mineral in CPC–chitosan–fiber matched that in CPC without chitosan and fibers. Hence, adding chitosan and fibers, which reinforced the CPC, did not compromise hBMSC osteodifferentiation and mineral synthesis. In conclusion, hBMSCs were encapsulated in CPC and CPC–chitosan–fiber scaffolds for the first time. The encapsulated cells remained viable, osteodifferentiated and synthesized bone minerals. These self-setting, hBMSC-encapsulating CPC-based constructs may be promising for bone tissue engineering applications. PMID:20451676

Effects of electroacupuncture combined with stem cell transplantation on anal sphincter injury-induced faecal incontinence in a rat model.

Science.gov (United States)

Li, Xiaojia; Guo, Xiutian; Jin, Weiqi; Lu, Jingen

2018-03-08

Bone marrow mesenchymal stem cells (BMSCs) and acupuncture are known to mitigate tissue damage. This study aimed to investigate the therapeutic effects of combined electroacupuncture (EA) stimulation and BMSC injection in a rat model of anal sphincter injury-induced faecal incontinence (FI). 60 Sprague-Dawley rats were randomly divided into five groups: sham-operated control, FI, FI+EA, FI+BMSC, and FI+BMSC+EA. The anorectal tissues were collected on days 1, 3, 7 and 14. Repair of the injured anal sphincter was compared using haematoxylin and eosin (HE) and immunocytochemiscal analyses with sarcomeric α actinin. The expression of stromal cell derived factor-1 (SDF-1) and monocyte chemoattractant protein-3 (MCP-3) was detected by quantitative reverse transcription PCR to evaluate the effects of EA on the homing of BMSCs. The therapeutic effect of combined EA+BMSCs on damaged tissue was the strongest among all the groups as indicated by HE and immunohistochemical staining. The expression of SDF-1 and MCP-3 was significantly increased by combined EA and BMSC treatment when compared with the other groups (P=0.01 to PFI secondary to muscle impairment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Associative Learning during Early Adulthood Enhances Later Memory Retention in Honeybees

Science.gov (United States)

Arenas, Andrés; Fernández, Vanesa M.; Farina, Walter M.

2009-01-01

Background Cognitive experiences during the early stages of life play an important role in shaping the future behavior in mammals but also in insects, in which precocious learning can directly modify behaviors later in life depending on both the timing and the rearing environment. However, whether olfactory associative learning acquired early in the adult stage of insects affect memorizing of new learning events has not been studied yet. Methodology Groups of adult honeybee workers that experienced an odor paired with a sucrose solution 5 to 8 days or 9 to 12 days after emergence were previously exposed to (i) a rewarded experience through the offering of scented food, or (ii) a non-rewarded experience with a pure volatile compound in the rearing environment. Principal Findings Early rewarded experiences (either at 1–4 or 5–8 days of adult age) enhanced retention performance in 9–12-day-conditioned bees when they were tested at 17 days of age. The highest retention levels at this age, which could not be improved with prior rewarded experiences, were found for memories established at 5–8 days of adult age. Associative memories acquired at 9–12 days of age showed a weak effect on retention for some pure pre-exposed volatile compounds; whereas the sole exposure of an odor at any younger age did not promote long-term effects on learning performance. Conclusions The associative learning events that occurred a few days after adult emergence improved memorizing in middle-aged bees. In addition, both the timing and the nature of early sensory inputs interact to enhance retention of new learning events acquired later in life, an important matter in the social life of honeybees. PMID:19956575

Associative learning during early adulthood enhances later memory retention in honeybees.

Directory of Open Access Journals (Sweden)

Andrés Arenas

Full Text Available BACKGROUND: Cognitive experiences during the early stages of life play an important role in shaping the future behavior in mammals but also in insects, in which precocious learning can directly modify behaviors later in life depending on both the timing and the rearing environment. However, whether olfactory associative learning acquired early in the adult stage of insects affect memorizing of new learning events has not been studied yet. METHODOLOGY: Groups of adult honeybee workers that experienced an odor paired with a sucrose solution 5 to 8 days or 9 to 12 days after emergence were previously exposed to (i a rewarded experience through the offering of scented food, or (ii a non-rewarded experience with a pure volatile compound in the rearing environment. PRINCIPAL FINDINGS: Early rewarded experiences (either at 1-4 or 5-8 days of adult age enhanced retention performance in 9-12-day-conditioned bees when they were tested at 17 days of age. The highest retention levels at this age, which could not be improved with prior rewarded experiences, were found for memories established at 5-8 days of adult age. Associative memories acquired at 9-12 days of age showed a weak effect on retention for some pure pre-exposed volatile compounds; whereas the sole exposure of an odor at any younger age did not promote long-term effects on learning performance. CONCLUSIONS: The associative learning events that occurred a few days after adult emergence improved memorizing in middle-aged bees. In addition, both the timing and the nature of early sensory inputs interact to enhance retention of new learning events acquired later in life, an important matter in the social life of honeybees.

Glucose enhancement of event-related potentials associated with episodic memory and attention

OpenAIRE

Brown, Louise; Riby, Leigh

2013-01-01

Previous studies have reported that increasing glycaemia by a glucose-containing drink enhances memory functioning. The aim of the present study was to extend this literature by examining the effects of glucose on episodic memory as well as attention processes, and to investigate associated event-related potential (ERP) markers. Fifteen minutes after treatment (25 g glucose or placebo drink), 35 participants performed an old/new recognition memory task and a Stroop colour naming task. Consist...

Trabecular bone strains around a dental implant and associated micromotions--a micro-CT-based three-dimensional finite element study.

NARCIS (Netherlands)

Limbert, G.; Lierde, C. van; Muraru, O.L.; Walboomers, X.F.; Frank, M.; Hansson, S.; Middleton, J.; Jaecques, S.

2010-01-01

The first objective of this computational study was to assess the strain magnitude and distribution within the three-dimensional (3D) trabecular bone structure around an osseointegrated dental implant loaded axially. The second objective was to investigate the relative micromotions between the

Co-culture of chondrocytes and bone marrow mesenchymal stem cells in vitro enhances the expression of cartilaginous extracellular matrix components

Directory of Open Access Journals (Sweden)

Chang Qing

2011-04-01

Full Text Available Chondrocytes and bone marrow mesenchymal stem cells (BMSCs are frequently used as seed cells in cartilage tissue engineering. In the present study, we determined if the co-culture of rabbit articular chondrocytes and BMSCs in vitro promotes the expression of cartilaginous extracellular matrix and, if so, what is the optimal ratio of the two cell types. Cultures of rabbit articular chondrocytes and BMSCs were expanded in vitro and then cultured individually or at a chondrocyte:BMSC ratio of 4:1, 2:1, 1:1, 1:2, 1:4 for 21 days and cultured in DMEM/F12. BMSCs were cultured in chondrogenic induction medium. Quantitative real-time RT-PCR and Western blot were used to evaluate gene expression. In the co-cultures, type II collagen and aggrecan expression increased on days 14 and 21. At the mRNA level, the expression of type II collagen and aggrecan on day 21 was much higher in the 4:1, 2:1, and 1:1 groups than in either the articular chondrocyte group or the induced BMSC group, and the best ratio of co-culture groups seems to be 2:1. Also on day 21, the expression of type II collagen and aggrecan proteins in the 2:1 group was much higher than in all other groups. The results demonstrate that the co-culture of rabbit chondrocytes and rabbit BMSCs at defined ratios can promote the expression of cartilaginous extracellular matrix. The optimal cell ratio appears to be 2:1 (chondrocytes:BMSCs. This approach has potential applications in cartilage tissue engineering since it provides a protocol for maintaining and promoting seed-cell differentiation and function.

Co-culture of chondrocytes and bone marrow mesenchymal stem cells in vitro enhances the expression of cartilaginous extracellular matrix components.

Science.gov (United States)

Qing, Chang; Wei-ding, Cui; Wei-min, Fan

2011-04-01

Chondrocytes and bone marrow mesenchymal stem cells (BMSCs) are frequently used as seed cells in cartilage tissue engineering. In the present study, we determined if the co-culture of rabbit articular chondrocytes and BMSCs in vitro promotes the expression of cartilaginous extracellular matrix and, if so, what is the optimal ratio of the two cell types. Cultures of rabbit articular chondrocytes and BMSCs were expanded in vitro and then cultured individually or at a chondrocyte:BMSC ratio of 4:1, 2:1, 1:1, 1:2, 1:4 for 21 days and cultured in DMEM/F12. BMSCs were cultured in chondrogenic induction medium. Quantitative real-time RT-PCR and Western blot were used to evaluate gene expression. In the co-cultures, type II collagen and aggrecan expression increased on days 14 and 21. At the mRNA level, the expression of type II collagen and aggrecan on day 21 was much higher in the 4:1, 2:1, and 1:1 groups than in either the articular chondrocyte group or the induced BMSC group, and the best ratio of co-culture groups seems to be 2:1. Also on day 21, the expression of type II collagen and aggrecan proteins in the 2:1 group was much higher than in all other groups. The results demonstrate that the co-culture of rabbit chondrocytes and rabbit BMSCs at defined ratios can promote the expression of cartilaginous extracellular matrix. The optimal cell ratio appears to be 2:1 (chondrocytes:BMSCs). This approach has potential applications in cartilage tissue engineering since it provides a protocol for maintaining and promoting seed-cell differentiation and function.

Improved dopamine transporter binding activity after bone marrow mesenchymal stem cell transplantation in a rat model of Parkinson's disease: small animal positron emission tomography study with F-18 FP-CIT

Energy Technology Data Exchange (ETDEWEB)

Park, Bok-Nam; Lee, Kwanjae; An, Young-Sil [School of Medicine, Ajou University, Department of Nuclear Medicine and Molecular Imaging, Woncheon-dong, Yeongtong-gu, Gyeonggi-do, Suwon (Korea, Republic of); Kim, Jang-Hee; Park, So Hyun [Ajou University School of Medicine, Department of Pathology, Suwon (Korea, Republic of)

2015-05-01

We evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) in a model of Parkinson's disease (PD) using serial F-18 fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) PET. Hemiparkinsonian rats were treated with intravenously injected BMSCs, and animals without stem cell therapy were used as the controls. Serial FP-CIT PET was performed after therapy. The ratio of FP-CIT uptake in the lesion side to uptake in the normal side was measured. The changes in FP-CIT uptake were also analyzed using SPM. Behavioural and histological changes were observed using the rotational test and tyrosine hydroxylase (TH)-reactive cells. FP-CIT uptake ratio was significantly different in the BMSCs treated group (n = 28) at each time point. In contrast, there was no difference in the ratio in control rats (n = 25) at any time point. SPM analysis also revealed that dopamine transporter binding activity was enhanced in the right basal ganglia area in only the BMSC therapy group. In addition, rats that received BMSC therapy also exhibited significantly improved rotational behaviour and preservation of TH-positive neurons compared to controls. The therapeutic effect of intravenously injected BMSCs in a rat model of PD was confirmed by dopamine transporter PET imaging, rotational functional studies, and histopathological evaluation. (orig.)

Improved dopamine transporter binding activity after bone marrow mesenchymal stem cell transplantation in a rat model of Parkinson's disease: small animal positron emission tomography study with F-18 FP-CIT

International Nuclear Information System (INIS)

Park, Bok-Nam; Lee, Kwanjae; An, Young-Sil; Kim, Jang-Hee; Park, So Hyun

2015-01-01

We evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) in a model of Parkinson's disease (PD) using serial F-18 fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) PET. Hemiparkinsonian rats were treated with intravenously injected BMSCs, and animals without stem cell therapy were used as the controls. Serial FP-CIT PET was performed after therapy. The ratio of FP-CIT uptake in the lesion side to uptake in the normal side was measured. The changes in FP-CIT uptake were also analyzed using SPM. Behavioural and histological changes were observed using the rotational test and tyrosine hydroxylase (TH)-reactive cells. FP-CIT uptake ratio was significantly different in the BMSCs treated group (n = 28) at each time point. In contrast, there was no difference in the ratio in control rats (n = 25) at any time point. SPM analysis also revealed that dopamine transporter binding activity was enhanced in the right basal ganglia area in only the BMSC therapy group. In addition, rats that received BMSC therapy also exhibited significantly improved rotational behaviour and preservation of TH-positive neurons compared to controls. The therapeutic effect of intravenously injected BMSCs in a rat model of PD was confirmed by dopamine transporter PET imaging, rotational functional studies, and histopathological evaluation. (orig.)

Vascular endothelial growth factor regulates melanoma cell adhesion and growth in the bone marrow microenvironment via tumor cyclooxygenase-2

Directory of Open Access Journals (Sweden)

Crende Olatz

2011-08-01

Full Text Available Abstract Background Human melanoma frequently colonizes bone marrow (BM since its earliest stage of systemic dissemination, prior to clinical metastasis occurrence. However, how melanoma cell adhesion and proliferation mechanisms are regulated within bone marrow stromal cell (BMSC microenvironment remain unclear. Consistent with the prometastatic role of inflammatory and angiogenic factors, several studies have reported elevated levels of cyclooxygenase-2 (COX-2 in melanoma although its pathogenic role in bone marrow melanoma metastasis is unknown. Methods Herein we analyzed the effect of cyclooxygenase-2 (COX-2 inhibitor celecoxib in a model of generalized BM dissemination of left cardiac ventricle-injected B16 melanoma (B16M cells into healthy and bacterial endotoxin lipopolysaccharide (LPS-pretreated mice to induce inflammation. In addition, B16M and human A375 melanoma (A375M cells were exposed to conditioned media from basal and LPS-treated primary cultured murine and human BMSCs, and the contribution of COX-2 to the adhesion and proliferation of melanoma cells was also studied. Results Mice given one single intravenous injection of LPS 6 hour prior to cancer cells significantly increased B16M metastasis in BM compared to untreated mice; however, administration of oral celecoxib reduced BM metastasis incidence and volume in healthy mice, and almost completely abrogated LPS-dependent melanoma metastases. In vitro, untreated and LPS-treated murine and human BMSC-conditioned medium (CM increased VCAM-1-dependent BMSC adherence and proliferation of B16M and A375M cells, respectively, as compared to basal medium-treated melanoma cells. Addition of celecoxib to both B16M and A375M cells abolished adhesion and proliferation increments induced by BMSC-CM. TNFα and VEGF secretion increased in the supernatant of LPS-treated BMSCs; however, anti-VEGF neutralizing antibodies added to B16M and A375M cells prior to LPS-treated BMSC-CM resulted in a

Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews

Directory of Open Access Journals (Sweden)

Liu-Lin Xiong

2017-06-01

Full Text Available Hemi-sectioned spinal cord injury (hSCI can lead to spastic paralysis on the injured side, as well as flaccid paralysis on the contralateral side, which can negatively affect a patient’s daily life. Stem-cell therapy may offer an effective treatment option for individuals with hSCI. To examine the role of bone marrow mesenchymal stem cells (BMSCs transplantation on hSCI and explore related mechanisms in the tree shrews, here, we created a model of hSCI by inducing injury at the tenth thoracic vertebra (T10. Hoechst 33342-labeled BMSCs derived from adult tree shrews were isolated, cultured, and implanted into the spinal cord around the injury site at 9 days after injury. The isolated BMSCs were able to survive, proliferate and release a variety of neurotrophic factors (NTFs both in vitro and in vivo. At 28 days after injury, compared with the sham group, the hSCI group displayed scar formation and dramatic elevations in the mean interleukin 1 beta (IL-1β density and cell apoptosis level, whereas the expression of signal transducer and activator of transcription 3 (STAT3 and ciliary neurotrophic factor (CNTF mRNA was reduced. Following BMSC transplantation, motoneurons extent of shrinkage were reduced and the animals’ Basso, Beattie, and Bresnahan (BBB locomotion scale scores were significantly higher at 21 and 28 days after injury when compared with the injured group. Moreover, the hSCI-induced elevations in scar formation, IL-1β, and cell apoptosis were reduced by BMSC transplantation to levels that were close to those of the sham group. Corresponding elevations in the expression of STAT3 and CNTF mRNA were observed in the hSCI + BMSCs group, and the levels were not significantly different from those observed in the sham group. Together, our results support that grafted BMSCs can significantly improve locomotor function in tree shrews subjected to hSCI and that this improvement is associated with the upregulation of CNTF and STAT3

The Bone Marrow-Derived Stromal Cells

DEFF Research Database (Denmark)

Tencerova, Michaela; Kassem, Moustapha

2016-01-01

Bone marrow (BM) microenvironment represents an important compartment of bone that regulates bone homeostasis and the balance between bone formation and bone resorption depending on the physiological needs of the organism. Abnormalities of BM microenvironmental dynamics can lead to metabolic bone...... diseases. BM stromal cells (also known as skeletal or mesenchymal stem cells) [bone marrow stromal stem cell (BMSC)] are multipotent stem cells located within BM stroma and give rise to osteoblasts and adipocytes. However, cellular and molecular mechanisms of BMSC lineage commitment to adipocytic lineage...

Synovitis assessed on static and dynamic contrast-enhanced magnetic resonance imaging and its association with pain in knee osteoarthritis

DEFF Research Database (Denmark)

Riis, Robert Gabriel Coumine; Gudbergsen, Henrik; Henriksen, Marius

2016-01-01

OBJECTIVES: To investigate the association between pain and peripatellar-synovitis on static and dynamic contrast-enhanced MRI in knee osteoarthritis. METHODS: In a cross-sectional setting, knee synovitis was assessed using 3-Tesla MRI and correlated with pain using the knee injury and osteoarthr......OBJECTIVES: To investigate the association between pain and peripatellar-synovitis on static and dynamic contrast-enhanced MRI in knee osteoarthritis. METHODS: In a cross-sectional setting, knee synovitis was assessed using 3-Tesla MRI and correlated with pain using the knee injury...

A survey of the governance capacity of national public health associations to enhance population health.

Science.gov (United States)

Chauvin, James; Shukla, Mahesh; Rice, James; Rispel, Laetitia

2016-03-11

National public health associations (PHAs) are key partners with governments and communities to improve, protect and promote the public's health. Governance and organizational capacity are among the key determinants of a PHA's effectiveness as an advocate for appropriate public health policies and practice. During 2014, the World Federation of Public Health Associations (WFPHA) conducted an on-line survey of its 82 PHA members, to identify the state of organizational governance of national public health associations, as well as the factors that influence optimal organizational governance. The survey consisted of 13 questions and focused on the main elements of organizational governance: cultivating accountability; engaging stakeholders; setting shared direction; stewarding resources; and, continuous governance enhancement. Four questions included a qualitative open-ended response for additional comments. The survey data were analyzed using Microsoft Excel. The qualitative data was analyzed using thematic content analysis Responses were received from 62 PHAs, constituting a 75.6 % response rate. The two most important factors that support governance effectiveness were a high degree of integrity and ethical behavior of the PHA's leaders (77 %) and the competence of people serving on the PHA's governing body (76 %). The lack of financial resources was considered as the most important factor that negatively affected organizational governance effectiveness (73 %). The lack of mentoring for future PHA leaders; ineffective or incompetent leadership; lack of understanding about good governance practices; and lack of accurate information for strategic planning were identified as factors influencing PHA governance effectiveness. Critical elements for PHA sustainability included diversity, gender-responsiveness and inclusive governance practices, and strategies to build the future generation of public health leaders. National PHA have a responsibility to put into place

Glucose enhancement of event-related potentials associated with episodic memory and attention.

Science.gov (United States)

Brown, Louise A; Riby, Leigh M

2013-04-30

Previous studies have reported that increasing glycaemia by a glucose-containing drink enhances memory functioning. The aim of the present study was to extend this literature by examining the effects of glucose on episodic memory as well as attention processes, and to investigate associated event-related potential (ERP) markers. Fifteen minutes after treatment (25 g glucose or placebo drink), 35 participants performed an old/new recognition memory task and a Stroop colour naming task. Consistent with previous research, when controlling for glucose regulation, cognitive facilitation was observed behaviourally for verbal memory, but there was also a trend towards attentional facilitation. Furthermore, across both domains, it was the most demanding task conditions that exhibited glucose sensitivity. In support of the behavioural results, the analysis of ERPs across treatment groups revealed an enhanced left-parietal old/new effect related to recollection, and also suggested modulation of attentional processes. The results suggest that glucose may facilitate attention as well as memory.

Non-coding genomic regions possessing enhancer and silencer potential are associated with healthy aging and exceptional survival.

Science.gov (United States)

Kim, Sangkyu; Welsh, David A; Myers, Leann; Cherry, Katie E; Wyckoff, Jennifer; Jazwinski, S Michal

2015-02-28

We have completed a genome-wide linkage scan for healthy aging using data collected from a family study, followed by fine-mapping by association in a separate population, the first such attempt reported. The family cohort consisted of parents of age 90 or above and their children ranging in age from 50 to 80. As a quantitative measure of healthy aging, we used a frailty index, called FI34, based on 34 health and function variables. The linkage scan found a single significant linkage peak on chromosome 12. Using an independent cohort of unrelated nonagenarians, we carried out a fine-scale association mapping of the region suggestive of linkage and identified three sites associated with healthy aging. These healthy-aging sites (HASs) are located in intergenic regions at 12q13-14. HAS-1 has been previously associated with multiple diseases, and an enhancer was recently mapped and experimentally validated within the site. HAS-2 is a previously uncharacterized site possessing genomic features suggestive of enhancer activity. HAS-3 contains features associated with Polycomb repression. The HASs also contain variants associated with exceptional longevity, based on a separate analysis. Our results provide insight into functional genomic networks involving non-coding regulatory elements that are involved in healthy aging and longevity.

Nano-biphasic calcium phosphate/polyvinyl alcohol composites with enhanced bioactivity for bone repair via low-temperature three-dimensional printing and loading with platelet-rich fibrin.

Science.gov (United States)

Song, Yue; Lin, Kaifeng; He, Shu; Wang, Chunmei; Zhang, Shuaishuai; Li, Donglin; Wang, Jimeng; Cao, Tianqing; Bi, Long; Pei, Guoxian

2018-01-01

As a newly emerging three-dimensional (3D) printing technology, low-temperature robocasting can be used to fabricate geometrically complex ceramic scaffolds at low temperatures. Here, we aimed to fabricate 3D printed ceramic scaffolds composed of nano-biphasic calcium phosphate (BCP), polyvinyl alcohol (PVA), and platelet-rich fibrin (PRF) at a low temperature without the addition of toxic chemicals. Corresponding nonprinted scaffolds were prepared using a freeze-drying method. Compared with the nonprinted scaffolds, the printed scaffolds had specific shapes and well-connected internal structures. The incorporation of PRF enabled both the sustained release of bioactive factors from the scaffolds and improved biocompatibility and biological activity toward bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. Additionally, the printed BCP/PVA/PRF scaffolds promoted significantly better BMSC adhesion, proliferation, and osteogenic differentiation in vitro than the printed BCP/PVA scaffolds. In vivo, the printed BCP/PVA/PRF scaffolds induced a greater extent of appropriate bone formation than the printed BCP/PVA scaffolds and nonprinted scaffolds in a critical-size segmental bone defect model in rabbits. These experiments indicate that low-temperature robocasting could potentially be used to fabricate 3D printed BCP/PVA/PRF scaffolds with desired shapes and internal structures and incorporated bioactive factors to enhance the repair of segmental bone defects.

Nanosized Hydroxyapatite Coating on PEEK Implants Enhances Early Bone Formation: A Histological and Three-Dimensional Investigation in Rabbit Bone

Directory of Open Access Journals (Sweden)

Pär Johansson

2015-06-01

Full Text Available Polyether ether ketone (PEEK has been frequently used in spinal surgery with good clinical results. The material has a low elastic modulus and is radiolucent. However, in oral implantology PEEK has displayed inferior ability to osseointegrate compared to titanium materials. One idea to reinforce PEEK would be to coat it with hydroxyapatite (HA, a ceramic material of good biocompatibility. In the present study we analyzed HA-coated PEEK tibial implants via histology and radiography when following up at 3 and 12 weeks. Of the 48 implants, 24 were HA-coated PEEK screws (test and another 24 implants served as uncoated PEEK controls. HA-coated PEEK implants were always osseointegrated. The total bone area (BA was higher for test compared to control implants at 3 (p < 0.05 and 12 weeks (p < 0.05. Mean bone implant contact (BIC percentage was significantly higher (p = 0.024 for the test compared to control implants at 3 weeks and higher without statistical significance at 12 weeks. The effect of HA-coating was concluded to be significant with respect to early bone formation, and HA-coated PEEK implants may represent a good material to serve as bone anchored clinical devices.

Short communication: Effect of commercial or depurinized milk diet on plasma advanced oxidation protein products, cardiovascular markers, and bone marrow CD34+ stem cell potential in rat experimental hyperuricemia.

Science.gov (United States)

Kocic, Gordana; Sokolovic, Dusan; Jevtovic, Tatjana; Cvetkovic, Tatjana; Veljkovic, Andrej; Kocic, Hristina; Stojanovic, Svetlana; Jovanovic, Aneta; Jovanovic, Jelena; Zivkovic, Petar

2014-11-01

Cardiovascular repair and myocardial contractility may be improved by migration of bone marrow stem cells (BMSC) and their delivery to the site of injury, a process known as BMSC homing. The aim of our study was to examine the dietary effect of a newly patented depurinized milk (DP) that is almost free of uric acid and purine and pyrimidine compounds compared with a standard commercial 1.5% fat UHT milk diet or allopurinol therapy in rat experimental hyperuricemia. Bone marrow stem cell potential (BMCD34(+), CD34-postive bone marrow cells), plasma oxidative stress parameters [advanced oxidation protein products, AOPP) and thiobarbituric acid reactive substances (TBARS)], myocardial damage markers [creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], plasma cholesterol, and high-density lipoprotein cholesterol were investigated. The DP milk diet significantly increased the number of BMCD34(+) stem cells compared with commercial UHT milk. Allopurinol given alone also increased the number of BMCD34(+). Hyperuricemia caused a significant increase in all plasma enzyme markers for myocardial damage (CPK, LDH, and AST). A cardioprotective effect was achieved with allopurinol but almost equally with DP milk and more than with commercial milk. Regarding plasma AOPP, TBARS, and cholesterol levels, the most effective treatment was DP milk. In conclusion, the protective role of a milk diet on cardiovascular function may be enhanced through the new depurinized milk diet, which may improve cardiovascular system function via increased bone marrow stem cell regenerative potential, decreased plasma oxidative stress parameters, and decreased levels of myocardial damage markers and cholesterol. New dairy technology strategies focused on eliminating harmful milk compounds should be completely nontoxic. Novel milk products should be tested for their ability to improve tissue repair and function. Copyright © 2014 American Dairy Science

Mesenchymal stem cells-seeded bio-ceramic construct for bone regeneration in large critical-size bone defect in rabbit

Directory of Open Access Journals (Sweden)

Maiti SK

2016-11-01

Full Text Available Bone marrow derived mesenchymal stem cells (BMSC represent an attractive cell population for tissue engineering purpose. The objective of this study was to determine whether the addition of recombinant human bone morphogenetic protein (rhBMP-2 and insulin-like growth factor (IGF-1 to a silica-coated calcium hydroxyapatite (HASi - rabbit bone marrow derived mesenchymal stem cell (rBMSC construct promoted bone healing in a large segmental bone defect beyond standard critical -size radial defects (15mm in rabbits. An extensively large 30mm long radial ostectomy was performed unilaterally in thirty rabbits divided equally in five groups. Defects were filled with a HASi scaffold only (group B; HASi scaffold seeded with rBMSC (group C; HASi scaffold seeded with rBMSC along with rhBMP-2 and IGF-1 in groups D and E respectively. The same number of rBMSC (five million cells and concentration of growth factors rhBMP-2 (50µg and IGF-1 (50µg was again injected at the site of bone defect after 15 days of surgery in their respective groups. An empty defect served as the control group (group A. Radiographically, bone healing was evaluated at 7, 15, 30, 45, 60 and 90 days post implantation. Histological qualitative analysis with microCT (µ-CT, haematoxylin and eosin (H & E and Masson’s trichrome staining were performed 90 days after implantation. All rhBMP-2-added constructs induced the formation of well-differentiated mineralized woven bone surrounding the HASi scaffolds and bridging bone/implant interfaces as early as eight weeks after surgery. Bone regeneration appeared to develop earlier with the rhBMP-2 constructs than with the IGF-1 added construct. Constructs without any rhBMP-2 or IGF-1 showed osteoconductive properties limited to the bone junctions without bone ingrowths within the implantation site. In conclusion, the addition of rhBMP-2 to a HASi scaffold could promote bone generation in a large critical-size-defect.

Bone Marrow Mesenchymal Stem Cell-Based Engineered Cartilage Ameliorates Polyglycolic Acid/Polylactic Acid Scaffold-Induced Inflammation Through M2 Polarization of Macrophages in a Pig Model.

Science.gov (United States)

Ding, Jinping; Chen, Bo; Lv, Tao; Liu, Xia; Fu, Xin; Wang, Qian; Yan, Li; Kang, Ning; Cao, Yilin; Xiao, Ran

2016-08-01

: The regeneration of tissue-engineered cartilage in an immunocompetent environment usually fails due to severe inflammation induced by the scaffold and their degradation products. In the present study, we compared the tissue remodeling and the inflammatory responses of engineered cartilage constructed with bone marrow mesenchymal stem cells (BMSCs), chondrocytes, or both and scaffold group in pigs. The cartilage-forming capacity of the constructs in vitro and in vivo was evaluated by histological, biochemical, and biomechanical analyses, and the inflammatory response was investigated by quantitative analysis of foreign body giant cells and macrophages. Our data revealed that BMSC-based engineered cartilage suppressed in vivo inflammation through the alteration of macrophage phenotype, resulting in better tissue survival compared with those regenerated with chondrocytes alone or in combination with BMSCs. To further confirm the macrophage phenotype, an in vitro coculture system established by engineered cartilage and macrophages was studied using immunofluorescence, enzyme-linked immunosorbent assay, and gene expression analysis. The results demonstrated that BMSC-based engineered cartilage promoted M2 polarization of macrophages with anti-inflammatory phenotypes including the upregulation of CD206, increased IL-10 synthesis, decreased IL-1β secretion, and alterations in gene expression indicative of M1 to M2 transition. It was suggested that BMSC-seeded constructs have the potential to ameliorate scaffold-induced inflammation and improve cartilaginous tissue regeneration through M2 polarization of macrophages. Finding a strategy that can prevent scaffold-induced inflammation is of utmost importance for the regeneration of tissue-engineered cartilage in an immunocompetent environment. This study demonstrated that bone marrow mesenchymal stem cell (BMSC)-based engineered cartilage could suppress inflammation by increasing M2 polarization of macrophages, resulting

Selective laser melting porous metallic implants with immobilized silver nanoparticles kill and prevent biofilm formation by methicillin-resistant Staphylococcus aureus

NARCIS (Netherlands)

van Hengel, Ingmar A. J.; Riool, Martijn; Fratila-Apachitei, Lidy E.; Witte-Bouma, Janneke; Farrell, Eric; Zadpoor, Amir A.; Zaat, Sebastian A. J.; Apachitei, Iulian

2017-01-01

Implant-associated infection and limited longevity are two major challenges that orthopedic devices need to simultaneously address. Additively manufactured porous implants have recently shown tremendous promise in improving bone regeneration and osseointegration, but, as any conventional implant,

Leptomeningeal Contrast Enhancement Is Associated with Disability Progression and Grey Matter Atrophy in Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Gleb Makshakov

2017-01-01

Full Text Available Leptomeningeal contrast enhancement (LMCE on magnetic resonance imaging (MRI is a newly recognized possible biomarker in multiple sclerosis (MS, associated with MS progression and cortical atrophy. In this study, we aimed to assess the prevalence of LMCE foci and their impact on neurodegeneration and disability. Materials. 54 patients with MS were included in the study. LMCE were detected with a 3 Tesla scanner on postcontrast fluid-attenuated inversion-recovery (FLAIR sequence. Expanded Disability Status Scale (EDSS score, number of relapses during 5 years from MS onset, and number of contrast-enhancing lesions on T1 weighted MRI were counted. Results. LMCE was detected in 41% (22/54 of patients. LMCE-positive patients had longer disease duration (p=0,0098 and higher EDSS score (p=0,039, but not a higher relapse rate (p=0,091. No association of LMCE with higher frequency of contrast-enhancing lesions on T1-weighted images was detected (p=0,3842. Analysis of covariates, adjusted for age, sex, and disease duration, revealed a significant effect of LMCE on the cortex volume (p=0.043, F=2.529, the total grey matter volume (p=0.043, F=2.54, and total ventricular volume (p=0.039, F=2.605. Conclusions. LMCE was shown to be an independent and significant biomarker of grey matter atrophy and disability in MS.

Drosophila TDP-43 RNA-Binding Protein Facilitates Association of Sister Chromatid Cohesion Proteins with Genes, Enhancers and Polycomb Response Elements.

Directory of Open Access Journals (Sweden)

Amanda Swain

2016-09-01

Full Text Available The cohesin protein complex mediates sister chromatid cohesion and participates in transcriptional control of genes that regulate growth and development. Substantial reduction of cohesin activity alters transcription of many genes without disrupting chromosome segregation. Drosophila Nipped-B protein loads cohesin onto chromosomes, and together Nipped-B and cohesin occupy essentially all active transcriptional enhancers and a large fraction of active genes. It is unknown why some active genes bind high levels of cohesin and some do not. Here we show that the TBPH and Lark RNA-binding proteins influence association of Nipped-B and cohesin with genes and gene regulatory sequences. In vitro, TBPH and Lark proteins specifically bind RNAs produced by genes occupied by Nipped-B and cohesin. By genomic chromatin immunoprecipitation these RNA-binding proteins also bind to chromosomes at cohesin-binding genes, enhancers, and Polycomb response elements (PREs. RNAi depletion reveals that TBPH facilitates association of Nipped-B and cohesin with genes and regulatory sequences. Lark reduces binding of Nipped-B and cohesin at many promoters and aids their association with several large enhancers. Conversely, Nipped-B facilitates TBPH and Lark association with genes and regulatory sequences, and interacts with TBPH and Lark in affinity chromatography and immunoprecipitation experiments. Blocking transcription does not ablate binding of Nipped-B and the RNA-binding proteins to chromosomes, indicating transcription is not required to maintain binding once established. These findings demonstrate that RNA-binding proteins help govern association of sister chromatid cohesion proteins with genes and enhancers.

Surface Modification of Titanium Using Anodization to Enhance Antimicrobial Properties and Osseointegration

Science.gov (United States)

Jain, Sakshi

Titanium and its alloys are frequently used in dental and orthopedic implants because they have good mechanical strength, chemical stability and biocompatibility. These properties can be further improved by surface treatments such as anodization that are able to grow thicker and produce crystalline oxide layers with controlled morphological and physico-chemical properties. Both anatase (A) and rutile (R) crystalline phases of titanium oxide have been shown to promote bioactivity and antimicrobial effects. In a previous study in our laboratories, four electrolyte mixtures were optimized to produce anodized layers on commercially pure titanium consisting of specific anatase and rutile oxide ratios at an endpoint forming voltage of 180 V. In the present study, changes that occurred in the anodized layers with increasing forming voltage including crystallinity, thickness, surface morphology, surface roughness, surface chemistry, fractal dimension, shear strength, and corrosion resistance were determined for each of these electrolytes. The results showed the crystallinity, thickness, surface pore sizes, and surface roughness increased with increasing forming voltage. Incorporation of phosphorus into the anodized layers was shown in phosphoric acid containing electrolytes at higher forming voltages. Decreases in corrosion resistance were also shown at higher forming voltages in each electrolyte due to increased pore interconnectivity within the anodized layers. In addition, the apatite inducing ability of anodized layers in SBF was examined for selected forming voltages in each electrolyte. Anodization in phosphoric acid containing electrolytes was shown to be more favorable for apatite formation. The streptococcal and MRSA bacterial attachment before and after UV treatments was determined for selected forming voltages in each electrolyte. Additionally, the killing efficacy after 10-minute pre-irradiation with UVA or UVC treatments was determined. UVA treatments showed trends of at least a 20% reduction in bacterial attachment regardless of the crystallinity within the oxide for S. sanguinis. The anodized layer with an approximately equal distribution of anatase and rutile phases showed bacterial killing efficacy over 50% for S. sanguinis and over 80% for MRSA after UVA or UVC treatments. Finally, two forming voltage sample groups in two of the electrolytes were examined for MC3T3E-1 cell attachment, proliferation, and differentiation. Total intracellular protein content, alkaline phosphatase (ALP) activity, osteocalcin (OCN) activity, and cellular mineralization were investigated for different time periods up to 21 days. All sample groups showed suitable cellular proliferation, differentiation, and maturation but those anodized in the phosphoric acid containing electrolyte showed delayed proliferation and early differentiation and maturation. Also, anodized samples containing at least 50% anatase were shown to produce higher osteoblast mineralization compared to majority rutile phase anodized layers.

[Effect of low dose aspirin on osseointegration around titanium implants in osteoporotic rats].

Science.gov (United States)

Yang, Q; Li, F L

2018-02-09

Objective: To investigate the effect of aspirin on osseointegration around titanium implants in ostoeporotic rats and to provide evidence for future researches and clinical application. Methods: A total of 60 female SD rats, aged 3-4 months, were divided into ovariectomy group (Ovx group, n= 48) and sham-ovariectomy group (Sham group, n= 12). The rats in Ovx group received ovariectomy and those in Sham group underwent sham-ovariectomy. Twelve weeks later, six rats in each group were randomly selected to confirm the osteoporosis models. The Ovx group was divided into 4 subgroups with 12 rats in each group, namely the osteoporosis group (OP group), and Aspirin groups (A1, A2, A3 group). Pure screw titanium implants were placed in the right tibia near metaphysis of all rats. Three days after implant surgery, aspirin groups were intragastrically administered aspirin at a dose of 2.06, 4.11, 8.21 mg·kg(-1)·d(-1) (A1, A2, A3), and OP group and Sham group were fed the same amount of normal saline. Four and 12 weeks following implantations surgery, half of the rats in each group were randomly chosen and sacrificed. Implant bone contact rate (IBCR), combined bone lamella width (CBLW) and trabercular width (TW) were observed and calculated using histomorphometric measurement. Results: Four weeks after implantations surgery, the TW and CBLW of rats in A1 group [(39.60±2.77) and (27.56±4.14) μm] and the IBCR, TW and CBLW of rats in A2 group and A3 group [A2: (47.21±4.19)%, (48.74±3.20) and (35.91±3.79) μm; A3: (47.35±6.07)%, (50.27±5.25) and (40.66±2.11) μm] were much higher than those in OP group [(33.89±7.17)%, (32.20±6.10) and (19.77±6.80) μm]( P 0.05). Twelve weeks after implantations surgery, the IBCR and CBLW of rats in A1 group [ (85.86±3.64) %, (53.12±8.68) μm], and the IBCR, TW and CBLW of rats in A2 group and A3 group [A2: (85.64±3.97)%, (69.42±6.78) and (54.19±3.12) μm; A3: (86.22±3.48)%, (75.43±3.50) and (55.79±5.60) μm] were much higher

Biocompatible cephalosporin-hydroxyapatite-poly(lactic-co-glycolic acid)-coatings fabricated by MAPLE technique for the prevention of bone implant associated infections

Science.gov (United States)

Rădulescu, Dragoş; Grumezescu, Valentina; Andronescu, Ecaterina; Holban, Alina Maria; Grumezescu, Alexandru Mihai; Socol, Gabriel; Oprea, Alexandra Elena; Rădulescu, Marius; Surdu, Adrian; Trusca, Roxana; Rădulescu, Radu; Chifiriuc, Mariana Carmen; Stan, Miruna S.; Constanda, Sabrina; Dinischiotu, Anca

2016-06-01

In this study we aimed to obtain functionalized thin films based on hydroxyapatite/poly(lactic-co-glycolic acid) (HAp/PLGA) containing ceftriaxone/cefuroxime antibiotics (ATBs) deposited by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The prepared thin films were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-Ray diffraction (XRD), selected area electron diffraction (SAED), and infra red (IR) analysis. HAp/PLGA/ATBs thin films sustained the growth of human osteoblasts, proving their good biocompatibility. The microscopic evaluation and the culture-based quantitative assay of the E. coli biofilm development showed that the thin films inhibited the initial step of microbial attachment as well as the subsequent colonization and biofilm development on the respective surfaces. This study demonstrates that MAPLE technique could represent an appealing technique for the fabrication of antibiotics-containing polymeric implant coatings. The bioevaluation results recommend this type of surfaces for the prevention of bone implant microbial contamination and for the enhanced stimulation of the implant osseointegration process.

A survey of the governance capacity of national public health associations to enhance population health

Directory of Open Access Journals (Sweden)

James Chauvin

2016-03-01

Full Text Available Abstract Background National public health associations (PHAs are key partners with governments and communities to improve, protect and promote the public’s health. Governance and organizational capacity are among the key determinants of a PHA’s effectiveness as an advocate for appropriate public health policies and practice. Methods During 2014, the World Federation of Public Health Associations (WFPHA conducted an on-line survey of its 82 PHA members, to identify the state of organizational governance of national public health associations, as well as the factors that influence optimal organizational governance. The survey consisted of 13 questions and focused on the main elements of organizational governance: cultivating accountability; engaging stakeholders; setting shared direction; stewarding resources; and, continuous governance enhancement. Four questions included a qualitative open-ended response for additional comments. The survey data were analyzed using Microsoft Excel. The qualitative data was analyzed using thematic content analysis Results Responses were received from 62 PHAs, constituting a 75.6 % response rate. The two most important factors that support governance effectiveness were a high degree of integrity and ethical behavior of the PHA’s leaders (77 % and the competence of people serving on the PHA’s governing body (76 %. The lack of financial resources was considered as the most important factor that negatively affected organizational governance effectiveness (73 %. The lack of mentoring for future PHA leaders; ineffective or incompetent leadership; lack of understanding about good governance practices; and lack of accurate information for strategic planning were identified as factors influencing PHA governance effectiveness. Critical elements for PHA sustainability included diversity, gender-responsiveness and inclusive governance practices, and strategies to build the future generation of public health

Cocaine-associated retiform purpura: a C5b-9-mediated microangiopathy syndrome associated with enhanced apoptosis and high levels of intercellular adhesion molecule-1 expression.

Science.gov (United States)

Magro, Cynthia M; Wang, Xuan

2013-10-01

Cocaine-associated retiform purpura is a recently described entity characterized by striking hemorrhagic necrosis involving areas of skin associated with administration of cocaine. Levamisole, an adulterant in cocaine, has been suggested as the main culprit pathogenetically. Four cases of cocaine-associated retiform purpura were encountered in the dermatopathology practice of C. M. Magro. The light microscopic findings were correlated with immunohistochemical and immunofluorescence studies. All 4 cases showed a very striking thrombotic diathesis associated with intravascular macrophage accumulation. Necrotizing vasculitis was noted in 1 case. Striking intercellular adhesion molecule-1 (ICAM-1)/CD54 expression in vessel wall along with endothelial expression of caspase 3 and extensive vascular C5b-9 deposition was observed in all biopsies examined. Cocaine-induced retiform purpura is a C5b-9-mediated microvascular injury associated with enhanced apoptosis and prominent vascular expression of ICAM-1, all of which have been shown in prior in vitro and in vivo murine models to be a direct effect of cocaine metabolic products. Antineutrophilic cytoplasmic antibody and antiphospholipid antibodies are likely the direct sequelae of the proapoptotic microenvironment. The inflammatory vasculitic lesion could reflect the downstream end point reflective of enhanced ICAM-1 expression and the development of antineutrophilic cytoplasmic antibody. Levamisole likely works synergistically with cocaine in the propagation of this syndromic complex.

A genetic variant within STS previously associated with inattention in boys with attention deficit hyperactivity disorder is associated with enhanced cognition in healthy adult males.

Science.gov (United States)

Humby, Trevor; Fisher, Amelia; Allen, Christopher; Reynolds, Meghann; Hartman, Annette; Giegling, Ina; Rujescu, Dan; Davies, William

2017-03-01

The enzyme steroid sulfatase (STS) converts sulfated steroids to their non-sulfated forms. Deficiency for this enzyme is associated with inattention but preserved response control. The polymorphism rs17268988 within the X-linked STS gene is associated with inattentive, but not other, symptoms in boys with attention deficit hyperactivity disorder (ADHD). We initially tested whether rs17268988 genotype was associated with attention, response control, and underlying aspects of cognition, using questionnaires and neuropsychological tasks, in two independent cohorts of healthy adult males. In an additional analysis based upon existing data, the performance of mice with genetic or pharmacological manipulations of the STS axis under attentionally demanding conditions was investigated. G-allele carriers at rs17268988 exhibited reduced reaction time, enhanced attention, and reduced reaction time variability relative to C-allele carriers. Mice with genetic or pharmacological manipulations of the STS axis were shown to have perturbed reaction time variability. Our findings provide additional support for an association between rs17268988 genotype and attention, which may be partially mediated by reaction time variability; they also indicate that, in contrast to the situation in boys with ADHD, in healthy men, the G-allele at rs17268988 is associated with enhanced cognition. As reaction time variability is a predictor of well-being, rs17268988 genotype may represent a biomarker for long-term health.

Nanostructured calcium phosphate coatings on magnesium alloys: characterization and cytocompatibility with mesenchymal stem cells.

Science.gov (United States)

Iskandar, Maria Emil; Aslani, Arash; Tian, Qiaomu; Liu, Huinan

2015-05-01

This article reports the deposition and characterization of nanostructured calcium phosphate (nCaP) on magnesium-yttrium alloy substrates and their cytocompatibility with bone marrow derived mesenchymal stem cells (BMSCs). The nCaP coatings were deposited on magnesium and magnesium-yttrium alloy substrates using proprietary transonic particle acceleration process for the dual purposes of modulating substrate degradation and BMSC adhesion. Surface morphology and feature size were analyzed using scanning electron microscopy and quantitative image analysis tools. Surface elemental compositions and phases were analyzed using energy dispersive X-ray spectroscopy and X-ray diffraction, respectively. The deposited nCaP coatings showed a homogeneous particulate surface with the dominant feature size of 200-500 nm in the long axis and 100-300 nm in the short axis, and a Ca/P atomic ratio of 1.5-1.6. Hydroxyapatite was the major phase identified in the nCaP coatings. The modulatory effects of nCaP coatings on the sample degradation and BMSC behaviors were dependent on the substrate composition and surface conditions. The direct culture of BMSCs in vitro indicated that multiple factors, including surface composition and topography, and the degradation-induced changes in media composition, influenced cell adhesion directly on the sample surface, and indirect adhesion surrounding the sample in the same culture. The alkaline pH, the indicator of Mg degradation, played a role in BMSC adhesion and morphology, but not the sole factor. Additional studies are necessary to elucidate BMSC responses to each contributing factor.

In vitro mesenchymal trilineage differentiation and extracellular matrix production by adipose and bone marrow derived adult equine multipotent stromal cells on a collagen scaffold.

Science.gov (United States)

Xie, Lin; Zhang, Nan; Marsano, Anna; Vunjak-Novakovic, Gordana; Zhang, Yanru; Lopez, Mandi J

2013-12-01

Directed differentiation of adult multipotent stromal cells (MSC) is critical for effective treatment strategies. This study was designed to evaluate the capability of equine MSC from bone marrow (BMSC) and adipose tissue (ASC) on a type I collagen (COLI) scaffold to undergo chondrogenic, osteogenic and adipogenic differentiation and form extracellular matrix (ECM) in vitro. Following determination of surface antigen expression, MSC were loaded into scaffolds in a perfusion bioreactor and loading efficiency was quantified. Cell-scaffold constructs were assessed after loading and 7, 14 and 21 days of culture in stromal or induction medium. Cell number was determined with DNA content, cell viability and spatial uniformity with confocal laser microscopy and cell phenotype and matrix production with light and scanning electron microscopy and mRNA levels. The MSC were positive for CD29 (>90 %), CD44 (>99 %), and CD105 (>60 %). Loading efficiencies were >70 %. The ASC and BMSC cell numbers on scaffolds were affected by culture in induction medium differently. Viable cells remained uniformly distributed in scaffolds for up to 21 days and could be directed to differentiate or to maintain an MSC phenotype. Micro- and ultrastructure showed lineage-specific cell and ECM changes. Lineage-specific mRNA levels differed between ASC and BMSC with induction and changed with time. Based on these results, equine ASC and BMSC differentiate into chondrogenic, osteogenic and adipogenic lineages and form ECM similarly on COLI scaffolds. The collected data supports the potential for equine MSC-COLI constructs to support diverse equine tissue formation for controlled biological studies.

Cell-based Assay System for Predicting Bone Regeneration in Patient Affected by Aseptic Nonunion and Treated with Platelet Rich Fibrin.

Science.gov (United States)

Perut, Francesca; Dallari, Dante; Rani, Nicola; Baldini, Nicola; Granchi, Donatella

Regenerative strategies based on the use of platelet concentrates as an autologous source of growth factors (GF) has been proposed to promote the healing of long bone nonunions. However, the relatively high failure rate stimulates interest in growing knowledge and developing solutions to obtain the best results from the regenerative approach. In this study we evaluated whether a cell-based assay system could be able to recognize patients who will benefit or not from the use of autologous platelet preparations. The autologous serum was used in culture medium to promote the osteogenic differentiation of normal bone-marrow stromal cells (BMSC). Blood samples were collected from 16 patients affected by aseptic long bone nonunion who were candidates to the treatment with autologous platelet-rich fibrin. The osteoinductive effect was detected by measuring the BMSC proliferation, the mineralization activity, and the expression of bone-related genes. Serum level of basic fibroblast growth factor (bFGF) was considered as a representative marker of the delivery of osteogenic GFs from platelets. Laboratory results were related to the characteristics of the disease before the treatment and to the outcome at 12 months. Serum samples from "good responders" showed significantly higher levels of bFGF and were able to induce a significantly higher proliferation of BMSC, while no significant differences were observed in terms of osteoblast differentiation. BMSC-based assay could be a useful tool to recognize patients who have a low probability to benefit from the use of autologous platelet concentrate to promote the healing of long bone nonunion.

The effect of polystyrene sodium sulfonate grafting on polyethylene terephthalate artificial ligaments on in vitro mineralisation and in vivo bone tissue integration

Science.gov (United States)

Vaquette, Cédryck; Viateau, Véronique; Guérard, Sandra; Anagnostou, Fani; Manassero, Mathieu; Castner, David G.; Migonney, Véronique

2013-01-01

This study investigates the impact of polystyrene sodium sulfonate (PolyNaSS) grafting onto the osseointegration of a polyethylene terephthalate artificial ligament (Ligament Advanced Reinforcement System, LARS™) used for Anterior Cruciate Ligament (ACL). The performance of grafted and non-grafted ligaments was assessed in vitro by culturing human osteoblasts under osteogenic induction and this demonstrated that the surface modification was capable of up-regulating the secretion of ALP and induced higher level of mineralisation as measured 6 weeks post-seeding by Micro-Computed Tomography. Grafted and non-grafted LARS™ were subsequently implanted in an ovine model for ACL reconstruction and the ligament-to-bone interface was evaluated by histology and biomechanical testing 3 and 12 months post-implantation. The grafted ligaments exhibited more frequent direct ligament-to-bone contact and bone formation in the core of the ligament at the later time point than the nongrafted specimens, the grafting also significantly reduced the fibrous encapsulation of the ligament 12 months post-implantation. However, this improved osseo-integration was not translated into a significant increase in the biomechanical pull-out loads. These results provide evidences that PolyNaSS grafting improved the osseo-integration of the artificial ligament within the bone tunnels. This might positively influence the outcome of the surgical reconstructions, as higher ligament stability is believed to limit micro-movement and therefore permits earlier and enhanced healing. PMID:23790438

Contrast-enhanced ultrasound imaging of active bleeding associated with hepatic and splenic trauma.

Science.gov (United States)

Lv, F; Tang, J; Luo, Y; Li, Z; Meng, X; Zhu, Z; Li, T

2011-10-01

The aim of this study was to evaluate contrast-enhanced ultrasound (CEUS) imaging of active bleeding from hepatic and splenic trauma. Three hundred and ninety-two patients with liver or/and spleen trauma (179 liver and 217 spleen injuries), who underwent CEUS examinations following contrast-enhanced computed tomography (CT), were enrolled in this retrospective study over a period of >4 years. CEUS detected contrast medium extravasation or pooling in 16% (63/396) of liver or spleen lesions in 61 patients, which was confirmed by contrast-enhanced CT. Special attention was paid to observing the presence, location, and characteristics of the extravasated or pooled contrast medium. The CEUS detection rate for active bleeding was not different from that of contrast-enhanced CT (p=0.333). Information from surgery, minimally invasive treatment and conservative treatment was used as reference standard, and the sensitivities of the two techniques were not different (p=0.122). Of 63 lesions in 61 patients, CEUS showed that 74.6% (47/63) (21 liver lesions and 26 spleen lesions) presented contrast medium extravasation or pooling, both in the organ and out the capsule, in 14.3% (9/63) and only outside the capsule in 11.1% (7/63). CEUS imaging of active bleeding from hepatic and splenic trauma presented various characteristics, and the sizes and shapes of the active bleeding due to contrast medium extravasation or pooling were variable. CEUS can show the active bleeding associated with hepatic and splenic trauma with various imaging characteristics, thus making it possible to diagnose active bleeding using CEUS.

Identifying A Molecular Phenotype for Bone Marrow Stromal Cells With In Vivo Bone Forming Capacity

DEFF Research Database (Denmark)

Larsen, Kenneth H; Frederiksen, Casper M; Burns, Jorge S

2009-01-01

(17% versus 5%) and a larger percentage of genes with predicted SP3 transcription factor binding sites in their promoter region (21% versus 8%). On the other hand, hBMSC-TERT(-Bone) cells expressed a larger number of immune-response related genes (26% versus 8%). In order to test for the predictive...... value of these markers, we studied the correlation between their expression levels in 6 different hBMSC-derived clones and the ability to form bone in vivo. We found a significant correlation for, decorin, lysyl oxidase-like 4, natriuretic peptide receptor C, and tetranectin. No significant positive...

Enhancement of associated H{sup {+-}}W{sup -+} productionin the NMSSM

Energy Technology Data Exchange (ETDEWEB)

Enberg, R. [Uppsala Univ., Uppsala (Sweden). Dept. of Physics and Astronomy; Pasechnik, R. [Lund Univ., Lund (Sweden). Dept. of Astronomy and Theoretical Physics; Staal, O. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

2011-12-15

We study the associated production of a charged Higgs and a W boson in high-energy pp collisions at the Large Hadron Collider. This is an interesting process for charged Higgs discovery, or exclusion, since the production cross section could depend strongly on the model, offering potential discriminating power between supersymmetric extensions of the Standard Model with minimal or extended Higgs sectors. We compute the cross section for this process in the next-to-minimal supersymmetric Standard Model (NMSSM), at the tree level for quark-quark scattering and at one-loop level for gluon-gluon scattering. The most important corrections beyond leading order are taken into account using an improved Born approximation. We find that the pp {yields} H{sup {+-}}W{sup -+} cross section can be resonantly enhanced by up to an order of magnitude over its MSSM value (both for {radical}(s)=7 TeV and 14 TeV) through the contributions of heavy, neutral, singlet-dominated Higgs bosons appearing in the s-channel. Since such Higgs mass configurations are normally not possible in the MSSM, the observation of associated H{sup {+-}}W{sup -+} production at the LHC could provide a striking, although indirect, signature of a more complicated Higgs sector. (orig.)

Adeno-associated virus type 2 enhances goose parvovirus replication in embryonated goose eggs

International Nuclear Information System (INIS)

Malkinson, Mertyn; Winocour, Ernest

2005-01-01

The autonomous goose parvovirus (GPV) and the human helper-dependent adeno-associated virus type 2 (AAV2) share a high degree of homology. To determine if this evolutionary relationship has a biological impact, we studied viral replication in human 293 cells and in embryonated goose eggs coinfected with both viruses. Similar experiments were performed with the minute virus of mice (MVM), an autonomous murine parvovirus with less homology to AAV2. In human 293 cells, both GPV and MVM augmented AAV2 replication. In contrast, AAV2 markedly enhanced GPV replication in embryonated goose eggs under conditions where a similar effect was not observed with MVM. AAV2 did not replicate in embryonated goose eggs and AAV2 inactivated by UV-irradiation also enhanced GPV replication. To our knowledge, this is the first report that a human helper-dependent member of the Parvoviridae can provide helper activity for an autonomous parvovirus in a natural host

The role of nanocrystalline titania coating on nanostructured austenitic stainless steel in enhancing osteoblasts functions for regeneration of tissue

Energy Technology Data Exchange (ETDEWEB)

Shah, J.S.; Venkatsurya, P.K.C.; Thein-Han, W.W. [Biomaterials and Biomedical Engineering Research Laboratory, Center for Structural and Functional Materials, University of Louisiana at Lafayette, P.O. Box 44130, Lafayette, LA 70504 (United States); Misra, R.D.K., E-mail: dmisra@louisiana.edu [Biomaterials and Biomedical Engineering Research Laboratory, Center for Structural and Functional Materials, University of Louisiana at Lafayette, P.O. Box 44130, Lafayette, LA 70504 (United States); Pesacreta, T.C. [Department of Biology, University of Louisiana at Lafayette, P.O. Box 42451, Lafayette, LA 70504 (United States); Somani, M.C.; Karjalainen, L.P. [Department of Mechanical Engineering, University of Oulu, P.O. Box 4200, 90014 Oulu (Finland)

2011-03-12

In the context of osseointegration of metallic implants, while nanostructuring the surface favorably modulates cellular response, the disinfective attributes required during the healing process are not available. Thus, in the present study, we demonstrate that nanocrystalline titania provides cumulative benefit of enhancing osteoblasts functions to promote the efficacy of metal implants together with the disinfective attributes. To this end, the primary objective here is to examine the select functions of bone forming cells (osteoblasts) on electrocrystallized nanonodular titania-coated nanograined/ultrafine grained (NG/UFG) austenitic stainless steel. The accompanying objective is to study the disinfective/antimicrobial activity. To the best of our understanding this is the first study of nanophase titania on a non-titanium substrate. The osteoblasts functions were investigated in terms of cell attachment, proliferation, and quantitative analysis of proteins, actin and vinculin. In comparison to the bare NG/UFG substrate, the nanophase titania-coated substrate exhibited higher degree of cell attachment and proliferation which are regulated via cellular and molecular interactions with proteins, actin and vinculin. The enhanced functions of osteoblasts suggest that nanophase titania adsorbs extracellular matrix proteins, fibronectin and vitronectin from serum enhancing protein, with subsequent binding of integrins and osteoblasts precursor to titania. The antimicrobial attributes assessed in terms of degradation of methyl orange and effectiveness in killing E. coli supports the viewpoint that large surface area of titania would be instrumental in reducing the detrimental effect of biologically reactive oxygen species produced by macrophages in the vicinity of the metal bone/implant interface. In summary, the study provides some new insights concerning nanostructuring of metallic substrates with specific physical and surface properties for medical devices with

State of the Art on the Evidence Base in Cardiac Regenerative Therapy: Overview of 41 Systematic Reviews

Directory of Open Access Journals (Sweden)

Mariangela Peruzzi

2015-01-01

Full Text Available Objectives. To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Study Design and Setting. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. Results. After a systematic database search, we short-listed 41 reviews (660 patients. Twenty-two (54% reviews focused on acute myocardial infarction (AMI, 19 (46% on chronic ischemic heart disease (IHD or heart failure (HF, 29 (71% on bone marrow-derived stem-cells (BMSC, and 36 (88% to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median 9 [minimum 3]; 1st quartile 9; 3rd quartile 10; maximum 11, effect estimates (change in ejection fraction from baseline to follow-up: 3.47% [0.02%; 2.90%; 4.22%; 6.11%], and citations (Web of Science yearly citations: 4.1 [0; 2.2; 6.5; 68.9]. No significant association was found between these three features. However, reviews focusing on BMSC therapy had higher validity scores (P=0.008 and showed more pronounced effect estimates (P=0.002. Higher citations were associated with journal impact factor (P=0.007, corresponding author from North America/Europe (P=0.022, and inclusion of nonrandomized trials (P=0.046. Conclusions. Substantial heterogeneity is apparent among these reviews in terms of quality and effect estimates.

Structure, MC3T3-E1 cell response, and osseointegration of macroporous titanium implants covered by a bioactive microarc oxidation coating with microporous structure.

Science.gov (United States)

Zhou, Rui; Wei, Daqing; Cheng, Su; Feng, Wei; Du, Qing; Yang, Haoyue; Li, Baoqiang; Wang, Yaming; Jia, Dechang; Zhou, Yu

2014-04-09

Macroporous Ti with macropores of 50-400 μm size is prepared by sintering Ti microbeads with different diameters of 100, 200, 400, and 600 μm. Bioactive microarc oxidation (MAO) coatings with micropores of 2-5 μm size are prepared on the macroporous Ti. The MAO coatings are composed of a few TiO2 nanocrystals and lots of amorphous phases with Si, Ca, Ti, Na, and O elements. Compared to compact Ti, the MC3T3-E1 cell attachment is prolonged on macroporous Ti without and with MAO coatings; however, the cell proliferation number increases. These results are contributed to the effects of the space structure of macroporous Ti and the surface chemical feature and element dissolution of the MAO coatings during the cell culture. Macroporous Ti both without and with MAO coatings does not cause any adverse effects in vivo. The new bone grows well into the macropores and micropores of macroporous Ti with MAO coatings, showing good mechanical properties in vivo compared to Ti, MAO-treated Ti, and macroporous Ti because of its excellent osseointegration. Moreover, the MAO coatings not only show a high interface bonding strength with new bones but also connect well with macroporous Ti. Furthermore, the pushing out force for macroporous Ti with MAO coatings increases significantly with increasing microbead diameter.

Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats.

Science.gov (United States)

Diefenbeck, M; Schrader, C; Gras, F; Mückley, T; Schmidt, J; Zankovych, S; Bossert, J; Jandt, K D; Völpel, A; Sigusch, B W; Schubert, H; Bischoff, S; Pfister, W; Edel, B; Faucon, M; Finger, U

2016-09-01

Implant related infection is one of the most feared and devastating complication associated with the use of orthopaedic implant devices. Development of anti-infective surfaces is the main strategy to prevent implant contamination, biofilm formation and implant related osteomyelitis. A second concern in orthopaedics is insufficient osseointegration of uncemented implant devices. Recently, we reported on a macroporous titanium-oxide surface (bioactive TiOB) which increases osseointegration and implant fixation. To combine enhanced osseointegration and antibacterial function, the TiOB surfaces were, in addition, modified with a gentamicin coating. A rat osteomyelitis model with bilateral placement of titanium alloy implants was employed to analyse the prophylactic effect of gentamicin-sodiumdodecylsulfate (SDS) and gentamicin-tannic acid coatings in vivo. 20 rats were randomly assigned to four groups: (A) titanium alloy; PBS inoculum (negative control), (B) titanium alloy, Staphylococcus aureus inoculum (positive control), (C) bioactive TiOB with gentamicin-SDS and (D) bioactive TiOB plus gentamicin-tannic acid coating. Contamination of implants, bacterial load of bone powder and radiographic as well as histological signs of implant-related osteomyelitis were evaluated after four weeks. Gentamicin-SDS coating prevented implant contamination in 10 of 10 tibiae and gentamicin-tannic acid coating in 9 of 10 tibiae (infection prophylaxis rate 100% and 90% of cases, respectively). In Group (D) one implant showed colonisation of bacteria (swab of entry point and roll-out test positive for S. aureus). The interobserver reliability showed no difference in the histologic and radiographic osteomyelitis scores. In both gentamicin coated groups, a significant reduction of the histological osteomyelitis score (geometric mean values: C = 0.111 ± 0.023; D = 0.056 ± 0.006) compared to the positive control group (B: 0.244 ± 0.015; p < 0.05) was observed. The

Reduction of radiation-induced damage to salivary gland by bone marrow derived stem cells

International Nuclear Information System (INIS)

Coppes, R.P.; Wierenga, P.K.; Kampinga, H.H.; De Hann, G.

2003-01-01

Irradiation of the salivary glands can result in severe side effects that reduce the patient's quality of life. Late damage to the salivary glands is mainly caused by exhaustion of the tissue's stem cells. Post-irradiation replacement of salivary gland stem cells with healthy donor stem cells may reduce complications. Bone marrow derived stem cells (BMSC) have been show to be multipotent and engraft in many tissue after injury. In this study we assessed the potential of BMSC to reduce irradiation-induced salivary gland damage. The salivary glands of wild type C57Bl/6 mice were locally irradiated with 20 Gy. Thirty days later, BMSC from transgenic eGFP+ C57Bl/6 mice were transplanted by i.v. injection or by direct injection into the salivary glands. In addition, animals were transplanted with eGFP + bone marrow after 9.5 Gy TBI excluding the salivary glands. Subsequently, the animals were locally irradiated to the salivary gland with 20 Gy. Thirty days later i.v. G-CSF mobilised eGFP + bone marrow derived stem cells to the peripheral blood. Again thirty days after mobilisation, the salivary gland were harvested. eGFP + cells were detected by confocal laser fluorescence scanning microscopy and flow cytometry and H and E histology was performed. eGFP + cells were detected in the salivary gland after all protocols. The number of eGFP + cells in irradiated salivary glands was highest in animals treated with G-CSF. Intraglandular transplantation, in contrast, was successful only in 1 out of 8 attempts. Immuno-histochemistry using a-SM-actin antibodies showed the close vicinity of actin and eGFP within the cells, demonstrating the occurrence of BMSC derived myoepithelial cells in irradiated salivary gland. Further, cell-type specific antibodies will reveal the nature of all eGFP + cells. H and E histology revealed improved gland morphology in animals treated with G-CSF after irradiation when compared to the non-treated animals. These preliminary results indicate that bone

Topical application of bFGF on acid-conditioned and non-conditioned dentin: effect on cell proliferation and gene expression in cells relevant for periodontal regeneration

Directory of Open Access Journals (Sweden)

Fernanda Regina Godoy Rocha

Full Text Available Abstract Periodontal regeneration is still a challenge in terms of predictability and magnitude of effect. In this study we assess the biological effects of combining chemical root conditioning and biological mediators on three relevant cell types for periodontal regeneration. Material and Methods: Bovine dentin slices were conditioned with 25% citric acid followed by topical application of basic fibroblast growth factor (bFGF, 10 and 50 ng. We used ELISA to assess the dynamics of bFGF release from the dentin surface and RT-qPCR to study the expression of Runx2, Col1a1, Bglap and fibronectin by periodontal ligament (PDL fibroblasts, cementoblasts and bone marrow stromal cells (BMSC grown onto these dentin slices. We also assessed the effects of topical application of bFGF on cell proliferation by quantification of genomic DNA. Results: Acid conditioning significantly increased the release of bFGF from dentin slices. Overall, bFGF application significantly (p<0.05 increased cell proliferation, except for BMSC grown on non-conditioned dentin slices. Dentin substrate discretely increased expression of Col1a1 in all cell types. Expression of Runx2, Col1a1 and Fn was either unaffected or inhibited by bFGF application in all cell types. We could not detect expression of the target genes on BMSC grown onto conditioned dentin. Conclusion: Acid conditioning of dentin improves the release of topically-applied bFGF. Topical application of bFGF had a stimulatory effect on proliferation of PDL fibroblasts, cementoblasts and BMSC, but did not affect expression of Runx2, Col1a1, Bglap and fibronectin by these cells.

Titanium biomaterials with complex surfaces induced aberrant peripheral circadian rhythms in bone marrow mesenchymal stromal cells.

Science.gov (United States)

Hassan, Nathaniel; McCarville, Kirstin; Morinaga, Kenzo; Mengatto, Cristiane M; Langfelder, Peter; Hokugo, Akishige; Tahara, Yu; Colwell, Christopher S; Nishimura, Ichiro

2017-01-01

Circadian rhythms maintain a high level of homeostasis through internal feed-forward and -backward regulation by core molecules. In this study, we report the highly unusual peripheral circadian rhythm of bone marrow mesenchymal stromal cells (BMSCs) induced by titanium-based biomaterials with complex surface modifications (Ti biomaterial) commonly used for dental and orthopedic implants. When cultured on Ti biomaterials, human BMSCs suppressed circadian PER1 expression patterns, while NPAS2 was uniquely upregulated. The Ti biomaterials, which reduced Per1 expression and upregulated Npas2, were further examined with BMSCs harvested from Per1::luc transgenic rats. Next, we addressed the regulatory relationship between Per1 and Npas2 using BMSCs from Npas2 knockout mice. The Npas2 knockout mutation did not rescue the Ti biomaterial-induced Per1 suppression and did not affect Per2, Per3, Bmal1 and Clock expression, suggesting that the Ti biomaterial-induced Npas2 overexpression was likely an independent phenomenon. Previously, vitamin D deficiency was reported to interfere with Ti biomaterial osseointegration. The present study demonstrated that vitamin D supplementation significantly increased Per1::luc expression in BMSCs, though the presence of Ti biomaterials only moderately affected the suppressed Per1::luc expression. Available in vivo microarray data from femurs exposed to Ti biomaterials in vitamin D-deficient rats were evaluated by weighted gene co-expression network analysis. A large co-expression network containing Npas2, Bmal1, and Vdr was observed to form with the Ti biomaterials, which was disintegrated by vitamin D deficiency. Thus, the aberrant BMSC peripheral circadian rhythm may be essential for the integration of Ti biomaterials into bone.

Stimulation of porcine bone marrow stromal cells by hyaluronan, dexamethasone and rhBMP-2

DEFF Research Database (Denmark)

Zou, Xuenong; Li, Haisheng; Chen, Li

2004-01-01

and 7. When BMSc were cultivated with HY of 4.0 mg/ml alone, its combinations with Dex (+) and 10 ng/ml rhBMP-2, and with DMEM/FBS alone, expression of bone-related marker genes was evaluated by real-time reverse transcription-polymerase chain reaction (Real-time RT-PCR) analysis. Osteocalcin was up...... collagen and type X collagen were down-regulated in the presence of 4 mg/ml HY by Day 7. These results suggest that HY stimulates BMSc proliferation, osteocalcin gene expression, and a secretion of enzymes such as that of ALP activity in vitro. More importantly, HY can interact with Dex and rhBMP-2...

Titanium implants in irradiated dog mandibles

International Nuclear Information System (INIS)

Schweiger, J.W.

1989-01-01

The use of osseointegrated titanium implants has been a great benefit to selected cancer patients who otherwise would not be able to wear conventional and/or maxillofacial prostheses. Cognizant of the risk of osteoradionecrosis, we used an animal model to seek experimental evidence for successful osseointegration in bone irradiated to tumoricidal levels. Five healthy male beagle dogs received 60 gray to a previously edentulated and healed area of the right hemimandible. The left hemimandible was kept as a nonirradiated control. After 9 months, titanium implants were placed and allowed an additional 5 1/2 months to osseointegrate. At that time, block specimens were obtained, radiographed, photographed, and analyzed histologically. Although statistical significance cannot be attached to the results, osseointegration was achieved in half of the irradiated specimens

Additively manufactured 3D porous Ti-6Al-4V constructs mimic trabecular bone structure and regulate osteoblast proliferation, differentiation and local factor production in a porosity and surface roughness dependent manner

International Nuclear Information System (INIS)

Cheng, Alice; Boyan, Barbara D; Humayun, Aiza; Cohen, David J; Schwartz, Zvi

2014-01-01

Additive manufacturing by laser sintering is able to produce high resolution metal constructs for orthopedic and dental implants. In this study, we used a human trabecular bone template to design and manufacture Ti-6Al-4V constructs with varying porosity via laser sintering. Characterization of constructs revealed interconnected porosities ranging from 15–70% with compressive moduli of 2579–3693 MPa. These constructs with macro porosity were further surface-treated to create a desirable multi-scale micro-/nano-roughness, which has been shown to enhance the osseointegration process. Osteoblasts (MG63 cells) exhibited high viability when grown on the constructs. Proliferation (DNA) and alkaline phosphatase specific activity, an early differentiation marker, decreased as porosity increased, while osteocalcin, a late differentiation marker, as well as osteoprotegerin, vascular endothelial growth factor and bone morphogenetic proteins 2 and 4 increased with increasing porosity. Three-dimensional (3D) constructs with the highest porosity and surface modification supported the greatest osteoblast differentiation and local factor production. These results indicate that additively manufactured 3D porous constructs mimicking human trabecular bone and produced with additional surface treatment can be customized for increased osteoblast response. Increased factors for osteoblast maturation and differentiation on high porosity constructs suggest the enhanced performance of these surfaces for increasing osseointegration in vivo. (paper)

Additively manufactured 3D porous Ti-6Al-4V constructs mimic trabecular bone structure and regulate osteoblast proliferation, differentiation and local factor production in a porosity and surface roughness dependent manner.

Science.gov (United States)

Cheng, Alice; Humayun, Aiza; Cohen, David J; Boyan, Barbara D; Schwartz, Zvi

2014-10-07

Additive manufacturing by laser sintering is able to produce high resolution metal constructs for orthopedic and dental implants. In this study, we used a human trabecular bone template to design and manufacture Ti-6Al-4V constructs with varying porosity via laser sintering. Characterization of constructs revealed interconnected porosities ranging from 15-70% with compressive moduli of 2579-3693 MPa. These constructs with macro porosity were further surface-treated to create a desirable multi-scale micro-/nano-roughness, which has been shown to enhance the osseointegration process. Osteoblasts (MG63 cells) exhibited high viability when grown on the constructs. Proliferation (DNA) and alkaline phosphatase specific activity, an early differentiation marker, decreased as porosity increased, while osteocalcin, a late differentiation marker, as well as osteoprotegerin, vascular endothelial growth factor and bone morphogenetic proteins 2 and 4 increased with increasing porosity. Three-dimensional (3D) constructs with the highest porosity and surface modification supported the greatest osteoblast differentiation and local factor production. These results indicate that additively manufactured 3D porous constructs mimicking human trabecular bone and produced with additional surface treatment can be customized for increased osteoblast response. Increased factors for osteoblast maturation and differentiation on high porosity constructs suggest the enhanced performance of these surfaces for increasing osseointegration in vivo.

Alkalescent nanotube films on a titanium-based implant: A novel approach to enhance biocompatibility

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yanxian [Corrosion and Protection Center, Key Laboratory for Corrosion and Protection (MOE), University of Science and Technology Beijing, Beijing 100083 (China); Dong, Chaofang, E-mail: cfdong@ustb.edu.cn [Corrosion and Protection Center, Key Laboratory for Corrosion and Protection (MOE), University of Science and Technology Beijing, Beijing 100083 (China); Yang, Sefei [Department of Stomatology, The PLA General Hospital, Beijing 100853 (China); Wu, Junsheng; Xiao, Kui; Huang, Yunhua; Li, Xiaogang [Corrosion and Protection Center, Key Laboratory for Corrosion and Protection (MOE), University of Science and Technology Beijing, Beijing 100083 (China)

2017-03-01

The interfacial pH value has a marked effect on cell viability because the pro-mineralization activity of osteoblasts increases at alkaline extracellular pH, whereas the pro-resorptive activity of osteoclasts increases under more acidic conditions. To obtain the more favorable alkaline interface, we developed a novel nanotube layer that was incorporated with magnesium oxide on a titanium implant substrate (MgO/NT/Ti) via ethylenediamine tetraacetic acid (EDTA) chelation. This facile immersion-annealing process successfully created a homogeneous magnesium oxide layer with sustained release kinetics and superior hydrophilicity according to the surface characterization and microenvironment measurement. The titania nanotubes on the substrate with an anatase phase exhibited a lower passivation current and a more positive corrosion potential compared with pure titanium, which guaranteed a reasonable corrosion resistance, even when it was wrapped with a magnesium oxide layer. In vitro cell cultures showed that MgO/NT/Ti significantly increased cell proliferation and alkaline phosphatase (ALP) activity. The resulting alkalescent microenvironment created by the MgO layer encouraged the cells to spread into polygonal shapes, accelerated the differentiation stage to osteoblast and induced a higher expression of vinculin. In summary, the incorporated alkalescent microenvironment of MgO/NT/Ti provided a viable approach to stimulate cell proliferation, adhesion, and differentiation and to improve the implant osseointegration. - Highlights: • We developed a novel nanotube layer incorporated with magnesium oxide to obtain a favorable alkaline interface. • The homogeneous magnesium oxide layer exhibited sustained release kinetics. • The resulting alkalescent microenvironment provided a viable approach to improve the implant osseointegration.

Serum-Induced Differentiation of Glioblastoma Neurospheres Leads to Enhanced Migration/Invasion Capacity That Is Associated with Increased MMP9.

Directory of Open Access Journals (Sweden)

Justin V Joseph

Full Text Available Glioblastoma (GBM is a highly infiltrative brain tumor in which cells with properties of stem cells, called glioblastoma stem cells (GSCs, have been identified. In general, the dominant view is that GSCs are responsible for the initiation, progression, invasion and recurrence of this tumor. In this study, we addressed the question whether the differentiation status of GBM cells is associated with their invasive capacity. For this, several primary GBM cell lines were used, cultured either as neurospheres known to enrich for GSCs or in medium supplemented with 10% FCS that promotes differentiation. The differentiation state of the cells was confirmed by determining the expression of stem cell and differentiation markers. The migration/invasion potential of these cells was tested using in vitro assays and intracranial mouse models. Interestingly, we found that serum-induced differentiation enhanced the invasive potential of GBM cells, which was associated with enhanced MMP9 expression. Chemical inhibition of MMP9 significantly reduced the invasive potential of differentiated cells in vitro. Furthermore, the serum-differentiated cells could revert back to an undifferentiated/stem cell state that were able to form neurospheres, although with a reduced efficiency as compared to non-differentiated counterparts. We propose a model in which activation of the differentiation program in GBM cells enhances their infiltrative potential and that depending on microenvironmental cues a significant portion of these cells are able to revert back to an undifferentiated state with enhanced tumorigenic potential. Thus, effective therapy should target both GSCs and differentiated offspring and targeting of differentiation-associated pathways may offer therapeutic opportunities to reduce invasive growth of GBM.

Clinical significance of nerve root enhancement in contrast-enhanced MR imaging of the postoperative lumbar spine

International Nuclear Information System (INIS)

Lee, Yeon Soo; Lee, Eun Ja; Kang, Si Won; Choi, Eun Seok; Song, Chang June; Kim, Jong Chul

2001-01-01

To determine the significance of nerve root contrast enhancement in patients with residual or recurrent symptomatic postoperative lumbar spine. Eighty-eight patients with 116 postoperative lumbar disc lesions causing radiating back pain underwent enhanced MR imaging. Intradural nerve root enhancement was quantified by pixel measurement, and affected nerve roots were compared before and after contrast administration. Extradural nerve root enhancement was assessed visually, and nerve root enhancement and clinical symptoms were correlated. Associated lesions such as recurrent disc herniation, scar tissue, nerve root thickening and nerve root displacement were also evaluated. Of 26 cases (22.4%) involving intradural nerve root enhancement, 22 (84.6%) showed significant clinical symptoms (p=0.002). and of 59 (50.9%) demonstrating extradural enhancement, clinical symptoms showed significant correlation in 47 (79.7%) (p=0.001). Nerve root enhancement, including eleven cases where this was both intra-and extradural, showed highly significant association with clinical symptoms in 74 of the 116 cases (63.8%) (p=0.000). Among 33 cases (28.4%) of recurrent disc herniation, nerve root enhancement was observed in 28 (84.8%) and in 24 of these 28 (85.7%), significant correlation with clinical symptoms was observed (p=0.000). Where epidural fibrosis was present, correlation between nerve root enhancement and clinical symptoms was not significant (p>0.05). Nerve root thickening and displaced nerve root were, however, significantly associated with symptoms (87.2% and 88.6%, respectively). In patients with postoperative lumbar spine, the association between nerve root enhancement revealed by MRI and clinical symptoms was highly significant

Association between salt substitutes/enhancers and changes in sodium levels in fast-food restaurants: a cross-sectional analysis.

Science.gov (United States)

Scourboutakos, Mary J; Murphy, Sarah A; L'Abbé, Mary R

2018-03-07

Restaurant foods have high sodium levels, and efforts have been made to promote reductions. The objective of this study was to understand if salt substitutes and enhancers are associated with changes in sodium levels in fast-food restaurants. A longitudinal database (MENU-FLIP) containing nutrition information for Canadian chain restaurants with 20 or more locations nationally was created in 2010 and updated in 2013 and 2016. In 2016, when available, ingredient lists were collected from restaurant websites and searched for the presence of salt substitutes/enhancers. Changes in sodium levels (per serving) and the prevalence of salt substitutes/enhancers in 222 foods from 12 of the leading fast-food restaurant chains were compared across 3 time points. Sixty-nine percent of foods contained a salt substitute/enhancer. Substitutes/enhancers were found in every restaurant chain ( n = 12) for which ingredient data were available. The most common substitutes/enhancers were yeast extracts (in 30% of foods), calcium chloride (28%), monosodium glutamate (14%) and potassium chloride (12%). Sodium levels in foods that contained substitutes/enhancers decreased significantly more (190 ± 42 mg/serving) over the study period than those in foods that did not contain a substitute/enhancer (40 ± 17 mg/serving, p restaurant foods and are one means by which restaurants may be lowering sodium levels in their foods. At this time, the potential consequences of these findings, if any, are uncertain. Copyright 2018, Joule Inc. or its licensors.

Disruption of Microtubules Post-Virus Entry Enhances Adeno-Associated Virus Vector Transduction

Science.gov (United States)

Xiao, Ping-Jie; Mitchell, Angela M.; Huang, Lu; Li, Chengwen; Samulski, R. Jude

2016-01-01

Perinuclear retention of viral particles is a poorly understood phenomenon observed during many virus infections. In this study, we investigated whether perinuclear accumulation acts as a barrier to limit recombinant adeno-associated virus (rAAV) transduction. After nocodazole treatment to disrupt microtubules at microtubule-organization center (MT-MTOC) after virus entry, we observed higher rAAV transduction. To elucidate the role of MT-MTOC in rAAV infection and study its underlying mechanisms, we demonstrated that rAAV's perinuclear localization was retained by MT-MTOC with fluorescent analysis, and enhanced rAAV transduction from MT-MTOC disruption was dependent on the rAAV capsid's nuclear import signals. Interestingly, after knocking down RhoA or inhibiting its downstream effectors (ROCK and Actin), MT-MTOC disruption failed to increase rAAV transduction or nuclear entry. These data suggest that enhancement of rAAV transduction is the result of increased trafficking to the nucleus via the RhoA-ROCK-Actin pathway. Ten-fold higher rAAV transduction was also observed by disrupting MT-MTOC in brain, liver, and tumor in vivo. In summary, this study indicates that virus perinuclear accumulation at MT-MTOC is a barrier-limiting parameter for effective rAAV transduction and defines a novel defense mechanism by which host cells restrain viral invasion. PMID:26942476

Storyline and Associations Pyramid as Methods of Creativity Enhancement: Comparison of Effectiveness in 5-Year-Old Children

Science.gov (United States)

Smogorzewska, Joanna

2012-01-01

This article presents the results of a study comparing the originality, the length, the number of neologisms and the syntactic complexity of fairy tales created with "Storyline" and "Associations Pyramid." Both methods were developed to enhance children's language abilities and their creative thinking. One hundred twenty eight 5-year-old children…

A partition enhanced mining algorithm for distributed association rule mining systems

Directory of Open Access Journals (Sweden)

A.O. Ogunde

2015-11-01

Full Text Available The extraction of patterns and rules from large distributed databases through existing Distributed Association Rule Mining (DARM systems is still faced with enormous challenges such as high response times, high communication costs and inability to adapt to the constantly changing databases. In this work, a Partition Enhanced Mining Algorithm (PEMA is presented to address these problems. In PEMA, the Association Rule Mining Coordinating Agent receives a request and decides the appropriate data sites, partitioning strategy and mining agents to use. The mining process is divided into two stages. In the first stage, the data agents horizontally segment the databases with small average transaction length into relatively smaller partitions based on the number of available sites and the available memory. On the other hand, databases with relatively large average transaction length were vertically partitioned. After this, Mobile Agent-Based Association Rule Mining-Agents, which are the mining agents, carry out the discovery of the local frequent itemsets. At the second stage, the local frequent itemsets were incrementally integrated by the from one data site to another to get the global frequent itemsets. This reduced the response time and communication cost in the system. Results from experiments conducted on real datasets showed that the average response time of PEMA showed an improvement over existing algorithms. Similarly, PEMA incurred lower communication costs with average size of messages exchanged lower when compared with benchmark DARM systems. This result showed that PEMA could be efficiently deployed for efficient discovery of valuable knowledge in distributed databases.

A Vavilovian approach to discovering crop-associated microbes with potential to enhance plant immunity

Directory of Open Access Journals (Sweden)

Iago Lowe Hale

2014-09-01

Full Text Available Through active associations with a diverse community of largely non-pathogenic microbes, a plant may be thought of as possessing an extended genotype, an interactive cross-organismal genome with potential, exploitable implications for plant immunity. The successful enrichment of plant microbiomes with beneficial species has led to numerous commercial applications, and the hunt for new biocontrol organisms continues. Increasingly flexible and affordable sequencing technologies, supported by increasingly comprehensive taxonomic databases, make the characterization of non-model crop-associated microbiomes a widely accessible research method toward this end; and such studies are becoming more frequent. A summary of this emerging literature reveals, however, the need for a more systematic research lens in the face of what is already a metagenomics data deluge. Considering the processes and consequences of crop evolution and domestication, we assert that the judicious integration of in situ crop wild relatives into phytobiome research efforts presents a singularly powerful tool for separating signal from noise, thereby facilitating a more efficient means of identifying candidate plant-associated microbes with the potential for enhanci

Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility

Science.gov (United States)

Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

2014-01-01

A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis. PMID:24997565

Evaluation of solution and rheological properties for hydrophobically associated polyacrylamide copolymer as a promised enhanced oil recovery candidate

Directory of Open Access Journals (Sweden)

A.N. El-hoshoudy

2017-09-01

Full Text Available Crude oil is the most critical energy source in the world, especially for transportation, provision of heat and light as there has not been a sufficient energy source to replace crude oil has broadly integrated, so there is an urgent need to maximize the extraction of the original oil in-place for every reservoir, and accelerating the development of enhanced oil recovery (EOR technologies. Polymer flooding by hydrophobically associated polyacrylamides (HAPAM is a widely used technique through EOR technology. For successful application of these polymers, one should evaluate rheological and solution properties at simulated reservoir conditions as a function of polymer concentration, salinity, temperature and shear rate. The results showed that these copolymers exhibit favorable salt tolerance, temperature resistance, and recoverable viscosity after shearing, reasonable thickening behavior and improved viscosity enhancement properties due to presence of hydrophobic association in the copolymer main chains. Moreover, its capacity for oil production improvement was evaluated during flooding experiments through one dimensional sandstone model at simulated reservoir conditions.

Titania-polymeric powder coatings with nano-topography support enhanced human mesenchymal cell responses.

Science.gov (United States)

Mozumder, Mohammad Sayem; Zhu, Jesse; Perinpanayagam, Hiran

2012-10-01

Titanium implant osseointegration is dependent on the cellular response to surface modifications and coatings. Titania-enriched nanocomposite polymeric resin coatings were prepared through the application of advanced ultrafine powder coating technology. Their surfaces were readily modified to create nano-rough (topographies that supported human embryonic palatal mesenchymal cell responses. Energy dispersive x-ray spectroscopy confirmed continuous and homogenous coatings with a similar composition and even distribution of titanium. Scanning electron microscopy (SEM) showed complex micro-topographies, and atomic force microscopy revealed intricate nanofeatures and surface roughness. Cell counts, mitochondrial enzyme activity reduction of yellow 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) to dark purple, SEM, and inverted fluorescence microscopy showed a marked increase in cell attachment, spreading, proliferation, and metabolic activity on the nanostructured surfaces. Reverse Transcription- Polymerase Chain Reaction (RT-PCR) analysis showed that type I collagen and Runx2 expression were induced, and Alizarin red staining showed that mineral deposits were abundant in the cell cultures grown on nanosurfaces. This enhancement in human mesenchymal cell attachment, growth, and osteogenesis were attributed to the nanosized surface topographies, roughness, and moderate wetting characteristics of the coatings. Their dimensional similarity to naturally occurring matrix proteins and crystals, coupled with their increased surface area for protein adsorption, may have facilitated the response. Therefore, this application of ultrafine powder coating technology affords highly biocompatible surfaces that can be readily modified to accentuate the cellular response. Copyright © 2012 Wiley Periodicals, Inc.

Major depression is not associated with blunting of aversive responses; evidence for enhanced anxious anticipation.

Directory of Open Access Journals (Sweden)

Christian Grillon

Full Text Available According to the emotion-context insensitivity (ECI hypothesis, major depressive disorder (MDD is associated with a diminished ability to react emotionally to positive stimuli and with blunting of defensive responses to threat. That defensive responses are blunted in MDD seems inconsistent with the conceptualization and diagnostic nosology of MDD. The present study tested the ECI hypothesis in MDD using a threat of shock paradigm. Twenty-eight patients with MDD (35.5±10.4 years were compared with 28 controls (35.1±7.4 years. Participants were exposed to three conditions: no shock, predictable shock, and unpredictable shock. Startle magnitude was used to assess defensive responses. Inconsistent with the ECI hypothesis, startle potentiation to predictable and unpredictable shock was not reduced in the MDD group. Rather, MDD patients showed elevated startle throughout testing as well as increased contextual anxiety during the placement of the shock electrodes and in the predictable condition. A regression analysis indicated that illness duration and Beck depression inventory scores explained 37% (p<.005 of the variance in patients' startle reactivity. MDD is not associated with emotional blunting but rather enhanced defensive reactivity during anticipation of harm. These results do not support a strong version of the ECI hypothesis. Understanding the nature of stimuli or situations that lead to blunted or enhanced defensive reactivity will provide better insight into dysfunctional emotional experience in MDD.

Major Depression Is Not Associated with Blunting of Aversive Responses; Evidence for Enhanced Anxious Anticipation

Science.gov (United States)

Grillon, Christian; Franco-Chaves, Jose A.; Mateus, Camilo F.; Ionescu, Dawn F.; Zarate, Carlos A.

2013-01-01

According to the emotion-context insensitivity (ECI) hypothesis, major depressive disorder (MDD) is associated with a diminished ability to react emotionally to positive stimuli and with blunting of defensive responses to threat. That defensive responses are blunted in MDD seems inconsistent with the conceptualization and diagnostic nosology of MDD. The present study tested the ECI hypothesis in MDD using a threat of shock paradigm. Twenty-eight patients with MDD (35.5±10.4 years) were compared with 28 controls (35.1±7.4 years). Participants were exposed to three conditions: no shock, predictable shock, and unpredictable shock. Startle magnitude was used to assess defensive responses. Inconsistent with the ECI hypothesis, startle potentiation to predictable and unpredictable shock was not reduced in the MDD group. Rather, MDD patients showed elevated startle throughout testing as well as increased contextual anxiety during the placement of the shock electrodes and in the predictable condition. A regression analysis indicated that illness duration and Beck depression inventory scores explained 37% (p<.005) of the variance in patients’ startle reactivity. MDD is not associated with emotional blunting but rather enhanced defensive reactivity during anticipation of harm. These results do not support a strong version of the ECI hypothesis. Understanding the nature of stimuli or situations that lead to blunted or enhanced defensive reactivity will provide better insight into dysfunctional emotional experience in MDD. PMID:23951057

Autogenous bone graft and ePTFE membrane in the treatment of peri-implantitis. II. Stereologic and histologic observations in cynomolgus monkeys

DEFF Research Database (Denmark)

Schou, Søren; Holmstrup, Palle; Skovgaard, Lene Theil

2003-01-01

autogenous bone graft; guided bone regeneration; histology; membrane; non-human primates; oral implants; osseointegration; pathalogy; peri-implantitis; stereology; treatment......autogenous bone graft; guided bone regeneration; histology; membrane; non-human primates; oral implants; osseointegration; pathalogy; peri-implantitis; stereology; treatment...

Source memory enhancement for emotional words.

Science.gov (United States)

Doerksen, S; Shimamura, A P

2001-03-01

The influence of emotional stimuli on source memory was investigated by using emotionally valenced words. The words were colored blue or yellow (Experiment 1) or surrounded by a blue or yellow frame (Experiment 2). Participants were asked to associate the words with the colors. In both experiments, emotionally valenced words elicited enhanced free recall compared with nonvalenced words; however, recognition memory was not affected. Source memory for the associated color was also enhanced for emotional words, suggesting that even memory for contextual information is benefited by emotional stimuli. This effect was not due to the ease of semantic clustering of emotional words because semantically related words were not associated with enhanced source memory, despite enhanced recall (Experiment 3). It is suggested that enhancement resulted from facilitated arousal or attention, which may act to increase organization processes important for source memory.

Association between mammogram density and background parenchymal enhancement of breast MRI

Science.gov (United States)

Aghaei, Faranak; Danala, Gopichandh; Wang, Yunzhi; Zarafshani, Ali; Qian, Wei; Liu, Hong; Zheng, Bin

2018-02-01

Breast density has been widely considered as an important risk factor for breast cancer. The purpose of this study is to examine the association between mammogram density results and background parenchymal enhancement (BPE) of breast MRI. A dataset involving breast MR images was acquired from 65 high-risk women. Based on mammography density (BIRADS) results, the dataset was divided into two groups of low and high breast density cases. The Low-Density group has 15 cases with mammographic density (BIRADS 1 and 2), while the High-density group includes 50 cases, which were rated by radiologists as mammographic density BIRADS 3 and 4. A computer-aided detection (CAD) scheme was applied to segment and register breast regions depicted on sequential images of breast MRI scans. CAD scheme computed 20 global BPE features from the entire two breast regions, separately from the left and right breast region, as well as from the bilateral difference between left and right breast regions. An image feature selection method namely, CFS method, was applied to remove the most redundant features and select optimal features from the initial feature pool. Then, a logistic regression classifier was built using the optimal features to predict the mammogram density from the BPE features. Using a leave-one-case-out validation method, the classifier yields the accuracy of 82% and area under ROC curve, AUC=0.81+/-0.09. Also, the box-plot based analysis shows a negative association between mammogram density results and BPE features in the MRI images. This study demonstrated a negative association between mammogram density and BPE of breast MRI images.

Evaluation of fixation of expandable implants in the mandibles of ovariectomized sheep.

Science.gov (United States)

Xiao, Jian-Rui; Li, De-Hua; Chen, Yu-Xuan; Chen, Shu-Jun; Guan, Su-Min; Kong, Liang

2013-04-01

This study aimed to investigate the effects of an expandable implant (EI) in ovariectomized sheep. The EI and taper implant (control group) were produced and placed in mandibles of ovariectomized sheep. Twelve weeks after implantation, resonance frequency analysis, biomechanical tests, histomorphometry, and micro-computed tomography were applied to detect the osseointegration in the 2 groups. The implant stability quotient values, maximal pullout forces, and bone-implant contact (BIC) were 60.3 ± 7.9, 511.0 ± 18.7 N, and 53.14% ± 4.56%, respectively, in the EI group and 58.3 ± 8.9, 394.5 ± 54.5 N, and 46.85% ± 5.04%, respectively, in the control group. There was no significant difference between the 2 groups in implant stability quotient values (P > .05); however, in the EI group the maximal pullout force and BIC were increased significantly (P bone volume/total volume ratio and trabecular number increased significantly (P < .01) and trabecular separation decreased significantly (P < .05) in the EI group. EI could improve osseointegration in osteoporosis after 12 weeks of implantation by increasing BIC around the implant and by supplying an extra osseointegration surface. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Clinical utility of dual-energy contrast-enhanced spectral mammography for breast microcalcifications without associated mass: a preliminary analysis.

Science.gov (United States)

Cheung, Yun-Chung; Tsai, Hsiu-Pei; Lo, Yung-Feng; Ueng, Shir-Hwa; Huang, Pei-Chin; Chen, Shin-Chih

2016-04-01

To assess the utility of dual-energy contrast-enhanced spectral mammography (DE-CESM) for evaluation of suspicious malignant microcalcifications. Two hundred and fifty-six DE-CESMs were reviewed from 2012-2013, 59 cases fulfilled the following criteria and were enrolled for analysis: (1) suspicious malignant microcalcifications (BI-RADS 4) on mammogram, (2) no related mass, (3) with pathological diagnoses. The microcalcification morphology and associated enhancement were reviewed to analyse the accuracy of the diagnosis and cancer size measurements versus the results of pathology. Of the 59 microcalcifications, 22 were diagnosed as cancers, 19 were atypical lesions and 18 were benign lesions. Twenty (76.9 %) cancers, three (11.55 %) atypia and three (11.55 %) benign lesions revealed enhancement. The true-positive rate of intermediate- and high-concern microcalcifications was significantly higher than that of low-concern lesions (93.75 % vs. 50 %). Overall, the diagnostic sensitivity of enhancement was 90.9 %, with 83.78 % specificity, 76.92 % positive predictive value, 93.94 % negative predictive value and 86.4 % accuracy. Performance was good (AUC = 0.87) according to a ROC curve and cancer size correlation with a mean difference of 0.05 cm on a Bland-Altman plot. DE-CESM provides additional enhancement information for diagnosing breast microcalcifications and measuring cancer sizes with high correlation to surgicohistology. • DE-CESM provides additional enhancement information for diagnosing suspicious breast microcalcifications. • The enhanced cancer size closely correlates to microscopy by Bland-Altman plot. • DE-CESM could be considered for evaluation of suspicious malignant microcalcifications.

Cell-associated flagella enhance the protection conferred by mucosally-administered attenuated Salmonella Paratyphi A vaccines.

Directory of Open Access Journals (Sweden)

Orit Gat

2011-11-01

Full Text Available Antibiotic-resistant Salmonella enterica serovar Paratyphi A, the agent of paratyphoid A fever, poses an emerging public health dilemma in endemic areas of Asia and among travelers, as there is no licensed vaccine. Integral to our efforts to develop a S. Paratyphi A vaccine, we addressed the role of flagella as a potential protective antigen by comparing cell-associated flagella with exported flagellin subunits expressed by attenuated strains.S. Paratyphi A strain ATCC 9150 was first deleted for the chromosomal guaBA locus, creating CVD 1901. Further chromosomal deletions in fliD (CVD 1901D or flgK (CVD 1901K were then engineered, resulting in the export of unpolymerized FliC, without impairing its overall expression. The virulence of the resulting isogenic strains was examined using a novel mouse LD(50 model to accommodate the human-host restricted S. Paratyphi A. The immunogenicity of the attenuated strains was then tested using a mouse intranasal model, followed by intraperitoneal challenge with wildtype ATCC 9150.Mucosal (intranasal immunization of mice with strain CVD 1901 expressing cell-associated flagella conferred superior protection (vaccine efficacy [VE], 90% against a lethal intraperitoneal challenge, compared with the flagellin monomer-exporting mutants CVD 1901K (30% VE or CVD 1901D (47% VE. The superior protection induced by CVD 1901 with its cell-attached flagella was associated with an increased IgG2a:IgG1 ratio of FliC-specific antibodies with enhanced opsonophagocytic capacity.Our results clearly suggest that enhanced anti-FliC antibody-mediated clearance of S. Paratyphi A by phagocytic cells, induced by vaccines expressing cell-associated rather than exported FliC, might be contributing to the vaccine-induced protection from S. Paratyphi A challenge in vivo. We speculate that an excess of IgG1 anti-FliC antibodies induced by the exported FliC may compete with the IgG2a subtype and block binding to specific phagocyte Fc

Titanium: the innovators metal. Historical case studies tracing titanium process and product innovation [Conference paper

CSIR Research Space (South Africa)

Oosthuizen, SJ

2010-10-01

Full Text Available Magn Reson., Vol 4, Pp. 423–430. 18. Branemark, P. 1983. Osseointegration and its experimental background. The Journal of Prosthetic Dentistry, Vol 50. Pp 399-410. 19. Brånemark Osseointegration Center. 2009. [Online] Available from: http...

Titanium: the innovators’ metal. Historical case studies tracing titanium process and product innovation [Journal Article

CSIR Research Space (South Africa)

Oosthuizen, SJ

2011-11-01

Full Text Available . pp. 423?430. 18. BRANEMARK, P. Osseointegration and its experimental background. Journal of Prosthetic Dentistry, vol. 50, 1983. pp. 399?410. 19. Br?nemark Osseointegration Center. [Online] http://www.branemark.com/ Accessed: 15-03-2009. 2009. 20...

* Hypoxia Biomimicry to Enhance Monetite Bone Defect Repair.

Science.gov (United States)

Drager, Justin; Ramirez-GarciaLuna, Jose Luis; Kumar, Abhishek; Gbureck, Uwe; Harvey, Edward J; Barralet, Jake E

2017-12-01

Tissue hypoxia is a critical driving force for angiogenic and osteogenic responses in bone regeneration and is, at least partly, under the control of the Hypoxia Inducible Factor-1α (HIF-1α) pathway. Recently, the widely used iron chelator deferoxamine (DFO) has been found to elevate HIF-1α levels independent of oxygen concentrations, thereby, creating an otherwise normal environment that mimics the hypoxic state. This has the potential to augment the biological properties of inorganic scaffolds without the need of recombinant growth factors. This pilot study investigates the effect of local delivery of DFO on bone formation and osseointegration of an anatomically matched bone graft substitute, in the treatment of segmental bone defects. Three-dimensional printing was used to create monetite grafts, which were implanted into 10 mm midshaft ulnar defects in eight rabbits. Starting postoperative day 4, one graft site in each animal was injected with 600 μL (200 μM) of DFO every 48 h for six doses. Saline was injected in the contralateral limb as a control. At 8 weeks, micro-CT and histology were used to determine new bone growth, vascularity, and assess osseointegration. Six animals completed the protocol. Bone metric analysis using micro-CT showed a significantly greater amount of new bone formed (19.5% vs. 13.65% p = 0.042) and an increase in bone-implant contact area (63.1 mm 2 vs. 33.2 mm 2 p = 0.03) in the DFO group compared with control. Vascular channel volume was significantly greater in the DFO group (20.9% vs. 16.2% p = 0.004). Histology showed increased bone formation within the osteotomy gap, more bone integrated with the graft surface as well as more matured soft tissue callus in the DFO group. This study demonstrates a significant increase in new bone formation after delivery of DFO in a rabbit long bone defect bridged by a 3D-printed bioresorbable bone graft substitute. Given the safety, ease of handling, and low expense of

Practicing a musical instrument in childhood is associated with enhanced verbal ability and nonverbal reasoning.

Science.gov (United States)

Forgeard, Marie; Winner, Ellen; Norton, Andrea; Schlaug, Gottfried

2008-01-01

In this study we investigated the association between instrumental music training in childhood and outcomes closely related to music training as well as those more distantly related. Children who received at least three years (M = 4.6 years) of instrumental music training outperformed their control counterparts on two outcomes closely related to music (auditory discrimination abilities and fine motor skills) and on two outcomes distantly related to music (vocabulary and nonverbal reasoning skills). Duration of training also predicted these outcomes. Contrary to previous research, instrumental music training was not associated with heightened spatial skills, phonemic awareness, or mathematical abilities. While these results are correlational only, the strong predictive effect of training duration suggests that instrumental music training may enhance auditory discrimination, fine motor skills, vocabulary, and nonverbal reasoning. Alternative explanations for these results are discussed.

Suppression of LFA-1 expression by spermine is associated with enhanced methylation of ITGAL, the LFA-1 promoter area.

Directory of Open Access Journals (Sweden)

Yoshihiko Kano

Full Text Available Spermine and spermidine, natural polyamines, suppress lymphocyte function-associated antigen 1 (LFA-1 expression and its associated cellular functions through mechanisms that remain unknown. Inhibition of ornithine decarboxylase, which is required for polyamine synthesis, in Jurkat cells by 3 mM D,L-alpha-difluoromethylornithine hydrochloride (DFMO significantly decreased spermine and spermidine concentrations and was associated with decreased DNA methyltransferase (Dnmt activity, enhanced demethylation of the LFA-1 gene (ITGAL promoter area, and increased CD11a expression. Supplementation with extracellular spermine (500 µM of cells pretreated with DFMO significantly increased polyamine concentrations, increased Dnmt activity, enhanced methylation of the ITGAL promoter, and decreased CD11a expression. It has been shown that changes in intracellular polyamine concentrations affect activities of -adenosyl-L-methionine-decaroboxylase, and, as a result, affect concentrations of the methyl group donor, S-adenosylmethionine (SAM, and of the competitive Dnmt inhibitor, decarboxylated SAM. Additional treatments designed to increase the amount of SAM and decrease the amount of decarboxylated SAM-such as treatment with methylglyoxal bis-guanylhydrazone (an inhibitor of S-adenosyl-L-methionine-decaroboxylase and SAM supplementation-successfully decreased CD11a expression. Western blot analyses revealed that neither DFMO nor spermine supplementation affected the amount of active Ras-proximate-1, a member of the Ras superfamily of small GTPases and a key protein for regulation of CD11a expression. The results of this study suggest that polyamine-induced suppression of LFA-1 expression occurs via enhanced methylation of ITGAL.

Enhancement of the proline and nitric oxide synthetic pathway improves fermentation ability under multiple baking-associated stress conditions in industrial baker's yeast.

Science.gov (United States)

Sasano, Yu; Haitani, Yutaka; Hashida, Keisuke; Ohtsu, Iwao; Shima, Jun; Takagi, Hiroshi

2012-04-01

During the bread-making process, industrial baker's yeast, mostly Saccharomyces cerevisiae, is exposed to baking-associated stresses, such as air-drying and freeze-thaw stress. These baking-associated stresses exert severe injury to yeast cells, mainly due to the generation of reactive oxygen species (ROS), leading to cell death and reduced fermentation ability. Thus, there is a great need for a baker's yeast strain with higher tolerance to baking-associated stresses. Recently, we revealed a novel antioxidative mechanism in a laboratory yeast strain that is involved in stress-induced nitric oxide (NO) synthesis from proline via proline oxidase Put1 and N-acetyltransferase Mpr1. We also found that expression of the proline-feedback inhibition-less sensitive mutant γ-glutamyl kinase (Pro1-I150T) and the thermostable mutant Mpr1-F65L resulted in an enhanced fermentation ability of baker's yeast in bread dough after freeze-thaw stress and air-drying stress, respectively. However, baker's yeast strains with high fermentation ability under multiple baking-associated stresses have not yet been developed. We constructed a self-cloned diploid baker's yeast strain with enhanced proline and NO synthesis by expressing Pro1-I150T and Mpr1-F65L in the presence of functional Put1. The engineered strain increased the intracellular NO level in response to air-drying stress, and the strain was tolerant not only to oxidative stress but also to both air-drying and freeze-thaw stresses probably due to the reduced intracellular ROS level. We also showed that the resultant strain retained higher leavening activity in bread dough after air-drying and freeze-thaw stress than that of the wild-type strain. On the other hand, enhanced stress tolerance and fermentation ability did not occur in the put1-deficient strain. This result suggests that NO is synthesized in baker's yeast from proline in response to oxidative stresses that induce ROS generation and that increased NO plays an important

Enhancement of the proline and nitric oxide synthetic pathway improves fermentation ability under multiple baking-associated stress conditions in industrial baker's yeast

Directory of Open Access Journals (Sweden)

Sasano Yu

2012-04-01

Full Text Available Abstract Background During the bread-making process, industrial baker's yeast, mostly Saccharomyces cerevisiae, is exposed to baking-associated stresses, such as air-drying and freeze-thaw stress. These baking-associated stresses exert severe injury to yeast cells, mainly due to the generation of reactive oxygen species (ROS, leading to cell death and reduced fermentation ability. Thus, there is a great need for a baker's yeast strain with higher tolerance to baking-associated stresses. Recently, we revealed a novel antioxidative mechanism in a laboratory yeast strain that is involved in stress-induced nitric oxide (NO synthesis from proline via proline oxidase Put1 and N-acetyltransferase Mpr1. We also found that expression of the proline-feedback inhibition-less sensitive mutant γ-glutamyl kinase (Pro1-I150T and the thermostable mutant Mpr1-F65L resulted in an enhanced fermentation ability of baker's yeast in bread dough after freeze-thaw stress and air-drying stress, respectively. However, baker's yeast strains with high fermentation ability under multiple baking-associated stresses have not yet been developed. Results We constructed a self-cloned diploid baker's yeast strain with enhanced proline and NO synthesis by expressing Pro1-I150T and Mpr1-F65L in the presence of functional Put1. The engineered strain increased the intracellular NO level in response to air-drying stress, and the strain was tolerant not only to oxidative stress but also to both air-drying and freeze-thaw stresses probably due to the reduced intracellular ROS level. We also showed that the resultant strain retained higher leavening activity in bread dough after air-drying and freeze-thaw stress than that of the wild-type strain. On the other hand, enhanced stress tolerance and fermentation ability did not occur in the put1-deficient strain. This result suggests that NO is synthesized in baker's yeast from proline in response to oxidative stresses that induce ROS

Enhancement of the proline and nitric oxide synthetic pathway improves fermentation ability under multiple baking-associated stress conditions in industrial baker's yeast

Science.gov (United States)

2012-01-01

Background During the bread-making process, industrial baker's yeast, mostly Saccharomyces cerevisiae, is exposed to baking-associated stresses, such as air-drying and freeze-thaw stress. These baking-associated stresses exert severe injury to yeast cells, mainly due to the generation of reactive oxygen species (ROS), leading to cell death and reduced fermentation ability. Thus, there is a great need for a baker's yeast strain with higher tolerance to baking-associated stresses. Recently, we revealed a novel antioxidative mechanism in a laboratory yeast strain that is involved in stress-induced nitric oxide (NO) synthesis from proline via proline oxidase Put1 and N-acetyltransferase Mpr1. We also found that expression of the proline-feedback inhibition-less sensitive mutant γ-glutamyl kinase (Pro1-I150T) and the thermostable mutant Mpr1-F65L resulted in an enhanced fermentation ability of baker's yeast in bread dough after freeze-thaw stress and air-drying stress, respectively. However, baker's yeast strains with high fermentation ability under multiple baking-associated stresses have not yet been developed. Results We constructed a self-cloned diploid baker's yeast strain with enhanced proline and NO synthesis by expressing Pro1-I150T and Mpr1-F65L in the presence of functional Put1. The engineered strain increased the intracellular NO level in response to air-drying stress, and the strain was tolerant not only to oxidative stress but also to both air-drying and freeze-thaw stresses probably due to the reduced intracellular ROS level. We also showed that the resultant strain retained higher leavening activity in bread dough after air-drying and freeze-thaw stress than that of the wild-type strain. On the other hand, enhanced stress tolerance and fermentation ability did not occur in the put1-deficient strain. This result suggests that NO is synthesized in baker's yeast from proline in response to oxidative stresses that induce ROS generation and that increased NO

Dural enhancement with primary calvarial lesions.

Science.gov (United States)

Arana, E; Martí-Bonmatí, L; Ricart, V; Pérez-Ebrí, M

2004-11-01

The purpose of this study was to relate the pathological and imaging features of dural enhancement and meningeal sign ("dural tail") on contrast-enhanced T1-weighted magnetic resonance (MR) images from patients with primary calvarial lesions as well to assess the accuracy of MR imaging in predicting dural invasion. Thirty-two calvarial tumors studied with contrast-enhanced MR imaging and histopathological examination of the dural specimens were reviewed. Sixteen patients presented dural enhancement, eight with tumor invasion. Tumoral invasion of the dura was observed in one case without enhancement. Malignant lesions showed enhanced dura more commonly than benign lesions (P=0.02). Nodular and discontinuous dural enhancement was statistically associated with dural invasion (P=0.05). Dural tail did not show a specific pathological association. Meningeal enhancement is a nonspecific reaction to calvarial lesions unless nodular and discontinuous. False-negative and -positive cases of dural invasion imply some limitation of contrast-enhanced MR imaging in predicting dural invasion by calvarial neoplasms.

Dural enhancement with primary calvarial lesions

Energy Technology Data Exchange (ETDEWEB)

Arana, E. [Clinica Quiron, Department of Radiology, Valencia (Spain); Marti-Bonmati, L. [Clinica Quiron, Department of Radiology, Valencia (Spain); Hospital Universitario Dr. Peset, Department of Radiology, Valencia (Spain); Ricart, V. [Hospital de la Ribera, Department of Radiology, Valencia (Spain); Perez-Ebri, M. [Hospital Universitario Dr. Peset, Department of Pathology, Valencia (Spain)

2004-11-01

The purpose of this study was to relate the pathological and imaging features of dural enhancement and meningeal sign (''dural tail'') on contrast-enhanced T1-weighted magnetic resonance (MR) images from patients with primary calvarial lesions as well to assess the accuracy of MR imaging in predicting dural invasion. Thirty-two calvarial tumors studied with contrast-enhanced MR imaging and histopathological examination of the dural specimens were reviewed. Sixteen patients presented dural enhancement, eight with tumor invasion. Tumoral invasion of the dura was observed in one case without enhancement. Malignant lesions showed enhanced dura more commonly than benign lesions (P=0.02). Nodular and discontinuous dural enhancement was statistically associated with dural invasion (P=0.05). Dural tail did not show a specific pathological association. Meningeal enhancement is a nonspecific reaction to calvarial lesions unless nodular and discontinuous. False-negative and -positive cases of dural invasion imply some limitation of contrast-enhanced MR imaging in predicting dural invasion by calvarial neoplasms. (orig.)

The osteogenic capacity of biomimetic hierarchical micropore/nanorod-patterned Sr-HA coatings with different interrod spacings.

Science.gov (United States)

Zhou, Jianhong; Li, Bo; Han, Yong; Zhao, Lingzhou

2016-07-01

Advanced titanium based bone implant with fast established, rigid and stable osseointegration is stringently needed in clinic. Here the hierarchical micropore/nanorod-patterned strontium doped hydroxyapatite (Ca9Sr1(PO4)6(OH)2, Sr1-HA) coatings (MNRs) with different interrod spacings varying from about 300 to 33nm were developed. MNRs showed dramatically differential biological performance closely related to the interrod spacing. Compared to micropore/nanogranule-patterned Sr1-HA coating (MNG), MNRs with an interrod spacing of larger than 137nm resulted in inhibited in vitro mesenchymal stem cell functions and in vivo osseointegration, while those of smaller than 96nm gave rise to dramatically enhanced the biological effect, especially those of mean 67nm displayed the best effect. The differential biological effect of MNRs was related to their modulation on the focal adhesion mediated mechanotransduction. These results suggest that MNRs with a mean interrod spacing of 67nm may give rise to an advanced implant of improved clinical performance. Copyright © 2016 Elsevier Inc. All rights reserved.

Histomorphometric and histologic evaluation of titanium-zirconium (aTiZr) implants with anodized surfaces.

Science.gov (United States)

Sharma, Ajay; McQuillan, A James; Shibata, Yo; Sharma, Lavanya A; Waddell, John Neil; Duncan, Warwick John

2016-05-01

The choice of implant surface has a significant influence on osseointegration. Modification of TiZr surface by anodization is reported to have the potential to modulate the osteoblast cell behaviour favouring more rapid bone formation. The aim of this study is to investigate the effect of anodizing the surface of TiZr discs with respect to osseointegration after four weeks implantation in sheep femurs. Titanium (Ti) and TiZr discs were anodized in an electrolyte containing DL-α-glycerophosphate and calcium acetate at 300 V. The surface characteristics were analyzed by scanning electron microscopy, electron dispersive spectroscopy, atomic force microscopy and goniometry. Forty implant discs with thickness of 1.5 and 10 mm diameter (10 of each-titanium, titanium-zirconium, anodized titanium and anodized titanium-zirconium) were placed in the femoral condyles of 10 sheep. Histomorphometric and histologic analysis were performed 4 weeks after implantation. The anodized implants displayed hydrophilic, porous, nano-to-micrometer scale roughened surfaces. Energy dispersive spectroscopy analysis revealed calcium and phosphorous incorporation into the surface of both titanium and titanium-zirconium after anodization. Histologically there was new bone apposition on all implanted discs, slightly more pronounced on anodised discs. The percentage bone-to-implant contact measurements of anodized implants were higher than machined/unmodified implants but there was no significant difference between the two groups with anodized surfaces (P > 0.05, n = 10). The present histomorphometric and histological findings confirm that surface modification of titanium-zirconium by anodization is similar to anodised titanium enhances early osseointegration compared to machined implant surfaces.

Intracranial arterial wall enhancement using gadolinium-enhanced 3D black-blood T1-weighted imaging

Energy Technology Data Exchange (ETDEWEB)

Takano, Koichi, E-mail: k-takano@fukuoka-u.ac.jp; Hida, Kosuke; Kuwabara, Yasuo; Yoshimitsu, Kengo

2017-01-15

Purpose: We investigated the enhancement of the intracranial arterial walls with gadolinium-enhanced, black-blood three-dimensional T1-weighted imaging (Gd-3DBB) by using an improved motion-sensitized driven-equilibrium (iMSDE)—prepared volumetric isotropic turbo spin-echo acquisition (VISTA). Methods: A total of 115 patients underwent FLAIR, 3D-TOF-MRA and Gd-3DBB with a 1.5-T scanner. The degree and distribution of the arterial wall enhancement on Gd-3DBB was assessed. The association of the degree of wall enhancement with brain infarction/ischemic lesions on FLAIR, luminal changes on 3D-TOF-MRA, and cardiovascular risk factors (CVRFs) was investigated by univariate and multiple logistic regression analyses. Results: Strong enhancement of the arterial walls was observed in 77 vertebral arteries (33.5%), 4 basilar arteries (3.5%), 31 supraclinoid internal carotid arteries (ICAs) (13.5%) and 8 middle cerebral arteries (3.5%). In addition, 221 intrapetrous ICAs (96.1%) showed strong enhancement. After adjusting for confounding factors, multivariate analyses showed that the patient age was independently associated with the strong wall enhancement of the arteries for both the posterior (OR, 1.088; 95% CI, 1.034–1.146) and the anterior circulation (OR, 1.098, 95% CI 1.029–1.172). In addition, the presence of the supratentorial brain infarctions was independently associated with the strong wall enhancement in the anterior circulation excluding the intrapetrous ICAs (OR, 4.097; 95% CI, 1.483–11.319). Conclusions: Although the arterial wall enhancement on the Gd-3DBB probably reflects normal aging, the enhancement in the anterior circulation might be related to brain infarctions. On the other hand, the intrapetrous ICA enhancement is considered a nonspecific finding and should not be mistaken for arterial pathologies such as atherosclerosis or arteritis.

Intracranial arterial wall enhancement using gadolinium-enhanced 3D black-blood T1-weighted imaging

International Nuclear Information System (INIS)

Takano, Koichi; Hida, Kosuke; Kuwabara, Yasuo; Yoshimitsu, Kengo

2017-01-01

Purpose: We investigated the enhancement of the intracranial arterial walls with gadolinium-enhanced, black-blood three-dimensional T1-weighted imaging (Gd-3DBB) by using an improved motion-sensitized driven-equilibrium (iMSDE)—prepared volumetric isotropic turbo spin-echo acquisition (VISTA). Methods: A total of 115 patients underwent FLAIR, 3D-TOF-MRA and Gd-3DBB with a 1.5-T scanner. The degree and distribution of the arterial wall enhancement on Gd-3DBB was assessed. The association of the degree of wall enhancement with brain infarction/ischemic lesions on FLAIR, luminal changes on 3D-TOF-MRA, and cardiovascular risk factors (CVRFs) was investigated by univariate and multiple logistic regression analyses. Results: Strong enhancement of the arterial walls was observed in 77 vertebral arteries (33.5%), 4 basilar arteries (3.5%), 31 supraclinoid internal carotid arteries (ICAs) (13.5%) and 8 middle cerebral arteries (3.5%). In addition, 221 intrapetrous ICAs (96.1%) showed strong enhancement. After adjusting for confounding factors, multivariate analyses showed that the patient age was independently associated with the strong wall enhancement of the arteries for both the posterior (OR, 1.088; 95% CI, 1.034–1.146) and the anterior circulation (OR, 1.098, 95% CI 1.029–1.172). In addition, the presence of the supratentorial brain infarctions was independently associated with the strong wall enhancement in the anterior circulation excluding the intrapetrous ICAs (OR, 4.097; 95% CI, 1.483–11.319). Conclusions: Although the arterial wall enhancement on the Gd-3DBB probably reflects normal aging, the enhancement in the anterior circulation might be related to brain infarctions. On the other hand, the intrapetrous ICA enhancement is considered a nonspecific finding and should not be mistaken for arterial pathologies such as atherosclerosis or arteritis.

In vitro and in vivo studies of ultrafine-grain Ti as dental implant material processed by ECAP

Energy Technology Data Exchange (ETDEWEB)

An, Baili; Li, Zhirui; Diao, Xiaoou [State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi' an 710032 (China); National Clinical Research Center for Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi' an 710032 (China); Shannxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi' an 710032 (China); Xin, Haitao, E-mail: xhthmj@fmmu.edu.cn [State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi' an 710032 (China); National Clinical Research Center for Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi' an 710032 (China); Shannxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi' an 710032 (China); Zhang, Qiang; Jia, Xiaorui; Wu, Yulu; Li, Kai [State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi' an 710032 (China); National Clinical Research Center for Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi' an 710032 (China); Shannxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi' an 710032 (China); Guo, Yazhou [School of Aeronautics, Northwestern Polytechnical University, Xi' an 710032 (China)

2016-10-01

The aim of this study was to investigate the surface characterization of ultrafine-grain pure titanium (UFG-Ti) after sandblasting and acid-etching (SLA) and to evaluate its biocompatibility as dental implant material in vitro and in vivo. UFG-Ti was produced by equal channel angular pressing (ECAP) using commercially pure titanium (CP-Ti). Microstructure and yield strength were investigated. The morphology, wettability and roughness of the specimens were analyzed after they were modified by SLA. MC3T3-E1 osteoblasts were seeded onto the specimens to evaluate its biocompatibility in vitro. For the in vivo study, UFG-Ti implants after SLA were embedded into the femurs of New Zealand rabbits. Osseointegration was investigated though micro-CT analysis, histological assessment and pull-out test. The control group was CP-Ti. UFG-Ti with enhanced mechanical properties was produced by four passes of ECAP in B{sub C} route at room temperature. After SLA modification, the hierarchical porous structure on its surface exhibited excellent wettability. The adhesion, proliferation and viability of cells cultured on the UFG-Ti were superior to that of CP-Ti. In the in vivo study, favorable osseointegration occurred between the implant and bone in CP and UFG-Ti groups. The combination intensity of UF- Ti with bone was higher according to the pull-out test. This study supports the claim that UFG-Ti has grain refinement with outstanding mechanical properties and, with its excellent biocompatibility, has potential for use as dental implant material. - Highlights: • Yield strength and Vickers hardness of Ti are improved significantly after it is grain-refined by ECAP process. • The hierarchical micro-porous structure with superior wettability could be formed on the surface of ECAP Ti after SLA. • The results in vitro exhibited excellent cell biocompatibility of UFG-Ti after sandblasting and acid-etching. • The osseointegration between UFG-Ti implant and surrounding bone could

In vitro and in vivo studies of ultrafine-grain Ti as dental implant material processed by ECAP

International Nuclear Information System (INIS)

An, Baili; Li, Zhirui; Diao, Xiaoou; Xin, Haitao; Zhang, Qiang; Jia, Xiaorui; Wu, Yulu; Li, Kai; Guo, Yazhou

2016-01-01

The aim of this study was to investigate the surface characterization of ultrafine-grain pure titanium (UFG-Ti) after sandblasting and acid-etching (SLA) and to evaluate its biocompatibility as dental implant material in vitro and in vivo. UFG-Ti was produced by equal channel angular pressing (ECAP) using commercially pure titanium (CP-Ti). Microstructure and yield strength were investigated. The morphology, wettability and roughness of the specimens were analyzed after they were modified by SLA. MC3T3-E1 osteoblasts were seeded onto the specimens to evaluate its biocompatibility in vitro. For the in vivo study, UFG-Ti implants after SLA were embedded into the femurs of New Zealand rabbits. Osseointegration was investigated though micro-CT analysis, histological assessment and pull-out test. The control group was CP-Ti. UFG-Ti with enhanced mechanical properties was produced by four passes of ECAP in B_C route at room temperature. After SLA modification, the hierarchical porous structure on its surface exhibited excellent wettability. The adhesion, proliferation and viability of cells cultured on the UFG-Ti were superior to that of CP-Ti. In the in vivo study, favorable osseointegration occurred between the implant and bone in CP and UFG-Ti groups. The combination intensity of UF- Ti with bone was higher according to the pull-out test. This study supports the claim that UFG-Ti has grain refinement with outstanding mechanical properties and, with its excellent biocompatibility, has potential for use as dental implant material. - Highlights: • Yield strength and Vickers hardness of Ti are improved significantly after it is grain-refined by ECAP process. • The hierarchical micro-porous structure with superior wettability could be formed on the surface of ECAP Ti after SLA. • The results in vitro exhibited excellent cell biocompatibility of UFG-Ti after sandblasting and acid-etching. • The osseointegration between UFG-Ti implant and surrounding bone could be

CLINICAL CONSIDERATIONS OF DENTAL IMPLANT SYSTEM IN IMMEDIATE LOADING IMPLANT CASES

Directory of Open Access Journals (Sweden)

Carolina Damayanti Marpaung

2015-06-01

Full Text Available Immediate loading of dental implant has been researched intensively in the development of Branemark’s early concept of 2 stages implant placement. This was embarked from both patients and practiitioner’s convenience towards a simpler protocol and shorter time frame. Many recent researchers later found that micromotions derived from occlusal loading for a certain degree, instead of resulting a fibrous tissue encapsulation, can enhance the osseointegration process. Dental Implant system enhancement towards maximizing the primary stability held a key factor in Branemark’s concept development. Surgical protocol and implant design was found to give a significant contribution to the prognosis of immediate-loading implants.

Enhanced molecular aging in late-life depression: the Senescent Associated Secretory Phenotype

Science.gov (United States)

Diniz, Breno Satler; Reynolds, Charles F.; Sibille, Etienne; Lin, Chien-Wei; Tseng, George; Lotrich, Francis; Aizenstein, Howard J.; Butters, Meryl A.

2016-01-01

Objective This study aims to investigate whether a systemic molecular pattern associated with aging (senescent-associated secretory phenotype – SASP) is elevated in adults with late-life depression (LLD), compared to never-depressed elderly comparison participants. Design Cross-sectional study. Participants We included 111 older adults (80 with LLD and 31 comparison participants) in this study. Measurement A panel of 22 SASP-related proteins was extracted from a previous multiplex protein panel performed in these participants. We conducted a principal component analysis to create the SASP index based on individual weights of each of protein. Results Participants with LLD showed a significantly increased SASP index compared to comparison participants, after controlling for age, depressive symptoms, medical comorbidity (CIRS-G) scores, gender, and cognitive performance (F(1,98)=7.3, p=0.008). Correlation analyses revealed that the SASP index was positively correlated with age (r=0.2, p = 0.03) and CIRS score (r=0.27, p=0.005), and negatively correlated with information processing speed (r=−0.34, p=0.001), executive function (r=−0.27, p=0.004) and global cognitive performance (r=−0.28, p=0.007). Conclusions To the best of our knowledge, this is the first study to show that a set of proteins (i.e., SASP index) primarily associated with cellular aging, is abnormally regulated and elevated in LLD. These results suggest that individuals with LLD display enhanced aging-related molecular patterns that are associated with higher medical comorbidity and worse cognitive function. Finally, we provide a set of proteins that can serve as potential therapeutic targets and biomarkers to monitor the effects of therapeutic or preventative interventions in LLD. PMID:27856124

Convection Enhanced Delivery of Recombinant Adeno-associated Virus into the Mouse Brain.

Science.gov (United States)

Nash, Kevin R; Gordon, Marcia N

2016-01-01

Recombinant adeno-associated virus (rAAV) has become an extremely useful tool for the study of gene over expression or knockdown in the central nervous system of experimental animals. One disadvantage of intracranial injections of rAAV vectors into the brain parenchyma has been restricted distribution to relatively small volumes of the brain. Convection enhanced delivery (CED) is a method for delivery of clinically relevant amounts of therapeutic agents to large areas of the brain in a direct intracranial injection procedure. CED uses bulk flow to increase the hydrostatic pressure and thus improve volume distribution. The CED method has shown robust gene transfer and increased distribution within the CNS and can be successfully used for different serotypes of rAAV for increased transduction of the mouse CNS. This chapter details the surgical injection of rAAV by CED into a mouse brain.

Surface modification of TiO{sub 2} nanotubes with osteogenic growth peptide to enhance osteoblast differentiation

Energy Technology Data Exchange (ETDEWEB)

Lai, Min, E-mail: minlai@jsnu.edu.cn [School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116 (China); Jin, Ziyang [School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116 (China); Su, Zhiguo [Department of Pharmacy, The Affiliated hospital of Qingdao University, Qingdao, Shandong 266555 (China)

2017-04-01

To investigate the influence of surface-biofunctionalized substrates on osteoblast behavior, a layer of aligned TiO{sub 2} nanotubes with a diameter of around 70 nm was fabricated on titanium surface by anodization, and then osteogenic growth peptide (OGP) was conjugated onto TiO{sub 2} nanotubes through the intermediate layer of polydopamine. The morphology, composition and wettability of different surfaces were characterized by field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and contact angle measurements, respectively. The effects of OGP-modified TiO{sub 2} nanotube substrates on the morphology, proliferation and differentiation of osteoblasts were examined in vitro. Immunofluorescence staining revealed that the OGP-functionalized TiO{sub 2} nanotubes were favorable for cell spreading. However, there was no significant difference in cell proliferation observed among the different groups. Cells grown onto OGP-functionalized TiO{sub 2} nanotubes showed significantly higher (p < 0.05 or p < 0.01) levels of alkaline phosphatase (ALP) and mineralization after 4, 7 and 14 days of culture, respectively. Cells grown on OGP-functionalized TiO{sub 2} nanotubes had significantly higher (p < 0.05 or p < 0.01) expression of osteogenic-related genes including runt related transcription factor 2 (Runx2), ALP, collagen type I (Col I), osteopontin (OPN) and osteocalcin (OC) after 14 days of culture. These data suggest that surface functionalization of TiO{sub 2} nanotubes with OGP was beneficial for cell spreading and differentiation. This study provides a novel platform for the development and fabrication of titanium-based implants that enhance the propensity for osseointegration between the native tissue and implant interface. - Highlights: • The OGP functionalized TiO{sub 2} nanotube substrates were successfully fabricated through a direct and effective method. • The OGP functionalized substrates

Probing around implants and teeth with healthy or inflamed peri-implant mucosa/gingival. A histologic comparison in cynomolgus monkeys. (Macaca fascicularis)

DEFF Research Database (Denmark)

Schou, Søren; Holmstrup, Palle; Stoltze, K.

2002-01-01

Osseointegrated oral implants; teeth; phathology; peri-implant mucositis; gingivitis; peri-implantitis; periodontitis; diagnosis; probing depth; non-human primates; cynomolgus monkeys: Macaca fascicularis......Osseointegrated oral implants; teeth; phathology; peri-implant mucositis; gingivitis; peri-implantitis; periodontitis; diagnosis; probing depth; non-human primates; cynomolgus monkeys: Macaca fascicularis...

Contrast-enhanced ultrasound study of primary hepatic angiosarcoma: A pitfall of non-enhancement

International Nuclear Information System (INIS)

Wang, Liang; Lv, Ke; Chang, Xiao-Yan; Xia, Yu; Yang, Zhi-Ying; Jiang, Yu-Xin; Dai, Qing; Tan, Li; Li, Jian-Chu

2012-01-01

Highlights: ► The contrast-enhanced ultrasound (CEUS) characteristics of primary hepatic angiosarcoma (PHA) in three patients were retrospectively analyzed. ► PHA appeared similar peripheral enhancement pattern in our series. ► Non-necrotic tumor tissue of PHA unexpectedly demonstrated non-enhancement on CEUS. ► It may be associated with the very low velocity of blood flow in the central region of tumors. ► This interesting finding warrants further investigations, particularly on intratumoral hemodynamics. -- Abstract: Objective: To investigate the contrast-enhanced ultrasound (CEUS) characteristics of primary hepatic angiosarcoma (PHA). Methods: The sonographic findings and CEUS images of PHA in three patients were retrospectively analyzed. Results: In our study, 3 cases of PHA (2 multiple nodules and 1 solitary mass) showed similar enhancement pattern on CEUS, characterized by remarkable central non-enhancement and peripheral irregular enhancement in the arterial and portal phase, and complete wash-out in the late phase. Furthermore, we unexpectedly found that abundant neoplastic tissues were present in the central area of non-enhancement on pathological evaluation. Based on literature review, we supposed that the unusual finding may be associated with the very low velocity of blood flow in the central region of tumors. Conclusion: CEUS could well depict PHA with some common features, which may provide valuable clues in diagnosis of this rare disease. And non-necrotic tumor tissue of PHA could also demonstrate non-enhancement on CEUS, which warrant further investigations

Placement of endosseous implant in infected alveolar socket with large fenestration defect: A comparative case report

Directory of Open Access Journals (Sweden)

Balaji Anitha

2010-01-01

Full Text Available Placement of endosseous implants into infected bone is often deferred or avoided due to fear of failure. However, with the development of guided bone regeneration [GBR], some implantologists have reported successful implant placement in infected sockets, even those with fenestration defects. We had the opportunity to compare the osseointegration of an immediate implant placed in an infected site associated with a large buccal fenestration created by the removal of a root stump with that of a delayed implant placed 5 years after extraction. Both implants were placed in the same patient, in the same dental quadrant by the same implantologist. GBR was used with the fenestration defect being filled with demineralized bone graftFNx01 and covered with collagen membraneFNx08. Both implants were osseointegrated and functional when followed up after 12 months.

High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study

Energy Technology Data Exchange (ETDEWEB)

Puig, Josep; Blasco, Gerard; Remollo, Sebastian; Hernandez, David; Pedraza, Salvador [Hospital Universitari Dr Josep Trueta, Research Unit of Diagnostic Imaging Institute (IDI), Department of Radiology [Girona Biomedical Research Institute] IDIBGI, Girona (Spain); Daunis-i-Estadella, Josep; Mateu, Gloria [University of Girona, Department of Computer Science, Applied Mathematics and Statistics, Girona (Spain); Alberich-Bayarri, Angel [La Fe Polytechnics and University Hospital, Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, Valencia (Spain); Essig, Marco [University of Manitoba, Department of Radiology, Winnipeg (Canada); Jain, Rajan [NYU School of Medicine, Division of Neuroradiology, Department of Radiology, New York, NY (United States); Puigdemont, Montserrat [Hospital Universitari Dr Josep Trueta, Catalan Institute of Oncology (ICO), Hospital Cancer Registry, Girona (Spain); Sanchez-Gonzalez, Javier [Philips Healthcare Iberica, Madrid (Spain); Wintermark, Max [Stanford University, Department of Radiology, Neuroradiology Division, Palo Alto, CA (United States)

2016-01-15

The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival. (orig.)

An in vivo cis-regulatory screen at the type 2 diabetes associated TCF7L2 locus identifies multiple tissue-specific enhancers.

Directory of Open Access Journals (Sweden)

Daniel Savic

Full Text Available Genome-wide association studies (GWAS have repeatedly shown an association between non-coding variants in the TCF7L2 locus and risk for type 2 diabetes (T2D, implicating a role for cis-regulatory variation within this locus in disease etiology. Supporting this hypothesis, we previously localized complex regulatory activity to the TCF7L2 T2D-associated interval using an in vivo bacterial artificial chromosome (BAC enhancer-trapping reporter strategy. To follow-up on this broad initial survey of the TCF7L2 regulatory landscape, we performed a fine-mapping enhancer scan using in vivo mouse transgenic reporter assays. We functionally interrogated approximately 50% of the sequences within the T2D-associated interval, utilizing sequence conservation within this 92-kb interval to determine the regulatory potential of all evolutionary conserved sequences that exhibited conservation to the non-eutherian mammal opossum. Included in this study was a detailed functional interrogation of sequences spanning both protective and risk alleles of single nucleotide polymorphism (SNP rs7903146, which has exhibited allele-specific enhancer function in pancreatic beta cells. Using these assays, we identified nine segments regulating various aspects of the TCF7L2 expression profile and that constitute nearly 70% of the sequences tested. These results highlight the regulatory complexity of this interval and support the notion that a TCF7L2 cis-regulatory disruption leads to T2D predisposition.

Emotion Regulation through Movement: Unique Sets of Movement Characteristics are Associated with and Enhance Basic Emotions.

Science.gov (United States)

Shafir, Tal; Tsachor, Rachelle P; Welch, Kathleen B

2015-01-01

We have recently demonstrated that motor execution, observation, and imagery of movements expressing certain emotions can enhance corresponding affective states and therefore could be used for emotion regulation. But which specific movement(s) should one use in order to enhance each emotion? This study aimed to identify, using Laban Movement Analysis (LMA), the Laban motor elements (motor characteristics) that characterize movements whose execution enhances each of the basic emotions: anger, fear, happiness, and sadness. LMA provides a system of symbols describing its motor elements, which gives a written instruction (motif) for the execution of a movement or movement-sequence over time. Six senior LMA experts analyzed a validated set of video clips showing whole body dynamic expressions of anger, fear, happiness and sadness, and identified the motor elements that were common to (appeared in) all clips expressing the same emotion. For each emotion, we created motifs of different combinations of the motor elements common to all clips of the same emotion. Eighty subjects from around the world read and moved those motifs, to identify the emotion evoked when moving each motif and to rate the intensity of the evoked emotion. All subjects together moved and rated 1241 motifs, which were produced from 29 different motor elements. Using logistic regression, we found a set of motor elements associated with each emotion which, when moved, predicted the feeling of that emotion. Each emotion was predicted by a unique set of motor elements and each motor element predicted only one emotion. Knowledge of which specific motor elements enhance specific emotions can enable emotional self-regulation through adding some desired motor qualities to one's personal everyday movements (rather than mimicking others' specific movements) and through decreasing motor behaviors which include elements that enhance negative emotions.

Emotion regulation through movement: Unique sets of movement characteristics are associated with and enhance basic emotions

Directory of Open Access Journals (Sweden)

Tal eShafir

2016-01-01

Full Text Available We have recently demonstrated that motor execution, observation and imagery of movements expressing certain emotions can enhance corresponding affective states and therefore could be used for emotion regulation. But which specific movement(s should one use in order to enhance each emotion? This study aimed to identify, using Laban Movement Analysis (LMA, the Laban motor elements (motor characteristics that characterize movements whose execution enhances each of the basic emotions: anger, fear happiness, and sadness. LMA provides a system of symbols describing its motor elements, which gives a written instruction (motif for the execution of a movement or movement-sequence over time. Six senior LMA experts analyzed a validated set of video clips showing whole body dynamic expressions of anger, fear, happiness and sadness, and identified the motor elements that were common to (appeared in all clips expressing the same emotion. For each emotion, we created motifs of different combinations of the motor elements common to all clips of the same emotion. Eighty subjects from around the world read and moved those motifs, to identify the emotion evoked when moving each motif and to rate the intensity of the evoked emotion. All subjects together moved and rated 1241 motifs, which were produced from 29 different motor elements. Using logistic regression, we found a set of motor elements associated with each emotion which, when moved, predicted the feeling of that emotion. Each emotion was predicted by a unique set of motor elements and each motor element predicted only one emotion. Knowledge of which specific motor elements enhance specific emotions can enable emotional self-regulation through adding some desired motor qualities to one’s personal everyday movements (rather than mimicking others’ specific movements and through decreasing motor behaviors which include elements that enhance negative emotions.

Association of dynamic susceptibility contrast enhanced MR Perfusion parameters with prognosis in elderly patients with glioblastomas

Energy Technology Data Exchange (ETDEWEB)

Jabehdar Maralani, Pejman [University of Toronto, Department of Medical Imaging, Sunnybrook Health Sciences Center, Toronto, ON (Canada); Melhem, Elias R.; Herskovits, Edward H. [University of Maryland Medical Center, Department of Radiology, Baltimore, MD (United States); Wang, Sumei; Voluck, Matthew R.; Learned, Kim O.; Mohan, Suyash [Perelman School of Medicine at University of Pennsylvania, Department of Radiology, Division of Neuroradiology, Philadelphia, PA (United States); Kim, Sang Joon [University of Ulsan Asan Medical Center, Department of Radiology, Songpa-gu, Seoul (Korea, Republic of); O' Rourke, Donald M. [Perelman School of Medicine at University of Pennsylvania, Department of Surgery, Division of Neurosurgery, Philadelphia, PA (United States)

2015-09-15

We aimed to evaluate the prognostic value of dynamic susceptibility contrast (DSC) MR perfusion in elderly patients with glioblastomas (GBM). Thirty five patients aged ≥65 and 35 aged <65 years old, (referred to as elderly and younger, respectively) were included in this retrospective study. The median relative cerebral volume (rCBV) from the enhancing region (rCBV{sub ER-Med}) and immediate peritumoral region (rCBV{sub IPR-Med}) and maximum rCBV from the enhancing region of the tumor (rCBV{sub ER-Max}) were compared and correlated with survival data. Analysis was repeated after rCBVs were dichotomized into high and low values and after excluding elderly patients who did not receive postoperative chemoradiation (34.3 %). Kaplan-Meyer survival curves and parametric and semi-parametric regression tests were used for analysis. All rCBV parameters were higher in elderly compared to younger patients (p < 0.05). After adjustment for age, none were independently associated with shorter survival (p > 0.05). After rCBV dichotomization into high and low values, high rCBV in elderly was independently associated with shorter survival compared to low rCBV in elderly, or any rCBV in younger patients (p < 0.05). rCBV can be an imaging biomarker to identify a subgroup of GBM patients in the elderly with worse prognosis compared to others. (orig.)

Integrin α4 Enhances Metastasis and May Be Associated with Poor Prognosis in MYCN-low Neuroblastoma.

Directory of Open Access Journals (Sweden)

Shanique A Young

Full Text Available High-risk neuroblastoma is associated with an overall survival rate of 30-50%. Neuroblastoma-expressed cell adhesion receptors of the integrin family impact cell adhesion, migration, proliferation and survival. Integrin α4 is essential for neural crest cell motility during development, is highly expressed on leukocytes, and is critical for transendothelial migration. Thus, cancer cells that express this receptor may exhibit increased metastatic potential. We show that α4 expression in human and murine neuroblastoma cell lines selectively enhances in vitro interaction with the alternatively spliced connecting segment 1 of fibronectin, as well as vascular cell adhesion molecule-1 and increases migration. Integrin α4 expression enhanced experimental metastasis in a syngeneic tumor model, reconstituting a pattern of organ involvement similar to that seen in patients. Accordingly, antagonism of integrin α4 blocked metastasis, suggesting adhesive function of the integrin is required. However, adhesive function was not sufficient, as mutants of integrin α4 that conserved the matrix-adhesive and promigratory function in vitro were compromised in their metastatic capacity in vivo. Clinically, integrin α4 is more frequently expressed in non-MYNC amplified tumors, and is selectively associated with poor prognosis in this subset of disease. These results reveal an unexpected role for integrin α4 in neuroblastoma dissemination and identify α4 as a potential prognostic indicator and therapeutic target.

Enhanced recovery from surgery in the UK: an audit of the enhanced recovery partnership programme 2009-2012.

Science.gov (United States)

Simpson, J C; Moonesinghe, S R; Grocott, M P W; Kuper, M; McMeeking, A; Oliver, C M; Galsworthy, M J; Mythen, M G

2015-10-01

The UK Department of Health Enhanced Recovery Partnership Programme collected data on 24 513 surgical patients in the UK from 2009-2012. Enhanced Recovery is an approach to major elective surgery aimed at minimizing perioperative stress for the patient. Previous studies have shown Enhanced Recovery to be associated with reduced hospital length of stay and perioperative morbidity. In this national clinical audit, National Health Service hospitals in the UK were invited to submit patient-level data. The data regarding length of stay and compliance with each element of Enhanced Recovery protocols for colorectal, orthopaedic, urological and gynaecological surgery patients were analysed. The relationship between Enhanced Recovery protocol compliance and length of stay was measured. From 16 267 patients from 61 hospital trusts, three out of four surgical specialties showed Enhanced Recovery, compliance being weakly associated with shorter length of stay (correlation coefficients -0.18, -0.14, -0.25 in colorectal, orthopaedics and gynaecology respectively). At a cut-off of 80% compliance, good compliance was associated with two, one and three day reductions in median length of stay respectively in colorectal, orthopaedic and urological surgeries, with no saving in gynaecology. This study is the largest assessment of the relationship between Enhanced Recovery protocol compliance and outcome in four surgical specialties. The data suggest that higher compliance with an Enhanced Recovery protocol has a weak association with shorter length of stay. This suggests that changes in process, resulting from highly protocolised pathways, may be as important in reducing perioperative length of stay as any individual element of Enhanced Recovery protocols in isolation. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cell transplantation for the treatment of spinal cord injury - bone marrow stromal cells and choroid plexus epithelial cells

Directory of Open Access Journals (Sweden)

Chizuka Ide

2016-01-01

Full Text Available Transplantation of bone marrow stromal cells (BMSCs enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury (SCI. BMSCs did not survive long-term, disappearing from the spinal cord within 2-3 weeks after transplantation. Astrocyte-devoid areas, in which no astrocytes or oligodendrocytes were found, formed at the epicenter of the lesion. It was remarkable that numerous regenerating axons extended through such astrocyte-devoid areas. Regenerating axons were associated with Schwann cells embedded in extracellular matrices. Transplantation of choroid plexus epithelial cells (CPECs also enhanced axonal regeneration and locomotor improvements in rats with SCI. Although CPECs disappeared from the spinal cord shortly after transplantation, an extensive outgrowth of regenerating axons occurred through astrocyte-devoid areas, as in the case of BMSC transplantation. These findings suggest that BMSCs and CPECs secret neurotrophic factors that promote tissue repair of the spinal cord, including axonal regeneration and reduced cavity formation. This means that transplantation of BMSCs and CPECs promotes "intrinsic" ability of the spinal cord to regenerate. The treatment to stimulate the intrinsic regeneration ability of the spinal cord is the safest method of clinical application for SCI. It should be emphasized that the generally anticipated long-term survival, proliferation and differentiation of transplanted cells are not necessarily desirable from the clinical point of view of safety.

Effects of Na/K-ATPase and its ligands on bone marrow stromal cell differentiation

Directory of Open Access Journals (Sweden)

Moustafa Sayed

2014-07-01

Full Text Available Endogenous ligands of Na/K-ATPase have been demonstrated to increase in kidney dysfunction and heart failure. It is also reported that Na/K-ATPase signaling function effects stem cell differentiation. This study evaluated whether Na/K-ATPase activation through its ligands and associated signaling functions affect bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells differentiation capacity. BMSCs were isolated from male Sprague–Dawley rats and cultured in minimal essential medium alpha (MEM-α supplemented with 15% Fetal Bovine serum (FBS. The results showed that marinobufagenin (MBG, a specific Na/K-ATPase ligand, potentiated rosiglitazone-induced adipogenesis in these BMSCs. Meanwhile, it attenuated BMSC osteogenesis. Mechanistically, MBG increased CCAAT/enhancer binding protein alpha (C/EBPα protein expression through activation of an extracellular regulated kinase (ERK signaling pathway, which leads to enhanced rosiglitazone-induced adipogenesis. Inhibition of ERK activation by U0126 blocks the effect of MBG on C/EBPα expression and on rosiglitazone-induced adipogenesis. Reciprocally, MBG reduced runt-related transcription factor 2 (RunX2 expression, which resulted in the inhibition of osteogenesis induced by β-glycerophosphate/ascorbic acid. MBG also potentiated rosiglitazone-induced adipogenesis in 3T3-L1 cells and in mouse BMSCs. These results suggest that Na/K-ATPase and its signaling functions are involved in the regulation of BMSCs differentiation.

Increased residual force enhancement in older adults is associated with a maintenance of eccentric strength.

Directory of Open Access Journals (Sweden)

Geoffrey A Power

Full Text Available Despite an age-related loss of voluntary isometric and concentric strength, muscle strength is well maintained during lengthening muscle actions (i.e., eccentric strength in old age. Additionally, in younger adults during lengthening of an activated skeletal muscle, the force level observed following the stretch is greater than the isometric force at the same muscle length. This feature is termed residual force enhancement (RFE and is believed to be a combination of active and passive components of the contractile apparatus. The purpose of this study was to provide an initial assessment of RFE in older adults and utilize aging as a muscle model to explore RFE in a system in which isometric force production is compromised, but structural mechanisms of eccentric strength are well-maintained. Therefore, we hypothesised that older adults will experience greater RFE compared with young adults. Following a reference maximal voluntary isometric contraction (MVC of the dorsiflexors in 10 young (26.1 ± 2.7 y and 10 old (76.0 ± 6.5 y men, an active stretch was performed at 15°/s over a 30° ankle joint excursion ending at the same muscle length as the reference MVCs (40° of plantar flexion. Any additional torque compared with the reference MVC therefore represented RFE. In older men RFE was ~2.5 times greater compared to young. The passive component of force enhancement contributed ~37% and ~20% to total force enhancement, in old and young respectively. The positive association (R(2 = 0.57 between maintained eccentric strength in old age and RFE indicates age-related mechanisms responsible for the maintenance of eccentric strength likely contributed to the observed elevated RFE. Additionally, as indicated by the greater passive force enhancement, these mechanisms may be related to increased muscle series elastic stiffness in old age.

MRI Background Parenchymal Enhancement Is Not Associated with Breast Cancer.

Directory of Open Access Journals (Sweden)

Barbara Bennani-Baiti

Full Text Available Previously, a strong positive association between background parenchymal enhancement (BPE at magnetic resonance imaging (MRI and breast cancer was reported in high-risk populations. We sought to determine, whether this was also true for non-high-risk patients.540 consecutive patients underwent breast MRI for assessment of breast findings (BI-RADS 0-5, non-high-risk screening (no familial history of breast cancer, no known genetic mutation, no prior chest irradiation, or previous breast cancer diagnosis and subsequent histological work-up. For this IRB-approved study, BPE and fibroglandular tissue FGT were retrospectively assessed by two experienced radiologists according to the BI-RADS lexicon. Pearson correlation coefficients were calculated to explore associations between BPE, FGT, age and final diagnosis of breast cancer. Subsequently, multivariate logistic regression analysis, considering covariate colinearities, was performed, using final diagnosis as the target variable and BPE, FGT and age as covariates.Age showed a moderate negative correlation with FGT (r = -0.43, p<0.001 and a weak negative correlation with BPE (r = -0.28, p<0.001. FGT and BPE correlated moderately (r = 0.35, p<0.001. Final diagnosis of breast cancer displayed very weak negative correlations with FGT (r = -0.09, p = 0.046 and BPE (r = -0.156, p<0.001 and weak positive correlation with age (r = 0.353, p<0.001. On multivariate logistic regression analysis, the only independent covariate for prediction of breast cancer was age (OR 1.032, p<0.001.Based on our data, neither BPE nor FGT independently correlate with breast cancer risk in non-high-risk patients at MRI. Our model retained only age as an independent risk factor for breast cancer in this setting.

Evaluation of the early enhancement of coronary atherosclerotic plaque by contrast-enhanced MR angiography

Energy Technology Data Exchange (ETDEWEB)

Li Tao [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Zhao Xihai [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Liu Xin [Paul C. Lauterbur Biomedical Imaging Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen 518067 (China); Gao Jianhua [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Zhao Shaohong [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Li Xin; Zhou Weihua [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Cai Zulong [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Zhang Weiguo [Cardiovascular and Neurological Consulting Institute, 6771 San Fernando, Irving, TX 75039 (United States); Yang Li, E-mail: Yangli301@yahoo.com [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China)

2011-10-15

Purpose: To evaluate the early enhancement of coronary atherosclerotic plaque using contrast-enhanced MR angiography (CE-MRA) and investigate the association between unstable angina pectoris (UAP) and early enhancement of the plaque. Methods: Forty-one patients presenting with angina pectoris and demonstrating single-vessel disease with non-calcified plaque and significant coronary stenosis ({>=}50%) on CTA were consecutively recruited for coronary CE-MRA. Contrast-to-noise ratio of the culprit plaque guided by CTA was measured on a cross-sectional multi-planar reconstruction image of the plaque on both pre- and post-CE-MRA. A 50% increasing of CNR was defined as plaque enhancement. The association between early enhancement of the plaques and UAP was analyzed. Results: Thirty-seven non-calcified plaques with significant coronary stenosis were detected in the 37 patients on MRA. 4 subjects were excluded because coronary atherosclerotic plaques were inadequate for identification on MRA. Of the 37 patients, 18 patients had UAP and other 19 patients presented stable angina pectoris (SAP). Of the 37 plaques on CE-MRA, 13 and 24 plaques presented early enhancement and no enhancement, respectively. Of the 13 early-enhanced plaques, 11 (85%) and 2 (15%) were found in the patients with UAP and SAP, respectively (p < 0.01). Of the 37 patients, 11 (61%) with UAP and 2 (11%) with SAP had early-enhanced plaques, respectively (p < 0.01). Conclusion: CE-MRA allows detection of early enhancement of coronary atherosclerotic plaque. The early enhancement is common in unstable angina and could be a sign of vulnerability.

Skeletal (stromal) stem cells: an update on intracellular signaling pathways controlling osteoblast differentiation.

Science.gov (United States)

Abdallah, Basem M; Jafari, Abbas; Zaher, Walid; Qiu, Weimin; Kassem, Moustapha

2015-01-01

Skeletal (marrow stromal) stem cells (BMSCs) are a group of multipotent cells that reside in the bone marrow stroma and can differentiate into osteoblasts, chondrocytes and adipocytes. Studying signaling pathways that regulate BMSC differentiation into osteoblastic cells is a strategy for identifying druggable targets for enhancing bone formation. This review will discuss the functions and the molecular mechanisms of action on osteoblast differentiation and bone formation; of a number of recently identified regulatory molecules: the non-canonical Notch signaling molecule Delta-like 1/preadipocyte factor 1 (Dlk1/Pref-1), the Wnt co-receptor Lrp5 and intracellular kinases. This article is part of a Special Issue entitled: Stem Cells and Bone. Copyright © 2014 Elsevier Inc. All rights reserved.

Integrative Approach to Facilitate Fracture Healing: Topical Chinese Herbal Paste with Oral Strontium Ranelate

Directory of Open Access Journals (Sweden)

Wing-Sum Siu

2017-01-01

Full Text Available Strontium ranelate (SrR is one of the pharmaceutical agents reported to be effective on the promotion of fracture healing. This study aimed to evaluate the integrative effect of the oral SrR with a topical Chinese herbal paste, namely, CDR, on facilitation of bone healing. The in vivo efficacy was evaluated using rats with tibial fracture. They were treated with either CDR topically, or SrR orally, or their combined treatments. The in vivo results illustrated a significant additive effect of CDR on SrR in increasing the yield load of the fractured tibia. The in vitro results showed that neither SrR nor CDR exhibited a cytotoxic effect on UMR106 and bone-marrow stem cell (BMSC, but both of them increased the proliferation of BMSC at low concentrations. The combination of CDR at 200 μg/mL with SrR at 200 or 400 μg/ml also showed an additive effect on increasing the ALP activity of BMSC. Both SrR and CDR alone reduced osteoclast formation, and the effective concentration of SrR to inhibit osteoclastogenesis was reduced in the presence of CDR. This integrative approach by combining oral SrR and topical CDR is effective in promoting fracture healing properly due to their additive effects on proosteogenic and antiosteoclastogenic properties.

Immunotherapy with Dendritic Cells Modified with Tumor-Associated Antigen Gene Demonstrates Enhanced Antitumor Effect Against Lung Cancer

Directory of Open Access Journals (Sweden)

Tao Jiang

2017-04-01

Full Text Available BACKGROUND: Immunotherapy using dendritic cell (DC vaccine has the potential to overcome the bottleneck of cancer therapy. METHODS: We engineered Lewis lung cancer cells (LLCs and bone marrow–derived DCs to express tumor-associated antigen (TAA ovalbumin (OVA via lentiviral vector plasmid encoding OVA gene. We then tested the antitumor effect of modified DCs both in vitro and in vivo. RESULTS: The results demonstrated that in vitro modified DCs could dramatically enhance T-cell proliferation (P < .01 and killing of LLCs than control groups (P < .05. Moreover, modified DCs could reduce tumor size and prolong the survival of LLC tumor-bearing mice than control groups (P < .01 and P < .01, respectively. Mechanistically, modified DCs demonstrated enhanced homing to T-cell–rich compartments and triggered more naive T cells to become cytotoxic T lymphocytes, which exhibited significant infiltration into the tumors. Interestingly, modified DCs also markedly reduced tumor cells harboring stem cell markers in mice (P < .05, suggesting the potential role on cancer stem-like cells. CONCLUSION: These findings suggested that DCs bioengineered with TAA could enhance antitumor effect and therefore represent a novel anticancer strategy that is worth further exploration.

Nicotine disrupts safety learning by enhancing fear associated with a safety cue via the dorsal hippocampus.

Science.gov (United States)

Connor, David A; Kutlu, Munir G; Gould, Thomas J

2017-07-01

Learned safety, a learning process in which a cue becomes associated with the absence of threat, is disrupted in individuals with post-traumatic stress disorder (PTSD). A bi-directional relationship exists between smoking and PTSD and one potential explanation is that nicotine-associated changes in cognition facilitate PTSD emotional dysregulation by disrupting safety associations. Therefore, we investigated whether nicotine would disrupt learned safety by enhancing fear associated with a safety cue. In the present study, C57BL/6 mice were administered acute or chronic nicotine and trained over three days in a differential backward trace conditioning paradigm consisting of five trials of a forward conditioned stimulus (CS)+ (Light) co-terminating with a footshock unconditioned stimulus followed by a backward CS- (Tone) presented 20 s after cessation of the unconditioned stimulus. Summation testing found that acute nicotine disrupted learned safety, but chronic nicotine had no effect. Another group of animals administered acute nicotine showed fear when presented with the backward CS (Light) alone, indicating the formation of a maladaptive fear association with the backward CS. Finally, we investigated the brain regions involved by administering nicotine directly into the dorsal hippocampus, ventral hippocampus, and prelimbic cortex. Infusion of nicotine into the dorsal hippocampus disrupted safety learning.

Recipient bone marrow-derived stromal cells prolong graft survival in a rat hind limb allotransplantation model.

Science.gov (United States)

Ikeguchi, Ryosuke; Kakinoki, Ryosuke; Ohta, Souichi; Oda, Hiroki; Yurie, Hirofumi; Kaizawa, Yukitoshi; Mitsui, Hiroto; Aoyama, Tomoki; Toguchida, Junya; Matsuda, Shuichi

2017-09-01

Recent studies have indicated that bone marrow-derived stromal cells (BMSCs) have immunomodulatory properties that suppress the T cell responses that cause graft rejection. The purpose of this study is to evaluate the effect of recipient BMSCs intravenous infusion for immunomodulation in a rat vascularized composite allotransplantation model. A total of nine Wistar (WIS) rats and thirty Lewis (LEW) rats were used. BMSCs were harvested from three LEW rats. Twenty-four LEW rats were used as recipients and divided randomly into four groups: BMSC group, FK group, UT group, and Iso group. In the BMSC group, orthotopic rat hind limb transplantation was performed between WIS donor and LEW recipient rats. Recipient rats were injected intravenously with 2 × 10 6 recipient BMSCs on day 6, and with 0.2 mg/kg/day tacrolimus administered over 7 days (n = 6). In the FK group, recipient rats were treated with tacrolimus alone (n = 6). Rats in the UT group received no immunosuppressive treatment (n = 6). In the Iso group, transplantation was performed from three LEW donor rats to six LEW recipient rats without any immunosuppressive treatment (n = 6). Graft survival was assessed by daily inspection and histology. The immunological reactions of recipients were also evaluated. The graft survival of recipient rats in the BMSC group (24.5 days) was significantly prolonged in comparison with that of the FK group (18 days) (P Recipient rats in the BMSC group had significantly reduced serum IFN-γ cytokine levels (1.571 ± 0.779 pg/ml) in comparison with that of the FK group (7.059 ± 1.522 pg/ml) (P = .001). In in vitro study, BMSCs induce T cell hyporesponsiveness in a mixed lymphocyte reaction. BMSCs induce T cell hyporesponsiveness and prolong graft survival in the rat vascularized composite allotransplantation model. BMSCs exhibit immunomodulatory properties against acute rejection that can be realized without the need for significant recipient

Simultaneous nitrogen and phosphorus removal in the sulfur cycle-associated Enhanced Biological Phosphorus Removal (EBPR) process.

Science.gov (United States)

Wu, Di; Ekama, George A; Wang, Hai-Guang; Wei, Li; Lu, Hui; Chui, Ho-Kwong; Liu, Wen-Tso; Brdjanovic, Damir; van Loosdrecht, Mark C M; Chen, Guang-Hao

2014-02-01

Hong Kong has practiced seawater toilet flushing since 1958, saving 750,000 m(3) of freshwater every day. A high sulfate-to-COD ratio (>1.25 mg SO4(2-)/mg COD) in the saline sewage resulting from this practice has enabled us to develop the Sulfate reduction, Autotrophic denitrification and Nitrification Integrated (SANI(®)) process with minimal sludge production and oxygen demand. Recently, the SANI(®) process has been expanded to include Enhanced Biological Phosphorus Removal (EBPR) in an alternating anaerobic/limited-oxygen (LOS-EBPR) aerobic sequencing batch reactor (SBR). This paper presents further development - an anaerobic/anoxic denitrifying sulfur cycle-associated EBPR, named as DS-EBPR, bioprocess in an alternating anaerobic/anoxic SBR for simultaneous removal of organics, nitrogen and phosphorus. The 211 day SBR operation confirmed the sulfur cycle-associated biological phosphorus uptake utilizing nitrate as electron acceptor. This new bioprocess cannot only reduce operation time but also enhance volumetric loading of SBR compared with the LOS-EBPR. The DS-EBPR process performed well at high temperatures of 30 °C and a high salinity of 20% seawater. A synergistic relationship may exist between sulfur cycle and biological phosphorus removal as the optimal ratio of P-release to SO4(2-)-reduction is close to 1.0 mg P/mg S. There were no conventional PAOs in the sludge. Copyright © 2013 Elsevier Ltd. All rights reserved.

Characterizations of Nanofluid Heat Transfer Enhancements

Science.gov (United States)

2013-09-06

nanoparticles are thought to play important roles. Dispersed nanoparticles and associated nanoparticle Brownian movements are purported to cause the enhancements...Dispersed nanoparticles and associated nanoparticle Brownian movements are purported to cause the enhancements by mixing mechanisms whereas aggregated...Engineering Data, 1994. 39(1): p. 186-190. 30. Einstein, A., Investigations on the theory of the brownian movement . 1915, E. P. Dutton and Company

Focal adhesion interactions with topographical structures: a novel method for immuno-SEM labelling of focal adhesions in S-phase cells.

Science.gov (United States)

Biggs, M J P; Richards, R G; Wilkinson, C D W; Dalby, M J

2008-07-01

Current understanding of the mechanisms involved in osseointegration following implantation of a biomaterial has led to adhesion quantification being implemented as an assay of cytocompatibility. Such measurement can be hindered by intra-sample variation owing to morphological changes associated with the cell cycle. Here we report on a new scanning electron microscopical method for the simultaneous immunogold labelling of cellular focal adhesions and S-phase nuclei identified by BrdU incorporation. Prior to labelling, cellular membranes are removed by tritonization and antigens of non-interest blocked by serum incubation. Adhesion plaque-associated vinculin and S-phase nuclei were both separately labelled with a 1.4 nm gold colloid and visualized by subsequent colloid enhancement via silver deposition. This study is specifically concerned with the effects microgroove topographies have on adhesion formation in S-phase osteoblasts. By combining backscattered electron (BSE) imaging with secondary electron (SE) imaging it was possible to visualize S-phase nuclei and the immunogold-labelled adhesion sites in one energy 'plane' and the underlying nanotopography in another. Osteoblast adhesion to these nanotopographies was ascertained by quantification of adhesion complex formation.

Association between penile dynamic contrast-enhanced MRI-derived quantitative parameters and self-reported sexual function in patients with newly diagnosed prostate cancer.

Science.gov (United States)

Vargas, Hebert Alberto; Donati, Olivio F; Wibmer, Andreas; Goldman, Debra A; Mulhall, John P; Sala, Evis; Hricak, Hedvig

2014-10-01

The high incidence of prostate cancer, coupled with excellent prostate cancer control rates, has resulted in growing interest in nononcological survivorship issues such as sexual function. Multiparametric magnetic resonance imaging (MRI) is increasingly being performed for local staging of prostate cancer, and due to the close anatomical relationship to the prostate, penile enhancement is often depicted in prostate MRI. To evaluate the associations between quantitative perfusion-related parameters derived from dynamic contrast-enhanced (DCE)-MRI of the penis and self-reported sexual function in patients with newly diagnosed prostate cancer. This retrospective study included 50 patients who underwent DCE-MRI for prostate cancer staging before prostatectomy. The following perfusion-related parameters were calculated: volume transfer constant (K(trans)), rate constant (k(ep)), extracellular-extravascular volume fraction (v(e)), contrast enhancement ratio (CER), area under the gadolinium curve after 180 seconds (AUC180), and slope of the time/signal intensity curve of the corpora cavernosa. Associations between perfusion-related parameters and self-reported sexual function were evaluated using the Wilcoxon Rank-Sum test. Patient responses to the sexual function domain of the Prostate Quality of Life survey. Five of the six DCE-MRI parameters (K(trans), v(e), CER, AUC180, and slope) were significantly associated with the overall score from the sexual domain of the survey (P = 0.0020-0.0252). CER, AUC180, and slope were significantly associated with the answers to all six questions (P = 0.0020-0.0483), ve was significantly associated with the answers to five of six questions (P = 0.0036-0.1029), and K(trans) was significantly associated with the answers to three of six questions (P = 0.0252-0.1023). k(ep) was not significantly associated with the overall survey score (P = 0.7665) or the answers to any individual questions (P = 0

Carbon dioxide efficiency of terrestrial enhanced weathering

OpenAIRE

Moosdorf, Nils; Renforth, Philip; Hartmann, Jens

2014-01-01

Terrestrial enhanced weathering, the spreading of ultramafic silicate rock flour to enhance natural weathering rates, has been suggested as part of a strategy to reduce global atmospheric CO2 levels. We budget potential CO2 sequestration against associated CO2 emissions to assess the net CO2 removal of terrestrial enhanced weathering. We combine global spatial data sets of potential source rocks, transport networks, and application areas with associated CO2 emissions in optimistic and pessimi...

Plasticity enhancement mechanisms in refractory metals and intermetallics

International Nuclear Information System (INIS)

Gibala, R.; Chang, H.; Czarnik, C.M.; Edwards, K.M.; Misra, A.

1993-01-01

Plasticity enhancement associated with surface films and precipitates or dispersoids in bcc refractory metals is operative in ordered intermetallic compounds. Some results are given for NiAl and MoSi 2 -based materials. The monotonic and cyclic plasticity of NiAl at room temperature can be enhanced by surface films. Ductile second phases also enhance the plasticity of NiAl. MoSi 2 exhibits similar effects of surface films and dispersoids, but primarily at elevated temperatures. The plasticity enhancement is associated with enhanced dislocation generation from constrained deformation at the film-substrate or precipitate/dispersoid-matrix interface of the composite systems

A unique method of retaining orbital prosthesis with attachment systems - a clinical report.

Science.gov (United States)

Guttal, Satyabodh S; Akash, N R; Prithviraj, D R; Lekha, K

2014-06-01

Diminution of the orbital contents post-surgical removal of a malignant tumor can have a severe psychological impact on the patient in terms of function and esthetics. Therefore, esthetic remedy should be planned subsequently, since tumor obliteration precedes cosmetic concern. A convenient option for successful rehabilitation in such patients is a simple, user-friendly, removable orbital prosthesis. Retention of the prosthesis is one of the key factors for the successful rehabilitation. Spectacle frame, conformers, adhesives, osseointegrated implants, magnets or buttons have been used to impart retention to the prosthesis. The use of semi precision attachments in maxillofacial prostheses is limited to the osseointegrated prostheses. This case report describes a conventional spectacle frame technique, to retain the silicone orbital prosthesis using two different types of stud attachments viz., dalla bona and O-ring attachment systems. Copyright © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Dreaming of a Learning Task is Associated with Enhanced Sleep-Dependent Memory Consolidation

Science.gov (United States)

Wamsley, Erin J.; Tucker, Matthew; Payne, Jessica D.; Benavides, Joseph; Stickgold, Robert

2010-01-01

Summary It is now well established that post-learning sleep is beneficial for human memory performance [1–5]. Meanwhile, human and animal studies demonstrate that learning-related neural activity is re-expressed during post-training non-rapid eye movement sleep (NREM) [6–9]. NREM sleep processes appear to be particularly beneficial for hippocampus-dependent forms of memory [1–3, 10]. These observations suggest that learning triggers the reactivation and reorganization of memory traces during sleep, a systems-level process that in turn enhances behavioral performance. Here, we hypothesized that dreaming about a learning experience during NREM sleep would be associated with improved performance on a hippocampus-dependent spatial memory task. Subjects (n=99) were trained on a virtual navigation task, and then retested on the same task 5 hours after initial training. Improved performance at retest was strongly associated with task-related dream imagery during an intervening afternoon nap. Task-related thoughts during wakefulness, in contrast, did not predict improved performance. These observations suggest that sleep-dependent memory consolidation in humans is facilitated by the offline reactivation of recently formed memories, and furthermore, that dream experiences reflect this memory processing. That similar effects were not seen during wakefulness suggests that these mnemonic processes are specific to the sleep state. PMID:20417102

Humor in Advertisements Enhances Product Liking by Mere Association

NARCIS (Netherlands)

Strick, M.A.; Baaren, R.B. van; Holland, R.W.; Knippenberg, A.F.M. van

2009-01-01

Humor in advertising is known to enhance product liking, but this attitude change is often considered nonpredictive of product choice. Previous research relied exclusively on explicit self-report measures to assess attitudes and purchase intentions. The present research shows that unobtrusive

Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function.

Science.gov (United States)

Stockburger, Carola; Miano, Davide; Pallas, Thea; Friedland, Kristina; Müller, Walter E

2016-01-01

The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4.

Science.gov (United States)

Herz, Hans-Martin; Mohan, Man; Garruss, Alexander S; Liang, Kaiwei; Takahashi, Yoh-Hei; Mickey, Kristen; Voets, Olaf; Verrijzer, C Peter; Shilatifard, Ali

2012-12-01

Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are implemented by Set1/COMPASS (complex of proteins associated with Set1), there are three classes of COMPASS-like complexes in Drosophila that could carry out H3K4me1 on enhancers: dSet1, Trithorax, and Trithorax-related (Trr). Here, we report that Trr, the Drosophila homolog of the mammalian Mll3/4 COMPASS-like complexes, can function as a major H3K4 monomethyltransferase on enhancers in vivo. Loss of Trr results in a global decrease of H3K4me1 and H3K27ac levels in various tissues. Assays with the cut wing margin enhancer implied a functional role for Trr in enhancer-mediated processes. A genome-wide analysis demonstrated that Trr is required to maintain the H3K4me1 and H3K27ac chromatin signature that resembles the histone modification patterns described for enhancers. Furthermore, studies in the mammalian system suggested a role for the Trr homolog Mll3 in similar processes. Since Trr and mammalian Mll3/4 complexes are distinguished by bearing a unique subunit, the H3K27 demethylase UTX, we propose a model in which the H3K4 monomethyltransferases Trr/Mll3/Mll4 and the H3K27 demethylase UTX cooperate to regulate the transition from inactive/poised to active enhancers.

Activating RNAs associate with Mediator to enhance chromatin architecture and transcription.

Science.gov (United States)

Lai, Fan; Orom, Ulf A; Cesaroni, Matteo; Beringer, Malte; Taatjes, Dylan J; Blobel, Gerd A; Shiekhattar, Ramin

2013-02-28

Recent advances in genomic research have revealed the existence of a large number of transcripts devoid of protein-coding potential in multiple organisms. Although the functional role for long non-coding RNAs (lncRNAs) has been best defined in epigenetic phenomena such as X-chromosome inactivation and imprinting, different classes of lncRNAs may have varied biological functions. We and others have identified a class of lncRNAs, termed ncRNA-activating (ncRNA-a), that function to activate their neighbouring genes using a cis-mediated mechanism. To define the precise mode by which such enhancer-like RNAs function, we depleted factors with known roles in transcriptional activation and assessed their role in RNA-dependent activation. Here we report that depletion of the components of the co-activator complex, Mediator, specifically and potently diminished the ncRNA-induced activation of transcription in a heterologous reporter assay using human HEK293 cells. In vivo, Mediator is recruited to ncRNA-a target genes and regulates their expression. We show that ncRNA-a interact with Mediator to regulate its chromatin localization and kinase activity towards histone H3 serine 10. The Mediator complex harbouring disease- displays diminished ability to associate with activating ncRNAs. Chromosome conformation capture confirmed the presence of DNA looping between the ncRNA-a loci and its targets. Importantly, depletion of Mediator subunits or ncRNA-a reduced the chromatin looping between the two loci. Our results identify the human Mediator complex as the transducer of activating ncRNAs and highlight the importance of Mediator and activating ncRNA association in human disease.

The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

Energy Technology Data Exchange (ETDEWEB)

Wu, Tzu-Chin [Chest Clinic, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Yi-Chin [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Chen, Hsiao-Ling [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Huang, Pei-Ru; Liu, Shang-Yu [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Yeh, Shu-Lan, E-mail: suzyyeh@csmu.edu.tw [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China)

2016-02-01

Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.

The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

International Nuclear Information System (INIS)

Wu, Tzu-Chin; Lin, Yi-Chin; Chen, Hsiao-Ling; Huang, Pei-Ru; Liu, Shang-Yu; Yeh, Shu-Lan

2016-01-01

Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.

Antibacterial ability and angiogenic activity of Cu-Ti-O nanotube arrays

International Nuclear Information System (INIS)

Zong, Mingxiang; Bai, Long; Liu, Yanlian; Wang, Xin; Zhang, Xiangyu; Huang, Xiaobo; Hang, Ruiqiang; Tang, Bin

2017-01-01

Bacterial infection and loosening of orthopedic implants remain two disastrously postoperative complications. Angiogenesis is critical important to facilitate implant osseointegration in vivo. TiO 2 nanotubes arrays (NTAs) with proper dimensions possess good osseointegration ability. Accordingly, the present work incorporated copper (Cu) into TiO 2 NTAs (Cu-Ti-O NTAs) to enhance their antibacterial ability and angiogenesis activity, which was realized through anodizing magnetron-sputtered TiCu coatings with different Cu contents on pure titanium (Ti). Our results show ordered Cu-Ti-O NTAs can be produced under proper Cu content (< 15.14%) in TiCu coatings. The NTAs possess excellent long-term antibacterial ability against Staphylococcus aureus (S. aureus), which may be ascribed to sustained release of Cu 2+ . The cytotoxicity of Cu-Ti-O NTAs to endothelial cells (ECs) could be negligible and can even promote cell proliferation as revealed by live/dead staining and MTT. Meanwhile, Cu-Ti-O NTAs can up-regulate nitric oxide (NO) synthesis and vascular endothelial growth factors (VEGF) secretion of ECs on the sample surfaces compared with that of pure TiO 2 NTAs (control). Furthermore, the angiogenic activity is also enhanced in ionic extracts of Cu-Ti-O NTAs compared with the control. The excellent long-term antibacterial ability and favorable angiogenic activity render Cu-Ti-O NTAs to be promising implant coatings. - Highlights: • Cu-Ti-O NTAs possess long-term antibacterial ability against Staphylococcus aureus. • Cu-Ti-O NTAs can up-regulate nitric oxide synthesis and vascular endothelial growth factors secretion of endothelial cells. • Cu-Ti-O NTAs can enhance in vitro angiogenesis activity of endothelial cells.

Antibacterial ability and angiogenic activity of Cu-Ti-O nanotube arrays

Energy Technology Data Exchange (ETDEWEB)

Zong, Mingxiang; Bai, Long; Liu, Yanlian; Wang, Xin; Zhang, Xiangyu; Huang, Xiaobo; Hang, Ruiqiang, E-mail: hangruiqiang@tyut.edu.cn; Tang, Bin

2017-02-01

Bacterial infection and loosening of orthopedic implants remain two disastrously postoperative complications. Angiogenesis is critical important to facilitate implant osseointegration in vivo. TiO{sub 2} nanotubes arrays (NTAs) with proper dimensions possess good osseointegration ability. Accordingly, the present work incorporated copper (Cu) into TiO{sub 2} NTAs (Cu-Ti-O NTAs) to enhance their antibacterial ability and angiogenesis activity, which was realized through anodizing magnetron-sputtered TiCu coatings with different Cu contents on pure titanium (Ti). Our results show ordered Cu-Ti-O NTAs can be produced under proper Cu content (< 15.14%) in TiCu coatings. The NTAs possess excellent long-term antibacterial ability against Staphylococcus aureus (S. aureus), which may be ascribed to sustained release of Cu{sup 2+}. The cytotoxicity of Cu-Ti-O NTAs to endothelial cells (ECs) could be negligible and can even promote cell proliferation as revealed by live/dead staining and MTT. Meanwhile, Cu-Ti-O NTAs can up-regulate nitric oxide (NO) synthesis and vascular endothelial growth factors (VEGF) secretion of ECs on the sample surfaces compared with that of pure TiO{sub 2} NTAs (control). Furthermore, the angiogenic activity is also enhanced in ionic extracts of Cu-Ti-O NTAs compared with the control. The excellent long-term antibacterial ability and favorable angiogenic activity render Cu-Ti-O NTAs to be promising implant coatings. - Highlights: • Cu-Ti-O NTAs possess long-term antibacterial ability against Staphylococcus aureus. • Cu-Ti-O NTAs can up-regulate nitric oxide synthesis and vascular endothelial growth factors secretion of endothelial cells. • Cu-Ti-O NTAs can enhance in vitro angiogenesis activity of endothelial cells.

Selective Activation of M4 Muscarinic Acetylcholine Receptors Reverses MK-801-Induced Behavioral Impairments and Enhances Associative Learning in Rodents

Science.gov (United States)

2015-01-01

Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor (mAChR) represent a novel approach for the treatment of psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. We recently reported that the selective M4 PAM VU0152100 produced an antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest that enhanced cholinergic activity may also improve cognitive function and reverse deficits observed with reduced signaling through the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) in the central nervous system. Prior to this study, the M1 mAChR subtype was viewed as the primary candidate for these actions relative to the other mAChR subtypes. Here we describe the discovery of a novel M4 PAM, VU0467154, with enhanced in vitro potency and improved pharmacokinetic properties relative to other M4 PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801. VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant-induced deficits in M4 KO mice. VU0467154 also enhanced the acquisition of both contextual and cue-mediated fear conditioning when administered alone in wild-type mice. These novel findings suggest that M4 PAMs may provide a strategy for addressing the more complex affective and cognitive disruptions associated with schizophrenia and other neuropsychiatric disorders. PMID:25137629

Humor in Advertisements Enhances Product Liking by Mere Association

NARCIS (Netherlands)

Strick, M.A.; Baaren, R.B. van; Holland, R.W.; Knippenberg, A.F.M. van

2011-01-01

This reprinted article originally appeared in the Journal of Experimental Psychology: Applied, 2009 (Mar), Vol 15(1), 35-45. (The following abstract of the original article appeared in record 2009-03685-005). Humor in advertising is known to enhance product liking, but this attitude change is often

Nanofiber scaffolds influence organelle structure and function in bone marrow stromal cells.

Science.gov (United States)

Tutak, Wojtek; Jyotsnendu, Giri; Bajcsy, Peter; Simon, Carl G

2017-07-01

Recent work demonstrates that osteoprogenitor cell culture on nanofiber scaffolds can promote differentiation. This response may be driven by changes in cell morphology caused by the three-dimensional (3D) structure of nanofibers. We hypothesized that nanofiber effects on cell behavior may be mediated by changes in organelle structure and function. To test this hypothesis, human bone marrow stromal cells (hBMSCs) were cultured on poly(ε-caprolactone) (PCL) nanofibers scaffolds and on PCL flat spuncoat films. After 1 day-culture, hBMSCs were stained for actin, nucleus, mitochondria, and peroxisomes, and then imaged using 3D confocal microscopy. Imaging revealed that the hBMSC cell body (actin) and peroxisomal volume were reduced during culture on nanofibers. In addition, the nucleus and peroxisomes occupied a larger fraction of cell volume during culture on nanofibers than on films, suggesting enhancement of the nuclear and peroxisomal functional capacity. Organelles adopted morphologies with greater 3D-character on nanofibers, where the Z-Depth (a measure of cell thickness) was increased. Comparisons of organelle positions indicated that the nucleus, mitochondria, and peroxisomes were closer to the cell center (actin) for nanofibers, suggesting that nanofiber culture induced active organelle positioning. The smaller cell volume and more centralized organelle positioning would reduce the energy cost of inter-organelle vesicular transport during culture on nanofibers. Finally, hBMSC bioassay measurements (DNA, peroxidase, bioreductive potential, lactate, and adenosine triphosphate (ATP)) indicated that peroxidase activity may be enhanced during nanofiber culture. These results demonstrate that culture of hBMSCs on nanofibers caused changes in organelle structure and positioning, which may affect organelle functional capacity and transport. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. J Biomed Mater Res Part B: Appl

Preparation of high bioactivity multilayered bone-marrow mesenchymal stem cell sheets for myocardial infarction using a 3D-dynamic system.

Science.gov (United States)

Wang, Yingwei; Zhang, Jianhua; Qin, Zixi; Fan, Zepei; Lu, Cheng; Chen, Baoxin; Zhao, Jupeng; Li, Xiaojuan; Xiao, Fei; Lin, Xi; Wu, Zheng

2018-05-01

Cell sheet techniques offer a promising future for myocardial infarction (MI) therapy; however, insufficient nutrition supply remains the major limitation in maintaining stem cell bioactivity in vitro. In order to enhance cell sheet mechanical strength and bioactivity, a decellularized porcine pericardium (DPP) scaffold was prepared by the phospholipase A2 method, and aspartic acid was used as a spacer arm to improve the vascular endothelial growth factor crosslink efficiency on the DPP scaffold. Based on this scaffold, multilayered bone marrow mesenchymal stem cell sheets were rapidly constructed, using RAD16-I peptide hydrogel as a temporary 3D scaffold, and cell sheets were cultured in either the 3D-dynamic system (DCcs) or the traditional static condition (SCcs). The multilayered structure, stem cell bioactivity, and ultrastructure of DCcs and SCcs were assessed. The DCcs exhibited lower apoptosis, lower differentiation, and an improved paracrine effect after a 48 h culture in vitro compared to the SCcs. Four groups were set to evaluate the cell sheet effect in rat MI model: sham group, MI control group, DCcs group, and SCcs group. The DCcs group improved cardiac function and decreased the infarcted area compared to the MI control group, while no significant improvements were observed in the SCcs group. Improved cell survival, angiogenesis, and Sca-1 + cell and c-kit + cell amounts were observed in the DCcs group. In conclusion, the DCcs maintained higher stem cell bioactivity by using the 3D-dynamic system to provide sufficient nutrition, and transplanting DCcs significantly improved the cardiac function and angiogenesis. This study provides an efficient method to prepare vascular endothelial growth factor covalent decellularized pericardium scaffold with aspartic acid, and a multilayered bone marrow mesenchymal stem cell (BMSC) sheet is constructed on it using a 3D-dynamic system. The dynamic nutrition supply showed a significant benefit on BMSC bioactivity

Suppressing miRNA-15a/-16 expression by interleukin-6 enhances drug-resistance in myeloma cells

Directory of Open Access Journals (Sweden)

Chang Hong

2011-09-01

Full Text Available Abstract The bone marrow microenvironment facilitates the survival, differentiation, and proliferation of myeloma (MM cells. This study identified that microRNA-15a and -16 expressions tightly correlated with proliferation and drug sensitivity of MM cells. miRNA-15a/-16 expression in MM cells was significantly increased after treatment with cytotoxic agents. The interaction of bone marrow stromal cells (BMSC with MM cells resulted in decreased miRNA-15a/-16 expression and promoted the survival of the MM cells. Interleukin-6 (IL-6 produced by BMSCs suppressed the expression of miRNA-15a and 16 in a time- and dose- dependent pattern, with the suppression on miRNA-15a being more significant than on miRNA-16. miRNA-15a-transfected MM cells were found to be arrested in G1/S checkpoint, and the transfected MM cells had decreased growth and survival. In conclusion, our data suggest that via suppressing miRNA-15a and -16 expressions, IL-6 secreted by BMSCs promotes drug-resistance in myeloma cells.

Effects of gold coating on experimental implant fixation

DEFF Research Database (Denmark)

Zainali, Kasra; Danscher, Gorm; Jakobsen, Thomas

2009-01-01

Insertions of orthopedic implants are traumatic procedures that trigger an inflammatory response. Macrophages have been shown to liberate gold ions from metallic gold. Gold ions are known to act in an antiinflammatory manner by inhibiting cellular NF-kappa B-DNA binding and suppressing I-kappa B......-kinase activation. The present study investigated whether gilding implant Surfaces augmented early implant osseointegration and implant fixation by its modulatory effect on the local inflammatory response. Ion release was traced by autometallographic silver enhancement. Gold-coated cylindrical porous coated Ti6Al4V...

Dual Action of Lysophosphatidate-Functionalised Titanium: Interactions with Human (MG63) Osteoblasts and Methicillin Resistant Staphylococcus aureus

DEFF Research Database (Denmark)

Skindersø, Mette Elena; Krogfelt, Karen Angeliki; Blom, Ashley

2015-01-01

Titanium (Ti) is a widely used material for surgical implants; total joint replacements (TJRs), screws and plates for fixing bones and dental implants are forged from Ti. Whilst Ti integrates well into host tissue approximately 10% of TJRs will fail in the lifetime of the patient through a process...... known as aseptic loosening. These failures necessitate revision arthroplasties which are more complicated and costly than the initial procedure. Finding ways of enhancing early (osseo)integration of TJRs is therefore highly desirable and continues to represent a research priority in current biomaterial...

Shared Reproductive State Enhances Female Associations in Dolphins

International Nuclear Information System (INIS)

Moller, L.M.; Harcourt, R.G.

2007-01-01

Female bottle nose dolphins (genus Tursiops) usually associate at moderate level with other females within social clusters called bands or cliques. It has been suggested that reproductive state may play the predominant role in determining associations within female T. truncatus bands. Here, we test the hypothesis that reproductive state correlates with associations of female Indo-Pacific bottle nose dolphins (T. aduncus). We found that females in similar reproductive state, which included females from late pregnancy to the first year of their calves' life or females from early pregnancy to their calves' newborn period, had higher-association coefficients with each other than they did with females in different reproductive states (females with older calves or without calves). This was observed both within and across social clusters suggesting that reproductive state, at least for pregnant females and those with young calves, plays an important role in determining who to associate with. However, a female's most frequent associate was not always with another in similar reproductive state. We suggest that several factors, including reproductive state, may be of importance in determining associations of female bottle nose dolphins

Shared Reproductive State Enhances Female Associations in Dolphins

Directory of Open Access Journals (Sweden)

Luciana M. Möller

2008-01-01

Full Text Available Female bottlenose dolphins (genus Tursiops usually associate at moderate level with other females within social clusters called bands or cliques. It has been suggested that reproductive state may play the predominant role in determining associations within female T. truncatus bands. Here, we test the hypothesis that reproductive state correlates with associations of female Indo-Pacific bottlenose dolphins (T. aduncus. We found that females in similar reproductive state, which included females from late pregnancy to the first year of their calves' life or females from early pregnancy to their calves' newborn period, had higher-association coefficients with each other than they did with females in different reproductive states (females with older calves or without calves. This was observed both within and across social clusters suggesting that reproductive state, at least for pregnant females and those with young calves, plays an important role in determining who to associate with. However, a female's most frequent associate was not always with another in similar reproductive state. We suggest that several factors, including reproductive state, may be of importance in determining associations of female bottlenose dolphins.

ULF waves associated with enhanced subauroral proton precipitation

Science.gov (United States)

Immel, Thomas J.; Mende, S. B.; Frey, H. U.; Patel, J.; Bonnell, J. W.; Engebretson, M. J.; Fuselier, S. A.

Several types of sub-auroral proton precipitation events have been identified using the Spectrographic Imager (SI) onboard the NASA-IMAGE satellite, including dayside subauroral proton flashes and detached proton arcs in the dusk sector. These have been observed at various levels of geomagnetic activity and solar wind conditions and the mechanism driving the precipitation has often been assumed to be scattering of protons into the loss cone by enhancement of ion-cyclotron waves in the interaction of the thermal plasmaspheric populations and more energetic ring current particles. Indeed, recent investigation of the detached arcs using the MPA instruments aboard the LANL geosynchronous satellites has shown there are nearly always heightened densities of cold plasma on high-altitude field lines which map down directly to the sub-auroral precipitation. If the ion-cyclotron instability is a causative mechanism, the enhancement of wave activity at ion-cyclotron frequencies should be measurable. It is here reported that magnetic pulsations in the Pc1 range occur in the vicinity of each of 4 detached arcs observed in 2000-2002, though with widely varying signatures. Additionally, longer period pulsations in the Pc5 ranges are also observed in the vicinity of the arcs, leading to the conclusion that a bounce-resonance of ring-current protons with the azimuthal Pc5 wave structure may also contribute to the detached precipitation.

Enhanced Store-Operated Calcium Entry in Platelets is Associated with Peripheral Artery Disease in Type 2 Diabetes

Directory of Open Access Journals (Sweden)

Weijie Xia

2015-11-01

Full Text Available Background/Aims: Platelet dysfunction plays an important role in thrombosis in diabetes with peripheral artery disease (PAD. Store-operated calcium entry (SOCE and stromal interaction molecule 1 (STIM1 regulate platelet activity by modulating calcium influx. We hypothesized that enhanced SOCE in platelets is associated with diabetes with PAD. Methods: We studied the activity of platelets from healthy participants and from type 2 diabetic patients. Platelet calcium influx and protein expression of STIM1 and sarcoendoplasmic reticulum Ca2+-ATPase 3 (SERCA3 were investigated. Results: Compared with platelets from diabetic patients without PAD, platelets from diabetic patients with PAD exhibited significantly increased SOCE . Menthol administration completely inhibited calcium influx in platelets from diabetic patients without PAD, but this effect was blunted in those from diabetic patients with PAD. Furthermore, the increase in SOCE was correlated with the ankle brachial index (ABI in diabetic patients. High glucose significantly up-regulated STIM1 and SERCA3 protein expression and induced the phosphorylation of phospholipase C (PLC in platelets from healthy participants. This effect was attenuated in the presence of menthol or U73122, an inhibitor of PLC. Similarly, significant increases in STIM1 and SERCA3 protein expression were found in platelets from diabetic patients compared to those from healthy participants. Conclusion: Platelets from diabetic patients with PAD exhibited enhanced Store-operated calcium influx, which was associated with elevated STIM1/SERCA3 expression via a PLC-dependent pathway and was inhibited by menthol.

Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells

OpenAIRE

Baghdadi, Muhammad; Wada, Haruka; Nakanishi, Sayaka; Abe, Hirotake; Han, Nanumi; Putra, Wira Eka; Endo, Daisuke; Watari, Hidemichi; Sakuragi, Noriaki; Hida, Yasuhiro; Kaga, Kichizo; Miyagi, Yohei; Yokose, Tomoyuki; Takano, Atsushi; Daigo, Yataro

2016-01-01

The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance lo...

Reducing macrophages to improve bone marrow stromal cell survival in the contused spinal cord.

NARCIS (Netherlands)

Ritfeld, G.J.; Nandoe Tewarie, R.D.S.; Rahiem, S.T.; Hurtado, A.; Roos, R.A.; Grotenhuis, A.; Oudega, M.

2010-01-01

We tested whether reducing macrophage infiltration would improve the survival of allogeneic bone marrow stromal cells (BMSC) transplanted in the contused adult rat thoracic spinal cord. Treatment with cyclosporine, minocycline, or methylprednisolone all resulted in a significant decrease in

Enhanced resolution of eosinophilic liver abscess associated with toxocariasis by albendazole treatment.

Science.gov (United States)

Jang, Eun Young; Choi, Moon Seok; Gwak, Geum Youn; Koh, Kwang Cheol; Paik, Seung Woon; Lee, Joon Hyeok; Paik, Yong Han; Yoo, Byung Chul

2015-04-01

Visceral larva migrans, caused by Toxocara canis and Toxocara cati, has emerged as a significant cause of eosinophilic liver abscess (ELA). Differentiation of ELA associated with toxocariasis (ELA-T) from metastasis or primary liver malignancy is sometimes difficult. However, the role of albendazole treatment remains uncertain in this condition. The aim of this study was to evaluate whether albendazole can enhance the radiologic resolution of ELA-T. We retrospectively reviewed the medical records of the patients diagnosed with ELA-T at our institution between January 2008 and December 2011. ELA-T was diagnosed based on the imaging findings on computed tomography or magnetic resonance imaging and the presence of positive serum IgG antibody for Toxocara canis. Among a total of 163 patients, 32 patients received albendazole (albendazole group) and 131 did not (control group). Baseline characteristics and fate of liver nodules were compared between the two groups. Baseline characteristics (age, sex, number and maximal size of lesions, eosinophil count) were similar between the two groups. Median duration for achieving radiologic resolution in the albendazole group was significantly shorter than in the control group (207 days [range 186-228] vs. 302 days [range 224-380], p=0.023). In Cox regression analysis of the cumulative rates of radiologic resolution, the hazard ratio for albendazole treatment was 1.99 (95% confidence interval, 1.22-3.23). Radiologic resolution of ELA-T can be accelerated with albendazole treatment. Hence, inconvenience associated with long-term follow-up and unnecessary worries among patients can be eliminated with albendazole treatment.

Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function

Directory of Open Access Journals (Sweden)

Carola Stockburger

2016-01-01

Full Text Available The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer’s disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

High strength, surface porous polyether-ether-ketone for load-bearing orthopaedic implants

Science.gov (United States)

Evans, Nathan T.; Torstrick, F. Brennan; Lee, Christopher S.D.; Dupont, Kenneth M.; Safranski, David L.; Chang, W. Allen; Macedo, Annie E.; Lin, Angela; Boothby, Jennifer M.; Whittingslow, Daniel C.; Carson, Robert A.; Guldberg, Robert E.; Gall, Ken

2015-01-01

Despite its widespread clinical use in load-bearing orthopaedic implants, polyether-ether-ketone (PEEK) is often associated with poor osseointegration. In this study, a surface porous PEEK material (PEEK-SP) was created using a melt extrusion technique. The porous layer thickness was 399.6±63.3 µm and possessed a mean pore size of 279.9±31.6 µm, strut spacing of 186.8±55.5 µm, porosity of 67.3±3.1%, and interconnectivity of 99.9±0.1%. Monotonic tensile tests showed that PEEK-SP preserved 73.9% of the strength (71.06±2.17 MPa) and 73.4% of the elastic modulus (2.45±0.31 GPa) of as-received, injection molded PEEK. PEEK-SP further demonstrated a fatigue strength of 60.0 MPa at one million cycles, preserving 73.4% of the fatigue resistance of injection molded PEEK. Interfacial shear testing showed the pore layer shear strength to be 23.96±2.26 MPa. An osseointegration model in the rat revealed substantial bone formation within the pore layer at 6 and 12 weeks via µCT and histological evaluation. Ingrown bone was more closely apposed to the pore wall and fibrous tissue growth was reduced in PEEK-SP when compared to non-porous PEEK controls. These results indicate that PEEK-SP could provide improved osseointegration while maintaining the structural integrity necessary for load-bearing orthopaedic applications. PMID:25463499

Mineralization of LCFA associated with anaerobic sludge: Kinetics, enhancement of methanogenic activity, and effect of VFA.

Science.gov (United States)

Pereira, M A; Sousa, D Z; Mota, M; Alves, M M

2004-11-20

Long-chain fatty acids (LCFA) associated with anaerobic sludge by mechanisms of precipitation, adsorption, or entrapment can be biodegraded to methane. The mineralization kinetics of biomass-associated LCFA were established according to an inhibition model based on Haldane's enzymatic inhibition kinetics. A value around 1,000 mg COD-LCFA..g VSS(-1) was obtained for the optimal specific LCFA content that allowed the maximal mineralization rate. For sludge with specific LCFA contents of 2,838 +/- 63 and 4,571 +/- 257 mg COD-LCFA..g VSS(-1), the specific methanogenic activities in the presence of acetate, butyrate, and H(2)/CO(2) were significantly enhanced after the mineralization of the biomass-associated LCFA. For sludge with a specific LCFA content near the optimal value defined by the kinetic model, the effect of adding VFA to the medium was studied during the mineralization of the biomass-associated LCFA. Different patterns were obtained for each individual substrate. Acetate and butyrate were preferentially consumed by the consortium, but in the case of propionate no evidence of a sequential consumption pattern could be withdrawn. It was concluded that LCFA do not exert a bactericidal neither a permanent toxic effect toward the anaerobic consortia. A discussion is addressed to the relative roles of a reversible inhibitory effect and a transport limitation effect imposed by the LCFA surrounding the cells. (c) 2004 Wiley Periodicals, Inc

Regulation of the neuropathy-associated Pmp22 gene by a distal super-enhancer.

Science.gov (United States)

Pantera, Harrison; Moran, John J; Hung, Holly A; Pak, Evgenia; Dutra, Amalia; Svaren, John

2018-05-16

Peripheral nerve myelination is adversely affected in the most common form of the hereditary peripheral neuropathy called Charcot-Marie-Tooth Disease. This form, classified as CMT1A, is caused by a 1.4 Mb duplication on chromosome 17, which includes the abundantly expressed Schwann cell myelin gene, Peripheral Myelin Protein 22 (PMP22). This is one of the most common copy number variants causing neurological disease. Overexpression of Pmp22 in rodent models recapitulates several aspects of neuropathy, and reduction of Pmp22 in such models results in amelioration of the neuropathy phenotype. Recently we identified a potential super-enhancer approximately 90-130 kb upstream of the Pmp22 transcription start sites. This super-enhancer encompasses a cluster of individual enhancers that have the acetylated histone H3K27 active enhancer mark, and coincides with smaller duplications identified in patients with milder CMT1A-like symptoms, where the PMP22 coding region itself was not part of the duplication. In this study, we have utilized genome editing to create a deletion of this super-enhancer to determine its role in Pmp22 regulation. Our data show a significant decrease in Pmp22 transcript expression using allele-specific internal controls. Moreover, the P2 promoter of the Pmp22 gene, which is used in other cell types, is affected, but we find that the Schwann cell-specific P1 promoter is disproportionately more sensitive to loss of the super-enhancer. These data show for the first time the requirement of these upstream enhancers for full Pmp22 expression.

Conservative surgical and microsurgical techniques for the management of dental implants that impinge on the inferior alveolar nerve.

Science.gov (United States)

Gennaro, Paolo; Chisci, Glauco; Gabriele, Guido; Iannetti, Giorgio

2014-07-01

Loss of sensation in the lip after insertion of an implant is annoying. The aim of this paper was to describe two techniques for management of osseointegrated dental implants that impinge on the mandibular nerve, the purpose of which is to improve sensation without unscrewing the dental implant. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Periodontal ligament influence on the stress distribution in a removable partial denture supported by implant: a finite element analysis

Directory of Open Access Journals (Sweden)

Carlos Marcelo Archangelo

2012-06-01

Full Text Available OBJECTIVES: The non-homogenous aspect of periodontal ligament (PDL has been examined using finite element analysis (FEA to better simulate PDL behavior. The aim of this study was to assess, by 2-D FEA, the influence of non-homogenous PDL on the stress distribution when the free-end saddle removable partial denture (RPD is partially supported by an osseointegrated implant. MATERIAL AND METHODS: Six finite element (FE models of a partially edentulous mandible were created to represent two types of PDL (non-homogenous and homogenous and two types of RPD (conventional RPD, supported by tooth and fibromucosa; and modified RPD, supported by tooth and implant [10.00x3.75 mm]. Two additional Fe models without RPD were used as control models. The non-homogenous PDL was modeled using beam elements to simulate the crest, horizontal, oblique and apical fibers. The load (50 N was applied in each cusp simultaneously. Regarding boundary conditions the border of alveolar ridge was fixed along the x axis. The FE software (Ansys 10.0 was used to compute the stress fields, and the von Mises stress criterion (svM was applied to analyze the results. RESULTS: The peak of svM in non-homogenous PDL was higher than that for the homogenous condition. The benefits of implants were enhanced for the non-homogenous PDL condition, with drastic svM reduction on the posterior half of the alveolar ridge. The implant did not reduce the stress on the support tooth for both PDL conditions. Conclusion: The PDL modeled in the non-homogeneous form increased the benefits of the osseointegrated implant in comparison with the homogeneous condition. Using the non-homogenous PDL, the presence of osseointegrated implant did not reduce the stress on the supporting tooth.

Enhancer-binding proteins with a forkhead-associated domain and the sigma(54) regulon in Myxococcus xanthus fruiting body development

DEFF Research Database (Denmark)

Jelsbak, Lars; Givskov, Michael Christian; Kaiser, D.

2005-01-01

-binding proteins. Here we report the finding of an unusual group of 12 genes encoding sigma(54)-dependent enhancer-binding proteins containing a forkhead-associated (FHA) domain as their N-terminal sensory domain. FHA domains in other proteins recognize phosphothreonine residues. An insertion mutation in one...... donor cell. Because FHA domains respond to phosphothreonine-containing proteins, these results suggest a regulatory link to the abundant Ser/Thr protein kinases in M. xanthus....

The proteomic dataset for bone marrow derived human mesenchymal stromal cells: Effect of in vitro passaging

Directory of Open Access Journals (Sweden)

Samuel T. Mindaye

2015-12-01

Full Text Available Bone-marrow derived mesenchymal stromal cells (BMSCs have been in clinical trials for therapy. One major bottleneck in the advancement of BMSC-based products is the challenge associated with cell isolation, characterization, and ensuring cell fitness over the course of in vitro cell propagation steps. The data in this report is part of publications that explored the proteomic changes following in vitro passaging of BMSCs [4] and the molecular heterogeneity in cultures obtained from different human donors [5,6].The methodological details involving cell manufacturing, proteome harvesting, protein identification and quantification as well as the bioinformatic analyses were described to ensure reproducibility of the results.

Cooperation between the Russian Federation and the United States to enhance the existing nuclear-material protection, control, and accounting systems at Mayak Production Association

International Nuclear Information System (INIS)

Starodubtsev, G.S.; Prishchepov, A.I.; Zatorsky, Y.M.; James, L.T.

1997-01-01

The Ministry of the Russian Federation for Atomic Energy (MINATOM) and the US Department of Energy (DOE) are engaged in joint, cooperative efforts to reduce the likelihood of nuclear proliferation by enhancing Material Protection, Control and Accounting (MPC ampersand A) systems in both countries. Mayak Production Association (MPA) is a major Russian nuclear enterprise within the nuclear complex that is operated by MINATOM. This paper describes the nature, scope, and status of the joint, cooperative efforts to enhance existing MPC ampersand A systems at MPA. Current cooperative efforts are focused on enhancements to the existing MPC ampersand A systems at four plants that are operated by MPA and that produce, process, handle and/or store proliferation-sensitive nuclear materials

Cooperation Between the Russian Federation and the United States to Enhance the Existing Nuclear-Material Protection, Control, and Accounting Systems at Mayak Production Association

International Nuclear Information System (INIS)

Cahalane, P.T.; Ehinger, M.H.; James, L.T.; Jarrett, J.H.; Lundgren, R.A.; Manatt, D.R.; Niederauer, G.F.; Olivos, J.D.; Prishchepov, A.I.; Starodubtsev, G.S.; Suda, S.C.; Tittemore, G.W.; Zatorsky, Y.M.

1999-01-01

The Ministry of the Russian Federation for Atomic Energy (MINATOM) and the US Department of Energy (DOE) are engaged in joint, cooperative efforts to reduce the likelihood of nuclear proliferation by enhancing Material Protection, Control and Accounting (MPC and A) systems in both countries. Mayak Production Association (Mayak) is a major Russian nuclear enterprise within the nuclear complex that is operated by lylINATOM. This paper describes the nature, scope, and status of the joint, cooperative efforts to enhance existing MPC and A systems at Mayak. Current cooperative efforts are focused on enhancements to the existing MPC and A systems at two of the plants operated by Mayak that work with proliferation-sensitive nuclear materials

Cooperation between the Russian Federation and the United States to enhance the existing nuclear-material protection, control, and accounting systems at Mayak Production Association

Energy Technology Data Exchange (ETDEWEB)

Starodubtsev, G.S.; Prishchepov, A.I.; Zatorsky, Y.M.; James, L.T. [and others

1997-11-01

The Ministry of the Russian Federation for Atomic Energy (MINATOM) and the US Department of Energy (DOE) are engaged in joint, cooperative efforts to reduce the likelihood of nuclear proliferation by enhancing Material Protection, Control and Accounting (MPC&A) systems in both countries. Mayak Production Association (MPA) is a major Russian nuclear enterprise within the nuclear complex that is operated by MINATOM. This paper describes the nature, scope, and status of the joint, cooperative efforts to enhance existing MPC&A systems at MPA. Current cooperative efforts are focused on enhancements to the existing MPC&A systems at four plants that are operated by MPA and that produce, process, handle and/or store proliferation-sensitive nuclear materials.

Biomimetic bonelike composites and novel bioactive glasscoatings

Energy Technology Data Exchange (ETDEWEB)

Tomsia, A.P.; Saiz, E.; Song, J.; Bertozzi, C.R.

2005-06-01

Metallic orthopaedic implants have been successfully used for decades but they have serious shortcomings related to their osseointegration and the fact that their mechanical properties do not match those of bone. This paper reviews recent advances in the fabrication of novel coatings to improve implant osseointegration and in the development of a new generation of hybrid organic-inorganic implant materials specifically designed for orthopaedic applications.

Associations between the Big Five Personality Traits and the Non-Medical Use of Prescription Drugs for Cognitive Enhancement

Directory of Open Access Journals (Sweden)

Sebastian eSattler

2016-01-01

Full Text Available While the number of studies of the non-medical use of prescription drugs to augment cognitive functions is growing steadily, psychological factors that can potentially help explain variance in such pharmaceutical cognitive enhancement (CE behavior are often neglected in research.This study investigates the association between the Big Five personality traits and a retrospective (prior CE-drug use as well as a prospective (willingness to use CE drugs measure of taking prescription drugs with the purpose of augmenting one’s cognitive functions (e.g. concentration, memory, or vigilance without medical necessity. We use data from a large representative survey of German employees (N= 6,454, response rate= 29.8%. The Five Factor Model (FFM of Personality was measured with a short version of the Big Five Personality Traits Inventory (BFI-S, which includes: openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism. Together with this, demographic variables such as gender, age, education, and income were used as potential confounders in multiple logistic regression models. Our results show a 2.96% lifetime prevalence of CE-drug use and a 10.45% willingness to (reuse such drugs in the future. We found that less conscientious and more neurotic respondents have a higher probability of prior CE-drug use and a greater willingness to use CE drugs in the future. No significant effects were found for openness, extraversion, or agreeableness. Prior CE-drug use was strongly associated with a greater willingness to take such drugs in the future.This study shows that specific personality traits are not only associated with prior enhancement behavior, but also affect the willingness to (reuse such drugs. It helps increase understanding of the risk factors of CE-drug use, which is a health-related behavior that can entail severe side-effects for consumers. The knowledge gathered can thus help improve interventions aimed at minimizing

Associations Between the Big Five Personality Traits and the Non-Medical Use of Prescription Drugs for Cognitive Enhancement.

Science.gov (United States)

Sattler, Sebastian; Schunck, Reinhard

2015-01-01

While the number of studies of the non-medical use of prescription drugs to augment cognitive functions is growing steadily, psychological factors that can potentially help explain variance in such pharmaceutical cognitive enhancement (CE) behavior are often neglected in research. This study investigates the association between the Big Five personality traits and a retrospective (prior CE-drug use) as well as a prospective (willingness to use CE drugs) measure of taking prescription drugs with the purpose of augmenting one's cognitive functions (e.g., concentration, memory, or vigilance) without medical necessity. We use data from a large representative survey of German employees (N = 6454, response rate = 29.8%). The Five Factor Model (FFM) of Personality was measured with a short version of the Big Five Personality Traits Inventory (BFI-S), which includes: openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism. Together with this, demographic variables such as gender, age, education, and income were used as potential confounders in multiple logistic regression models. Our results show a 2.96% lifetime prevalence of CE-drug use and a 10.45% willingness to (re)use such drugs in the future. We found that less conscientious and more neurotic respondents have a higher probability of prior CE-drug use and a greater willingness to use CE drugs in the future. No significant effects were found for openness, extraversion, or agreeableness. Prior CE-drug use was strongly associated with a greater willingness to take such drugs in the future. This study shows that specific personality traits are not only associated with prior enhancement behavior, but also affect the willingness to (re)use such drugs. It helps increase understanding of the risk factors of CE-drug use, which is a health-related behavior that can entail severe side-effects for consumers. The knowledge gathered can thus help improve interventions aimed at minimizing health

Diagnostic Utility of Contrast-enhanced 3D T1-weighted Imaging in Acute Cerebral Infarction Associated with Graves Disease.

Science.gov (United States)

Gon, Yasufumi; Sakaguchi, Manabu; Oyama, Naoki; Mochizuki, Hideki

2017-02-01

Graves disease is rarely complicated with cerebrovascular steno-occlusive diseases. Previous studies have suggested several hypotheses for this occurrence, including excess thyroid hormone, which stimulates the sympathetic nervous system, which in turn causes an abnormal hemodynamic response with consequent atherosclerotic changes, and antithyroid antibodies cause local vascular inflammation in patients with Graves disease. However, radiological findings of vasculitis in patients with Graves disease and cerebral infarction remain less known. We report the case of a 30-year-old Japanese woman with acute cerebral infarction due to vasculitis associated with Graves disease. She was admitted to our hospital with a 4-day history of intermittent transient dysarthria and limb shaking of the left leg when standing. Three weeks before admission, she went to a local hospital because of general malaise and was diagnosed with Graves disease. Neurological examination revealed paralytic dysarthria, left central facial nerve palsy, and left hemiparesis (manual muscle testing, 4 of 5). Blood examinations showed hyperthyroidism (thyroid-stimulating hormone ≤.010 µU/mL; free T3 ≥25.0 pg/mL; free T4 ≥8.0 ng/dL) and elevation of antithyroid antibody levels (thyroid peroxidase antibody, 87 IU/mL). The vessel wall of the right internal carotid artery was markedly enhanced on contrast-enhanced three-dimensional T1-weighted magnetic resonance imaging, suggesting vasculitis. Magnetic resonance angiography revealed right internal carotid artery occlusion after the branching ophthalmic artery. Arterial stenosis due to vasculitis was considered the cause of hemodynamic ischemic stroke. Vessel wall imaging such as high-resolution contrast-enhanced T1-weighted imaging seems useful for assessing the underlying mechanism of stroke in patients with Graves disease. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Overexpression of wheat ferritin gene TaFER-5B enhances tolerance to heat stress and other abiotic stresses associated with the ROS scavenging.

Science.gov (United States)

Zang, Xinshan; Geng, Xiaoli; Wang, Fei; Liu, Zhenshan; Zhang, Liyuan; Zhao, Yue; Tian, Xuejun; Ni, Zhongfu; Yao, Yingyin; Xin, Mingming; Hu, Zhaorong; Sun, Qixin; Peng, Huiru

2017-01-14

The yield of wheat (Triticum aestivum L.), an important crop, is adversely affected by heat stress in many regions of the world. However, the molecular mechanisms underlying thermotolerance are largely unknown. A novel ferritin gene, TaFER, was identified from our previous heat stress-responsive transcriptome analysis of a heat-tolerant wheat cultivar (TAM107). TaFER was mapped to chromosome 5B and named TaFER-5B. Expression pattern analysis revealed that TaFER-5B was induced by heat, polyethylene glycol (PEG), H 2 O 2 and Fe-ethylenediaminedi(o-hydroxyphenylacetic) acid (Fe-EDDHA). To confirm the function of TaFER-5B in wheat, TaFER-5B was transformed into the wheat cultivar Jimai5265 (JM5265), and the transgenic plants exhibited enhanced thermotolerance. To examine whether the function of ferritin from mono- and dico-species is conserved, TaFER-5B was transformed into Arabidopsis, and overexpression of TaFER-5B functionally complemented the heat stress-sensitive phenotype of a ferritin-lacking mutant of Arabidopsis. Moreover, TaFER-5B is essential for protecting cells against heat stress associated with protecting cells against ROS. In addition, TaFER-5B overexpression also enhanced drought, oxidative and excess iron stress tolerance associated with the ROS scavenging. Finally, TaFER-5B transgenic Arabidopsis and wheat plants exhibited improved leaf iron content. Our results suggest that TaFER-5B plays an important role in enhancing tolerance to heat stress and other abiotic stresses associated with the ROS scavenging.

Porous tantalum coatings prepared by vacuum plasma spraying enhance bmscs osteogenic differentiation and bone regeneration in vitro and in vivo.

Directory of Open Access Journals (Sweden)

Ze Tang

Full Text Available Tantalum, as a potential metallic implant biomaterial, is attracting more and more attention because of its excellent anticorrosion and biocompatibility. However, its significantly high elastic modulus and large mechanical incompatibility with bone tissue make it unsuitable for load-bearing implants. In this study, porous tantalum coatings were first successfully fabricated on titanium substrates by vacuum plasma spraying (VPS, which would exert the excellent biocompatibility of tantalum and alleviate the elastic modulus of tantalum for bone tissue. We evaluated cytocompatibility and osteogenesis activity of the porous tantalum coatings using human bone marrow stromal cells (hBMSCs and its ability to repair rabbit femur bone defects. The morphology and actin cytoskeletons of hBMSCs were observed via electron microscopy and confocal, and the cell viability, proliferation and osteogenic differentiation potential of hBMSCs were examined quantitatively by PrestoBlue assay, Ki67 immunofluorescence assay, real-time PCR technology and ALP staining. For in vivo detection, the repaired femur were evaluated by histomorphology and double fluorescence labeling 3 months postoperation. Porous tantalum coating surfaces promoted hBMSCs adhesion, proliferation, osteogenesis activity and had better osseointegration and faster new bone formation rate than titanium coating control. Our observation suggested that the porous tantalum coatings had good biocompatibility and could enhance osseoinductivity in vitro and promote new bone formation in vivo. The porous tantalum coatings prepared by VPS is a promising strategy for bone regeneration.

Plant growth enhancement and associated physiological responses are coregulated by ethylene and gibberellin in response to harpin protein Hpa1.

Science.gov (United States)

Li, Xiaojie; Han, Bing; Xu, Manyu; Han, Liping; Zhao, Yanying; Liu, Zhilan; Dong, Hansong; Zhang, Chunling

2014-04-01

The harpin protein Hpa1 produced by the bacterial blight pathogen of rice induces several growth-promoting responses in plants, activating the ethylene signaling pathway, increasing photosynthesis rates and EXPANSIN (EXP) gene expression levels, and thereby enhancing the vegetative growth. This study was attempted to analyze any mechanistic connections among the above and the role of gibberellin in these responses. Hpa1-induced growth enhancement was evaluated in Arabidopsis, tomato, and rice. And growth-promoting responses were determined mainly as an increase of chlorophyll a/b ratio, which indicates a potential elevation of photosynthesis rates, and enhancements of photosynthesis and EXP expression in the three plant species. In Arabidopsis, Hpa1-induced growth-promoting responses were partially compromised by a defect in ethylene perception or gibberellin biosynthesis. In tomato and rice, compromises of Hpa1-induced growth-promoting responses were caused by a pharmacological treatment with an ethylene perception inhibitor or a gibberellin biosynthesis inhibitor. In the three plant species, moreover, Hpa1-induced growth-promoting responses were significantly impaired, but not totally eliminated, by abolishing ethylene perception or gibberellin synthesis. However, simultaneous nullifications in both ethylene perception and gibberellin biosynthesis almost canceled the full effects of Hpa1 on plant growth, photosynthesis, and EXP2 expression. Theses results suggest that ethylene and gibberellin coregulate Hpa1-induced plant growth enhancement and associated physiological and molecular responses.

Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Promote Tumor Growth Through Hedgehog Signaling Pathway

Directory of Open Access Journals (Sweden)

Jin Qi

2017-08-01

Full Text Available Background/Aims: Mesenchymal stem/stromal cells (MSCs are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. Methods: MSCs derived from human bone marrow (hBMSCs were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation. Osteosarcoma (MG63 and gastric cancer (SGC7901 cells, respectively, were treated with hBMSC-derived exosomes in the presence or absence of a small molecule inhibitor of Hedgehog pathway. Cell viability was measured by transwell invasion assay, scratch migration assay and CCK-8 test. The expression of the signaling molecules Smoothened, Patched-1, Gli1 and the ligand Shh were tested by western blot and RT-PCR. Results: In this study, we found that hBMSC-derived exosomes promoted MG63 and SGC7901 cell growth through the activation of Hedgehog signaling pathway. Inhibition of Hedgehog signaling pathway significantly suppressed the process of hBMSC-derived exosomes on tumor growth. Conclusion: Our findings demonstrated the new roles of hedgehog signaling pathway in the hBMSCs-derived exosomes induced tumor progression.

Low level light promotes the proliferation and differentiation of bone marrow derived mesenchymal stem cells

Science.gov (United States)

Ahn, Jin-Chul; Rhee, Yun-Hee; Choi, Sun-Hyang; Kim, Dae Yu; Chung, Phil-Sang

2015-03-01

Low-level light irradiation (LLLI) reported to stimulate the proliferation or differentiation of a variety of cell types. However, very little is known about the effect of light therapy on stem cells. The aim of the present study was to evaluate the effect of LLLI on the molecular physiological change of human bone marrow derived stem cells (hBMSC) by wavelength (470, 630, 660, 740 and 850, 50mW). The laser diode was performed with different time interval (0, 7.5, 15, 30J/cm2, 50mW) on hBMSC. To determine the molecular physiological changes of cellular level of hBMSC, the clonogenic assay, ATP assay, reactive oxygen species (ROS) detection, mitochondria membrane potential (MMPΦ) staining and calcium efflux assay were assessed after irradiation. There was a difference between with and without irradiation on hBMSCs. An energy density up to 30 J/cm² improved the cell proliferation in comparison to the control group. Among these irradiated group, 630 and 660nm were significantly increased the cell proliferation. The cellular level of ATP and calcium influx was increased with energy dose-dependent in all LLLI groups. Meanwhile, ROS and MMPΦ were also increased after irradiation except 470nm. It can be concluded that LLLI using infrared light and an energy density up to 30 J/cm² has a positive stimulatory effect on the proliferation or differentiation of hBMSCs. Our results suggest that LLLI may influence to the mitochondrial membrane potential activity through ATP synthesis and increased cell metabolism which leads to cell proliferation and differentiation.

Enhancement pattern of small hepatocellular carcinoma (HCC) at contrast-enhanced US (CEUS), MDCT, and MRI: Intermodality agreement and comparison of diagnostic sensitivity between 2005 and 2010 American Association for the Study of Liver Diseases (AASLD) guidelines

International Nuclear Information System (INIS)

Furlan, Alessandro; Marin, Daniele; Cabassa, Paolo; Taibbi, Adele; Brunelli, Elena; Agnello, Francesco; Lagalla, Roberto; Brancatelli, Giuseppe

2012-01-01

Objective: To evaluate agreement between contrast-enhanced ultrasound (CEUS), multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI) for the assessment of typical and atypical enhancement patterns of small hepatocellular carcinoma (HCC); and to compare diagnostic sensitivity of 2005 and 2010 American Association for the Study of Liver Diseases (AASLD) guidelines. Materials and methods: Between January 2008 and December 2009, we included cirrhotic patients with newly diagnosed 10–20 mm HCC imaged at two contrast-enhanced imaging techniques among CEUS, MDCT, and MRI. Dynamic studies were reviewed by two radiologists to assess enhancement pattern. Percentage of cases with concordant findings and Cohen coefficient (k) were calculated. McNemar's test was used to compare sensitivity between 2005 and 2010 AASLD guidelines. Results: There were 91 patients (69 M; 22 F; mean age, 68 years) with 96 HCCs, studied with a combination of CEUS and MDCT (n = 59), CEUS and MRI (n = 26), or MDCT and MRI (n = 11). Intermodality agreement for assessment of tumor enhancement pattern was 67% (k = 0.294, P = 0.001). Typical enhancement pattern was detected coincidentally at two imaging modalities in 50 (52%) HCCs. Sensitivity for the diagnosis of HCC increased significantly using the 2010 AASLD (81/96 (84%) vs. 50/96 (52%), P < 0.001). Conclusions: Agreement between two imaging modalities for the detection of typical tumor enhancement pattern was reached in 52% of cases. The 2010 AASLD guidelines significantly increased the sensitivity for the diagnosis of HCC

High Frequency Sonar Elastic Image Enhancements: Ray Theory

National Research Council Canada - National Science Library

Marston, Philip

2001-01-01

.... All of the enhancements considered are associated with the target's mechanical response. An enhancement is discovered and analyzed for plastic and rubber cylinders usually considered to have weak backscattering...

Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory.

Science.gov (United States)