Age-related contrast enhancement study of normal bone marrow in lumbar spinal MR imaging

International Nuclear Information System (INIS)

Kim, Young A; Ha, Doo Hoe

1999-01-01

The purpose of this study was to evaluate the degree of contrast enhancement of normal bone marrow in L-spine relating to aging and to determine the range of contrast enhancement in normal bone marrow. We analyzed a total of 120 patients (20 per decade) who had undergone lumbar spinal MRI and who ranged in age from the 2nd decade to more than the 7th. Bone marrow revealed no abnormal pathology. Sagittal T1-weighted spin echo sequences were obtained before and after gadolinium administration. For each sequence, a region of interest was drawn within the L1 vertebral body from the midsagittal slice. Signal intensity (SI) values of each sequence were ascertained and the percentage increase in SI was calculated. After contrast enhancement, lumbar MRI revealed no statistically significant in the percentage increase in SI of normal bone marrow in relation to aging. Most patients (99%) however showed an SI increase of between 10% and 49%. In only four, none of whom were aged over 40, was this increase above 50%. Lumbar MRI, revealed no statistically significant difference in percentage increase in SI in normal bone marrow relating to aging, but when the increase is above 50% in a patient aged over 40, bone marrow pathology should be further investigated

Demineralized bone matrix and human cancellous bone enhance fixation of titanium implants

DEFF Research Database (Denmark)

Babiker, Hassan; Ding, Ming; Overgaard, Søren

Best Poster 5Demineralized bone matrix and human cancellous bone enhance fixation of titanium implants AuthorsBabiker , H.; Ding M.; Overgaard S.InstitutionOrthopaedic Research Laboratory, Department of Orthopaedic Surgery, Odense University Hospital, Clinical Institute, University of Southern...... from human tissue were included (IsoTis OrthoBiologics, Inc. USA). Both materials are commercially available. Titanium alloy implants (Biomet Inc.) of 10 mm in length and 10 mm in diameter were inserted bilaterally into the femoral condyles of 8 skeletally mature sheep. Thus four implants...... with a concentric gap of 2 mm were implanted in each sheep. The gap was filled with: DBM; DBM/CB with ratio of 1/3; DBM/allograft with ratio of 1/3; or allograft (Gold standard), respectively. Standardised surgical procedure was used1. At sacrifice, 6 weeks after surgery, both distal femurs were harvested...

Enhanced bioactive scaffolds for bone tissue regeneration

Science.gov (United States)

Karnik, Sonali

Bone injuries are commonly termed as fractures and they vary in their severity and causes. If the fracture is severe and there is loss of bone, implant surgery is prescribed. The response to the implant depends on the patient's physiology and implant material. Sometimes, the compromised physiology and undesired implant reactions lead to post-surgical complications. [4, 5, 20, 28] Efforts have been directed towards the development of efficient implant materials to tackle the problem of post-surgical implant failure. [ 15, 19, 24, 28, 32]. The field of tissue engineering and regenerative medicine involves the use of cells to form a new tissue on bio-absorbable or inert scaffolds. [2, 32] One of the applications of this field is to regenerate the damaged or lost bone by using stem cells or osteoprogenitor cells on scaffolds that can integrate in the host tissue without causing any harmful side effects. [2, 32] A variety of natural, synthetic materials and their combinations have been used to regenerate the damaged bone tissue. [2, 19, 30, 32, 43]. Growth factors have been supplied to progenitor cells to trigger a sequence of metabolic pathways leading to cellular proliferation, differentiation and to enhance their functionality. [56, 57] The challenge persists to supply these proteins, in the range of nano or even picograms, and in a sustained fashion over a period of time. A delivery system has yet to be developed that would mimic the body's inherent mechanism of delivering the growth factor molecules in the required amount to the target organ or tissue. Titanium is the most preferred metal for orthopedic and orthodontic implants. [28, 46, 48] Even though it has better osteogenic properties as compared to other metals and alloys, it still has drawbacks like poor integration into the surrounding host tissue leading to bone resorption and implant failure. [20, 28, 35] It also faces the problem of postsurgical infections that contributes to the implant failure. [26, 37

Evaluation of the effect of platelet rich plasma (PRP) on enhancement of bone healing in diaphyseal bone defects by radiography and computed tomography

International Nuclear Information System (INIS)

Özak, Ahmet; Yardimci, Cenk; Nİsbet, Özlem H.; Bayrak, İlkay Koray; Nİsbet, Cevat

2010-01-01

The effect of platelet-rich plasma (PRP) with autogenous cancellous bone graft on enhancement of bone healing in diaphyseal bone defects was evaluated. A 4-mm defect was created in the middiaphysis of the tibias of 20 rabbits. Rabbits were divided into two groups of ten animals each: only autogenous cancellous graft, PRP and autogenous cancellous graft. In animals of group 1, only autogenous cancellous grafts, and to those in group 2, PRP and autogenous cancellous grafts, were applied to the defect. Radiographical and computed tomography (CT) views were taken and evaluated on postoperative days 0, 15, 30, 60, and 90. According to the bone formation, union, and remodeling scores, group 1 had better scores than group 2 on days 30, 60, and 90. The density was significantly increased on day 60 than on days 0, 15, and 30 in group 1. In conclusion, it was evaluated that PRP could not enhance the bone regeneration in diaphyseal defects when used with autogenous cancellous bone graft

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

Purpose: To evaluate the osteo-regenerative potential of Titanium (Ti) modified by Light Amplification by Stimulated Emission of Radiation (LASER) beam (Yb-YAG) upon culture with human Skeletal Stem Cells (hSSCs{sup 1}). Methods: Human skeletal cell populations were isolated from the bone marrow of haematologically normal patients undergoing primary total hip replacement following appropriate consent. STRO-1{sup +} hSSC{sup 1} function was examined for 10 days across four groups using Ti discs: i) machined Ti surface group in basal media (Mb{sup 2}), ii) machined Ti surface group in osteogenic media (Mo{sup 3}), iii) LASER-modified Ti group in basal media (Lb{sup 4}) and, iv) LASER-modified Ti group in osteogenic media (Lo{sup 5}). Molecular analysis and qRT-PCR as well as functional analysis including biochemistry (DNA, Alkaline Phosphatase (ALP{sup 6}) specific activity), live/dead immunostaining (Cell Tracker Green (CTG{sup 7})/Ethidium Homodimer-1 (EH-1{sup 8})), and fluorescence staining (for vinculin and phalloidin) were undertaken. Inverted, confocal and Scanning Electron Microscopy (SEM) approaches were used to characterise cell adherence, proliferation, and phenotype. Results: Enhanced cell spreading and morphological rearrangement, including focal adhesions were observed following culture of hSSCs{sup 1} on LASER surfaces in both basal and osteogenic conditions. Biochemical analysis demonstrated enhanced ALP{sup 6} specific activity on the hSSCs{sup 1}-seeded on LASER-modified surface in basal culture media. Molecular analysis demonstrated enhanced ALP{sup 6} and osteopontin expression on titanium LASER treated surfaces in basal conditions. SEM, inverted microscopy and confocal laser scanning microscopy confirmed extensive proliferation and migration of human bone marrow stromal cells on all surfaces evaluated. Conclusions: LASER-modified Ti surfaces modify the behaviour of hSSCs.{sup 1} In particular, SSC{sup 1} adhesion, osteogenic gene expression, cell

Porous surface modified bioactive bone cement for enhanced bone bonding.

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Qiang He

Full Text Available Polymethylmethacrylate bone cement cannot provide an adhesive chemical bonding to form a stable cement-bone interface. Bioactive bone cements show bone bonding ability, but their clinical application is limited because bone resorption is observed after implantation. Porous polymethylmethacrylate can be achieved with the addition of carboxymethylcellulose, alginate and gelatin microparticles to promote bone ingrowth, but the mechanical properties are too low to be used in orthopedic applications. Bone ingrowth into cement could decrease the possibility of bone resorption and promote the formation of a stable interface. However, scarce literature is reported on bioactive bone cements that allow bone ingrowth. In this paper, we reported a porous surface modified bioactive bone cement with desired mechanical properties, which could allow for bone ingrowth.The porous surface modified bioactive bone cement was evaluated to determine its handling characteristics, mechanical properties and behavior in a simulated body fluid. The in vitro cellular responses of the samples were also investigated in terms of cell attachment, proliferation, and osteoblastic differentiation. Furthermore, bone ingrowth was examined in a rabbit femoral condyle defect model by using micro-CT imaging and histological analysis. The strength of the implant-bone interface was also investigated by push-out tests.The modified bone cement with a low content of bioactive fillers resulted in proper handling characteristics and adequate mechanical properties, but slightly affected its bioactivity. Moreover, the degree of attachment, proliferation and osteogenic differentiation of preosteoblast cells was also increased. The results of the push-out test revealed that higher interfacial bonding strength was achieved with the modified bone cement because of the formation of the apatite layer and the osseointegration after implantation in the bony defect.Our findings suggested a new bioactive

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.

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

Application of VEGFA and FGF-9 enhances angiogenesis, osteogenesis and bone remodeling in type 2 diabetic long bone regeneration.

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Christoph Wallner

Full Text Available Although bone regeneration is typically a reliable process, type 2 diabetes is associated with impaired or delayed healing processes. In addition, angiogenesis, a crucial step in bone regeneration, is often altered in the diabetic state. In this study, different stages of bone regeneration were characterized in an unicortical bone defect model comparing transgenic type 2 diabetic (db-/db- and wild type (WT mice in vivo. We investigated angiogenesis, callus formation and bone remodeling at early, intermediate and late time points by means of histomorphometry as well as protein level analyses. In order to enhance bone regeneration, defects were locally treated with recombinant FGF-9 or VEGFA. Histomorphometry of aniline blue stained sections indicated that bone regeneration is significantly decreased in db-/db- as opposed to WT mice at intermediate (5 days post operation and late stages (7 days post operation of bone regeneration. Moreover, immunohistochemical analysis revealed significantly decreased levels of RUNX-2, PCNA, Osteocalcin and PECAM-1 in db-/db- defects. In addition, osteoclastogenesis is impaired in db-/db- indicating altered bone remodeling. These results indicate significant impairments in angiogenesis and osteogenesis in type 2 diabetic bones. Importantly, angiogenesis, osteogenesis and bone remodeling could be reconstituted by application of recombinant FGF-9 and, in part, by VEGFA application. In conclusion, our study demonstrates that type 2 diabetes affects angiogenesis, osteogenesis and subsequently bone remodeling, which in turn leads to decreased bone regeneration. These effects could be reversed by local application of FGF-9 and to a lesser degree VEGFA. These data could serve as a basis for future therapeutic applications aiming at improving bone regeneration in the type 2 diabetic patient population.

Dual delivery of rhPDGF-BB and bone marrow mesenchymal stromal cells expressing the BMP2 gene enhance bone formation in a critical-sized defect model.

Science.gov (United States)

Park, Shin-Young; Kim, Kyoung-Hwa; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo; Seol, Yang-Jo

2013-11-01

Bone tissue healing is a dynamic, orchestrated process that relies on multiple growth factors and cell types. Platelet-derived growth factor-BB (PDGF-BB) is released from platelets at wound sites and induces cellular migration and proliferation necessary for bone regeneration in the early healing process. Bone morphogenetic protein-2 (BMP-2), the most potent osteogenic differentiation inducer, directs new bone formation at the sites of bone defects. This study evaluated a combinatorial treatment protocol of PDGF-BB and BMP-2 on bone healing in a critical-sized defect model. To mimic the bone tissue healing process, a dual delivery approach was designed to deliver the rhPDGF-BB protein transiently during the early healing phase, whereas BMP-2 was supplied by rat bone marrow stromal cells (BMSCs) transfected with an adenoviral vector containing the BMP2 gene (AdBMP2) for prolonged release throughout the healing process. In in vitro experiments, the dual delivery of rhPDGF-BB and BMP2 significantly enhanced cell proliferation. However, the osteogenic differentiation of BMSCs was significantly suppressed even though the amount of BMP-2 secreted by the AdBMP2-transfected BMSCs was not significantly affected by the rhPDGF-BB treatment. In addition, dual delivery inhibited the mRNA expression of BMP receptor type II and Noggin in BMSCs. In in vivo experiments, critical-sized calvarial defects in rats showed enhanced bone regeneration by dual delivery of autologous AdBMP2-transfected BMSCs and rhPDGF-BB in both the amount of new bone formed and the bone mineral density. These enhancements in bone regeneration were greater than those observed in the group treated with AdBMP2-transfected BMSCs alone. In conclusion, the dual delivery of rhPDGF-BB and AdBMP2-transfected BMSCs improved the quality of the regenerated bone, possibly due to the modulation of PDGF-BB on BMP-2-induced osteogenesis.

Dynamic contrast-enhanced MR imaging of the water fraction of normal bone marrow and diffuse bone marrow disease

Energy Technology Data Exchange (ETDEWEB)

Katsuya, Tomoo; Inoue, Tomio; Ishizaka, Hiroshi; Aoki, Jun; Endo, Keigo [Gunma Univ., Maebashi (Japan). School of Medicine

2000-10-01

To clarify the contrast-enhancement pattern of the normal hematopoietic element by isolating the signal of the water fraction in vertebral bone marrow and to investigate whether this approach can be used to characterize bone marrow pathology in several diffuse bone marrow diseases. Two groups were examined: 30 normal healthy volunteers and 19 patients with primary diffuse bone marrow disease (aplastic anemia [n=8], myelodysplastic syndrome (MDS) [n=5], chronic myelogenic leukemia (CML) [n=4], polycythemia vera [n=2]). Isolation of the signal of hematopoietic tissue was done by the chemical-shift misregistration effect. Twenty consecutive T1-weighted midsagittal lumber vertebral images were obtained immediately after the intravenous administration of Gd-DTPA of 0.1 mmol/kg body weight, and the pattern of the time-intensity curve, the peak contrast-enhancement (CE) ratio, and the washout rate (%/min) of bone marrow in normal volunteers were compared with those in patients suffering from primary diffuse bone marrow disease. The pattern of the time-intensity curve of patients with aplastic anemia showed a low peak value followed by a slow washout. However, the pattern of time-intensity curves in patients with MDS, CML, and polycythemia vera was similar to that of normal volunteers. The peak CE ratio of the water fraction in normal marrow ranged from 0.45 to 1.26 (mean {+-}S.D.: 0.87{+-}0.18). Patients with aplastic anemia showed an abnormally lower peak CE ratio of the water fraction (mean {+-}S.D.: 0.34{+-}0.19, p<0.0001). On the other hand, the peak CE ratio of the water fraction in patients with MDS was significantly higher than that of normal volunteers (mean {+-}S.D. 1.35{+-}0.39, p<0.05). In contrast, the peak CE ratio of patients with CML or polycythemia vera did not differ significantly from that of normal volunteers. The mean washout rate of patients with aplastic anemia was significantly lower than that of normal volunteers (mean {+-}S.D.: 3.50{+-}2.51 %/min

Dynamic contrast-enhanced MR imaging of the water fraction of normal bone marrow and diffuse bone marrow disease

International Nuclear Information System (INIS)

Katsuya, Tomoo; Inoue, Tomio; Ishizaka, Hiroshi; Aoki, Jun; Endo, Keigo

2000-01-01

To clarify the contrast-enhancement pattern of the normal hematopoietic element by isolating the signal of the water fraction in vertebral bone marrow and to investigate whether this approach can be used to characterize bone marrow pathology in several diffuse bone marrow diseases. Two groups were examined: 30 normal healthy volunteers and 19 patients with primary diffuse bone marrow disease (aplastic anemia [n=8], myelodysplastic syndrome (MDS) [n=5], chronic myelogenic leukemia (CML) [n=4], polycythemia vera [n=2]). Isolation of the signal of hematopoietic tissue was done by the chemical-shift misregistration effect. Twenty consecutive T1-weighted midsagittal lumber vertebral images were obtained immediately after the intravenous administration of Gd-DTPA of 0.1 mmol/kg body weight, and the pattern of the time-intensity curve, the peak contrast-enhancement (CE) ratio, and the washout rate (%/min) of bone marrow in normal volunteers were compared with those in patients suffering from primary diffuse bone marrow disease. The pattern of the time-intensity curve of patients with aplastic anemia showed a low peak value followed by a slow washout. However, the pattern of time-intensity curves in patients with MDS, CML, and polycythemia vera was similar to that of normal volunteers. The peak CE ratio of the water fraction in normal marrow ranged from 0.45 to 1.26 (mean ±S.D.: 0.87±0.18). Patients with aplastic anemia showed an abnormally lower peak CE ratio of the water fraction (mean ±S.D.: 0.34±0.19, p<0.0001). On the other hand, the peak CE ratio of the water fraction in patients with MDS was significantly higher than that of normal volunteers (mean ±S.D. 1.35±0.39, p<0.05). In contrast, the peak CE ratio of patients with CML or polycythemia vera did not differ significantly from that of normal volunteers. The mean washout rate of patients with aplastic anemia was significantly lower than that of normal volunteers (mean ±S.D.: 3.50±2.51 %/min vs. 7.13±1

Si-doping bone composite based on protein template-mediated assembly for enhancing bone regeneration

Science.gov (United States)

Yang, Qin; Du, Yingying; Wang, Yifan; Wang, Zhiying; Ma, Jun; Wang, Jianglin; Zhang, Shengmin

2017-06-01

Bio-inspired hybrid materials that contain organic and inorganic networks interpenetration at the molecular level have been a particular focus of interest on designing novel nanoscale composites. Here we firstly synthesized a series of hybrid bone composites, silicon-hydroxyapatites/silk fibroin/collagen, based on a specific molecular assembled strategy. Results of material characterization confirmed that silicate had been successfully doped into nano-hydroxyapatite lattice. In vitro evaluation at the cellular level clearly showed that these Si-doped composites were capable of promoting the adhesion and proliferation of rat mesenchymal stem cells (rMSCs), extremely enhancing osteoblastic differentiation of rMSCs compared with silicon-free composite. More interestingly, we found there was a critical point of silicon content in the composition on regulating multiple cell behaviors. In vivo animal evaluation further demonstrated that Si-doped composites enabled to significantly improve the repair of cranial bone defect. Consequently, our current work not only suggests fabricating a potential bone repair materials by integrating element-doping and molecular assembled strategy in one system, but also paves a new way for constructing multi-functional composite materials in the future.

Si-doping bone composite based on protein template-mediated assembly for enhancing bone regeneration

Institute of Scientific and Technical Information of China (English)

Qin YANG; Yingying DU; Yifan WANG; Zhiying WANG; Jun MA; Jianglin WANG; Shengmin ZHANG

2017-01-01

Bio-inspired hybrid materials that contain organic and inorganic networks interpenetration at the molecular level have been a particular focus of interest on designing novel nanoscale composites.Here we firstly synthesized a series of hybrid bone composites,silicon-hydroxyapatites/silk fibroin/collagen,based on a specific molecular assembled strategy.Results of material characterization confirmed that silicate had been successfully doped into nano-hydroxyapatite lattice.In vitro evaluation at the cellular level clearly showed that these Si-doped composites were capable of promoting the adhesion and proliferation of rat mesenchymal stem cells (rMSCs),extremely enhancing osteoblastic differentiation of rMSCs compared with silicon-free composite.More interestingly,we found there was a critical point of silicon content in the composition on regulating multiple cell behaviors.In vivo animal evaluation further demonstrated that Si-doped composites enabled to significantly improve the repair of cranial bone defect.Consequently,our current work not only suggests fabricating a potential bone repair materials by integrating element-doping and molecular assembled strategy in one system,but also paves a new way for constructing multi-functional composite materials in the future.

Demineralized bone matrix and human cancellous bone enhance fixation of porous-coated titanium implants in sheep

DEFF Research Database (Denmark)

Babiker, Hassan; Ding, Ming; Overgaard, Søren

2016-01-01

matrix (DBM), alone or in combination with allograft or commercially available human cancellous bone (CB), may replace allografts, as they have the capability of inducing new bone and improving implant fixation through enhancing bone ongrowth. The purpose of this study was to investigate the effect...... of DBM alone, DBM with CB, or allograft on the fixation of porous-coated titanium implants. DBM100 and CB produced from human tissue were included. Both materials are commercially available. DBM granules are placed in pure DBM and do not contain any other carrier. Titanium alloy implants, 10 mm long × 10...... mm diameter, were inserted bilaterally into the femoral condyles of eight skeletally mature sheep. Thus, four implants with a concentric gap of 2 mm were implanted in each sheep. The gap was filled with: (a) DBM; (b) DBM:CB at a ratio of 1:3; (c) DBM:allograft at a ratio of 1:3; or (d) allograft...

Enhancement of tendon–bone healing via the combination of biodegradable collagen-loaded nanofibrous membranes and a three-dimensional printed bone-anchoring bolt

Directory of Open Access Journals (Sweden)

Chou YC

2016-08-01

Full Text Available Ying-Chao Chou,1,2 Wen-Lin Yeh,2 Chien-Lin Chao,1 Yung-Heng Hsu,1,2 Yi-Hsun Yu,1,2 Jan-Kan Chen,3 Shih-Jung Liu1,2 1Department of Mechanical Engineering, Chang Gung University, 2Department of Orthopedic Surgery, Chang Gung Memorial Hospital, 3Department of Physiology and Pharmacology, Chang Gung University, Taoyuan, Taiwan Abstract: A composite biodegradable polymeric model was developed to enhance tendon graft healing. This model included a biodegradable polylactide (PLA bolt as the bone anchor and a poly(D,L-lactide-co-glycolide (PLGA nanofibrous membrane embedded with collagen as a biomimic patch to promote tendon–bone interface integration. Degradation rate and compressive strength of the PLA bolt were measured after immersion in a buffer solution for 3 months. In vitro biochemical characteristics and the nanofibrous matrix were assessed using a water contact angle analyzer, pH meter, and tetrazolium reduction assay. In vivo efficacies of PLGA/collagen nanofibers and PLA bolts for tendon–bone healing were investigated on a rabbit bone tunnel model with histological and tendon pullout tests. The PLGA/collagen-blended nanofibrous membrane was a hydrophilic, stable, and biocompatible scaffold. The PLA bolt was durable for tendon–bone anchoring. Histology showed adequate biocompatibility of the PLA bolt on a medial cortex with progressive bone ingrowth and without tissue overreaction. PLGA nanofibers within the bone tunnel also decreased the tunnel enlargement phenomenon and enhanced tendon–bone integration. Composite polymers of the PLA bolt and PLGA/collagen nanofibrous membrane can effectively promote outcomes of tendon reconstruction in a rabbit model. The composite biodegradable polymeric system may be useful in humans for tendon reconstruction. Keywords: polylactide–polyglycolide nanofibers, PLGA, collagen, 3D printing, polylactide, PLA, bone-anchoring bolts, tendon healing

Bone regeneration in critical bone defects using three-dimensionally printed β-tricalcium phosphate/hydroxyapatite scaffolds is enhanced by coating scaffolds with either dipyridamole or BMP-2.

Science.gov (United States)

Ishack, Stephanie; Mediero, Aranzazu; Wilder, Tuere; Ricci, John L; Cronstein, Bruce N

2017-02-01

Bone defects resulting from trauma or infection need timely and effective treatments to restore damaged bone. Using specialized three-dimensional (3D) printing technology we have created custom 3D scaffolds of hydroxyapatite (HA)/beta-tri-calcium phosphate (β-TCP) to promote bone repair. To further enhance bone regeneration we have coated the scaffolds with dipyridamole, an agent that increases local adenosine levels by blocking cellular uptake of adenosine. Nearly 15% HA:85% β-TCP scaffolds were designed using Robocad software, fabricated using a 3D Robocasting system, and sintered at 1100°C for 4 h. Scaffolds were coated with BMP-2 (200 ng mL -1 ), dypiridamole 100 µM or saline and implanted in C57B6 and adenosine A2A receptor knockout (A2AKO) mice with 3 mm cranial critical bone defects for 2-8 weeks. Dipyridamole release from scaffold was assayed spectrophotometrically. MicroCT and histological analysis were performed. Micro-computed tomography (microCT) showed significant bone formation and remodeling in HA/β-TCP-dipyridamole and HA/β-TCP-BMP-2 scaffolds when compared to scaffolds immersed in vehicle at 2, 4, and 8 weeks (n = 5 per group; p ≤ 0.05, p ≤ 0.05, and p ≤ 0.01, respectively). Histological analysis showed increased bone formation and a trend toward increased remodeling in HA/β-TCP- dipyridamole and HA/β-TCP-BMP-2 scaffolds. Coating scaffolds with dipyridamole did not enhance bone regeneration in A2AKO mice. In conclusion, scaffolds printed with HA/β-TCP promote bone regeneration in critical bone defects and coating these scaffolds with agents that stimulate A2A receptors and growth factors can further enhance bone regeneration. These coated scaffolds may be very useful for treating critical bone defects due to trauma, infection or other causes. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 366-375, 2017. © 2015 Wiley Periodicals, Inc.

Dynamic Contrast Enhanced Magnetic Resonance Imaging of Diffuse Spinal Bone Marrow Infiltration in Patients with Hematological Malignancies

International Nuclear Information System (INIS)

Zha, Yunfei; Li, Maojin; Yang, Jianyong

2010-01-01

To investigate the significance of the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters of diffuse spinal bone marrow infiltration in patients with hematological malignancies. Dynamic gadolinium-enhanced MR imaging of the lumbar spine was performed in 26 patients with histologically proven diffuse bone marrow infiltration, including multiple myeloma (n = 6), acute lymphoblastic leukemia (n = 6), acute myeloid leukemia (n = 5), chronic myeloid leukemia (n = 7), and non-Hodgkin lymphoma (n = 2). Twenty subjects whose spinal MRI was normal, made up the control group. Peak enhancement percentage (E max ), enhancement slope (ES), and time to peak (TTP) were determined from a time intensity curve (TIC) of lumbar vertebral bone marrow. A comparison between baseline and follow-up MR images and its histological correlation were evaluated in 10 patients. The infiltration grade of hematopoietic marrow with plasma cells was evaluated by a histological assessment of bone marrow. Differences in E max , ES, and TTP values between the control group and the patients with diffuse bone marrow infiltration were significant (t = -11.51, -9.81 and 3.91, respectively, p max , ES, and TTP values were significantly different between bone marrow infiltration groups Grade 1 and Grade 2 (Z = -2.72, -2.24 and -2.89 respectively, p max , ES and TTP values were not significantly different between bone marrow infiltration groups Grade 2 and Grade 3 (Z = -1.57, -1.82 and -1.58 respectively, p > 0.05). A positive correlation was found between E max , ES values and the histological grade of bone marrow infiltration (r = 0.86 and 0.84 respectively, p max and ES values was observed with increased TTP values after treatment in all of the 10 patients who responded to treatment (t = -7.92, -4.55, and 5.12, respectively, p max , ES, and TTP can reflect the malignancies' histological grade

Calcium citrate: a new biomaterial that can enhance bone formation in situ

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WANG Li-ming

2012-11-01

Full Text Available 【Abstract】 Objective: To investigate the effect of a new biomaterial combining calcium citrate and recombinant human bone morphogenetic protein-2 (rhBMP-2 on bone regeneration in a bone defect rabbit model. Methods: Totally 30 male New Zealand white rabbits were randomly and equally divided into calcium citrate-rhBMP-2 (CC-rhBMP-2 group and rhBMP-2 only group. Two 10 mm-long and 5 mm-deep bone defects were respec-tively created in the left and right femoral condyles of the rabbits. Subsequently 5 pellets of calcium citrate (10 mg combined with rhBMP-2 (2 mg or rhBMP-2 alone were im-planted into the bone defects and compressed with cotton swab. Bone granules were obtained at 2, 4 and 6 weeks after procedure and received histological analysis. LSD t-test and a subsequent t-test were adopted for statistical analysis. Results: Histomorphometric analysis revealed newly formed bones, and calcium citrate has been absorbed in the treatment group. The percent of newly formed bone area in femoral condyle in control group and CC-rhBMP-2 group was respectively 31.73%±1.26% vs 48.21%±2.37% at 2 weeks; 43.40%±1.65% vs 57.32%±1.47% at 4 weeks, and 51.32%±7.80% vs 66.74%±4.05% at 6 weeks (P<0.05 for all. At 2 weeks, mature cancellous bone was observed to be already formed in the treatment group. Conclusion: From this study, it can be concluded that calcium citrate combined with rhBMP-2 signifcantly en-hances bone regeneration in bone defects. This synthetic gelatin matrix stimulates formation of new bone and bone marrow in the defect areas by releasing calcium ions. Key words: Bone morphogenetic protein-2; Biocompatible materials; Calcium citrate; Gelatin

Evaluation of bone marrow by opposed phase T1-weighted images and enhanced MR imaging

International Nuclear Information System (INIS)

Amano, Yasuo; Tanabe, Yoshihiro; Miyashita, Tsuguhiro; Hayashi, Hiromitsu; Horiuchi, Junichi; Nomura, Takeo; Kumazaki, Tatsuo

1994-01-01

We investigated bone marrow in a control group, cases of aplastic anemia and post-irradiation patients by examining T1-weighted (T1W1), short T1 inversion recovery (STIR), opposed phase T1W1 (op-T1W1) and Gd-DTPA enhanced op-T1W1 images obtained by 0.5 T MRI. Bone marrow was classified into four types based on MR findings. Normal marrow showed low intensity on op-T1W1 and STIR images without enhancement (I). Fatty marrow, which showed high intensity on T1W1 and op-T1W1 images was observed in aplastic anemia and post-irradiation patients (II). Hematopoietic marrow (III) showed low intensity on op-T1W1 and enhanced, while active hematopoietic marrow (IV) revealed high intensity on both STIR and op-T1W1 images and was enhanced following Gd-DTPA infusion. Aplastic anemia of moderate grade included types II, III and IV. Enhanced MR was needed to differentiate between types I and III since both types showed low intensity on op-T1W1 images. Furthermore, type IV was considered as hyperplastic compared with type III. Enhanced MR and op-T1W1 images were useful in evaluating hematopoiesis of bone marrow. (author)

Evaluation of bone marrow by opposed phase T1-weighted images and enhanced MR imaging

Energy Technology Data Exchange (ETDEWEB)

Amano, Yasuo; Tanabe, Yoshihiro; Miyashita, Tsuguhiro; Hayashi, Hiromitsu; Horiuchi, Junichi; Nomura, Takeo; Kumazaki, Tatsuo (Nippon Medical School, Tokyo (Japan))

1994-09-01

We investigated bone marrow in a control group, cases of aplastic anemia and post-irradiation patients by examining T1-weighted (T1W1), short T1 inversion recovery (STIR), opposed phase T1W1 (op-T1W1) and Gd-DTPA enhanced op-T1W1 images obtained by 0.5 T MRI. Bone marrow was classified into four types based on MR findings. Normal marrow showed low intensity on op-T1W1 and STIR images without enhancement (I). Fatty marrow, which showed high intensity on T1W1 and op-T1W1 images was observed in aplastic anemia and post-irradiation patients (II). Hematopoietic marrow (III) showed low intensity on op-T1W1 and enhanced, while active hematopoietic marrow (IV) revealed high intensity on both STIR and op-T1W1 images and was enhanced following Gd-DTPA infusion. Aplastic anemia of moderate grade included types II, III and IV. Enhanced MR was needed to differentiate between types I and III since both types showed low intensity on op-T1W1 images. Furthermore, type IV was considered as hyperplastic compared with type III. Enhanced MR and op-T1W1 images were useful in evaluating hematopoiesis of bone marrow. (author).

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging.

Science.gov (United States)

Wagner, A; Sachse, A; Keller, M; Aurich, M; Wetzel, W-D; Hortschansky, P; Schmuck, K; Lohmann, M; Reime, B; Metge, J; Arfelli, F; Menk, R; Rigon, L; Muehleman, C; Bravin, A; Coan, P; Mollenhauer, J

2006-03-07

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging

Energy Technology Data Exchange (ETDEWEB)

Wagner, A [Department of Orthopaedics of the University of Jena at the Waldkrankenhaus ' Rudolf Elle' , Jena (Germany); Sachse, A [Department of Orthopaedics of the University of Jena at the Waldkrankenhaus ' Rudolf Elle' , Jena (Germany); Keller, M [Department of Orthopaedics of the University of Jena at the Waldkrankenhaus ' Rudolf Elle' , Jena (Germany); Aurich, M [Department of Orthopaedics of the University of Jena at the Waldkrankenhaus ' Rudolf Elle' , Jena (Germany); Wetzel, W-D [Department of Orthopaedics of the University of Jena at the Waldkrankenhaus ' Rudolf Elle' , Jena (Germany); Hortschansky, P [Hans-Knoell-Institut fuer Naturstoffforschung, Jena (Germany); Schmuck, K [DePuy Biotech GmbH, Jena (Germany); Lohmann, M [Hasylab at DESY, Hamburg (Germany); Reime, B [Hasylab at DESY, Hamburg (Germany); Metge, J [CELLS-ALBA, Universitat Autonoma de Barcelona (Spain); Arfelli, F [Department of Physics, University of Trieste, Trieste (Italy); Menk, R [ELETTRA, Trieste (Italy); Rigon, L [ELETTRA, Trieste (Italy); Muehleman, C [Department of Biochemistry, Rush Medical College, Chicago, IL (United States); Bravin, A [European Synchrotron Radiation Facility, BP220 38043, Grenoble (France); Coan, P [European Synchrotron Radiation Facility, BP220 38043, Grenoble (France); Mollenhauer, J [Department of Orthopaedics of the University of Jena at the Waldkrankenhaus ' Rudolf Elle' , Jena (Germany)

2006-03-07

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging

International Nuclear Information System (INIS)

Wagner, A; Sachse, A; Keller, M; Aurich, M; Wetzel, W-D; Hortschansky, P; Schmuck, K; Lohmann, M; Reime, B; Metge, J; Arfelli, F; Menk, R; Rigon, L; Muehleman, C; Bravin, A; Coan, P; Mollenhauer, J

2006-01-01

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging

Science.gov (United States)

Wagner, A.; Sachse, A.; Keller, M.; Aurich, M.; Wetzel, W.-D.; Hortschansky, P.; Schmuck, K.; Lohmann, M.; Reime, B.; Metge, J.; Arfelli, F.; Menk, R.; Rigon, L.; Muehleman, C.; Bravin, A.; Coan, P.; Mollenhauer, J.

2006-03-01

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

Dynamic Contrast Enhanced Magnetic Resonance Imaging of Diffuse Spinal Bone Marrow Infiltration in Patients with Hematological Malignancies

Energy Technology Data Exchange (ETDEWEB)

Zha, Yunfei; Li, Maojin [Renmin Hospital of Wuhan University, Wuhan (China); Yang, Jianyong [the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China)

2010-04-15

To investigate the significance of the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters of diffuse spinal bone marrow infiltration in patients with hematological malignancies. Dynamic gadolinium-enhanced MR imaging of the lumbar spine was performed in 26 patients with histologically proven diffuse bone marrow infiltration, including multiple myeloma (n = 6), acute lymphoblastic leukemia (n = 6), acute myeloid leukemia (n = 5), chronic myeloid leukemia (n = 7), and non-Hodgkin lymphoma (n = 2). Twenty subjects whose spinal MRI was normal, made up the control group. Peak enhancement percentage (E{sub max}), enhancement slope (ES), and time to peak (TTP) were determined from a time intensity curve (TIC) of lumbar vertebral bone marrow. A comparison between baseline and follow-up MR images and its histological correlation were evaluated in 10 patients. The infiltration grade of hematopoietic marrow with plasma cells was evaluated by a histological assessment of bone marrow. Differences in E{sub max}, ES, and TTP values between the control group and the patients with diffuse bone marrow infiltration were significant (t = -11.51, -9.81 and 3.91, respectively, p < 0.01). E{sub max}, ES, and TTP values were significantly different between bone marrow infiltration groups Grade 1 and Grade 2 (Z = -2.72, -2.24 and -2.89 respectively, p < 0.05). E{sub max}, ES and TTP values were not significantly different between bone marrow infiltration groups Grade 2 and Grade 3 (Z = -1.57, -1.82 and -1.58 respectively, p > 0.05). A positive correlation was found between E{sub max}, ES values and the histological grade of bone marrow infiltration (r = 0.86 and 0.84 respectively, p < 0.01). A negative correlation was found between the TTP values and bone marrow infiltration histological grade (r = -0.54, p < 0.01). A decrease in the E{sub max} and ES values was observed with increased TTP values after treatment in all of the 10 patients who responded to treatment (t

Enhanced Healing of Segmental Bone Defects by Modulation of the Mechanical Environment

Science.gov (United States)

2013-10-01

Employment opportunities received based upon experience/ training supported by this award Partly based upon her research during the completion of...School, Coventry CV4 7AL, United Kingdom References 1. Stevenson S. Enhancement of fracture healing with autogenous and allogeneic bone grafts. Clin

Ossificans myositis: inflammatory changes and contrast enhancement of adjacent bone shown by MR imaging

International Nuclear Information System (INIS)

David, H.; Jolles, E.; Le Friant, G.; Silvestre, A.; Sarrazin, J.L.; Gordoliani, Y.S.

1995-01-01

The authors report a case of ossificans myositis, in which magnetic resonance imaging (MRI) showed inflammatory changes of the adjacent bone. T 1 weighted fat saturation sequence with gadolinium injection showed enhancement of medullary and cortical bone. This potentially mistaking pattern must be known, to avoid mis diagnosing with malignant osseous tumor, specially before achievement of the characteristic pattern of zonal maturation and its calcified rim. (authors). 15 refs., 6 figs

Diffusion-weighted imaging and dynamic contrast-enhanced MRI of experimental breast cancer bone metastases – A correlation study with histology

Energy Technology Data Exchange (ETDEWEB)

Merz, Maximilian [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Seyler, Lisa; Bretschi, Maren; Semmler, Wolfhard [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Bäuerle, Tobias, E-mail: tobias.baeuerle@uk-erlangen.de [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Institute of Radiology, University Medical Center Erlangen, Palmsanlage 5, 90154 Erlangen (Germany)

2015-04-15

Purpose: To validate imaging parameters from diffusion-weighted imaging and dynamic contrast-enhanced MRI with immunohistology and to non-invasively assess microstructure of experimental breast cancer bone metastases. Materials and methods: Animals bearing breast cancer bone metastases were imaged in a clinical 1.5 T MRI scanner. HASTE sequences were performed to calculate apparent diffusion coefficients. Saturation recovery turbo FLASH sequences were conducted while infusing 0.1 mmol/l Gd–DTPA for dynamic contrast-enhanced MRI to quantify parameters amplitude A and exchange rate constant k{sub ep}. After imaging, bone metastases were analyzed immunohistologically. Results: We found correlations of the apparent diffusion coefficients from diffusion-weighted imaging with tumor cellularity as assessed with cell nuclei staining. Histological vessel maturity was correlated negatively with parameters A and k{sub ep} from dynamic contrast-enhanced MRI. Tumor size correlated inversely with cell density and vessel permeability as well as positively with mean vessel calibers. Parameters from the rim of bone metastases differed significantly from values of the center. Conclusion: In vivo diffusion-weighted imaging and dynamic contrast-enhanced MRI in experimental bone metastases provide information about tumor cellularity and vascularity and correlate well with immunohistology.

Next generation bone tissue engineering: non-viral miR-133a inhibition using collagen-nanohydroxyapatite scaffolds rapidly enhances osteogenesis

Science.gov (United States)

Mencía Castaño, Irene; Curtin, Caroline M.; Duffy, Garry P.; O'Brien, Fergal J.

2016-06-01

Bone grafts are the second most transplanted materials worldwide at a global cost to healthcare systems valued over $30 billion every year. The influence of microRNAs in the regenerative capacity of stem cells offers vast therapeutic potential towards bone grafting; however their efficient delivery to the target site remains a major challenge. This study describes how the functionalisation of porous collagen-nanohydroxyapatite (nHA) scaffolds with miR-133a inhibiting complexes, delivered using non-viral nHA particles, enhanced human mesenchymal stem cell-mediated osteogenesis through the novel focus on a key activator of osteogenesis, Runx2. This study showed enhanced Runx2 and osteocalcin expression, as well as increased alkaline phosphatase activity and calcium deposition, thus demonstrating a further enhanced therapeutic potential of a biomaterial previously optimised for bone repair applications. The promising features of this platform offer potential for a myriad of applications beyond bone repair and tissue engineering, thus presenting a new paradigm for microRNA-based therapeutics.

Enhancement of the grafting efficiency by the new method of fetal liver-bone marrow scheduled transplantation

International Nuclear Information System (INIS)

Xiang Yingsong; Yang Rujun; Yang Ping; Cai Jianming; Min Rui

2000-01-01

To enhance the grafting efficiency of bone marrow transplantation, lethally Irradiated recipient Kunming mice were transplantation with fetal liver-bone marrow scheduled transplantation. (FL-BMST) The numbers of WBC, nucleated cells were near to normal level 17 d after irradiation in FL-BMST group transplantation with 1 x 10 6 bone marrow cells, the indexes of CFU-E, CFU-GM, CFU-F, CFU-S, were returned to normal; the degree of GVHD in the FL-BMST group was slighter than that in sing bone marrow transplantation group; and the survival rate of mice was 60%, which was significantly higher than that of routine single bone marrow transplantation group. 'Niches' vacated each time could be fully used and be improved, be increased by fetal liver-bone marrow scheduled transplantation, so the homing of stem cells was increased, and the number of transplanted bone marrow cells could be decreased. So this new method was a better method than routine bone singe marrow transplantation

Strontium hydroxyapatite/chitosan nanohybrid scaffolds with enhanced osteoinductivity for bone tissue engineering

International Nuclear Information System (INIS)

Lei, Yong; Xu, Zhengliang; Ke, Qinfei; Yin, Wenjing; Chen, Yixuan; Zhang, Changqing; Guo, Yaping

2017-01-01

For the clinical application of bone tissue engineering with the combination of biomaterials and mesenchymal stem cells (MSCs), bone scaffolds should possess excellent biocompatibility and osteoinductivity to accelerate the repair of bone defects. Herein, strontium hydroxyapatite [SrHAP, Ca 10−x Sr x (PO 4 ) 6 (OH) 2 ]/chitosan (CS) nanohybrid scaffolds were fabricated by a freeze-drying method. The SrHAP nanocrystals with the different x values of 0, 1, 5 and 10 are abbreviated to HAP, Sr1HAP, Sr5HAP and Sr10HAP, respectively. With increasing x values from 0 to 10, the crystal cell volumes and axial lengths of SrHAP become gradually large because of the greater ion radius of Sr 2+ than Ca 2+ , while the crystal sizes of SrHAP decrease from 70.4 nm to 46.7 nm. The SrHAP/CS nanohybrid scaffolds exhibits three-dimensional (3D) interconnected macropores with pore sizes of 100–400 μm, and the SrHAP nanocrystals are uniformly dispersed within the scaffolds. In vitro cell experiments reveal that all the HAP/CS, Sr1HAP/CS, Sr5HAP/CS and Sr10HAP/CS nanohybrid scaffolds possess excellent cytocompatibility with the favorable adhesion, spreading and proliferation of human bone marrow mesenchymal stem cells (hBMSCs). The Sr5HAP nanocrystals in the scaffolds do not affect the adhesion, spreading of hBMSCs, but they contribute remarkably to cell proliferation and osteogenic differentiation. As compared with the HAP/CS nanohybrid scaffold, the released Sr 2+ ions from the SrHAP/CS nanohybrid scaffolds enhance alkaline phosphatase (ALP) activity, extracellular matrix (ECM) mineralization and osteogenic-related COL-1 and ALP expression levels. Especially, the Sr5HAP/CS nanohybrid scaffolds exhibit the best osteoinductivity among four groups because of the synergetic effect between Ca 2+ and Sr 2+ ions. Hence, the Sr5HAP/CS nanohybrid scaffolds with excellent cytocompatibility and osteogenic property have promising application for bone tissue engineering. - Highlights: • We

Local vibration enhanced the efficacy of passive exercise on mitigating bone loss in hindlimb unloading rats

Science.gov (United States)

Huang, Yunfei; Luan, Huiqin; Sun, Lianwen; Bi, Jingfang; Wang, Ying; Fan, Yubo

2017-08-01

Spaceflight induced bone loss is seriously affecting astronauts. Mechanical stimulation from exercise has been shown to restrain bone resorption as well as improve bone formation. Current exercise countermeasures in space cannot prevent it completely. Active exercise may convert to passive exercise in some ways because of the loss of gravity stimulus and inertia of exercise equipment. The aim of this study was to compare the efficacy of passive exercise or/and local vibration on counteracting the deterioration of the musculoskeletal system, including bone, muscle and tendons in tail-suspended rats. We hypothesized that local vibration could enhance the efficacy of passive exercise on countering bone loss. 40 Sprague Dawley rats were randomly distributed into five groups (n = 8, each): tail-suspension (TS), TS+35 Hz vibration (TSV), TS + passive exercise (TSP), TS + passive exercise coupled with 35 Hz vibration (TSPV) and control (CON). Passive exercise or/and local vibration was performed for 21 days. On day 0 and 21, bone mineral density (BMD) was observed by dual energy X-ray absorptiometry (DXA), and trabecular microstructure was evaluated by microcomputer tomography (μCT) analysis in vivo. Mechanical properties of tibia and tendon were determined by a mechanical testing system. Soleus and bone ash weight was tested by an electronic balance. Results showed that the passive exercise could not prevent the decrease of trabecular BMD, microstructure and bone ash weight induced by TS, whereas vibration and passive exercise coupled with local vibration (PV) could. Biomechanical properties of the tibia and tendon in TSPV group significantly increased compared with TS group. In summary, PV in this study was the best method in preventing weightlessness-induced bone loss. Consistent with our hypothesis, local vibration partly enhanced the effect of passive exercise. Furthermore, this study will be useful in improving countermeasure for astronauts, but also for the

Pharmacological Inhibition of Protein Kinase G1 Enhances Bone Formation by Human Skeletal Stem Cells Through Activation of RhoA-Akt Signaling

DEFF Research Database (Denmark)

Kermani, Abbas Jafari; Siersbaek, Majken S; Chen, Li

2015-01-01

for several malignant and nonmalignant conditions. We screened a library of kinase inhibitors to identify small molecules that enhance bone formation by human skeletal (stromal or mesenchymal) stem cells (hMSC). We identified H-8 (known to inhibit protein kinases A, C, and G) as a potent enhancer of ex vivo......Development of novel approaches to enhance bone regeneration is needed for efficient treatment of bone defects. Protein kinases play a key role in regulation of intracellular signal transduction pathways, and pharmacological targeting of protein kinases has led to development of novel treatments...

Psoralidin, a prenylated coumestan, as a novel anti-osteoporosis candidate to enhance bone formation of osteoblasts and decrease bone resorption of osteoclasts

DEFF Research Database (Denmark)

Zhai, Yuankun; Li, Yingying; Wang, Yanping

2017-01-01

Traditional Chinese medicines (TCM) have been proven to prevent osteoporosis, but their clinical applications are not widely recognized due to their complicated ingredients. Psoralidin, a prenylated coumestan, has been reported to prevent bone loss of ovariectomized rats, but detailed mechanisms...... and osteoclastic bone resorption, as demonstrated by the lower tartrate-resistant acid phosphatase activity and smaller area, with fewer resorption pits formed. Interestingly, psoralidin showed much stronger effects than coumestrol at enhancing osteoblast proliferation/differentiation or inhibiting osteoclast...... differentiation and bone resorption. Moreover, we found that both psoralidin and coumestrol suppressed COX-2 and ROS production in rat osteoblastic calvarias cells, and psoralidin showed stronger effects than coumestrol. Furthermore, we detected that by blocking estrogen receptors with ICI 182.780 (an estrogen...

Hypoxia-Inducible Factor-1α: A Potential Factor for the Enhancement of Osseointegration between Dental Implants and Tissue-Engineered Bone

Directory of Open Access Journals (Sweden)

Duohong Zou

2011-07-01

Full Text Available Introduction: Tissue-engineered bones are widely utilized to protect healthy tissue, reduce pain, and increase the success rate of dental implants. one of the most challenging obstacles lies in obtaining effective os-seointegration between dental implants and tissue-engineered structures. Deficiencies in vascularization, osteogenic factors, oxygen, and other nutrients inside the tissue-engineered bone during the early stages following implantation all inhibit effective osseointe-gration. Oxygen is required for aerobic metabolism in bone and blood vessel tissues, but oxygen levels inside tissue-engineered bone are not suf-ficient for cell proliferation. HIF-1α is a pivotal regulator of hypoxic and ischemic vascular responses, driving transcriptional activation of hundreds of genes involved in vascular reactivity, angiogenesis, arteriogenesis, and osteogenesis.The hypothesis: Hypoxia-Inducible Factor-1α seems a potential factor for the enhancement of osseointegration between dental implants and tissue-engineered bone.Evaluation of the hypothesis: Enhancement of HIF-1α protein expression is recognized as the most promising approach for angiogenesis, because it can induce multiple angiogenic targets in a coordinated manner. Therefore, it will be a novel potential therapeutic methods targeting HIF-1α expression to enhance osseointegration be-tween dental implants and tissue-engineered bone.

Enhancement of the repair of dog alveolar cleft by an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture.

Science.gov (United States)

Yuanzheng, Chen; Yan, Gao; Ting, Li; Yanjie, Fu; Peng, Wu; Nan, Bai

2015-05-01

-rich fibrin are capable of improving the repair of dog alveolar cleft, and the mixture of them is more potent than each one of them used singly for enhancing new bone regeneration.

Does Periosteal Graft Combined With Platelet-Rich Plasma Enhance the Healing of Bone Defect?

Science.gov (United States)

Türkseven, Arzu; Özçelik, Derya; Çaliş, Mert; Celik, Hakan Hamdi; Yilmaz, Fahri; Önbaş, Ömer; Vatansever, Alper; Toplu, Gaye

2018-02-12

This study investigated the effect of periosteal graft + platelet-rich plasma (PRP) combination on facial bone defect healing. Five-millimeter critical sized defects in zygomatic arches of 12 adult New Zealand rabbits were created. Rabbits were randomly divided into 3 groups: First group (control group): bone defects of left zygomatic arches of 6 rabbits were wrapped with a silicone tube. Second group (periosteal graft group): bone defects of left zygomatic arches of 6 rabbits were wrapped with periosteal graft. Third group (experimental group): bone defects of right zygomatic arches of 12 rabbits were wrapped with periosteal graft-PRP combination. New bone formation was evaluated at 8th and 16th weeks. One rabbit was sacrificed at 8th week. Remaining 11 rabbits were imaged with 3-dimensional computed tomography (CT) at 16th week; then, zygomatic arches were removed for micro-CT and histologic examinations. Three-dimensional CT analysis at 16th week revealed no significant difference between groups regarding new bone formation (P = 0.232). Micro-CT analysis of new regenerated bone at 16th week displayed significant differences between groups 1 and 3 regarding mean bone volume (BV, mm) (P = 0.028) and mean bone mineral density (BMD, mm) (P = 0.001). There was no difference between groups 2 and 3 or between groups 1 and 2, regarding BV or BMD. Histological Bone Regeneration Scorings at 16th week displayed significant difference between groups (P = 0.015). Negative correlation between 3-dimensional CT and histologic results (r = 0.120); positive correlations between BV/BMD values in micro-CT and histologic results (r = 0.524 and r = 0.456) were found. By enhancing bone formation capacity of periosteal grafts, periosteal graft-PRP combination provided bone formation having more volume and density comparing with silicone tube application.

Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.

Science.gov (United States)

Graham, Lucia S; Parhami, Farhad; Tintut, Yin; Kitchen, Christina M R; Demer, Linda L; Effros, Rita B

2009-11-01

Osteoporosis is a systemic disease that is associated with increased morbidity, mortality and health care costs. Whereas osteoclasts and osteoblasts are the main regulators of bone homeostasis, recent studies underscore a key role for the immune system, particularly via activation-induced T lymphocyte production of receptor activator of NFkappaB ligand (RANKL). Well-documented as a mediator of T lymphocyte/dendritic cell interactions, RANKL also stimulates the maturation and activation of bone-resorbing osteoclasts. Given that lipid oxidation products mediate inflammatory and metabolic disorders such as osteoporosis and atherosclerosis, and since oxidized lipids affect several T lymphocyte functions, we hypothesized that RANKL production might also be subject to modulation by oxidized lipids. Here, we show that short term exposure of both unstimulated and activated human T lymphocytes to minimally oxidized low density lipoprotein (LDL), but not native LDL, significantly enhances RANKL production and promotes expression of the lectin-like oxidized LDL receptor-1 (LOX-1). The effect, which is also observed with 8-iso-Prostaglandin E2, an inflammatory isoprostane produced by lipid peroxidation, is mediated via the NFkappaB pathway, and involves increased RANKL mRNA expression. The link between oxidized lipids and T lymphocytes is further reinforced by analysis of hyperlipidemic mice, in which bone loss is associated with increased RANKL mRNA in T lymphocytes and elevated RANKL serum levels. Our results suggest a novel pathway by which T lymphocytes contribute to bone changes, namely, via oxidized lipid enhancement of RANKL production. These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.

Multiwalled carbon nanotubes enhance electrochemical properties of titanium to determine in situ bone formation

Energy Technology Data Exchange (ETDEWEB)

Sirivisoot, Sirinrath; Webster, Thomas J [Division of Engineering, Brown University, Providence, RI 02912 (United States)], E-mail: Thomas_Webster@Brown.edu

2008-07-23

Multiwalled carbon nanotubes (MWCNTs) enhance osteoblast (bone-forming cell) calcium deposition compared to currently implanted materials (such as titanium). In this study, MWCNTs were grown out of nanopores anodized on titanium (MWCNT-Ti). The electrochemical responses of MWCNT-Ti were investigated in an attempt to ascertain if MWCNT-Ti can serve as novel in situ sensors of bone formation. For this purpose, MWCNT-Ti was subjected to a ferri/ferrocyanide redox couple and its electrochemical behavior measured. Cyclic voltammograms (CVs) showed an enhanced redox potential for the MWCNT-Ti. These redox signals were superior to that obtained with bare unmodified Ti, which did not sense either oxidation or reduction peaks in the CVs. A further objective of this study was to investigate the redox reactions of MWCNT-Ti in a solution of extracellular components secreted by osteoblasts in vitro. It was found that MWCNT-Ti exhibited well-defined and persistent CVs, similar to the ferri/ferrocyanide redox reaction. The higher electrodic performance and electrocatalytic activity of the MWCNT-Ti compared to the bare titanium observed in this study were likely due to the fact that MWCNTs enhanced direct electron transfer and facilitated double-layer effects, leading to a strong redox signal. Thus these results encourage the further study and modification of MWCNT-Ti to sense new bone growth in situ next to orthopedic implants and perhaps monitor other events (such as infection and/or harmful scar tissue formation) to improve the current clinical diagnosis of orthopedic implants.

Multiwalled carbon nanotubes enhance electrochemical properties of titanium to determine in situ bone formation

International Nuclear Information System (INIS)

Sirivisoot, Sirinrath; Webster, Thomas J

2008-01-01

Multiwalled carbon nanotubes (MWCNTs) enhance osteoblast (bone-forming cell) calcium deposition compared to currently implanted materials (such as titanium). In this study, MWCNTs were grown out of nanopores anodized on titanium (MWCNT-Ti). The electrochemical responses of MWCNT-Ti were investigated in an attempt to ascertain if MWCNT-Ti can serve as novel in situ sensors of bone formation. For this purpose, MWCNT-Ti was subjected to a ferri/ferrocyanide redox couple and its electrochemical behavior measured. Cyclic voltammograms (CVs) showed an enhanced redox potential for the MWCNT-Ti. These redox signals were superior to that obtained with bare unmodified Ti, which did not sense either oxidation or reduction peaks in the CVs. A further objective of this study was to investigate the redox reactions of MWCNT-Ti in a solution of extracellular components secreted by osteoblasts in vitro. It was found that MWCNT-Ti exhibited well-defined and persistent CVs, similar to the ferri/ferrocyanide redox reaction. The higher electrodic performance and electrocatalytic activity of the MWCNT-Ti compared to the bare titanium observed in this study were likely due to the fact that MWCNTs enhanced direct electron transfer and facilitated double-layer effects, leading to a strong redox signal. Thus these results encourage the further study and modification of MWCNT-Ti to sense new bone growth in situ next to orthopedic implants and perhaps monitor other events (such as infection and/or harmful scar tissue formation) to improve the current clinical diagnosis of orthopedic implants

Role of intensity transformation function for enhancement of bone scintigraphic images.

Science.gov (United States)

Pandey, Anil Kumar; Dhiman, Vishali; Sharma, Akshima; ArunRaj, Sreedharan Thankarajan; Baghel, Vivek; Patel, Chetan; Sharma, Param Dev; Bal, Chandrasekhar; Kumar, Rakesh

2018-03-29

The bone scintigraphic image might exceed the dynamic range (the ratio between the highest and the lowest brightness a monitor is capable of displaying) of display monitor. In this case, a high intensity area, and loss of the details of other structures in the displayed image makes the clinical interpretation a challenging task. We have investigated the role of intensity transformation function for enhancement of these types of images. Methods: Forty high dynamic range bone scintigraphic images were processed using intensity transformation (IT) function. The IT function has two parameters: threshold and slope. Keeping the threshold equal to mean counts of the image, the value of slope was varied from 1 to 20. In-house application program written in MATLAB R2013b was used to process images. Twenty output images corresponding to one input image were visually inspected by two experienced nuclear medicine (NM) physicians to select diagnostic quality images, and from their selection the standardized slope (value of slope parameter) that produced maximum numbers of diagnostic images was determined. They also rated the image quality of input and output images (at standardized slope) on scale 1 to 5 [where 1 is for poor and 5 if for the excellent diagnostic quality]. Student's t-test was used to test the significance of difference between the mean image quality score assigned to input and processed images at significance level α = 0.05. Results: The application of IT functions with standardized parameters significantly improved the quality of high dynamic range bone scintigraphic images ( P enhancement. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Strontium hydroxyapatite/chitosan nanohybrid scaffolds with enhanced osteoinductivity for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Lei, Yong [The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234 (China); Xu, Zhengliang [Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, 600 Yishan Road, Shanghai 200233 (China); Ke, Qinfei [The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234 (China); Yin, Wenjing; Chen, Yixuan [Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, 600 Yishan Road, Shanghai 200233 (China); Zhang, Changqing, E-mail: zhangcq@sjtu.edu.cn [Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, 600 Yishan Road, Shanghai 200233 (China); Guo, Yaping, E-mail: ypguo@shnu.edu.cn [The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234 (China)

2017-03-01

For the clinical application of bone tissue engineering with the combination of biomaterials and mesenchymal stem cells (MSCs), bone scaffolds should possess excellent biocompatibility and osteoinductivity to accelerate the repair of bone defects. Herein, strontium hydroxyapatite [SrHAP, Ca{sub 10−x}Sr{sub x}(PO{sub 4}){sub 6}(OH){sub 2}]/chitosan (CS) nanohybrid scaffolds were fabricated by a freeze-drying method. The SrHAP nanocrystals with the different x values of 0, 1, 5 and 10 are abbreviated to HAP, Sr1HAP, Sr5HAP and Sr10HAP, respectively. With increasing x values from 0 to 10, the crystal cell volumes and axial lengths of SrHAP become gradually large because of the greater ion radius of Sr{sup 2+} than Ca{sup 2+}, while the crystal sizes of SrHAP decrease from 70.4 nm to 46.7 nm. The SrHAP/CS nanohybrid scaffolds exhibits three-dimensional (3D) interconnected macropores with pore sizes of 100–400 μm, and the SrHAP nanocrystals are uniformly dispersed within the scaffolds. In vitro cell experiments reveal that all the HAP/CS, Sr1HAP/CS, Sr5HAP/CS and Sr10HAP/CS nanohybrid scaffolds possess excellent cytocompatibility with the favorable adhesion, spreading and proliferation of human bone marrow mesenchymal stem cells (hBMSCs). The Sr5HAP nanocrystals in the scaffolds do not affect the adhesion, spreading of hBMSCs, but they contribute remarkably to cell proliferation and osteogenic differentiation. As compared with the HAP/CS nanohybrid scaffold, the released Sr{sup 2+} ions from the SrHAP/CS nanohybrid scaffolds enhance alkaline phosphatase (ALP) activity, extracellular matrix (ECM) mineralization and osteogenic-related COL-1 and ALP expression levels. Especially, the Sr5HAP/CS nanohybrid scaffolds exhibit the best osteoinductivity among four groups because of the synergetic effect between Ca{sup 2+} and Sr{sup 2+} ions. Hence, the Sr5HAP/CS nanohybrid scaffolds with excellent cytocompatibility and osteogenic property have promising application for

Bone marrow blood supply in gadolinium-enhanced magnetic resonance imaging

International Nuclear Information System (INIS)

Saifuddin, A.; Bann, K.; Ridgway, J.P.; Butt, W.P.

1994-01-01

A retrospective study was performed to determine whether bone blood supply can be assessed on gadolinium-enhanced magnetic resonance imaging. Lumbar spine magnetic resonance imaging (MRI) examinations of 49 patients attending for post-laminectomy examination were reviewed (30 male, 19 female, mean age 46.4 years, age range 23-84 years). Each study included sagittal T1-weighted spin echo sequences before and after gadolinium administration. Regions of interest were drawn within the L3 vertebral body from a parasagittal slice from each sequence. Signal intensity (SI) values were ascertained and the percentage increase in SI was calculated. For each patient, changes in receiver gain for pre- and post-gadolinium images were corrected by an image scaling factor. In all cases, a measurable increase in SI was found (mean 15.3%, range 4.4-55.7) due to bone vascularity. The results give no indication of the quantity or timing of blood supply but provide a basis for further work. (orig.)

Enhancement by dimethyl myleran of donor type chimerism in murine recipients of bone marrow allografts

International Nuclear Information System (INIS)

Lapidot, T.; Terenzi, A.; Singer, T.S.; Salomon, O.; Reisner, Y.

1989-01-01

A major problem in using murine models for studies of bone marrow allograft rejection in leukemia patients is the narrow margin in which graft rejection can be analyzed. In mice irradiated with greater than 9 Gy total body irradiation (TBI) rejection is minimal, whereas after administration of 8 Gy TBI, which spares a significant number of clonable T cells, a substantial frequency of host stem cells can also be detected. In current murine models, unlike in humans, bone marrow allograft rejection is generally associated with full autologous hematopoietic reconstitution. In the present study, we investigated the effect of the myeloablative drug dimethyl myleran (DMM) on chimerism status following transplantation of T cell-depleted allogenic bone marrow (using C57BL/6 donors and C3H/HeJ recipients, conditioned with 8 Gy TBI). Donor type chimerism 1 to 2 months post-transplant of 1 to 3 x 10(6) bone marrow cells was markedly enhanced by using DMM one day after TBI and prior to transplantation. Conditioning with cyclophosphamide instead of DMM, in combination with 8 Gy TBI, did not enhance engraftment of donor type cells. Artificial reconstitution of T cells, after conditioning with TBI plus DMM, by adding mature thymocytes, or presensitization with irradiated donor type spleen cells 1 week before TBI and DMM, led to strong graft rejection and consequently to severe anemia. The anti-donor responses in these models were proportional to the number of added T cells and to the number of cells used for presensitization, and they could be neutralized by increasing the bone marrow inoculum

Does PEEK/HA Enhance Bone Formation Compared With PEEK in a Sheep Cervical Fusion Model?

Science.gov (United States)

Walsh, William R; Pelletier, Matthew H; Bertollo, Nicky; Christou, Chris; Tan, Chris

2016-11-01

Polyetheretherketone (PEEK) has a wide range of clinical applications but does not directly bond to bone. Bulk incorporation of osteoconductive materials including hydroxyapatite (HA) into the PEEK matrix is a potential solution to address the formation of a fibrous tissue layer between PEEK and bone and has not been tested. Using in vivo ovine animal models, we asked: (1) Does PEEK-HA improve cortical and cancellous bone ongrowth compared with PEEK? (2) Does PEEK-HA improve bone ongrowth and fusion outcome in a more challenging functional ovine cervical fusion model? The in vivo responses of PEEK-HA Enhanced and PEEK-OPTIMA ® Natural were evaluated for bone ongrowth in the form of dowels implanted in the cancellous and cortical bone of adult sheep and examined at 4 and 12 weeks as well as interbody cervical fusion at 6, 12, and 26 weeks. The bone-implant interface was evaluated with radiographic and histologic endpoints for a qualitative assessment of direct bone contact of an intervening fibrous tissue later. Gamma-irradiated cortical allograft cages were evaluated as well. Incorporating HA into the PEEK matrix resulted in more direct bone apposition as opposed to the fibrous tissue interface with PEEK alone in the bone ongrowth as well as interbody cervical fusions. No adverse reactions were found at the implant-bone interface for either material. Radiography and histology revealed resorption and fracture of the allograft devices in vivo. Incorporating HA into PEEK provides a more favorable environment than PEEK alone for bone ongrowth. Cervical fusion was improved with PEEK-HA compared with PEEK alone as well as allograft bone interbody devices. Improving the bone-implant interface with a PEEK device by incorporating HA may improve interbody fusion results and requires further clinical studies.

Enhanced release of bone morphogenetic proteins from demineralized bone matrix by gamma irradiation

International Nuclear Information System (INIS)

Sung, Nak-Yun; Choi, Jong-il

2015-01-01

Gamma irradiation is a useful method for sterilizing demineralized bone matrix (DBM), but its effect on the osteoinductivity of DBM is still controversial. In this study, the osteoinductive activity of gamma-irradiated DBM was examined using a mouse myoblastic cell line (C2C12). DBM was extracted from adult bovine bone and was irradiated at a dose of 25 kGy using a 60 cobalt gamma-irradiator. Cell proliferation with DBM was not affected by gamma-irradiation, but alkaline phosphatase and osteocalcin productions were significantly increased in C2C12 cell groups treated with gamma-irradiated DBM. It was reasoned that bone morphogenetic proteins were more efficiently released from gamma-irradiated DBM than from the non-irradiated control. This result suggests the effectiveness of radiation sterilization of bone implants - Highlights: • Demineralized bone matrix (DBM) was gamma-irradiated for sterilization. • Irradiated DBM had higher alkaline phosphatase and osteocalcin production. • It was reasoned the more released bone morphogenetic proteins by irradiation. • This result supports the application of radiation sterilization for bone implants

* 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

BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects.

Science.gov (United States)

Xiong, Long; Zeng, Jianhua; Yao, Aihua; Tu, Qiquan; Li, Jingtang; Yan, Liang; Tang, Zhiming

2015-01-01

The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 μm) with a core (60±18 μm) and a mesoporous shell (180±42 m(2)/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 μg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration.

Simvastatin enhances bone morphogenetic protein receptor type II expression

International Nuclear Information System (INIS)

Hu Hong; Sung, Arthur; Zhao, Guohua; Shi, Lingfang; Qiu Daoming; Nishimura, Toshihiko; Kao, Peter N.

2006-01-01

Statins confer therapeutic benefits in systemic and pulmonary vascular diseases. Bone morphogenetic protein (BMP) receptors serve essential signaling functions in cardiovascular development and skeletal morphogenesis. Mutations in BMP receptor type II (BMPR2) are associated with human familial and idiopathic pulmonary arterial hypertension, and pathologic neointimal proliferation of vascular endothelial and smooth muscle cells within small pulmonary arteries. In severe experimental pulmonary hypertension, simvastatin reversed disease and conferred a 100% survival advantage. Here, modulation of BMPR2 gene expression by simvastatin is characterized in human embryonic kidney (HEK) 293T, pulmonary artery smooth muscle, and lung microvascular endothelial cells (HLMVECs). A 1.4 kb BMPR2 promoter containing Egr-1 binding sites confers reporter gene activation in 293T cells which is partially inhibited by simvastatin. Simvastatin enhances steady-state BMPR2 mRNA and protein expression in HLMVEC, through posttranscriptional mRNA stabilization. Simvastatin induction of BMPR2 expression may improve BMP-BMPR2 signaling thereby enhancing endothelial differentiation and function

Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.

Science.gov (United States)

Jacobsen, Christina M; Schwartz, Marissa A; Roberts, Heather J; Lim, Kyung-Eun; Spevak, Lyudmila; Boskey, Adele L; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

2016-09-01

Osteogenesis Imperfecta (OI) comprises a group of genetic skeletal fragility disorders. The mildest form of OI, Osteogenesis Imperfecta type I, is frequently caused by haploinsufficiency mutations in COL1A1, the gene encoding the α1(I) chain of type 1 collagen. Children with OI type I have a 95-fold higher fracture rate compared to unaffected children. Therapies for OI type I in the pediatric population are limited to anti-catabolic agents. In adults with osteoporosis, anabolic therapies that enhance Wnt signaling in bone improve bone mass, and ongoing clinical trials are determining if these therapies also reduce fracture risk. We performed a proof-of-principle experiment in mice to determine whether enhancing Wnt signaling in bone could benefit children with OI type I. We crossed a mouse model of OI type I (Col1a1(+/Mov13)) with a high bone mass (HBM) mouse (Lrp5(+/p.A214V)) that has increased bone strength from enhanced Wnt signaling. Offspring that inherited the OI and HBM alleles had higher bone mass and strength than mice that inherited the OI allele alone. However, OI+HBM and OI mice still had bones with lower ductility compared to wild-type mice. We conclude that enhancing Wnt signaling does not make OI bone normal, but does improve bone properties that could reduce fracture risk. Therefore, agents that enhance Wnt signaling are likely to benefit children and adults with OI type 1. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysing the bioactive makeup of demineralised dentine matrix on bone marrow mesenchymal stem cells for enhanced bone repair.

Science.gov (United States)

Avery, S J; Sadaghiani, L; Sloan, A J; Waddington, R J

2017-07-10

Dentine matrix has proposed roles for directing mineralised tissue repair in dentine and bone; however, the range of bioactive components in dentine and specific biological effects on bone-derived mesenchymal stem cells (MSCs) in humans are less well understood. The aims of this study were to further elucidate the biological response of MSCs to demineralised dentine matrix (DDM) in enhancing wound repair responses and ascertain key contributing components. Dentine was obtained from human teeth and DDM proteins solubilised with ethylenediaminetetraacetic acid (EDTA). Bone marrow derived MSCs were commercially obtained. Cells with a more immature phenotype were then selected by preferential fibronectin adhesion (FN-BMMSCs) for use in subsequent in vitro assays. DDM at 10 µg/mL reduced cell expansion, attenuated apoptosis and was the minimal concentration capable of inducing osteoblastic differentiation. Enzyme-linked immunosorbent assay (ELISA) quantification of growth factors indicated physiological levels produced the above responses; transforming growth factor β (TGF-β1) was predominant (15.6 ng/mg DDM), with relatively lower concentrations of BMP-2, FGF, VEGF and PDGF (6.2-4.7 ng/mg DDM). Fractionation of growth factors from other DDM components by heparin affinity chromatography diminished osteogenic responses. Depletion of biglycan from DDM also attenuated osteogenic potency, which was partially rescued by the isolated biglycan. Decorin depletion from DDM had no influence on osteogenic potency. Collectively, these results demonstrate the potential of DDM for the delivery of physiological levels of growth factors for bone repair processes, and substantiate a role for biglycan as an additional adjuvant for driving osteogenic pathways.

Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone Resorption

Directory of Open Access Journals (Sweden)

Chen-he Zhou

2018-03-01

Full Text Available Osteoporosis is a common health problem worldwide caused by an imbalance of bone formation vs. bone resorption. However, current therapeutic approaches aimed at enhancing bone formation or suppressing bone resorption still have some limitations. In this study, we demonstrated for the first time that cepharanthine (CEP, derived from Stephania cepharantha Hayata exerted a protective effect on estrogen deficiency-induced bone loss. This protective effect was confirmed to be achieved through inhibition of bone resorption in vivo, rather than through enhancement of bone formation in vivo. Furthermore, the in vitro study revealed that CEP attenuated receptor activator of nuclear factor κB ligand (RANKL-induced osteoclast formation, and suppressed bone resorption by impairing the c-Jun N-terminal kinase (JNK and phosphatidylinositol 3-kinase (PI3K-AKT signaling pathways. The inhibitory effect of CEP could be partly reversed by treatment with anisomycin (a JNK and p38 agonist and/or SC79 (an AKT agonist in vitro. Our results thus indicated that CEP could prevent estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis. Hence, CEP might be a novel therapeutic agent for anti-osteoporosis therapy.

Reconstruction of segmental bone defect of long bones after tumor resection by devitalized tumor-bearing bone

OpenAIRE

Qu, Huayi; Guo, Wei; Yang, Rongli; Li, Dasen; Tang, Shun; Yang, Yi; Dong, Sen; Zang, Jie

2015-01-01

Background The reconstruction of an intercalary bone defect after a tumor resection of a long bone remains a challenge to orthopedic surgeons. Though several methods have been adopted to enhance the union of long segmental allografts or retrieved segmental autografts to the host bones, still more progresses are required to achieve a better union rate. Several methods have been adopted to devitalize tumor bone for recycling usage, and the results varied. We describe our experiences of using de...

Overexpression of Insulin-Like Growth Factor 1 Enhanced the Osteogenic Capability of Aging Bone Marrow Mesenchymal Stem Cells.

Science.gov (United States)

Chen, Ching-Yun; Tseng, Kuo-Yun; Lai, Yen-Liang; Chen, Yo-Shen; Lin, Feng-Huei; Lin, Shankung

2017-01-01

Many studies have indicated that loss of the osteoblastogenic potential in bone marrow mesenchymal stem cells (bmMSCs) is the major component in the etiology of the aging-related bone deficit. But how the bmMSCs lose osteogenic capability in aging is unclear. Using 2-dimentional cultures, we examined the dose response of human bmMSCs, isolated from adult and aged donors, to exogenous insulin-like growth factor 1 (IGF-1), a growth factor regulating bone formation. The data showed that the mitogenic activity and the osteoblastogenic potential of bmMSCs in response to IGF-1 were impaired with aging, whereas higher doses of IGF-1 increased the proliferation rate and osteogenic potential of aging bmMSCs. Subsequently, we seeded IGF-1-overexpressing aging bmMSCs into calcium-alginate scaffolds and incubated in a bioreactor with constant perfusion for varying time periods to examine the effect of IGF-1 overexpression to the bone-forming capability of aging bmMSCs. We found that IGF-1 overexpression in aging bmMSCs facilitated the formation of cell clusters in scaffolds, increased the cell survival inside the cell clusters, induced the expression of osteoblast markers, and enhanced the biomineralization of cell clusters. These results indicated that IGF-1 overexpression enhanced cells' osteogenic capability. Thus, our data suggest that the aging-related loss of osteogenic potential in bmMSCs can be attributed in part to the impairment in bmMSCs' IGF-1 signaling, and support possible application of IGF-1-overexpressing autologous bmMSCs in repairing bone defect of the elderly and in producing bone graft materials for repairing large scale bone injury in the elderly.

Enhanced Tendon-to-Bone Healing of Chronic Rotator Cuff Tears by Bone Marrow Aspirate Concentrate in a Rabbit Model

Science.gov (United States)

Liu, Xiao Ning; Yang, Cheol-Jung; Kim, Ji Eui; Du, Zhen Wu; Ren, Ming; Zhang, Wei; Zhao, Hong Yu; Kim, Kyung Ok

2018-01-01

Background To evaluate the influence of bone marrow aspirate concentrate (BMAC) on tendon-to-bone healing in a rabbit rotator cuff model and to characterize the composition of growth factors in BMAC. Methods In this in vivo study, 40 rabbits were allocated into five groups: control (C), repair + saline (RS), repair + platelet-rich plasma (PRP; RP), repair + BMAC (RB) and repair + PRP + BMAC (RPB). A tear model was created by supraspinatus tendon transection at the footprint. Six weeks after transection, the torn tendon was repaired along with BMAC or PRP administration. Six weeks after repair, shoulder samples were harvested for biomechanical and histological testing. Ten rabbits were used for processing PRP and BMAC, followed by analysis of blood cell composition and the levels of growth factors in vitro. Results The ultimate load-to-failure was significantly higher in RPB group compared to RS group (p = 0.025). BMAC-treated groups showed higher values of biomechanical properties than RS group. The histology of BMAC-treated samples showed better collagen fiber continuity and orientation than RS group. BMAC contained significantly higher levels of the several growth factors than PRP. Conclusions Locally administered BMAC enhanced tendon-to-bone healing and has potential for clinical applications. PMID:29564054

Cytokines and growth factors which regulate bone cell function

Science.gov (United States)

Seino, Yoshiki

Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

SWIMMING ENHANCES BONE MASS ACQUISITION IN GROWING FEMALE RATS

Directory of Open Access Journals (Sweden)

Joanne McVeigh

2010-12-01

Full Text Available Growing bones are most responsive to mechanical loading. We investigated bone mass acquisition patterns following a swimming or running exercise intervention of equal duration, in growing rats. We compared changes in bone mineral properties in female Sprague Dawley rats that were divided into three groups: sedentary controls (n = 10, runners (n = 8 and swimmers (n = 11. Runners and swimmers underwent a six week intervention, exercising five days per week, 30min per day. Running rats ran on an inclined treadmill at 0.33 m.s-1, while swimming rats swam in 25oC water. Dual energy X-ray absorptiometry scans measuring bone mineral content (BMC, bone mineral density (BMD and bone area at the femur, lumbar spine and whole body were recorded for all rats before and after the six week intervention. Bone and serum calcium and plasma parathyroid hormone (PTH concentrations were measured at the end of the 6 weeks. Swimming rats had greater BMC and bone area changes at the femur and lumbar spine (p < 0.05 than the running rats and a greater whole body BMC and bone area to that of control rats (p < 0.05. There were no differences in bone gain between running and sedentary control rats. There was no significant difference in serum or bone calcium or PTH concentrations between the groups of rats. A swimming intervention is able to produce greater beneficial effects on the rat skeleton than no exercise at all, suggesting that the strains associated with swimming may engender a unique mechanical load on the bone

Enhancement of osteogenesis and biodegradation control by brushite coating on Mg-Nd-Zn-Zr alloy for mandibular bone repair.

Science.gov (United States)

Guan, Xingmin; Xiong, Meiping; Zeng, Feiyue; Xu, Bin; Yang, Lingdi; Guo, Han; Niu, Jialin; Zhang, Jian; Chen, Chenxin; Pei, Jia; Huang, Hua; Yuan, Guangyin

2014-12-10

To diminish incongruity between bone regeneration and biodegradation of implant magnesium alloy applied for mandibular bone repair, a brushite coating was deposited on a matrix of a Mg-Nd-Zn-Zr (hereafter, denoted as JDBM) alloy to control the degradation rate of the implant and enhance osteogenesis of the mandible bone. Both in vitro and in vivo evaluations were carried out in the present work. Viability and adhesion assays of rabbit bone marrow mesenchyal stem cells (rBM-MSCs) were applied to determine the biocompatibility of a brushite-coated JDBM alloy. Osteogenic gene expression was characterized by quantitative real-time polymerase chain reaction (RT-PCR). Brushite-coated JDBM screws were implanted into mandible bones of rabbits for 1, 4, and 7 months, respectively, using 316L stainless steel screws as a control group. In vivo biodegradation rate was determined by synchrotron radiation X-ray microtomography, and osteogenesis was observed and evaluated using Van Gieson's picric acid-fuchsin. Both the naked JDBM and brushite-coated JDBM samples revealed adequate biosafety and biocompatibility as bone repair substitutes. In vitro results showed that brushite-coated JDBM considerably induced osteogenic differentiation of rBM-MSCs. And in vivo experiments indicated that brushite-coated JDBM screws presented advantages in osteoconductivity and osteogenesis of mandible bone of rabbits. Degradation rate was suppressed at a lower level at the initial stage of implantation when new bone tissue formed. Brushite, which can enhance oeteogenesis and partly control the degradation rate of an implant, is an appropriate coating for JDBM alloys used for mandibular repair. The Mg-Nd-Zn-Zr alloy with brushite coating possesses great potential for clinical applications for mandibular repair.

Combined VEGF and LMP-1 delivery enhances osteoprogenitor cell differentiation and ectopic bone formation.

Science.gov (United States)

Wang, Xiuli; Cui, Fuai; Madhu, Vedavathi; Dighe, Abhijit S; Balian, Gary; Cui, Quanjun

2011-02-01

A novel strategy to enhance bone repair is to combine angiogenic factors and osteogenic factors. We combined vascular endothelial growth factor (VEGF) and LIM mineralization protein-1 (LMP-1) by using an internal ribosome entry site to link the genes within a single plasmid. We then evaluated the effects on osteoblastic differentiation in vitro and ectopic bone formation in vivo with a subcutaneously placed PLAGA scaffold loaded with a cloned mouse osteoprogenitor cell line, D1, transfected with plasmids containing VEGF and LMP-1 genes. The cells expressing both genes elevated mRNA expression of RunX2 and β-catenin and alkaline phosphatase activity compared to cells from other groups. In vivo, X-ray and micro-CT analysis of the retrieved implants revealed more ectopic bone formation at 2 and 3 weeks but not at 4 weeks compared to other groups. The results indicate that the combination of the therapeutic growth factors potentiates cell differentiation and may promote osteogenesis.

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...

Effects of hot boning and moisture enhancement on the eating quality of cull cow beef.

Science.gov (United States)

Pivotto, L M; Campbell, C P; Swanson, K; Mandell, I B

2014-01-01

The effects of chilling method and moisture enhancement were examined for improving eating quality of semimembranosus (SM) and longissimus lumborum (LL) from 62 cull beef cows. Chilling method included hot boning muscles after 45 to 60 min postmortem or conventional chilling for 24 h. Moisture enhancement included 1) a non-injected control (CONT) or injection processing (10% of product weight) using 2) Sodium Tripolyphosphate/salt (Na/STP), 3) Sodium Citrate (NaCIT), 4) Calcium Ascorbate (CaASC), or 5) Citrus Juices (CITRUS). Chilling method by moisture enhancement treatment interactions (Pboned vs. conventionally chilled product (SM and LL) for CaASC vs. other moisture enhancement treatments. Chilling method by moisture enhancement treatment interactions (Pboned LL using CaASC vs. Na/STP. Moisture enhancement can improve tenderness of cull cow beef depending on combinations of chilling method and moisture enhancement treatments used. © 2013.

Aneurysmal bone cyst of the temporal bone

International Nuclear Information System (INIS)

Buxi, Tarvinder; Sud Seema; Vohra, Rakesh; Sud, Aditi; Singh, Satnam

2004-01-01

Aneurysmal bone cyst (ABC) of the temporal bone is rare. The nature of the underlying disorder that converted into the ABC might, however, be difficult to ascertain on imaging as well as on histopathology. The unusual CT and MRI findings in a case of ABC of the temporal bone are presented. This had transdural intracerebral spread with a large component of solid enhancing matrix but no peripheral calcific rim. The patient was an adult of 45 years with a history of headache for more than 1 year Copyright (2004) Blackwell Publishing Asia Pty Ltd

Gadolinium-DTPA enhanced magnetic resonance imaging of bone cysts in patients with rheumatoid arthritis.

Science.gov (United States)

Gubler, F M; Algra, P R; Maas, M; Dijkstra, P F; Falke, T H

1993-01-01

OBJECTIVES--To examine the contents of intraosseous cysts in patients with rheumatoid arthritis (RA) through the signal intensity characteristics on gadolinium-DTPA (Gd-DTPA) enhanced magnetic resonance imaging. METHODS--The hand or foot joints of nine patients with the cystic form of RA (where the initial radiological abnormality consisted of intraosseous cysts without erosions) were imaged before and after intravenous administration of Gd-DTPA. A 0.6 unit, T1 weighted spin echo and T2* weighted gradient echo were used to obtain images in at least two perpendicular planes. RESULTS--Most cysts showed a low signal intensity on the non-enhanced T1 weighted (spin echo) images and a high signal intensity on the T2* weighted (gradient echo) images, consistent with a fluid content. No cyst showed an enhancement of signal intensity on the T1 weighted images after intravenous administration of Gd-DTPA, whereas synovium hyperplasia at the site of bony erosions did show an increased signal intensity after Gd-DTPA. Magnetic resonance imaging detected more cysts (as small as 2 mm) than plain films, and the cysts were located truly intraosseously. In six patients no other joint abnormalities were identified by magnetic resonance imaging; the three other patients also showed, after Gd-DTPA administration, an enhanced synovium at the site of bony erosions. CONCLUSIONS--It is suggested that intraosseous bone cysts in patients with RA do not contain hyperaemic synovial proliferation. The bone cysts in patients with the cystic form of RA may be the only joint abnormality. Images PMID:8257207

Hydroxyapatite nanorod and microsphere functionalized with bioactive lactoferrin as a new biomaterial for enhancement bone regeneration.

Science.gov (United States)

Shi, Pujie; Wang, Qun; Yu, Cuiping; Fan, Fengjiao; Liu, Meng; Tu, Maolin; Lu, Weihong; Du, Ming

2017-07-01

Lactoferrin (LF) has been recently recognized as a promising new novel bone growth factor for the beneficial effects on bone cells and promotion of bone growth. Currently, it has been attracted wide attention in bone regeneration as functional food additives or a potential bioactive protein in bone tissue engineering. The present study investigated the possibility that hydroxyapatite (HAP) particles, a widely used bone substitute material for high biocompatibility and osteoconductivity, functionalized with lactoferrin as a composite material are applied to bone tissue engineering. Two kinds of hydroxyapatite samples with different sizes, including nanorods and microspheres particles, were functionalized with lactoferrin molecules, respectively. A detailed characterization of as-prepared HAP-LF complex is presented, combining thermal gravimetric analysis (TGA) and Fourier Transform Infrared Spectroscopy (FT-IR). Zeta potential and the analysis of electrostatic surface potential of lactoferrin were carried to reveal the mechanism of adsorption. The effects of HAP-LF complex on MC3T3-E1 osteoblast proliferation and morphology were systematically evaluated at different culture time. Interestingly, results showed that cell viability of HAP-LF group was significantly higher than HAP group indicating that the HAP-LF can improve the biocompatibility of HAP, which mainly originated from a combination of HAP-LF interaction. These results indicated that hydroxyapatite particles can work as a controlled releasing carrier of lactoferrin successfully, and lactoferrin showed better potentiality on using in the field of bone regeneration by coupling with hydroxyapatite. This study would provide a new biomaterial and might offer a new insight for enhancement of bone regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

TOB1 Deficiency Enhances the Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Tendon-Bone Healing in a Rat Rotator Cuff Repair Model

Directory of Open Access Journals (Sweden)

Yulei Gao

2016-01-01

Full Text Available Background/Aims: This study investigated the effect of silencing TOB1 (Transducer of ERBB2, 1 expression in bone marrow-derived mesenchymal stem cells (MSCs on MSC-facilitated tendon-bone healing in a rat supraspinatus repair model. Methods: Rat MSCs were transduced with a recombinant lentivirus encoding short hairpin RNA (shRNA against TOB1. MSC cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assays. The effect of MSCs with TOB1 deficiency on tendon-bone healing in a rat rotator cuff repair model was evaluated by biomechanical testing, histological analysis and collagen type I and II gene expression. An upstream regulator (miR-218 of TOB1 was determined in MSCs. Results: We found that knockdown of TOB1 significantly increased the proliferative activity of rat MSCs in vitro. When MSCs with TOB1 deficiency were injected into injured rat supraspinatus tendon-bone junctions, the effect on tendon-bone healing was enhanced compared to treatment with control MSCs with normal TOB1 expression, as evidenced by elevated levels of ultimate load to failure and stiffness, increased amount of fibrocartilage and augmented expression of collagen type I and type II genes. In addition, we found that the TOB1 3′ untranslated region is a direct target of miR-218. Similar to the effect of TOB1 deficiency, overexpression of miR-218 effectively promoted tendon-bone healing in rat. Conclusion: These results suggest that TOB1 may play a negative role in the effect of MSCs on tendon-bone healing, and imply that expression of TOB1 may be regulated by miR-218.

Novel strontium-doped bioactive glass nanoparticles enhance proliferation and osteogenic differentiation of human bone marrow stromal cells

Energy Technology Data Exchange (ETDEWEB)

Strobel, L. A. [University of Erlangen-Nuremberg Medical Center, Department of Plastic and Hand Surgery (Germany); Hild, N.; Mohn, D.; Stark, W. J. [ETH Zurich, Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering (Switzerland); Hoppe, A. [University of Erlangen-Nuremberg, Department of Materials Science and Engineering, Institute of Biomaterials (Germany); Gbureck, U. [University of Wuerzburg, Department for Functional Materials in Medicine and Dentistry (Germany); Horch, R. E.; Kneser, U. [University of Erlangen-Nuremberg Medical Center, Department of Plastic and Hand Surgery (Germany); Boccaccini, A. R., E-mail: aldo.boccaccini@ww.uni-erlangen.de [University of Erlangen-Nuremberg, Department of Materials Science and Engineering, Institute of Biomaterials (Germany)

2013-07-15

The present study investigates a new family of bioactive glass nanoparticles with and without Sr-doping focusing on the influence of the nanoparticles on human bone marrow stromal cells (hBMSCs) in vitro. The bioactive glass nanoparticles were fabricated by flame spray synthesis and a particle diameter of 30-35 nm was achieved. Glass nanoparticles were undoped (BG 13-93-0Sr) or doped with 5 wt% strontium (Sr) (BG 13-93-5Sr) and used at concentrations of 10 and 100 {mu}g/cm Superscript-Two (particles per culture plate area), respectively. Cells were cultured for 14 days after which the samples were analysed regarding metabolic activity and expression of various bone-specific genes. Cell growth and morphology indicated the high cytocompatibility of the nanoparticulate bioactive glass. The presence of the nanoparticles enhanced cell growth compared to the plain polystyrene control group. At a concentration of 100 {mu}g/cm Superscript-Two , Sr-doped particles led to significantly enhanced gene expression of osteocalcin, collagen type 1 and vascular endothelial growth factor. Thus, Sr-doped nanoparticles showing a dose-dependent increase of osteogenic differentiation in hBMSCs are a promising biomaterial for bone regeneration purposes.

Novel strontium-doped bioactive glass nanoparticles enhance proliferation and osteogenic differentiation of human bone marrow stromal cells

International Nuclear Information System (INIS)

Strobel, L. A.; Hild, N.; Mohn, D.; Stark, W. J.; Hoppe, A.; Gbureck, U.; Horch, R. E.; Kneser, U.; Boccaccini, A. R.

2013-01-01

The present study investigates a new family of bioactive glass nanoparticles with and without Sr-doping focusing on the influence of the nanoparticles on human bone marrow stromal cells (hBMSCs) in vitro. The bioactive glass nanoparticles were fabricated by flame spray synthesis and a particle diameter of 30–35 nm was achieved. Glass nanoparticles were undoped (BG 13-93-0Sr) or doped with 5 wt% strontium (Sr) (BG 13-93-5Sr) and used at concentrations of 10 and 100 μg/cm² (particles per culture plate area), respectively. Cells were cultured for 14 days after which the samples were analysed regarding metabolic activity and expression of various bone-specific genes. Cell growth and morphology indicated the high cytocompatibility of the nanoparticulate bioactive glass. The presence of the nanoparticles enhanced cell growth compared to the plain polystyrene control group. At a concentration of 100 μg/cm², Sr-doped particles led to significantly enhanced gene expression of osteocalcin, collagen type 1 and vascular endothelial growth factor. Thus, Sr-doped nanoparticles showing a dose-dependent increase of osteogenic differentiation in hBMSCs are a promising biomaterial for bone regeneration purposes

Novel strontium-doped bioactive glass nanoparticles enhance proliferation and osteogenic differentiation of human bone marrow stromal cells

Science.gov (United States)

Strobel, L. A.; Hild, N.; Mohn, D.; Stark, W. J.; Hoppe, A.; Gbureck, U.; Horch, R. E.; Kneser, U.; Boccaccini, A. R.

2013-07-01

The present study investigates a new family of bioactive glass nanoparticles with and without Sr-doping focusing on the influence of the nanoparticles on human bone marrow stromal cells (hBMSCs) in vitro. The bioactive glass nanoparticles were fabricated by flame spray synthesis and a particle diameter of 30-35 nm was achieved. Glass nanoparticles were undoped (BG 13-93-0Sr) or doped with 5 wt% strontium (Sr) (BG 13-93-5Sr) and used at concentrations of 10 and 100 μg/cm² (particles per culture plate area), respectively. Cells were cultured for 14 days after which the samples were analysed regarding metabolic activity and expression of various bone-specific genes. Cell growth and morphology indicated the high cytocompatibility of the nanoparticulate bioactive glass. The presence of the nanoparticles enhanced cell growth compared to the plain polystyrene control group. At a concentration of 100 μg/cm², Sr-doped particles led to significantly enhanced gene expression of osteocalcin, collagen type 1 and vascular endothelial growth factor. Thus, Sr-doped nanoparticles showing a dose-dependent increase of osteogenic differentiation in hBMSCs are a promising biomaterial for bone regeneration purposes.

Reaming debris as a novel source of autologous bone to enhance healing of bone defects

NARCIS (Netherlands)

Bakker, A.D.; Kroeze, R.J.; Korstjens, C.; de Kleine, R.H.; Frolke, J.P.M.; Klein-Nulend, J.

2011-01-01

Reaming debris is formed when bone defects are stabilized with an intramedullary nail, and contains viable osteoblast-like cells and growth factors, and might thus act as a natural osteoinductive scaffold. The advantage of using reaming debris over stem cells or autologous bone for healing bone

Reaming debris as a novel source of autologous bone to enhance healing of bone defects

NARCIS (Netherlands)

Bakker, Astrid D.; Kroeze, Robert Jan; Korstjens, Clara; de Kleine, Ruben H.; Frolke, Jan Paul M.; Klein-Nulend, Jenneke

Reaming debris is formed when bone defects are stabilized with an intramedullary nail, and contains viable osteoblast-like cells and growth factors, and might thus act as a natural osteoinductive scaffold. The advantage of using reaming debris over stem cells or autologous bone for healing bone

CT diagnosis of occipital bone pacchionian depression

International Nuclear Information System (INIS)

Zhu Jianguo; Xu Xiaolin

2004-01-01

Objective: To improve the recognition of the CT findings of occipital bone pacchionian depression, in order to avoid misdiagnosis. Methods: occipital bone pacchionian depression underwent CT with plain scan and intravenous contrast enhancement in 11 cases, and then the CT findings were analyzed. Results: Occipital bone pacchionian depression situated beside the torcular herophilia in 11 cases. The depression or bone defect were found at occipital bone inner plate, they can reach diploe or outer plate and had no enhancement after contrast injection. Conclusions: CT scans play an important role in diagnosis and differential diagnosis of occipital bone pacchionian depression

Bone compaction enhances implant fixation in a canine gap model

DEFF Research Database (Denmark)

Kold, Søren; Rahbek, Ole; Toft, Marianne

2005-01-01

A new bone preparation technique, compaction, has increased fixation of implants inserted with exact-fit or press-fit to bone. Furthermore, a demonstrated spring-back effect of compacted bone might be of potential value in reducing the initial gaps that often exist between clinical inserted...... implants and bone. However, it is unknown whether the compression and breakage of trabeculae during the compaction procedure results in impaired gap-healing of compacted bone. Therefore, we compared compaction with conventional drilling in a canine gap model. Grit-blasted titanium implants (diameter 6 mm...... that the beneficial effect of reduced gap size, as compacted bone springs back, is not eliminated by an impaired gap-healing of compacted bone....

Differential diagnosis of metastases in bone scans: chemotherapy induced bone necrosis

International Nuclear Information System (INIS)

Reuland, P.

1999-01-01

Aim: Influenced by the incorrect diagnosis of a bone metastasis caused by bone necrosis we evaluated reasons and frequency of bone necrosis in patients referred for bone scanning in follow-up of tumors. Methods: Bone scans performed within two years on patients with primary bone tumors or tumors metastatic to bone were reviewed in respect to the final diagnosis bone necrosis. Results: We found the cases of three young patients who presented the appearance of hot spots on bone scintigrams which were finally diagnosed as bone necrosis. In two cases the diagnosis was based on histological findings, in one case the diagnosis was made evident by follow-up. All the three patients had been treated by chemotherapy and presented no other reason for the development of bone necrosis. Enhanced tracer uptake in all sites decreased within eight weeks up to two years without therapy. Conclusion: Single and multiple hot spots after chemotherapy may be originated by bone necrosis but mimikry metastases. (orig.) [de

Strontium hydroxyapatite/chitosan nanohybrid scaffolds with enhanced osteoinductivity for bone tissue engineering.

Science.gov (United States)

Lei, Yong; Xu, Zhengliang; Ke, Qinfei; Yin, Wenjing; Chen, Yixuan; Zhang, Changqing; Guo, Yaping

2017-03-01

For the clinical application of bone tissue engineering with the combination of biomaterials and mesenchymal stem cells (MSCs), bone scaffolds should possess excellent biocompatibility and osteoinductivity to accelerate the repair of bone defects. Herein, strontium hydroxyapatite [SrHAP, Ca 10-x Sr x (PO 4 ) 6 (OH) 2 ]/chitosan (CS) nanohybrid scaffolds were fabricated by a freeze-drying method. The SrHAP nanocrystals with the different x values of 0, 1, 5 and 10 are abbreviated to HAP, Sr1HAP, Sr5HAP and Sr10HAP, respectively. With increasing x values from 0 to 10, the crystal cell volumes and axial lengths of SrHAP become gradually large because of the greater ion radius of Sr 2+ than Ca 2+ , while the crystal sizes of SrHAP decrease from 70.4nm to 46.7nm. The SrHAP/CS nanohybrid scaffolds exhibits three-dimensional (3D) interconnected macropores with pore sizes of 100-400μm, and the SrHAP nanocrystals are uniformly dispersed within the scaffolds. In vitro cell experiments reveal that all the HAP/CS, Sr1HAP/CS, Sr5HAP/CS and Sr10HAP/CS nanohybrid scaffolds possess excellent cytocompatibility with the favorable adhesion, spreading and proliferation of human bone marrow mesenchymal stem cells (hBMSCs). The Sr5HAP nanocrystals in the scaffolds do not affect the adhesion, spreading of hBMSCs, but they contribute remarkably to cell proliferation and osteogenic differentiation. As compared with the HAP/CS nanohybrid scaffold, the released Sr 2+ ions from the SrHAP/CS nanohybrid scaffolds enhance alkaline phosphatase (ALP) activity, extracellular matrix (ECM) mineralization and osteogenic-related COL-1 and ALP expression levels. Especially, the Sr5HAP/CS nanohybrid scaffolds exhibit the best osteoinductivity among four groups because of the synergetic effect between Ca 2+ and Sr 2+ ions. Hence, the Sr5HAP/CS nanohybrid scaffolds with excellent cytocompatibility and osteogenic property have promising application for bone tissue engineering. Copyright © 2016. Published

A Preliminary Evaluation of Lyophilized Gelatin Sponges, Enhanced with Platelet-Rich Plasma, Hydroxyapatite and Chitin Whiskers for Bone Regeneration

Directory of Open Access Journals (Sweden)

Andrew J. Spence

2013-04-01

Full Text Available The purpose of this study was to perform a number of preliminary in vitro evaluations on an array of modified gelatin gel sponge scaffolds for use in a bone graft application. The gelatin gels were modified through the addition of a number of components which each possess unique properties conducive to the creation and regeneration of bone: a preparation rich in growth factors (PRGF, a bioactive, lyophilized form of platelet-rich plasma, hydroxyapatite, and chitin whiskers. Platelet-rich plasma therapy is an emerging practice that has proven effective in a number of clinical applications, including enhancing bone repair through improved deposition of new bony matrix and angiogenesis. As such, the inclusion of PRGF in our gelatin scaffolds was intended to significantly enhance scaffold bioactivity, while the addition of hydroxyapatite and chitin whiskers were anticipated to increase scaffold strength. Additionally, the gelatin sponges, which readily dissolve in aqueous solutions, were subjected to 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC cross-linking, either during or post-gelation, to control their rate of degradation. Scaffolds were evaluated in vitro with respect to compressive strength, mass loss/degradation, protein release, and cellular interaction, with results demonstrating the potential of the gelatin gel sponge scaffold for use in the regeneration of bone.

A Preliminary Evaluation of Lyophilized Gelatin Sponges, Enhanced with Platelet-Rich Plasma, Hydroxyapatite and Chitin Whiskers for Bone Regeneration

Science.gov (United States)

Rodriguez, Isaac A.; Sell, Scott A.; McCool, Jennifer M.; Saxena, Gunjan; Spence, Andrew J.; Bowlin, Gary L.

2013-01-01

The purpose of this study was to perform a number of preliminary in vitro evaluations on an array of modified gelatin gel sponge scaffolds for use in a bone graft application. The gelatin gels were modified through the addition of a number of components which each possess unique properties conducive to the creation and regeneration of bone: a preparation rich in growth factors (PRGF, a bioactive, lyophilized form of platelet-rich plasma), hydroxyapatite, and chitin whiskers. Platelet-rich plasma therapy is an emerging practice that has proven effective in a number of clinical applications, including enhancing bone repair through improved deposition of new bony matrix and angiogenesis. As such, the inclusion of PRGF in our gelatin scaffolds was intended to significantly enhance scaffold bioactivity, while the addition of hydroxyapatite and chitin whiskers were anticipated to increase scaffold strength. Additionally, the gelatin sponges, which readily dissolve in aqueous solutions, were subjected to 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) cross-linking, either during or post-gelation, to control their rate of degradation. Scaffolds were evaluated in vitro with respect to compressive strength, mass loss/degradation, protein release, and cellular interaction, with results demonstrating the potential of the gelatin gel sponge scaffold for use in the regeneration of bone. PMID:24709699

Silk coating on a bioactive ceramic scaffold for bone regeneration: effective enhancement of mechanical and in vitro osteogenic properties towards load-bearing applications.

Science.gov (United States)

Li, Jiao Jiao; Roohani-Esfahani, Seyed-Iman; Kim, Kyungsook; Kaplan, David L; Zreiqat, Hala

2017-06-01

Bioactive ceramic scaffolds represent competitive choices for clinical bone reconstruction, but their widespread use is restricted by inherent brittleness and weak mechanical performance under load. This study reports the development of strong and tough bioactive scaffolds suitable for use in load-bearing bone reconstruction. A strong and bioactive ceramic scaffold (strontium-hardystonite-gahnite) is combined with single and multiple coating layers of silk fibroin to enhance its toughness, producing composite scaffolds which match the mechanical properties of cancellous bone and show enhanced capacity to promote in vitro osteogenesis. Also reported for the first time is a comparison of the coating effects obtained when a polymeric material is coated on ceramic scaffolds with differing microstructures, namely the strontium-hardystonite-gahnite scaffold with high-density struts as opposed to a conventional ceramic scaffold, such as biphasic calcium phosphate, with low-density struts. The results show that silk coating on a unique ceramic scaffold can lead to simple and effective enhancement of its mechanical and biological properties to suit a wider range of applications in clinical bone reconstruction, and also establish the influence of ceramic microstructure on the effectiveness of silk coating as a method of reinforcement when applied to different types of ceramic bone graft substitutes. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Bone marrow oedema associated with benign and malignant bone tumours

Energy Technology Data Exchange (ETDEWEB)

James, S.L.J. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham, B31 2AP (United Kingdom)], E-mail: steven.james@roh.nhs.uk; Panicek, D.M. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Davies, A.M. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham, B31 2AP (United Kingdom)

2008-07-15

Bone marrow oedema is associated with a wide variety of pathological processes including both benign and malignant bone tumours. This imaging finding in relation to intraosseous tumours can aid in providing a more focused differential diagnosis. In this review, we will discuss the MR imaging of bone marrow oedema surrounding intraosseous neoplasms. The different pulse sequences used in differentiating underlying tumour from surrounding oedema are discussed along with the role of dynamic contrast enhanced MRI. Benign lesions commonly associated with bone marrow oedema include osteoid osteoma, osteoblastoma, chondroblastoma and Langerhan's cell histiocytosis. Metastases and malignant primary bone tumours such as osteosarcoma, Ewing's sarcoma and chondrosarcoma may also be surrounded by bone marrow oedema. The imaging findings of these conditions are reviewed and illustrated. Finally, the importance of bone marrow oedema in assessment of post chemotherapeutic response is addressed.

Bone formation in cranial, mandibular, tibial and iliac bone grafts in rats

DEFF Research Database (Denmark)

Solheim, E; Pinholt, E M; Talsnes, O

1995-01-01

Several studies have suggested that grafts from membranous derived bone (e.g., calvarial grafts) retain their volume better than those from endochondral derived bone (e.g., iliac bone grafts). Increased osteogenesis in grafts of the former type has been offered as the explanation. However, simple...... volume measurements of the recovered grafts do not differentiate between viable and dead bone. We studied fresh syngeneic full-thickness bone grafts from calvaria, mandibula, tibia diaphysis, and iliac bone implanted in the back muscles of young Lewis rats. Bone formation in grafts recovered 3 weeks...... that the anatomical area of harvest is important regarding new bone formation in syngeneic bone grafts. However, the results do not support the contention that better maintenance of volume of calvarial grafts compared with iliac bone grafts is due to enhanced osteogenesis in the former....

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.

Characteristics of bone marrow with dynamic contrast-enhanced MR imaging in patients with haematological malignancies: preliminary results

International Nuclear Information System (INIS)

Zhang Lei; Yang Zhenyan; Pitman, A.G.

2007-01-01

Objective: To determine whether dynamic contrast-enhanced MR (DCE-MRI) can successfully predict the status of diffusely abnormal bone marrow, and so obviate some bone marrow biopsies done for this indication. Methods: DCE-MRI was performed in 25 patients with proven or known haematological malignancies. Time-signal intensity curves (TIC) analysis was generated from the region of the iliac crest corresponding to the planned biopsy site. Enhancement characteristics were analyzed, including peak enhance ratio (PER), maximum slope (Slope max ), time to peak (TTP), and mean time (MT). The parameters of the marrow histology included cellularity and tumour fraction (TF). Results: The median of PER, Slope max , TTP, and MT in bone marrow with haematological malignancies were 0.27, 0.21 s -1 , 79.08 s and 84.43 s, respectively. The median of DCE-MR variation in bone marrow for hypo-, normal, and hyper-, cellularity groups were PER (0.29, 0.24, 1.15), Slope max (0.20 s -1 , 0.21 s -1 1.28 s -1 ), TTP (96.67 s, 83.49 s, 25.52 s), MT(77.52 s, 86.25 s, 84.34 s), respectively. The median of PER, Slope max , TTP, and MT in bone marrow for the tumor recurrence group and the remission group were 0.32, 0.28 s -1 , 68.66 s, 84.34 s, and 0.20, 0.20 s -1 , 85.85 s, 84.52 s, respectively. There was significant difference for mean PER value between the tumor recurrence group and the remission group (P = 0.02). But there were no significant difference for mean S1ope max , TFP, and MT values between the tumor recurrence group and the remission group (P>0.05). A positive correlation was found between PER and cellularity (r=0.564, P=0.003), between S1ope max and cellularity (r=0.478, P=0.016), between MT and cellularity (r=0.186). A negative correlation was found between TTP and cellularity (r=-0.222). A positive correlation was found between PER and TF (r=0.561, P=0.004), between S1ope max and TF(r=0.318, P=0.121), between MT and TF (r=0.207, P>0.05). A negative correlation was found

Enhancing proliferation and optimizing the culture condition for human bone marrow stromal cells using hypoxia and fibroblast growth factor-2

Directory of Open Access Journals (Sweden)

Jung-Seok Lee

2018-04-01

Full Text Available This study aimed to determine the cellular characteristics and behaviors of human bone marrow stromal cells (hBMSCs expanded in media in a hypoxic or normoxic condition and with or without fibroblast growth factor-2 (FGF-2 treatment. hBMSCs isolated from the vertebral body and expanded in these four groups were evaluated for cellular proliferation/migration, colony-forming units, cell-surface characterization, in vitro differentiation, in vivo transplantation, and gene expression. Culturing hBMSCs using a particular environmental factor (hypoxia and with the addition of FGF-2 increased the cellular proliferation rate while enhancing the regenerative potential, modulated the multipotency-related processes (enhanced chondrogenesis-related processes/osteogenesis, but reduced adipogenesis, and increased cellular migration and collagen formation. The gene expression levels in the experimental samples showed activation of the hypoxia-inducible factor-1 pathway and glycolysis in the hypoxic condition, with this not being affected by the addition of FGF-2. The concurrent application of hypoxia and FGF-2 could provide a favorable condition for culturing hBMSCs to be used in clinical applications associated with bone tissue engineering, due to the enhancement of cellular proliferation and regenerative potential. Keywords: Bone marrow stromal cells, Hypoxia, Fibroblast growth factor, Tissue regeneration, Microenvironment interactions

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.

Dietary Pseudopurpurin Improves Bone Geometry Architecture and Metabolism in Red-Bone Guishan Goats

Science.gov (United States)

Han, TieSuo; Li, Peng; Wang, JianGuo; Liu, GuoWen; Wang, Zhe; Ge, ChangRong; Gao, ShiZheng

2012-01-01

Red-colored bones were found initially in some Guishan goats in the 1980s, and they were designated red-boned goats. However, it is not understood what causes the red color in the bone, or whether the red material changes the bone geometry, architecture, and metabolism of red-boned goats. Pseudopurpurin was identified in the red-colored material of the bone in red-boned goats by high-performance liquid chromatography–electrospray ionization–mass spetrometry and nuclear magnetic resonance analysis. Pseudopurpurin is one of the main constituents of Rubia cordifolia L, which is eaten by the goats. The assessment of the mechanical properties and micro-computed tomography showed that the red-boned goats displayed an increase in the trabecular volume fraction, trabecular thickness, and the number of trabeculae in the distal femur. The mean thickness, inner perimeter, outer perimeter, and area of the femoral diaphysis were also increased. In addition, the trabecular separation and structure model index of the distal femur were decreased, but the bone mineral density of the whole femur and the mechanical properties of the femoral diaphysis were enhanced in the red-boned goats. Meanwhile, expression of alkaline phosphatase and osteocalcin mRNA was higher, and the ratio of the receptor activator of the nuclear factor kappa B ligand to osteoprotegerin was markedly lower in the bone marrow of the red-boned goats compared with common goats. To confirm further the effect of pseudopurpurin on bone geometry, architecture, and metabolism, Wistar rats were fed diets to which pseudopurpurin was added for 5 months. Similar changes were observed in the femurs of the treated rats. The above results demonstrate that pseudopurpurin has a close affinity with the mineral salts of bone, and consequently a high level of mineral salts in the bone cause an improvement in bone strength and an enhancement in the structure and metabolic functions of the bone. PMID:22624037

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

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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

Comparison of half-dose and full-dose gadolinium MR contrast on the enhancement of bone and soft tissue tumors

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Costelloe, Colleen M. [University of Texas M. D. Anderson Cancer Center, Department of Diagnostic Radiology, Houston, Texas (United States); University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Murphy, William A.; Haygood, Tamara M.; Kumar, Rajendra; McEnery, Kevin W.; Madewell, John E. [University of Texas M. D. Anderson Cancer Center, Department of Diagnostic Radiology, Houston, Texas (United States); Stafford, R.J. [University of Texas M. D. Anderson Cancer Center, Department of Imaging Physics, Houston, Texas (United States); Roy, Anjali [Cancer Treatment Centers of America Medical Diagnostic Imaging Group, Arizona (United States); Bassett, Roland L.; Harrell, Robyn K. [University of Texas M. D. Anderson Cancer Center, Department of Biostatistics, Houston, Texas (United States)

2011-03-15

To evaluate the effect of half-dose intravenous gadolinium contrast on the enhancement of bone and soft tissue tumors. This study is HIPAA compliant and informed consent was waived by the institutional review board. An institutional database search was performed over a 1-year period for patients with full- and half-dose MR examinations performed for musculoskeletal oncologic indications. Examination pairs that were identical with regard to field strength and presence or absence of fat saturation were included, resulting in 29 paired examinations. When multiple, the lesion that was best delineated and enhanced well on the first examination in the pair was chosen, yielding 17 bone and 12 soft tissue. Five musculoskeletal radiologists blinded to dosages were asked to assess for a difference in enhancement when comparing the lesion on both examinations and to rate the degree of difference on a three-point scale. They were also asked to identify the examination on which the lesion enhanced less (tallied as low dose). Results were analyzed with the exact binomial test. The readers perceived an enhancement difference in 41% (59/145) of studies (p = 0.03) and the majority were rated as ''mild'' (66%, 39/59). The readers did not accurately identify the low-dose examinations (54% correctly identified, 32/59, p = 0.60). Half-dose gadolinium enhancement of lesions could not be accurately distinguished from full-dose enhancement upon review of the same lesion imaged at both concentrations. (orig.)

BONE GRAFTING ENHANCED BY PLATELET-RICH PLASMA IN TREATMENT OF AVASCULAR NECROSIS OF FEMORAL HEAD

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A. A. Korytkin

2018-01-01

Full Text Available Treatment of avascular necrosis of the femoral head is an issue of current interest while it affects young and employable people. So far there is no well-defined strategy of management which would help to postpone hip arthroplasty and further revision procedure. Hip sparing surgical treatment of avascular necrosis of the femoral head by bone grafting prior to head collapse proved to be a viable option not only during early stages of disease but also at advanced stages. Platelet-rich plasma (PRP addition to treatment plan potentially helps improving bone regeneration in situ.In this article the authors present a case of a 37 years old patient with avascular necrosis of the femoral head at a fragmentation stage (type 4B by ARCO. The authors centrifuged 15 ml of autologous whole blood (1500 RPM obtained by a special double-contoured syringe. During the surgical stage of treatment PRP and morselized bone graft were mixed to introduce and impact into the debrided zone of avascular necrosis. The authors also introduced 0.3–0.4 ml of PRP into the debrided zone of avascular necrosis after bone grafting. At 6 months follow-up CT images of the studied patient demonstrated signs of bone reorganization and no loss of femoral head sphericity. Preoperative Visual Analogue Scale (VAS, Harris Hip Score (HHS and Hip disability and Osteoarthritis Outcome Score (HOOS prior to treatment were 60, 45 and 33 points respectively. Postoperative VAS, HHS and HOOS scores were 10, 78 and 78 respectively. In the authors’ opinion, impaction bone grafting enhanced by PRP helps obtaining good and excellent outcomes not only at early but also at advanced stages of avascular necrosis.

High-Frequency, Low-Intensity Pulsed Ultrasound Enhances Alveolar Bone Healing of Extraction Sockets in Rats: A Pilot Study.

Science.gov (United States)

Kang, Kyung Lhi; Kim, Eun-Cheol; Park, Joon Bong; Heo, Jung Sun; Choi, Yumi

2016-02-01

Most studies of the beneficial effects of low-intensity pulsed ultrasound (LIPUS) on bone healing have used frequencies between 1.0 and 1.5 MHz. However, after consideration of ultrasound wave characteristics and depth of target tissue, higher-frequency LIPUS may have been more effective on superficially positioned alveolar bone. We investigated this hypothesis by applying LIPUS (frequency, 3.0 MHz; intensity, 30 mW/cm(2)) on shaved right cheeks over alveolar bones of tooth extraction sockets in rats for 10 min/d for 2 wk after tooth extraction; the control group (left cheek of the same rats) did not receive LIPUS treatment. Compared with the control group, the LIPUS group manifested more new bone growth inside the sockets on histomorphometric analysis (maximal difference = 2.5-fold on the seventh day after extraction) and higher expressions of osteogenesis-related mRNAs and proteins than the control group did. These findings indicate that 3.0-MHz LIPUS could enhance alveolar bone formation and calcification in rats. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Microfluidic enhancement of intramedullary pressure increases interstitial fluid flow and inhibits bone loss in hindlimb suspended mice.

Science.gov (United States)

Kwon, Ronald Y; Meays, Diana R; Tang, W Joyce; Frangos, John A

2010-08-01

Interstitial fluid flow (IFF) has been widely hypothesized to mediate skeletal adaptation to mechanical loading. Although a large body of in vitro evidence has demonstrated that fluid flow stimulates osteogenic and antiresorptive responses in bone cells, there is much less in vivo evidence that IFF mediates loading-induced skeletal adaptation. This is due in large part to the challenges associated with decoupling IFF from matrix strain. In this study we describe a novel microfluidic system for generating dynamic intramedullary pressure (ImP) and IFF within the femurs of alert mice. By quantifying fluorescence recovery after photobleaching (FRAP) within individual lacunae, we show that microfluidic generation of dynamic ImP significantly increases IFF within the lacunocanalicular system. In addition, we demonstrate that dynamic pressure loading of the intramedullary compartment for 3 minutes per day significantly eliminates losses in trabecular and cortical bone mineral density in hindlimb suspended mice, enhances trabecular and cortical structural integrity, and increases endosteal bone formation rate. Unlike previously developed modalities for enhancing IFF in vivo, this is the first model that allows direct and dynamic modulation of ImP and skeletal IFF within mice. Given the large number of genetic tools for manipulating the mouse genome, this model is expected to serve as a powerful investigative tool in elucidating the role of IFF in skeletal adaptation to mechanical loading and molecular mechanisms mediating this process.

Magnesium substitution in brushite cements for enhanced bone tissue regeneration

Energy Technology Data Exchange (ETDEWEB)

Cabrejos-Azama, Jatsue, E-mail: jacaza@farm.ucm.es [Departamento de Química-Física II, Facultad de Farmacia, UCM, Madrid (Spain); Departamento de Estomatología III, Facultad de Odontología UCM, Madrid (Spain); Alkhraisat, Mohammad Hamdan; Rueda, Carmen [Departamento de Química-Física II, Facultad de Farmacia, UCM, Madrid (Spain); Torres, Jesús [Facultad de Ciencias de la salud URJC, Alcorcón, Madrid (Spain); Blanco, Luis [Departamento de Estomatología III, Facultad de Odontología UCM, Madrid (Spain); López-Cabarcos, Enrique [Departamento de Química-Física II, Facultad de Farmacia, UCM, Madrid (Spain)

2014-10-01

We have synthesized calcium phosphate cements doped with different amounts of magnesium (Mg-CPC) with a twofold purpose: i) to evaluate in vitro the osteoblast cell response to this material, and ii) to compare the bone regeneration capacity of the doped material with a calcium cement prepared without magnesium (CPC). Cell proliferation and in vivo response increased in the Mg-CPCs in comparison with CPC. The Mg-CPCs have promoted higher new bone formation than the CPC (p < 0.05). The cytocompatibility and histomorfometric analysis performed in the rabbit calvaria showed that the incorporation of magnesium ions in CPC improves osteoblasts proliferation and provides higher new bone formation. The development of a bone substitute with controllable biodegradable properties and improved bone regeneration can be considered a step toward personalized therapy that can adapt to patient needs and clinical situations. - Highlights: • The Mg-CPCs promote higher new bone formation than the CPC. • The incorporation of magnesium ions in CPC improves osteoblasts proliferation. • Mg-CPC is a bone substitute with controllable biodegradable properties. • We suggest that the use of Mg ions could improve the clinical efficiency of CPCs.

UV-killed Staphylococcus aureus enhances adhesion and differentiation of osteoblasts on bone-associated biomaterials.

Science.gov (United States)

Somayaji, Shankari N; Huet, Yvette M; Gruber, Helen E; Hudson, Michael C

2010-11-01

Titanium alloys (Ti) are the preferred material for orthopedic applications. However, very often, these metallic implants loosen over a long period and mandate revision surgery. For implant success, osteoblasts must adhere to the implant surface and deposit a mineralized extracellular matrix (ECM). Here, we utilized UV-killed Staphylococcus aureus as a novel osteoconductive coating for Ti surfaces. S. aureus expresses surface adhesins capable of binding to bone and biomaterials directly. Furthermore, interaction of S. aureus with osteoblasts activates growth factor-related pathways that potentiate osteogenesis. Although UV-killed S. aureus cells retain their bone-adhesive ability, they do not stimulate significant immune modulator expression. All of the abovementioned properties were utilized for a novel implant coating so as to promote osteoblast recruitment and subsequent cell functions on the bone-implant interface. In this study, osteoblast adhesion, proliferation, and mineralized ECM synthesis were measured on Ti surfaces coated with fibronectin with and without UV-killed bacteria. Osteoblast adhesion was enhanced on Ti alloy surfaces coated with bacteria compared to uncoated surfaces, while cell proliferation was sustained comparably on both surfaces. Osteoblast markers such as collagen, osteocalcin, alkaline phosphatase activity, and mineralized nodule formation were increased on Ti alloy coated with bacteria compared to uncoated surfaces.

A study of 23 unicameral bone cysts of the calcaneus: open chip allogeneic bone graft versus percutaneous injection of bone powder with autogenous bone marrow.

Science.gov (United States)

Park, Il-Hyung; Micic, Ivan Dragoljub; Jeon, In-Ho

2008-02-01

The treatment of unicameral bone cyst varies from percutaneous needle biopsy, aspiration and local injection of steroid, autologous bone marrow, or demineralized bone matrix to curettage and open bone-grafting. The purpose of this study was to compare the results of open chip allogeneic bone graft versus percutaneous injection of demineralized bone powder with autogenous bone marrow in management of calcaneal cysts. Twenty-three calcaneal unicameral cysts in 20 patients were treated. Lyophilized irradiated chip allogeneic bone (CAB) and autogenous bone marrow were used for treatment of 13 cysts in 11 patients, and 10 cysts in 9 patients were treated with percutaneous injection of irradiated allogeneic demineralized bone powder (DBP) and autogenous bone marrow. There were 11 males and 9 female patients with mean age of 17 years. The patients were followed for an average of 49.4 months. Complete healing was achieved in 9 cysts treated with chip allogeneic bone and in 5 cysts treated with powdered bone. Four cysts treated with CAB and 3 cysts treated with DBP healed with a defect. Two cysts treated with powdered bone and autogenous bone marrow were classified as persistent. No infections or pathological fractures were observed during the followup period. Percutaneous injection of a mixture of allogeneic bone powder with autogenous bone marrow is a minimal invasive method and could be an effective alternative in the treatment of unicameral calcaneal bone cysts. The postoperative morbidity was low, the hospital stay was brief, and patient's comfort for unrestricted activity was enhanced.

Towards optical brain imaging: getting light through a bone

Science.gov (United States)

Thompson, J. V.; Hokr, B. H.; Nodurft, D. T.; Yakovlev, V. V.

2018-06-01

Optical imaging and detection in biological samples is severely limited by scattering effects. In particular, optical techniques for measuring conditions beneath the skull and within the bone marrow hold significant promise when it comes to speed, sensitivity and specificity. However, the strong optical scattering due to bone hinders the realization of these methods. In this article, we propose a technique to enhance the transmittance of light through bone. This is achieved by injecting light below the top surface of the bone and utilizing multiple scattering to increase transmittance. This technique suggests that enhancements of 2-6 times may be realized by injection of light 1 mm below the surface of the bone. By enhancing the transmittance of light through bone, we will greatly improve our ability to utilize optical methods to better understand and diagnose conditions within biological media.

MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.

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Takashi Watanabe

Full Text Available Mastermind-like 1 (MAML1 is a transcriptional co-activator in the Notch signaling pathway. Recently, however, several reports revealed novel and unique roles for MAML1 that are independent of the Notch signaling pathway. We found that MAML1 enhances the transcriptional activity of runt-related transcription factor 2 (Runx2, a transcription factor essential for osteoblastic differentiation and chondrocyte proliferation and maturation. MAML1 significantly enhanced the Runx2-mediated transcription of the p6OSE2-Luc reporter, in which luciferase expression was controlled by six copies of the osteoblast specific element 2 (OSE2 from the Runx2-regulated osteocalcin gene promoter. Interestingly, a deletion mutant of MAML1 lacking the N-terminal Notch-binding domain also enhanced Runx2-mediated transcription. Moreover, inhibition of Notch signaling did not affect the action of MAML1 on Runx2, suggesting that the activation of Runx2 by MAML1 may be caused in a Notch-independent manner. Overexpression of MAML1 transiently enhanced the Runx2-mediated expression of alkaline phosphatase, an early marker of osteoblast differentiation, in the murine pluripotent mesenchymal cell line C3H10T1/2. MAML1(-/- embryos at embryonic day 16.5 (E16.5 had shorter bone lengths than wild-type embryos. The area of primary spongiosa of the femoral diaphysis was narrowed. At E14.5, extended zone of collagen type II alpha 1 (Col2a1 and Sox9 expression, markers of chondrocyte differentiation, and decreased zone of collagen type X alpha 1 (Col10a1 expression, a marker of hypertrophic chondrocyte, were observed. These observations suggest that chondrocyte maturation was impaired in MAML1(-/- mice. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.

Toll-Like Receptor 2 Stimulation of Osteoblasts Mediates Staphylococcus Aureus Induced Bone Resorption and Osteoclastogenesis through Enhanced RANKL

Science.gov (United States)

Kassem, Ali; Lindholm, Catharina; Lerner, Ulf H

2016-01-01

Severe Staphylococcus aureus (S. aureus) infections pose an immense threat to population health and constitute a great burden for the health care worldwide. Inter alia, S. aureus septic arthritis is a disease with high mortality and morbidity caused by destruction of the infected joints and systemic bone loss, osteoporosis. Toll-Like receptors (TLRs) are innate immune cell receptors recognizing a variety of microbial molecules and structures. S. aureus recognition via TLR2 initiates a signaling cascade resulting in production of various cytokines, but the mechanisms by which S. aureus causes rapid and excessive bone loss are still unclear. We, therefore, investigated how S. aureus regulates periosteal/endosteal osteoclast formation and bone resorption. S. aureus stimulation of neonatal mouse parietal bone induced ex vivo bone resorption and osteoclastic gene expression. This effect was associated with increased mRNA and protein expression of receptor activator of NF-kB ligand (RANKL) without significant change in osteoprotegerin (OPG) expression. Bone resorption induced by S. aureus was abolished by OPG. S. aureus increased the expression of osteoclastogenic cytokines and prostaglandins in the parietal bones but the stimulatory effect of S. aureus on bone resorption and Tnfsf11 mRNA expression was independent of these cytokines and prostaglandins. Stimulation of isolated periosteal osteoblasts with S. aureus also resulted in increased expression of Tnfsf11 mRNA, an effect lost in osteoblasts from Tlr2 knockout mice. S. aureus stimulated osteoclastogenesis in isolated periosteal cells without affecting RANKL-stimulated resorption. In contrast, S. aureus inhibited RANKL-induced osteoclast formation in bone marrow macrophages. These data show that S. aureus enhances bone resorption and periosteal osteoclast formation by increasing osteoblast RANKL production through TLR2. Our study indicates the importance of using different in vitro approaches for studies of how S

Recombinant human IGF-1 produced by transgenic plant cell suspension culture enhances new bone formation in calvarial defects.

Science.gov (United States)

Poudel, Sher Bahadur; Bhattarai, Govinda; Kook, Sung-Ho; Shin, Yun-Ji; Kwon, Tae-Ho; Lee, Seung-Youp; Lee, Jeong-Chae

2017-10-01

Transgenic plant cell suspension culture systems have been utilized extensively as convenient and efficient expression systems for the production of recombinant human growth factors. We produced insulin-like growth factor-1 using a plant suspension culture system (p-IGF-1) and explored its effect on new bone formation in calvarial defects. We also compared the bone regenerating potential of p-IGF-1 with commercial IGF-1 derived from Escherichia coli (e-IGF-1). Male C57BL/6 mice underwent calvarial defect surgery, and the defects were loaded with absorbable collagen sponge (ACS) only (ACS group) or ACS impregnated with 13μg of p-IGF-1 (p-IGF-1 group) or e-IGF-1 (e-IGF-1 group). The sham group did not receive any treatment with ACS or IGFs after surgery. Live μCT and histological analyses showed critical-sized bone defects in the sham group, whereas greater bone formation was observed in the p-IGF-1 and e-IGF-1 groups than the ACS group both 5 and 10weeks after surgery. Bone mineral density, bone volume, and bone surface values were also higher in the IGF groups than in the ACS group. Local delivery of p-IGF-1 or e-IGF-1 more greatly enhanced the expression of osteoblast-specific markers, but inhibited osteoclast formation, in newly formed bone compared with ACS control group. Specifically, p-IGF-1 treatment induced higher expression of alkaline phosphatase, osteocalcin, and osteopontin in the defect site than did e-IGF-1. Furthermore, treatment with p-IGF-1, but not e-IGF-1, increased mineralization of MC3T3-E1 cells, with the attendant upregulation of osteogenic marker genes. Collectively, our findings suggest the potential of p-IGF-1 in promoting the processes required for bone regeneration. Copyright © 2017. Published by Elsevier Ltd.

Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair

Science.gov (United States)

Agarwal, Rachit; García, Andrés J.

2015-01-01

Bone tissue has a remarkable ability to regenerate and heal itself. However, large bone defects and complex fractures still present a significant challenge to the medical community. Current treatments center on metal implants for structural and mechanical support and auto- or allo-grafts to substitute long bone defects. Metal implants are associated with several complications such as implant loosening and infections. Bone grafts suffer from donor site morbidity, reduced bioactivity, and risk of pathogen transmission. Surgical implants can be modified to provide vital biological cues, growth factors and cells in order to improve osseointegration and repair of bone defects. Here we review strategies and technologies to engineer metal surfaces to promote osseointegration with the host tissue. We also discuss strategies for modifying implants for cell adhesion and bone growth via integrin signaling and growth factor and cytokine delivery for bone defect repair. PMID:25861724

Adipose-derived stem cells transfected with pEGFP-OSX enhance bone formation during distraction osteogenesis*

OpenAIRE

Lai, Qing-guo; Sun, Shao-long; Zhou, Xiao-hong; Zhang, Chen-ping; Yuan, Kui-feng; Yang, Zhong-jun; Luo, Sheng-lei; Tang, Xiao-peng; Ci, Jiang-bo

2014-01-01

This study was designed to investigate the effects of local delivery of adipose-derived stem cells (ADSCs) transfected with transcription factor osterix (OSX) on bone formation during distraction osteogenesis. New Zealand white rabbits (n=54) were randomly divided into three groups (18 rabbits per group). A directed cloning technique was used for the construction of recombinant plasmid pEGFP-OSX, where EGFP is the enhanced green fluorescence protein. After osteodistraction of the right mandib...

Bone-suppressed radiography using machine learning

Energy Technology Data Exchange (ETDEWEB)

Park, Jun Beom; Kim, Dae Cheon; Kim, Ho Kyung [KAERI, Daejeon (Korea, Republic of)

2016-05-15

The single-shot dual-energy imaging suffers from reduced contrast-to-noise ratio performance due to poor spectral separation. Tomosynthesis requires more complex motion equipment and may require higher patient dose. An alternative tissue-specific imaging technique was introduced. This alternative technique usually possesses a filter to generate bone-only images for given digital radiographs. Therefore, it provides soft-tissue-enhanced images from the subtraction of given radiographs and filtered bone-only images. Only bone-suppressed imaging capability is a limitation of the method. The filter can be obtained from a machine-learning algorithm, e.g. artificial neural network (ANN), with the dual-energy bone-only images (called 'teaching' images). We suspect the robustness of the filter may be dependent upon the number of teaching images and the number of patients from whose radiographs we obtain the teaching images. In this study, we design an ANN to obtain a bone-extracting filter from a radiograph, and investigate the filter properties with respect to various ANN parameters. Preliminary results are summarized in Fig. 3. We extracted 5,000 subregions in a 21x21 pixel format from the lung region in the bone-enhanced dual-energy image and we used them for teaching images during training the ANN. The resultant bone-enhanced image from the ANN nonlinear filter is shown in Fig. 3 (a). From the weighted logarithmic subtraction between Fig. 2 (a) and Fig. 3 (a), we could obtain the bone-suppressed image as shown in Fig. 3 (b). The quality of the bone-suppressed image is comparable to the ground truth Fig. 2 (c).

Bone-suppressed radiography using machine learning

International Nuclear Information System (INIS)

Park, Jun Beom; Kim, Dae Cheon; Kim, Ho Kyung

2016-01-01

The single-shot dual-energy imaging suffers from reduced contrast-to-noise ratio performance due to poor spectral separation. Tomosynthesis requires more complex motion equipment and may require higher patient dose. An alternative tissue-specific imaging technique was introduced. This alternative technique usually possesses a filter to generate bone-only images for given digital radiographs. Therefore, it provides soft-tissue-enhanced images from the subtraction of given radiographs and filtered bone-only images. Only bone-suppressed imaging capability is a limitation of the method. The filter can be obtained from a machine-learning algorithm, e.g. artificial neural network (ANN), with the dual-energy bone-only images (called 'teaching' images). We suspect the robustness of the filter may be dependent upon the number of teaching images and the number of patients from whose radiographs we obtain the teaching images. In this study, we design an ANN to obtain a bone-extracting filter from a radiograph, and investigate the filter properties with respect to various ANN parameters. Preliminary results are summarized in Fig. 3. We extracted 5,000 subregions in a 21x21 pixel format from the lung region in the bone-enhanced dual-energy image and we used them for teaching images during training the ANN. The resultant bone-enhanced image from the ANN nonlinear filter is shown in Fig. 3 (a). From the weighted logarithmic subtraction between Fig. 2 (a) and Fig. 3 (a), we could obtain the bone-suppressed image as shown in Fig. 3 (b). The quality of the bone-suppressed image is comparable to the ground truth Fig. 2 (c).

Perfusion of subchondral bone marrow in knee osteoarthritis: A dynamic contrast-enhanced magnetic resonance imaging preliminary study

Energy Technology Data Exchange (ETDEWEB)

Budzik, Jean-François, E-mail: Budzik.jean-francois@ghicl.net [Lille Catholic Hospitals, Imaging Department, Lille Catholic University, Lille (France); PMOI Physiopathology of Inflammatory Bone Diseases, EA 4490, Lille (France); Ding, Juliette, E-mail: Ding.juliette@gmail.com [Lille Catholic Hospitals, Imaging Department, Lille Catholic University, Lille (France); Norberciak, Laurène, E-mail: Norberciak.Laurene@ghicl.net [Lille Catholic Hospitals, Biostatistics Department, Lille Catholic University, Lille (France); Pascart, Tristan, E-mail: Pascart.tristan@ghicl.net [Lille Catholic Hospitals, Rheumatology Department, Lille Catholic University, Lille (France); Toumi, Hechmi, E-mail: hechmi.toumi@univ-orleans.fr [EA4708 I3MTO, Orleans Regional Hospital, University of Orleans, Orleans (France); Verclytte, Sébastien, E-mail: Verclytte.Sebastien@ghicl.net [Lille Catholic Hospitals, Imaging Department, Lille Catholic University, Lille (France); Coursier, Raphaël, E-mail: Coursier.Raphael@ghicl.net [Lille Catholic Hospitals, Orthopaedic Surgery Department, Lille Catholic University, Lille (France)

2017-03-15

The role of inflammation in the pathogenesis of osteoarthritis is being given major interest, and inflammation is closely linked with vascularization. It was recently demonstrated that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) could identify the subchondral bone marrow vascularization changes occurring in osteoarthritis in animals. These changes appeared before cartilage lesions were visible and were correlated with osteoarthritis severity. Thus the opportunity to obtain an objective assessment of bone vascularization in non-invasive conditions in humans might help better understanding osteoarthritis pathophysiology and finding new biomarkers. We hypothesized that, as in animals, DCE-MRI has the ability to identify subchondral bone marrow vascularization changes in human osteoarthritis. We performed knee MRI in 19 patients with advanced knee osteoarthritis. We assessed subchondral bone marrow vascularization in medial and lateral femorotibial compartments with DCE-MRI and graded osteoarthritis lesions on MR images. Statistical analysis assessed intra- and inter-observer agreement, compared DCE-MRI values between the different subchondral zones, and sought for an influence of age, sex, body mass index, and osteoarthritis garde on these values. The intra- and inter-observer agreement for DCE-MRI values were excellent. These values were significantly higher in the femorotibial compartment the most affected by osteoarthritis, both in femur and tibia (p < 0.0001) and were significantly and positively correlated with cartilage lesions (p = 0.02) and bone marrow oedema grade (p < 0.0001) after adjustment. We concluded that, as in animals, subchondral bone marrow vascularization changes assessed with DCE-MRI were correlated with osteoarthritis severity in humans.

Perfusion of subchondral bone marrow in knee osteoarthritis: A dynamic contrast-enhanced magnetic resonance imaging preliminary study

International Nuclear Information System (INIS)

Budzik, Jean-François; Ding, Juliette; Norberciak, Laurène; Pascart, Tristan; Toumi, Hechmi; Verclytte, Sébastien; Coursier, Raphaël

2017-01-01

The role of inflammation in the pathogenesis of osteoarthritis is being given major interest, and inflammation is closely linked with vascularization. It was recently demonstrated that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) could identify the subchondral bone marrow vascularization changes occurring in osteoarthritis in animals. These changes appeared before cartilage lesions were visible and were correlated with osteoarthritis severity. Thus the opportunity to obtain an objective assessment of bone vascularization in non-invasive conditions in humans might help better understanding osteoarthritis pathophysiology and finding new biomarkers. We hypothesized that, as in animals, DCE-MRI has the ability to identify subchondral bone marrow vascularization changes in human osteoarthritis. We performed knee MRI in 19 patients with advanced knee osteoarthritis. We assessed subchondral bone marrow vascularization in medial and lateral femorotibial compartments with DCE-MRI and graded osteoarthritis lesions on MR images. Statistical analysis assessed intra- and inter-observer agreement, compared DCE-MRI values between the different subchondral zones, and sought for an influence of age, sex, body mass index, and osteoarthritis garde on these values. The intra- and inter-observer agreement for DCE-MRI values were excellent. These values were significantly higher in the femorotibial compartment the most affected by osteoarthritis, both in femur and tibia (p < 0.0001) and were significantly and positively correlated with cartilage lesions (p = 0.02) and bone marrow oedema grade (p < 0.0001) after adjustment. We concluded that, as in animals, subchondral bone marrow vascularization changes assessed with DCE-MRI were correlated with osteoarthritis severity in humans.

A composite demineralized bone matrix--self assembling peptide scaffold for enhancing cell and growth factor activity in bone marrow.

Science.gov (United States)

Hou, Tianyong; Li, Zhiqiang; Luo, Fei; Xie, Zhao; Wu, Xuehui; Xing, Junchao; Dong, Shiwu; Xu, Jianzhong

2014-07-01

The need for suitable bone grafts is high; however, there are limitations to all current graft sources, such as limited availability, the invasive harvest procedure, insufficient osteoinductive properties, poor biocompatibility, ethical problems, and degradation properties. The lack of osteoinductive properties is a common problem. As an allogenic bone graft, demineralized bone matrix (DBM) can overcome issues such as limited sources and comorbidities caused by invasive harvest; however, DBM is not sufficiently osteoinductive. Bone marrow has been known to magnify osteoinductive components for bone reconstruction because it contains osteogenic cells and factors. Mesenchymal stem cells (MSCs) derived from bone marrow are the gold standard for cell seeding in tissue-engineered biomaterials for bone repair, and these cells have demonstrated beneficial effects. However, the associated high cost and the complicated procedures limit the use of tissue-engineered bone constructs. To easily enrich more osteogenic cells and factors to DBM by selective cell retention technology, DBM is modified by a nanoscale self-assembling peptide (SAP) to form a composite DBM/SAP scaffold. By decreasing the pore size and increasing the charge interaction, DBM/SAP scaffolds possess a much higher enriching yield for osteogenic cells and factors compared with DBM alone scaffolds. At the same time, SAP can build a cellular microenvironment for cell adhesion, proliferation, and differentiation that promotes bone reconstruction. As a result, a suitable bone graft fabricated by DBM/SAP scaffolds and bone marrow represents a new strategy and product for bone transplantation in the clinic. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biological methods to enhance bone healing and fracture repair.

Science.gov (United States)

Verdonk, René; Goubau, Yannick; Almqvist, Fredrik K; Verdonk, Peter

2015-04-01

This article looks into normal physiological fracture healing with special emphasis on the diamond concept. A precise definition of nonunion of long bones is described. Most often inadequate fixation (too rigid or too loose) is the reason for nonunion in long bone fractures. Because a critical bone defect cannot be bridged, it may lead directly or indirectly (lack of fixation) to nonunion. Individual inadequate local biological characteristics are also often found to be the cause; poor soft tissue coverage as well as a lack of periosteum and muscle or fascia or skin defects can lead to compromised vascularity in situ. Systemic factors are now much more recognized, e.g., smoking, diabetes, and cachexia, as well as the limited impact of some medications, e.g., nonsteroidal anti-inflammatory drugs and steroids. Today's mode of treatment for nonunion is approached in this article, and suggestions for appropriate treatment of long bone nonunion is presented. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Global MicroRNA Profiling in Human Bone Marrow Skeletal—Stromal or Mesenchymal–Stem Cells Identified Candidates for Bone Regeneration

DEFF Research Database (Denmark)

Chang, Chi Chih; Venø, Morten T.; Chen, Li

2018-01-01

Bone remodeling and regeneration are highly regulated multistep processes involving posttranscriptional regulation by microRNAs (miRNAs). Here, we performed a global profiling of differentially expressed miRNAs in bone-marrow-derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem......RNAs for enhancing bone tissue regeneration. Scaffolds functionalized with miRNA nano-carriers enhanced osteoblastogenesis in 3D culture and retained this ability at least 2 weeks after storage. Additionally, anti-miR-222 enhanced in vivo ectopic bone formation through targeting the cell-cycle inhibitor CDKN1B...... cells) during in vitro osteoblast differentiation. We functionally validated the regulatory effects of several miRNAs on osteoblast differentiation and identified 15 miRNAs, most significantly miR-222 and miR-423, as regulators of osteoblastogenesis. In addition, we tested the possible targeting of mi...

Femoral head vascularisation in Legg-Calve-Perthes disease: comparison of dynamic gadolinium-enhanced subtraction MRI with bone scintigraphy

International Nuclear Information System (INIS)

Lamer, Sylvie; Dorgeret, Sophie; Brillet, Pierre-Yves; Hassan, Max; Sebag, Guy H.; Khairouni, Abdeslam; Mazda, Keyvan; Bacheville, Eric; Pennecot, Georges F.; Bloch, Juliette

2002-01-01

Heading AbstractBackground. It has been reported that MRI using a dynamic gadolinium-enhanced subtraction technique can allow the early identification of ischaemia and the pattern of revascularisation in Legg-Calve-Perthes (LCP) disease with increased spatial and contrast resolution. Therefore, dynamic gadolinium-enhanced subtraction (DGS) MRI may be a possible non-ionising substitute for bone scintigraphy.Objective. The purpose of this prospective study was to compare DGS MRI and bone scintigraphy in the assessment of femoral head perfusion in LCP disease.Materials and methods. Twenty-six DGS MR images and bone scintigraphies of 25 hips in 23 children were obtained at different stages of LCP disease; three stage I, 12 stage II, six stage III and five stage IV (Waldenstroem classification). The extent of necrosis, epiphyseal revascularisation pathways (lateral pillar, medial pillar, and/or transphyseal perfusion) and metaphyseal changes were analysed.Results. Total agreement between both techniques was noted in the depiction of epiphyseal necrosis (kappa=1), and metaphyseal abnormalities (kappa=0.9). DGS MRI demonstrated better revascularisation in the lateral (kappa=0.62) and medial pillars (kappa=0.52). The presence of basal transphyseal reperfusion was more conspicuous with MRI.Conclusions. DGS MRI allows early detection of epiphyseal ischaemia and accurate analysis of the different revascularisation patterns. These changes are directly related to the prognosis of LCP disease and can aid therapeutic decision making. (orig.)

Autologous implantation of BMP2-expressing dermal fibroblasts to improve bone mineral density and architecture in rabbit long bones.

Science.gov (United States)

Ishihara, Akikazu; Weisbrode, Steve E; Bertone, Alicia L

2015-10-01

Cell-mediated gene therapy may treat bone fragility disorders. Dermal fibroblasts (DFb) may be an alternative cell source to stem cells for orthopedic gene therapy because of their rapid cell yield and excellent plasticity with bone morphogenetic protein-2 (BMP2) gene transduction. Autologous DFb or BMP2-expressing autologous DFb were administered in twelve rabbits by two delivery routes; a transcortical intra-medullar infusion into tibiae and delayed intra-osseous injection into femoral drill defects. Both delivery methods of DFb-BMP2 resulted in a successful cell engraftment, increased bone volume, bone mineral density, improved trabecular bone microarchitecture, greater bone defect filling, external callus formation, and trabecular surface area, compared to non-transduced DFb or no cells. Cell engraftment within trabecular bone and bone marrow tissue was most efficiently achieved by intra-osseous injection of DFb-BMP2. Our results suggested that BMP2-expressing autologous DFb have enhanced efficiency of engraftment in target bones resulting in a measurable biologic response by the bone of improved bone mineral density and bone microarchitecture. These results support that autologous implantation of DFb-BMP2 warrants further study on animal models of bone fragility disorders, such as osteogenesis imperfecta and osteoporosis to potentially enhance bone quality, particularly along with other gene modification of these diseases. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Transforming growth factor-β inhibits CCAAT/enhancer-binding protein expression and PPARγ activity in unloaded bone marrow stromal cells

International Nuclear Information System (INIS)

Ahdjoudj, S.; Kaabeche, K.; Holy, X.; Fromigue, O.; Modrowski, D.; Zerath, E.; Marie, P.J.

2005-01-01

The molecular mechanisms regulating the adipogenic differentiation of bone marrow stromal cells in vivo remain largely unknown. In this study, we investigated the regulatory effects of transforming growth factor beta-2 (TGF-β2) on transcription factors involved in adipogenic differentiation induced by hind limb suspension in rat bone marrow stromal cells in vivo. Time course real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis of gene expression showed that skeletal unloading progressively increases the expression of CCAAT/enhancer-binding protein (C/EBP)α and C/EBPβ α at 5 days in bone marrow stromal cells resulting in increased peroxisome proliferator-activated receptor γ (PPARγ2) transcripts at 7 days. TGF-β2 administration in unloaded rats corrected the rise in C/EBPα and C/EBPβ transcripts induced by unloading in bone marrow stromal cells. This resulted in inhibition of PPARγ2 expression that was associated with increased Runx2 expression. Additionally, the inhibition of C/EBPα and C/EBPβ expression by TGF-β2 was associated with increased PPARγ serine phosphorylation in bone marrow stromal cells, a mechanism that inhibits PPARγ transactivating activity. The sequential inhibitory effect of TGF-β2 on C/EBPα, C/EBPβ, and PPARγ2 resulted in reduced LPL expression and abolition of bone marrow stromal cell adipogenic differentiation, which contributed to prevent bone loss induced by skeletal unloading. We conclude that TGF-β2 inhibits the excessive adipogenic differentiation of bone marrow stromal cells induced by skeletal unloading by inhibiting C/EBPα, C/EBPβ, and PPARγ expression and activity, which provides a sequential mechanism by which TGF-β2 regulates adipogenic differentiation of bone marrow stromal cells in vivo

The effect of Hydroxyapatite/collagen I composites, bone marrow aspirate and bone graft on fixation of bone implants in sheep

DEFF Research Database (Denmark)

Babiker, Hassan

  The effect of Hydroxyapatite/collagen I composites, bone marrow aspirate and bone graft on fixation of bone implants IN SHEEP   Ph.D. Student, Hassan Babiker; Associate Professor, Ph.D. Ming Ding; Professor, dr.med., Soren Overgaard. Department of Orthopaedic Surgery, Odense University Hospital......, Odense, Denmark   Background: Hydroxyapatite and collagen composites (HA/coll) have the potential in mimicking and replacing skeletal bones. This study attempted to determine the effect of newly developed HA/coll-composites with and without bone marrow aspirate (BMA) in order to enhance the fixation...... of bone implants.   Materials and Methods: Titanium alloy implants were inserted into bilateral femoral condyles of 8 skeletally mature sheep, four in each sheep. The implant has a circumferential gap of 2 mm. The gap was filled with: HA/coll; HA/coll-BMA; autograft or allograft. Allograft was served...

Characterization of Bone Marrow Mononuclear Cells on Biomaterials for Bone Tissue Engineering In Vitro

OpenAIRE

Henrich, Dirk; Verboket, René; Schaible, Alexander; Kontradowitz, Kerstin; Oppermann, Elsie; Brune, Jan C.; Nau, Christoph; Meier, Simon; Bonig, Halvard; Marzi, Ingo; Seebach, Caroline

2015-01-01

Bone marrow mononuclear cells (BMCs) are suitable for bone tissue engineering. Comparative data regarding the needs of BMC for the adhesion on biomaterials and biocompatibility to various biomaterials are lacking to a large extent. Therefore, we evaluated whether a surface coating would enhance BMC adhesion and analyze the biocompatibility of three different kinds of biomaterials. BMCs were purified from human bone marrow aspirate samples. Beta tricalcium phosphate (?-TCP, without coating or ...

Ossificans myositis: inflammatory changes and contrast enhancement of adjacent bone shown by MR imaging; Myosite ossifiante circonscrite: remaniements osseux deceles en IRM

Energy Technology Data Exchange (ETDEWEB)

David, H.; Jolles, E.; Le Friant, G.; Silvestre, A.; Sarrazin, J.L.; Gordoliani, Y.S. [Hopital des Armees du Val-de-Grace, 75 - Paris (France)

1995-07-01

The authors report a case of ossificans myositis, in which magnetic resonance imaging (MRI) showed inflammatory changes of the adjacent bone. T 1 weighted fat saturation sequence with gadolinium injection showed enhancement of medullary and cortical bone. This potentially mistaking pattern must be known, to avoid mis diagnosing with malignant osseous tumor, specially before achievement of the characteristic pattern of zonal maturation and its calcified rim. (authors). 15 refs., 6 figs.

Reconstruction of segmental bone defect of long bones after tumor resection by devitalized tumor-bearing bone.

Science.gov (United States)

Qu, Huayi; Guo, Wei; Yang, Rongli; Li, Dasen; Tang, Shun; Yang, Yi; Dong, Sen; Zang, Jie

2015-09-24

The reconstruction of an intercalary bone defect after a tumor resection of a long bone remains a challenge to orthopedic surgeons. Though several methods have been adopted to enhance the union of long segmental allografts or retrieved segmental autografts to the host bones, still more progresses are required to achieve a better union rate. Several methods have been adopted to devitalize tumor bone for recycling usage, and the results varied. We describe our experiences of using devitalized tumor-bearing bones for the repairing of segmental defects after tumor resection. Twenty-seven eligible patients treated from February 2004 to May 2012 were included. The segmental tumor bone (mean length, 14 cm) was resected, and then devitalized in 20% sterile saline at 65 °C for 30 min after the tumor tissue was removed. The devitalized bone was implanted back into the defect by using nails or plates. Complete healing of 50 osteotomy ends was achieved at a median time of 11 months (interquartile range (IQR) 9-13 months). Major complications included bone nonunion in four bone junctions (7.4%), devitalized bone fracture in one patient (3.7%), deep infection in three patients (11.1%), and fixation failure in two patients (7.4%). The bone union rates at 1 and 2 years were 74.1 and 92.6%, respectively. The average functional score according to the Musculoskeletal Tumor Society (MSTS) 93 scoring system was 93 % (IQR 80-96.7%). Incubation in 20% sterile saline at 65 °C for 30 min is an effective method of devitalization of tumor-bearing bone. The retrieved bone graft may provide as a less expensive alternative for limb salvage. The structural bone and the preserved osteoinductivity of protein may improve bone union.

Bone induction by surface-double-modified true bone ceramics in vitro and in vivo

International Nuclear Information System (INIS)

Li, Jingfeng; Chen, Liaobin; Deng, Yu; Zheng, Qixin; Guo, Xiaodong; Zou, Zhenwei; Liu, Yudong; Lan, Shenghui

2013-01-01

True bone ceramic (TBC), obtained by twice sintering fresh bovine cancellous bone at high temperatures, is an osteoconductive and bioactive bone substitute material that exhibits excellent biocompatibility with hard tissue. The authors have previously synthesized a novel BMP-2-related peptide, P24, and found that it could enhance the osteoblastic differentiation of cells. The objective of the present study was to construct a double-modified TBC via mineralization into simulated body fluid and P24 incorporation for enhanced bone formation. In vitro experiments revealed that surface mineralization-modified (SMM) TBC scaffolds demonstrated efficiency for sustained release of P24. The P24/SMM-TBC composite exhibited increased osteogenic activity by cell adhesion rate determination, MTT assay, alkaline phosphatase staining, and calcium nodule staining with alizarin red compared with SMM-TBC and TBC. In vivo studies showed that the P24/SMM-TBC composite scaffold promoted significant bone defect repair, in marked contrast to stand-alone SMM-TBC and TBC, based on the results of radiographic evaluation and histological examination. These findings indicate that SMM-TBC is a good scaffold for the controlled release of P24 and that the P24/SMM-TBC composite could improve the adhesion, proliferation and differentiation of cells and repair bone defects. The double-modified P24/SMM-TBC composite biomaterial shows potential for clinical application in bone tissue engineering. (paper)

Deproteinized bovine bone functionalized with the slow delivery of BMP-2 for the repair of critical-sized bone defects in sheep

NARCIS (Netherlands)

Liu, T.; Wu, G.; Wismeijer, D.; Gu, Z.; Liu, Y.

2013-01-01

As an alternative to an autologous bone graft, deproteinized bovine bone (DBB) is widely used in the clinical dentistry. Although DBB provides an osteoconductive scaffold, it is not capable of enhancing bone regeneration because it is not osteoinductive. In order to render DBB osteoinductive, bone

Evaluation of bone viability in patients after girdlestone arthroplasty: comparison of bone SPECT/CT and MRI

Energy Technology Data Exchange (ETDEWEB)

Diederichs, G.; Collettini, F.; Hamm, B.; Makowski, M.R. [Department of Radiology, Berlin (Germany); Hoppe, P.; Brenner, W. [Department of Nuclear Medicine, Berlin (Germany); Wassilew, G. [Department of Orthopedic Surgery, Berlin (Germany)

2017-09-15

To test the diagnostic performance of bone SPECT/CT and MRI for the evaluation of bone viability in patients after girdlestone-arthroplasty with histopathology used as gold standard. In this cross-sectional study, patients after girdlestone-arthroplasty were imaged with single-photon-emission-computed-tomography/computed-tomography (SPECT/CT) bone-scans using 99mTc-DPD. Additionally, 1.5 T MRI was performed with turbo-inversion-recovery-magnitude (TIRM), contrast-enhanced T1-fat sat (FS) and T1-mapping. All imaging was performed within 24 h prior to revision total-hip-arthroplasty in patients with a girdlestone-arthroplasty. In each patient, four standardized bone-tissue-biopsies (14 patients) were taken intraoperatively at the remaining acetabulum superior/inferior and trochanter major/minor. Histopathological evaluation of bone samples regarding bone viability was used as gold standard. A total of 56 bone-segments were analysed and classified as vital (n = 39) or nonvital (n = 17) by histopathology. Mineral/late-phase SPECT/CT showed a high sensitivity (90%) and specificity (94%) to distinguish viable and nonviable bone tissue. TIRM (sensitivity 87%, specificity 88%) and contrast-enhanced T1-FS (sensitivity 90%, specificity 88%) also achieved a high sensitivity and specificity. T1-mapping achieved the lowest values (sensitivity 82%, specificity 82%). False positive results in SPECT/CT and MRI resulted from small bone fragments close to metal artefacts. Both bone SPECT/CT and MRI allow a reliable differentiation between viable and nonviable bone tissue in patients after girdlestone arthroplasty. The findings of this study could also be relevant for the evaluation of bone viability in the context of avascular bone necrosis. (orig.)

Evaluation of bone viability in patients after girdlestone arthroplasty: comparison of bone SPECT/CT and MRI

International Nuclear Information System (INIS)

Diederichs, G.; Collettini, F.; Hamm, B.; Makowski, M.R.; Hoppe, P.; Brenner, W.; Wassilew, G.

2017-01-01

To test the diagnostic performance of bone SPECT/CT and MRI for the evaluation of bone viability in patients after girdlestone-arthroplasty with histopathology used as gold standard. In this cross-sectional study, patients after girdlestone-arthroplasty were imaged with single-photon-emission-computed-tomography/computed-tomography (SPECT/CT) bone-scans using 99mTc-DPD. Additionally, 1.5 T MRI was performed with turbo-inversion-recovery-magnitude (TIRM), contrast-enhanced T1-fat sat (FS) and T1-mapping. All imaging was performed within 24 h prior to revision total-hip-arthroplasty in patients with a girdlestone-arthroplasty. In each patient, four standardized bone-tissue-biopsies (14 patients) were taken intraoperatively at the remaining acetabulum superior/inferior and trochanter major/minor. Histopathological evaluation of bone samples regarding bone viability was used as gold standard. A total of 56 bone-segments were analysed and classified as vital (n = 39) or nonvital (n = 17) by histopathology. Mineral/late-phase SPECT/CT showed a high sensitivity (90%) and specificity (94%) to distinguish viable and nonviable bone tissue. TIRM (sensitivity 87%, specificity 88%) and contrast-enhanced T1-FS (sensitivity 90%, specificity 88%) also achieved a high sensitivity and specificity. T1-mapping achieved the lowest values (sensitivity 82%, specificity 82%). False positive results in SPECT/CT and MRI resulted from small bone fragments close to metal artefacts. Both bone SPECT/CT and MRI allow a reliable differentiation between viable and nonviable bone tissue in patients after girdlestone arthroplasty. The findings of this study could also be relevant for the evaluation of bone viability in the context of avascular bone necrosis. (orig.)

Segmenting Bone Parts for Bone Age Assessment using Point Distribution Model and Contour Modelling

Science.gov (United States)

Kaur, Amandeep; Singh Mann, Kulwinder, Dr.

2018-01-01

Bone age assessment (BAA) is a task performed on radiographs by the pediatricians in hospitals to predict the final adult height, to diagnose growth disorders by monitoring skeletal development. For building an automatic bone age assessment system the step in routine is to do image pre-processing of the bone X-rays so that features row can be constructed. In this research paper, an enhanced point distribution algorithm using contours has been implemented for segmenting bone parts as per well-established procedure of bone age assessment that would be helpful in building feature row and later on; it would be helpful in construction of automatic bone age assessment system. Implementation of the segmentation algorithm shows high degree of accuracy in terms of recall and precision in segmenting bone parts from left hand X-Rays.

Contrast-enhanced Magnetic Resonance Imaging of Pelvic Bone Metastases at 3.0 T: Comparison Between 3-dimensional T1-weighted CAIPIRINHA-VIBE Sequence and 2-dimensional T1-weighted Turbo Spin-Echo Sequence.

Science.gov (United States)

Yoon, Min A; Hong, Suk-Joo; Lee, Kyu-Chong; Lee, Chang Hee

2018-06-12

This study aimed to compare 3-dimensional T1-weighted gradient-echo sequence (CAIPIRINHA-volumetric interpolated breath-hold examination [VIBE]) with 2-dimensional T1-weighted turbo spin-echo sequence for contrast-enhanced magnetic resonance imaging (MRI) of pelvic bone metastases at 3.0 T. Thirty-one contrast-enhanced MRIs of pelvic bone metastases were included. Two contrast-enhanced sequences were evaluated for the following parameters: overall image quality, sharpness of pelvic bone, iliac vessel clarity, artifact severity, and conspicuity and edge sharpness of the smallest metastases. Quantitative analysis was performed by calculating signal-to-noise ratio and contrast-to-noise ratio of the smallest metastases. Significant differences between the 2 sequences were assessed. CAIPIRINHA-VIBE had higher scores for overall image quality, pelvic bone sharpness, iliac vessel clarity, and edge sharpness of the metastatic lesions, and had less artifacts (all P 0.05). Our results suggest that CAIPIRINHA-VIBE may be superior to turbo spin-echo for contrast-enhanced MRI of pelvic bone metastases at 3.0 T.

Evaluation of cell binding peptide (p15) with silk fibre enhanced hydroxyappatite bone substitute for posterolateral spinal fusion in sheep

DEFF Research Database (Denmark)

Axelsen, M.; Jespersen, Stig; Overgaard, Søren

2015-01-01

Background: Spinal fusion is indicated in the surgical management of various spinal disorders. To ensure stabile fusion, bone graft materials are essential. Traditionally allo- or autograft has been used, but both are associated with limitations. Synthetic bone graft materials that reassemble today......: In this study, we compared fusion rates between silk fibre enhanced anorganic bovine derived hydroxyapatite matrix (ABM) with and without P15 peptide coating in uninstrumented PLF in a preclinical setting. Study design: Randomised prospective study in sheep. Method/materials: Twelve Tex/got sheep underwent open...

Resolution enhancement in MR spectroscopy of red bone marrow fat via intermolecular double-quantum coherences

Science.gov (United States)

Bao, Jianfeng; Cui, Xiaohong; Huang, Yuqing; Zhong, Jianhui; Chen, Zhong

2015-08-01

High-resolution 1H magnetic resonance spectroscopy (MRS) is generally inaccessible in red bone marrow (RBM) tissues using conventional MRS techniques. This is because signal from these tissues suffers from severe inhomogeneity in the main static B0 field originated from the intrinsic honeycomb structures in trabecular bone. One way to reduce effects of B0 field inhomogeneity is by using the intermolecular double quantum coherence (iDQC) technique, which has been shown in other systems to obtain signals insensitive to B0 field inhomogeneity. In the present study, we employed an iDQC approach to enhance the spectral resolution of RBM. The feasibility and performance of this method for achieving high resolution MRS was verified by experiments on phantoms and pig vertebral bone samples. Unsaturated fatty acid peaks which overlap in the conventional MRS were well resolved and identified in the iDQC spectrum. Quantitative comparison of fractions of three types of fatty acids was performed between iDQC spectra on the in situ RMB and conventional MRS on the extracted fat from the same RBM. Observations of unsaturated fatty acids with iDQC MRS may provide valuable information and may hold potential in diagnosis of diseases such as obesity, diabetes, and leukemia.

Comparison of the reaction of bone-derived cells to enhanced MgCl2-salt concentrations.

Science.gov (United States)

Burmester, Anna; Luthringer, Bérengère; Willumeit, Regine; Feyerabend, Frank

2014-01-01

Magnesium-based implants exhibit various advantages such as biodegradability and potential for enhanced in vivo bone formation. However, the cellular mechanisms behind this possible osteoconductivity remain unclear. To determine whether high local magnesium concentrations can be osteoconductive and exclude other environmental factors that occur during the degradation of magnesium implants, magnesium salt (MgCl2) was used as a model system. Because cell lines are preferred targets in studies of non-degradable implant materials, we performed a comparative study of 3 osteosarcoma-derived cell lines (MG63, SaoS2 and U2OS) with primary human osteoblasts. The correlation among cell count, viability, cell size and several MgCl2 concentrations was used to examine the influence of magnesium on proliferation in vitro. Moreover, bone metabolism alterations during proliferation were investigated by analyzing the expression of genes involved in osteogenesis. It was observed that for all cell types, the cell count decreases at concentrations above 10 mM MgCl2. However, detailed analysis showed that MgCl2 has a relevant but very diverse influence on proliferation and bone metabolism, depending on the cell type. Only for primary cells was a clear stimulating effect observed. Therefore, reliable results demonstrating the osteoconductivity of magnesium implants can only be achieved with primary osteoblasts.

The mechanical study of acrylic bone cement reinforced with carbon nanotube

International Nuclear Information System (INIS)

Nien, Yu-Hsun; Huang, Chiao-li

2010-01-01

Bone cement is used as filler between prosthesis and bone for fixation and force distribution. The major composition of bone cement is polymethylmethacrylate (PMMA). Some disadvantages of PMMA bone cement are found such as significant poor mechanical properties which may cause failure of the cement. In this paper, we exploited carbon nanotube to enhance the mechanical properties of bone cement. The mechanical properties of the bone cement were characterized using tensile and compressive analysis as well as dynamic mechanical analysis (DMA). The result shows that carbon nanotube is able to enhance the mechanical properties of the modified bone cement.

The mechanical study of acrylic bone cement reinforced with carbon nanotube

Energy Technology Data Exchange (ETDEWEB)

Nien, Yu-Hsun, E-mail: nienyh@yuntech.edu.tw [Department of Chemical and Materials Engineering, National Yunlin University of Science and Technology, Douliou, Yunlin 64002, Taiwan (China); Huang, Chiao-li [Department of Chemical and Materials Engineering, National Yunlin University of Science and Technology, Douliou, Yunlin 64002, Taiwan (China)

2010-05-25

Bone cement is used as filler between prosthesis and bone for fixation and force distribution. The major composition of bone cement is polymethylmethacrylate (PMMA). Some disadvantages of PMMA bone cement are found such as significant poor mechanical properties which may cause failure of the cement. In this paper, we exploited carbon nanotube to enhance the mechanical properties of bone cement. The mechanical properties of the bone cement were characterized using tensile and compressive analysis as well as dynamic mechanical analysis (DMA). The result shows that carbon nanotube is able to enhance the mechanical properties of the modified bone cement.

Assessing the osteoblast transcriptome in a model of enhanced bone formation due to constitutive G{sub s}–G protein signaling in osteoblasts

Energy Technology Data Exchange (ETDEWEB)

Wattanachanya, Lalita, E-mail: lalita_md@yahoo.com [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok (Thailand); Wang, Liping, E-mail: lipingwang05@yahoo.com [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); Millard, Susan M., E-mail: susan.millard@mater.uq.edu.au [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); Lu, Wei-Dar, E-mail: weidar_lu@yahoo.com [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); O’Carroll, Dylan, E-mail: dylancocarroll@gmail.com [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); Hsiao, Edward C., E-mail: Edward.Hsiao@ucsf.edu [Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA (United States); Conklin, Bruce R., E-mail: bconklin@gladstone.ucsf.edu [Gladstone Institute of Cardiovascular Disease, San Francisco, CA (United States); Department of Medicine, University of California, San Francisco, CA (United States); Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA (United States); Nissenson, Robert A., E-mail: Robert.Nissenson@ucsf.edu [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States)

2015-05-01

G protein-coupled receptor (GPCR) signaling in osteoblasts (OBs) is an important regulator of bone formation. We previously described a mouse model expressing Rs1, an engineered constitutively active G{sub s}-coupled GPCR, under the control of the 2.3 kb Col I promoter. These mice showed a dramatic age-dependent increase in trabecular bone of femurs. Here, we further evaluated the effects of enhanced G{sub s} signaling in OBs on intramembranous bone formation by examining calvariae of 1- and 9-week-old Col1(2.3)/Rs1 mice and characterized the in vivo gene expression specifically occurring in osteoblasts with activated G{sub s} G protein-coupled receptor signaling, at the cellular level rather than in a whole bone. Rs1 calvariae displayed a dramatic increase in bone volume with partial loss of cortical structure. By immunohistochemistry, Osterix was detected in cells throughout the inter-trabecular space while Osteocalcin was expressed predominantly in cells along bone surfaces, suggesting the role of paracrine mediators secreted from OBs driven by 2.3 kb Col I promoter could influence early OB commitment, differentiation, and/or proliferation. Gene expression analysis of calvarial OBs revealed that genes affected by Rs1 signaling include those encoding proteins important for cell differentiation, cytokines and growth factors, angiogenesis, coagulation, and energy metabolism. The set of G{sub s}-GPCRs and other GPCRs that may contribute to the observed skeletal phenotype and candidate paracrine mediators of the effect of G{sub s} signaling in OBs were also determined. Our results identify novel detailed in vivo cellular changes of the anabolic response of the skeleton to G{sub s} signaling in mature OBs. - Highlights: • OB expression of an engineered G{sub s}-coupled receptor dramatically increases bone mass. • We investigated the changes in gene expression in vivo in enhanced OB G{sub s} signaling. • Genes in cell cycle and transcription were increased in

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.

[Impact of thyroid diseases on bone].

Science.gov (United States)

Tsourdi, E; Lademann, F; Siggelkow, H

2018-05-09

Thyroid hormones are key regulators of skeletal development in childhood and bone homeostasis in adulthood, and thyroid diseases have been associated with increased osteoporotic fractures. Hypothyroidism in children leads to an impaired skeletal maturation and mineralization, but an adequate and timely substitution with thyroid hormones stimulates bone growth. Conversely, hyperthyroidism at a young age accelerates skeletal development, but may also cause short stature because of a premature fusion of the growth plates. Hypothyroidism in adults causes an increase in the duration of the remodeling cycle and, thus, leads to low bone turnover and enhanced mineralization, but an association with a higher fracture risk is less well established. In adults, a surplus of thyroid hormones enhances bone turnover, mostly due to an increased bone resorption driven by osteoclasts. Thus, hyperthyroidism is a well-recognized cause of high-bone turnover secondary osteoporosis, resulting in an increased susceptibility to fragility fractures. Subclinical hyperthyroidism, especially resulting from endogenous disease, also has an adverse effect on bone mineral density and is associated with fractures. In most patients with overt or subclinical hyperthyroidism restoration of the euthyroid status reverses bone loss. In postmenopausal women who receive thyroid-stimulating hormone suppression therapy because of thyroid cancer, antiresorptive treatments may be indicated. Overall, extensive data support the importance of a euthyroid status for bone mineral accrual and growth in childhood as well as maintenance of bone health in adulthood.

Injectable Shear-Thinning CaSO4/FGF-18-Incorporated Chitin-PLGA Hydrogel Enhances Bone Regeneration in Mice Cranial Bone Defect Model.

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Sivashanmugam, A; Charoenlarp, Pornkawee; Deepthi, S; Rajendran, Arunkumar; Nair, Shantikumar V; Iseki, Sachiko; Jayakumar, R

2017-12-13

For craniofacial bone regeneration, shear-thinning injectable hydrogels are favored over conventional scaffolds because of their improved defect margin adaptability, easier handling, and ability to be injected manually into deeper tissues. The most accepted method, after autografting, is the use of recombinant human bone morphogenetic protein-2 (BMP-2); however, complications such as interindividual variations, edema, and poor cost-efficiency in supraphysiological doses have been reported. The endogenous synthesis of BMP-2 is desirable, and a molecule which induces this is fibroblast growth factor-18 (FGF-18) because it can upregulate the BMP-2 expression  by supressing noggin. We developed a chitin-poly(lactide-co-glycolide) (PLGA) composite hydrogel by regeneration chemistry and then incorporated CaSO 4 and FGF-18 for this purpose. Rheologically, a 7-fold increase in the elastic modulus was observed in the CaSO 4 -incorporated chitin-PLGA hydrogels as compared to the chitin-PLGA hydrogel. Shear-thinning Herschel-Bulkley fluid nature was observed for both hydrogels. Chitin-PLGA/CaSO 4 gel showed sustained release of FGF-18. In vitro osteogenic differentiation showed an enhanced alkaline phosphatase (ALP) expression in the FGF-18-containing chitin-PLGA/CaSO 4 gel when compared to cells alone. Further, it was confirmed by studying the expression of osteogenic genes [RUNX2, ALP, BMP-2, osteocalcin (OCN), and osteopontin (OPN)], immunofluorescence staining of BMP-2, OCN, and OPN, and alizarin red S staining. Incorporation of FGF-18 in the hydrogel increased the endothelial cell migration. Further, the regeneration potential of the prepared hydrogels was tested in vivo, and longitudinal live animal μ-CT was performed. FGF-18-loaded chitin-PLGA/CaSO 4 showed early and almost complete bone healing in comparison with chitin-PLGA/CaSO 4 , chitin-PLGA/FGF-18, chitin-PLGA, and sham control systems, as confirmed by hematoxylin and eosin and osteoid tetrachrome stainings

Composite biopolymers for bone regeneration enhancement in bony defects.

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Jahan, K; Tabrizian, M

2016-01-01

For the past century, various biomaterials have been used in the treatment of bone defects and fractures. Their role as potential substitutes for human bone grafts increases as donors become scarce. Metals, ceramics and polymers are all materials that confer different advantages to bone scaffold development. For instance, biocompatibility is a highly desirable property for which naturally-derived polymers are renowned. While generally applied separately, the use of biomaterials, in particular natural polymers, is likely to change, as biomaterial research moves towards mixing different types of materials in order to maximize their individual strengths. This review focuses on osteoconductive biocomposite scaffolds which are constructed around natural polymers and their performance at the in vitro/in vivo stages and in clinical trials.

Bone-Inspired Spatially Specific Piezoelectricity Induces Bone Regeneration.

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Yu, Peng; Ning, Chengyun; Zhang, Yu; Tan, Guoxin; Lin, Zefeng; Liu, Shaoxiang; Wang, Xiaolan; Yang, Haoqi; Li, Kang; Yi, Xin; Zhu, Ye; Mao, Chuanbin

2017-01-01

The extracellular matrix of bone can be pictured as a material made of parallel interspersed domains of fibrous piezoelectric collagenous materials and non-piezoelectric non-collagenous materials. To mimic this feature for enhanced bone regeneration, a material made of two parallel interspersed domains, with higher and lower piezoelectricity, respectively, is constructed to form microscale piezoelectric zones (MPZs). The MPZs are produced using a versatile and effective laser-irradiation technique in which K 0.5 Na 0.5 NbO 3 (KNN) ceramics are selectively irradiated to achieve microzone phase transitions. The phase structure of the laser-irradiated microzones is changed from a mixture of orthorhombic and tetragonal phases (with higher piezoelectricity) to a tetragonal dominant phase (with lower piezoelectricity). The microzoned piezoelectricity distribution results in spatially specific surface charge distribution, enabling the MPZs to bear bone-like microscale electric cues. Hence, the MPZs induce osteogenic differentiation of stem cells in vitro and bone regeneration in vivo even without being seeded with stem cells. The concept of mimicking the spatially specific piezoelectricity in bone will facilitate future research on the rational design of tissue regenerative materials.

Combination of BMP-2-releasing gelatin/β-TCP sponges with autologous bone marrow for bone regeneration of X-ray-irradiated rabbit ulnar defects.

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Yamamoto, Masaya; Hokugo, Akishige; Takahashi, Yoshitake; Nakano, Takayoshi; Hiraoka, Masahiro; Tabata, Yasuhiko

2015-07-01

The objective of this study is to evaluate the feasibility of gelatin sponges incorporating β-tricalcium phosphate (β-TCP) granules (gelatin/β-TCP sponges) to enhance bone regeneration at a segmental ulnar defect of rabbits with X-ray irradiation. After X-ray irradiation of the ulnar bone, segmental critical-sized defects of 20-mm length were created, and bone morphogenetic protein-2 (BMP-2)-releasing gelatin/β-TCP sponges with or without autologous bone marrow were applied to the defects to evaluate bone regeneration. Both gelatin/β-TCP sponges containing autologous bone marrow and BMP-2-releasing sponges enhanced bone regeneration at the ulna defect to a significantly greater extent than the empty sponges (control). However, in the X-ray-irradiated bone, the bone regeneration either by autologous bone marrow or BMP-2 was inhibited. When combined with autologous bone marrow, the BMP-2 exhibited significantly high osteoinductivity, irrespective of the X-ray irradiation. The bone mineral content at the ulna defect was similar to that of the intact bone. It is concluded that the combination of bone marrow with the BMP-2-releasing gelatin/β-TCP sponge is a promising technique to induce bone regeneration at segmental bone defects after X-ray irradiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Porous tantalum coatings prepared by vacuum plasma spraying enhance bmscs osteogenic differentiation and bone regeneration in vitro and in vivo.

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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.

Characterisation of Bone Beneficial Components from Australian Wallaby Bone

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Lao, Weiguo; Jin, Xingliang; Tan, Yi; Xiao, Linda; Padula, Matthew P.; Bishop, David P.; Reedy, Brian; Ong, Madeleine; Kamal, Mohammad A.; Qu, Xianqin

2016-01-01

Background: Osteoporosis is a condition in which the bones become brittle, increasing the risk of fractures. Complementary medicines have traditionally used animal bones for managing bone disorders, such as osteoporosis. This study aimed to discover new natural products for these types of conditions by determining mineral and protein content of bone extracts derived from the Australian wallaby. Methods: Inductively coupled plasma-mass spectrometry and Fourier transform infrared spectroscopic analysis were used for mineral tests, proteome analysis was using LC/MS/MS and the effects of wallaby bone extracts (WBE)s on calcium deposition and alkaline phosphatase activity were evaluated in osteogenic cells derived from adipose tissue-derived stem cells (ADSCs). Results: Concentrations of calcium and phosphorus were 26.21% and 14.72% in WBE respectively. Additionally, minerals found were wide in variety and high in concentration, while heavy metal concentrations of aluminium, iron, zinc and other elements were at safe levels for human consumption. Proteome analysis showed that extracts contained high amounts of bone remodelling proteins, such as osteomodulin, osteopontin and osteoglycin. Furthermore, in vitro evaluation of WBEs showed increased deposition of calcium in osteoblasts with enhanced alkaline phosphatase activity in differentiated adipose-derived stem cells. Conclusion: Our results demonstrate that wallaby bone extracts possess proteins and minerals beneficial for bone metabolism. WBEs may therefore be used for developing natural products for conditions such as osteoporosis and further investigation to understand biomolecular mechanism by which WBEs prevent osteoporosis is warranted. PMID:28930133

Present status and future potential of enhancing bone healing using nanotechnology.

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Stylios, George; Wan, Taoyu; Giannoudis, Peter

2007-03-01

An overview of the current state of tissue engineering material systems used in bone healing is presented. A variety of fabrication processes have been developed that have resulted in porous implant substrates that can address unresolved clinical problems. The merits of these biomaterial systems are evaluated in the context of the mechanical properties and biomedical performances most suitable for bone healing. An optimal scaffold for bone tissue engineering applications should be biocompatible and act as a 3D template for in vitro and in vivo bone growth; in addition, its degradation products should be non-toxic and easily excreted by the body. To achieve these features, scaffolds must consist of an interconnected porous network of micro- and nanoscale to allow extensive body fluid transport through the pores, which will trigger bone ingrowth, cell migration, tissue ingrowth, and eventually vascularization.

Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the In Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration

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Todeschi, Maria Rosa; El Backly, Rania; Capelli, Chiara; Daga, Antonio; Patrone, Eugenio; Introna, Martino; Cancedda, Ranieri

2015-01-01

Umbilical cord mesenchymal stem cells (UC-MSCs) show properties similar to bone marrow mesenchymal stem cells (BM-MSCs), although controversial data exist regarding their osteogenic potential. We prepared clinical-grade UC-MSCs from Wharton's Jelly and we investigated if UC-MSCs could be used as substitutes for BM-MSCs in muscoloskeletal regeneration as a more readily available and functional source of MSCs. UC-MSCs were loaded onto scaffolds and implanted subcutaneously (ectopically) and in critical-sized calvarial defects (orthotopically) in mice. For live cell-tracking experiments, UC-MSCs were first transduced with the luciferase gene. Angiogenic properties of UC-MSCs were tested using the mouse metatarsal angiogenesis assay. Cell secretomes were screened for the presence of various cytokines using an array assay. Analysis of implanted scaffolds showed that UC-MSCs, contrary to BM-MSCs, remained detectable in the implants for 3 weeks at most and did not induce bone formation in an ectopic location. Instead, they induced a significant increase of blood vessel ingrowth. In agreement with these observations, UC-MSC-conditioned medium presented a distinct and stronger proinflammatory/chemotactic cytokine profile than BM-MSCs and a significantly enhanced angiogenic activity. When UC-MSCs were orthotopically transplanted in a calvarial defect, they promoted increased bone formation as well as BM-MSCs. However, at variance with BM-MSCs, the new bone was deposited through the activity of stimulated host cells, highlighting the importance of the microenvironment on determining cell commitment and response. Therefore, we propose, as therapy for bone lesions, the use of allogeneic UC-MSCs by not depositing bone matrix directly, but acting through the activation of endogenous repair mechanisms. PMID:25685989

Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using 18F FDG PET/CT and 99mTc HDP Bone Scintigraphy: Characteristics of Soft Tissue Formation

International Nuclear Information System (INIS)

Seo, Hyo Jung; Choi, Yun Jung; Kim, Hyun Jeong; Jeong, Youg Hyu; Cho, Arthur; Lee, Jae Hoon; Yun, Mijin; Choi, Hye Jin; Lee, Jong Doo; Kang, Won Jun

2011-01-01

Bone metastasis from hepatocellular carcinoma (HCC) can present with soft tissue formation, resulting in oncologic emergency. Contrast enhanced FDG PET/CT and bone scintigraphy were compared to evaluate characteristics of bone metastases with of without soft tissue formation from HCC. of 4,151 patients with HCC, 263 patients had bone metastases. Eighty five patients with bone metastasis from HCC underwent contrast enhanced FDG PET/CT. Fifty four of the enrolled subjects had recent 99mT c HDP bone scintigraphy available for comparison. Metastatic bone lesions were identified with visual inspection on FDG PET/CT, and maximum standardized uptake value (SUVmax) was used for the quantitative analysis. Confirmation of bone metastasis was based on histopathology, combined imaging modalities, or serial follow up studies. Forty seven patients (55%) presented with soft tissue formation, while the remaining 38 patients presented without soft tissue formation. Frequent sites of bone metastases from HCC were the spine (39%), pelvis (19%), and rib cage (14%). The soft tissue formation group had more frequent bone pain (77 vs. 37%, p<0.0001), higher SUVmax (6.02 vs. 3.52, p<0.007), and higher incidence of photon defect in bone scintigraphy (75 vs. 0%) compared to the non soft tissue formation group. FDG PET/CT had higher detection rate for bone metastasis than bone scintigraphy both in lesion based analysis (98 vs. 53%, p=0.0015) and in patient based analysis (100 vs. 80%, p<0.001). Bone metastasis from HCC showed a high incidence of soft tissue formation requiring emergency treatment. Although the characteristic findings for soft tissue formation such as photon defect in bone scintigraphy are helpful in detection, overall detectability of bone metastasis is higher in FDG PET/CT. Contrast enhanced PET/CT will be useful in finding and delineating soft tissue forming bone metastasis from HCC.

Perfluorodecalin and bone regeneration

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F Tamimi

2013-01-01

Full Text Available Perfluorodecalin (PFD is a chemically and biologically inert biomaterial and, as many perfluorocarbons, is also hydrophobic, radiopaque and has a high solute capacity for gases such as oxygen. In this article we have demonstrated, both in vitro and in vivo, that PFD may significantly enhance bone regeneration. Firstly, the potential benefit of PFD was demonstrated by prolonging the survival of bone marrow cells cultured in anaerobic conditions. These findings translated in vivo, where PFD incorporated into bone-marrow-loaded 3D-printed scaffolds substantially improved their capacity to regenerate bone. Secondly, in addition to biological applications, we have also shown that PFD improves the radiopacity of bone regeneration biomaterials, a key feature required for the visualisation of biomaterials during and after surgical implantation. Finally, we have shown how the extreme hydrophobicity of PFD enables the fabrication of highly cohesive self-setting injectable biomaterials for bone regeneration. In conclusion, perfluorocarbons would appear to be highly beneficial additives to a number of regenerative biomaterials, especially those for bone regeneration.

Enhanced Adipogenicity of Bone Marrow Mesenchymal Stem Cells in Aplastic Anemia

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Naresh Kumar Tripathy

2014-01-01

Full Text Available Fatty bone marrow (BM and defective hematopoiesis are a pathologic hallmark of aplastic anemia (AA. We have investigated adipogenic and osteogenic potential of BM mesenchymal stem cells (BM-MSC in 10 AA patients (08 males and 02 females with median age of 37 years (range: 06 to 79 years and in the same number of age and sex matched controls. It was observed that BM-MSC of AA patients had a morphology, phenotype, and osteogenic differentiation potential similar to control subjects but adipocytes differentiated from AA BM-MSC had a higher density and larger size of lipid droplets and they expressed significantly higher levels of adiponectin and FABP4 genes and proteins as compared to control BM-MSC (P<0.01 for both. Thus our data shows that AA BM-MSC have enhanced adipogenicity, which may have an important implication in the pathogenesis of the disease.

Tissue-engineered bone constructed in a bioreactor for repairing critical-sized bone defects in sheep.

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Li, Deqiang; Li, Ming; Liu, Peilai; Zhang, Yuankai; Lu, Jianxi; Li, Jianmin

2014-11-01

Repair of bone defects, particularly critical-sized bone defects, is a considerable challenge in orthopaedics. Tissue-engineered bones provide an effective approach. However, previous studies mainly focused on the repair of bone defects in small animals. For better clinical application, repairing critical-sized bone defects in large animals must be studied. This study investigated the effect of a tissue-engineered bone for repairing critical-sized bone defect in sheep. A tissue-engineered bone was constructed by culturing bone marrow mesenchymal-stem-cell-derived osteoblast cells seeded in a porous β-tricalcium phosphate ceramic (β-TCP) scaffold in a perfusion bioreactor. A critical-sized bone defect in sheep was repaired with the tissue-engineered bone. At the eighth and 16th week after the implantation of the tissue-engineered bone, X-ray examination and histological analysis were performed to evaluate the defect. The bone defect with only the β-TCP scaffold served as the control. X-ray showed that the bone defect was successfully repaired 16 weeks after implantation of the tissue-engineered bone; histological sections showed that a sufficient volume of new bones formed in β-TCP 16 weeks after implantation. Eight and 16 weeks after implantation, the volume of new bones that formed in the tissue-engineered bone group was more than that in the β-TCP scaffold group (P bone improved osteogenesis in vivo and enhanced the ability to repair critical-sized bone defects in large animals.

Positive modulator of bone morphogenic protein-2

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Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

2009-01-27

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

Positive modulator of bone morphogenic protein-2

Energy Technology Data Exchange (ETDEWEB)

Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua; Kazuyuki, Takahashi

2017-06-06

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

Thermal sensitivity and thermally enhanced radiosensitivity of murine bone marrow granulocyte-macrophage colony-forming units (CFU-GM)

International Nuclear Information System (INIS)

Yoshida, Hiroshi

1994-01-01

This study was to evaluate thermal response of granulocyte-macrophage colony-forming unit (CFU-GM) in vitro and to investigate the difference of thermally enhanced radiosensitivity on cell survivals of CFU-GM between in vitro and in vivo. In in vitro heating exposure, bone marrow suspensions, obtained from mouse femora or tibiae, were incubated; and in vivo heating exposure, the lower half-body of mice were immersed in a circulating hot water bath. For irradiation schedules, cell suspensions were irradiated in vitro or in vivo (whole-body irradiation). Thermal sensitivity curve, obtained by in vivo heating exposure, showed a shoulder region at short exposures followed by an exponential decline during longer heating exposures. The Arrhenius curve showed a break at 42.3deg C and inactivation enthalpy was 1836 kJ/mol (438 kcal/mole) below the break point and 704 kJ/mole (168 kcal/mole) above the point. When bone marrow suspensions, obtained after either in vitro or in vivo irradiation, were heated in vitro at 42deg C for 60 min, supura-additive effect on cell survivals was observed by in vivo irradiation, but not observed by in vitro irradiation. Thermal enhancement ratio (TER), defined as D 0 of combined in vivo irradiation and in vitro heating divided by D 0 of the sole in vivo irradiation, was 1.12. In vivo heating following in vivo irradiation also showed supra-additive effect, giving TER of 1.66. These findings indicated that murine marrow CFU-GM is sensitive to hyperthermia and that thermal radiosensitization is never negligible when hyperthermia is employed with preceding X-irradiation. Thus, combined use of radiotherapy and hyperthermia may decrease bone marrow function. (N.K.)

Gentamicin coating of nanotubular anodized titanium implant reduces implant-related osteomyelitis and enhances bone biocompatibility in rabbits

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Liu D

2017-07-01

Full Text Available Denghui Liu,1,* Chongru He,2,* Zhongtang Liu,2 Weidong Xu2 1Department of Orthopedics, the 113 Military Hospital, Ningbo, 2Department of Orthopedics, Changhai Hospital Affiliated to the Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Titanium and titanium alloy are widely used as orthopedic implants for their favorable mechanical properties and satisfactory biocompatibility. The aim of the present study was to investigate the antibacterial effect and bone cell biocompatibility of a novel implant made with nanotubular anodized titanium coated with gentamicin (NTATi-G through in vivo study in ­rabbits. The animals were divided into four groups, each receiving different kinds of implants, that is, NTATi-G, titanium coated with gentamicin (Ti-G, nanotubular anodized titanium uncoated with gentamicin (NTATi and titanium uncoated with gentamicin (Ti. The results showed that NTATi-G implant prevented implant-related osteomyelitis and enhanced bone biocompatibility in vivo. Moreover, the body temperature of rabbits in NTATi-G and Ti-G groups was lower than those in Ti groups, while the weight of rabbits in NTATi-G and Ti-G groups was heavier than those in NTATi and Ti groups, respectively. White blood cell counts in NTATi-G group were lower than NTATi and Ti groups. Features of myelitis were observed by X-ray films in the NTATi and Ti groups, but not in the NTATi-G and Ti-G groups. The radiographic scores, which assessed pathology and histopathology in bone tissues, were significantly lower in the NTATi-G and Ti-G groups than those in the NTATi and Ti groups, respectively (P<0.05. Meanwhile, explants and bone tissue culture demonstrated significantly less bacterial growth in the NTATi-G and Ti-G groups than in the NTATi and Ti groups, respectively (P<0.01. The bone volume in NTATi-G group was greater than Ti-G group, and little bone formation was seen in NTATi and Ti

Volleyball and Basketball Enhanced Bone Mass in Prepubescent Boys.

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Zouch, Mohamed; Chaari, Hamada; Zribi, Anis; Bouajina, Elyès; Vico, Laurence; Alexandre, Christian; Zaouali, Monia; Ben Nasr, Hela; Masmoudi, Liwa; Tabka, Zouhair

2016-01-01

The aim of this study was to examine the effect of volleyball and basketball practice on bone acquisition and to determine which of these 2 high-impact sports is more osteogenic in prepubertal period. We investigated 170 boys (aged 10-12 yr, Tanner stage I): 50 volleyball players (VB), 50 basketball players (BB), and 70 controls. Bone mineral content (BMC, g) and bone area (BA, cm(2)) were measured by dual-energy X-ray absorptiometry at different sites. We found that, both VB and BB have a higher BMC at whole body and most weight-bearing and nonweight-bearing sites than controls, except the BMC in head which was lower in VB and BB than controls. Moreover, only VB exhibited greater BMC in right and left ultra-distal radius than controls. No significant differences were observed between the 3 groups in lumbar spine, femoral neck, and left third D radius BMC. Athletes also exhibited a higher BA in whole body, limbs, lumbar spine, and femoral region than controls. In addition, they have a similar BA in head and left third D radius with controls. The VB exhibited a greater BA in most radius region than controls and a greater femoral neck BA than BB. A significant positive correlation was reported between total lean mass and both BMC and BA in whole body, lumbar spine, total hip, and right whole radius among VB and BB. In summary, we suggest that volleyball and basketball have an osteogenic effect BMC and BA in loaded sites in prepubescent boys. The increased bone mass induced by both volleyball and basketball training in the stressed sites was associated to a decreased skull BMC. Moreover, volleyball practice produces a more sensitive mechanical stress in loaded bones than basketball. This effect seems translated by femoral neck expansion. Copyright © 2016 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Enhancement of Osteoblastic-Like Cell Activity by Glow Discharge Plasma Surface Modified Hydroxyapatite/β-Tricalcium Phosphate Bone Substitute

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Eisner Salamanca

2017-11-01

Full Text Available Glow discharge plasma (GDP treatments of biomaterials, such as hydroxyapatite/β-tricalcium phosphate (HA/β-TCP composites, produce surfaces with fewer contaminants and may facilitate cell attachment and enhance bone regeneration. Thus, in this study we used argon glow discharge plasma (Ar-GDP treatments to modify HA/β-TCP particle surfaces and investigated the physical and chemical properties of the resulting particles (HA/β-TCP + Ar-GDP. The HA/β-TCP particles were treated with GDP for 15 min in argon gas at room temperature under the following conditions: power: 80 W; frequency: 13.56 MHz; pressure: 100 mTorr. Scanning electron microscope (SEM observations showed similar rough surfaces of HA/β-TCP + Ar-GDP HA/β-TCP particles, and energy dispersive spectrometry analyses showed that HA/β-TCP surfaces had more contaminants than HA/β-TCP + Ar-GDP surfaces. Ca/P mole ratios in HA/β-TCP and HA/β-TCP + Ar-GDP were 1.34 and 1.58, respectively. Both biomaterials presented maximal intensities of X-ray diffraction patterns at 27° with 600 a.u. At 25° and 40°, HA/β-TCP + Ar-GDP and HA/β-TCP particles had peaks of 200 a.u., which are similar to XRD intensities of human bone. In subsequent comparisons, MG-63 cell viability and differentiation into osteoblast-like cells were assessed on HA/β-TCP and HA/β-TCP + Ar-GDP surfaces, and Ar-GDP treatments led to improved cell growth and alkaline phosphatase activities. The present data indicate that GDP surface treatment modified HA/β-TCP surfaces by eliminating contaminants, and the resulting graft material enhanced bone regeneration.

High calcium concentration in bones promotes bone metastasis in renal cell carcinomas expressing calcium-sensing receptor.

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Joeckel, Elke; Haber, Tobias; Prawitt, Dirk; Junker, Kerstin; Hampel, Christian; Thüroff, Joachim W; Roos, Frederik C; Brenner, Walburgis

2014-02-28

The prognosis for renal cell carcinoma (RCC) is related to a high rate of metastasis, including 30% of bone metastasis. Characteristic for bone tissue is a high concentration of calcium ions. In this study, we show a promoting effect of an enhanced extracellular calcium concentration on mechanisms of bone metastasis via the calcium-sensing receptor (CaSR) and its downstream signaling molecules. Our analyses were performed using 33 (11/category) matched specimens of normal and tumor tissue and 9 (3/category) primary cells derived from RCC patients of the 3 categories: non-metastasized, metastasized into the lung and metastasized into bones during a five-year period after nephrectomy. Expression of CaSR was determined by RT-PCR, Western blot analyses and flow cytometry, respectively. Cells were treated by calcium and the CaSR inhibitor NPS 2143. Cell migration was measured in a Boyden chamber with calcium (10 μM) as chemotaxin and proliferation by BrdU incorporation. The activity of intracellular signaling mediators was quantified by a phospho-kinase array and Western blot. The expression of CaSR was highest in specimens and cells of patients with bone metastases. Calcium treatment induced an increased migration (19-fold) and proliferation (2.3-fold) exclusively in RCC cells from patients with bone metastases. The CaSR inhibitor NPS 2143 elucidated the role of CaSR on the calcium-dependent effects. After treatment with calcium, the activity of AKT, PLCγ-1, p38α and JNK was clearly enhanced and PTEN expression was almost completely abolished in bone metastasizing RCC cells. Our results indicate a promoting effect of extracellular calcium on cell migration and proliferation of bone metastasizing RCC cells via highly expressed CaSR and its downstream signaling pathways. Consequently, CaSR may be regarded as a new prognostic marker predicting RCC bone metastasis.

Delivery of S1P receptor-targeted drugs via biodegradable polymer scaffolds enhances bone regeneration in a critical size cranial defect.

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Das, Anusuya; Tanner, Shaun; Barker, Daniel A; Green, David; Botchwey, Edward A

2014-04-01

Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic-co-glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow-degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with micro-computed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. A 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in-growth and an increase in new bone formation. Copyright © 2013 Wiley Periodicals, Inc.

Delivery of S1P Receptor-Targeted Drugs via Biodegradable Polymer Scaffolds Enhances Bone Regeneration in a Critical Size Cranial Defect*

Science.gov (United States)

Das, Anusuya; Tanner, Shaun; Barker, Daniel A.; Green, David; Botchwey, Edward A.

2014-01-01

Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic-co-glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow-degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with microcomputed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in-growth and an increase in new bone formation. PMID:23640833

Bone and Gallium scintigraphy in primary malignant and benign bone tumors of the extremities

International Nuclear Information System (INIS)

Sepahdari, S.; Martin, W.B.; Ryan, J.; Simon, M.; Kirchner, P.

1985-01-01

A six yer prospective evaluation of 129 patients suspected of having a primary bone tumor included Tc-99m MDP bone scintigraphy followed by Ga-67 imaging at 48-72 hours. Blood pool images were part of bone scintigraphy in nearly half of the patients. Extent and intensity of tracer uptake in tumor and adjacent bone and joints were recorded for each tracer by two observers blind to the diagnosis. Tissue samples obtained in every patient by biopsy or tumor excision after scintigraphy, revealed 72 malignant and 57 benign bone tumors. The bone scan was positive in 95% (69/72) of malignancies. The scintigraphic intensity of benign and malignant lesions was comparable with both Tc-99m MDP and Ga-67. On the other hand, bone scintigraphy showed 72% (52/72) of bone malignancies to have abnormal proximal and distal bone/joint uptake whereas the Ga-67 images revealed this in only 6% (4/65) of malignancies. Benign lesions manifested this enhanced contiguous bone/joint uptake on only 8% (5/55) of bone and 0% of Ga-67 scans. This study concludes positive bone, blood pool, or Ga-67 images have less specificity for malignancy than the presence of increased Tc-99m MDP deposition in a contiguous bone/joint, but negative scintigraphic results strongly favor a benign lesion. Ga-67 was more accurate than Tc-99m MDP in portraying intraosseous extent of malignant tumors; however, this is now preferably done with C.T

The ACE-2/Ang1-7/Mas cascade enhances bone structure and metabolism following angiotensin-II type 1 receptor blockade.

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Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

2017-07-15

The renin angiotensin system (RAS) regulates numerous systemic functions and is expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial member of the RAS, and the therapeutic effects of a large number of angiotensin receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study examines whether the reported osteo-preservative effects of losartan are mediated through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d p.o.) for 6 weeks. A specific Mas receptor blocker (A-779) was delivered via mini-osmotic pumps during the losartan treatment period. Serum and urine bone metabolism biomarker levels were measured. Bone trabecular and cortical morphometry were quantified in distal femurs, whereas mineral contents were estimated in ashed bones, serum and urine. Finally, the expression of RAS components, the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) was determined. Losartan significantly improved the elevated bone metabolism marker levels and altered trabecular and cortical structures in OVX animals, and restored normal urinary and skeletal mineral levels. Mas receptor inhibition significantly abolished all osteo-protective effects of losartan and enhanced the deleterious effects of OVX. Losartan enhanced OVX-induced up-regulation of ACE-1, AngII, angiotensin type 1 (AT 1 ) receptor and RANKL expression, and increased ACE-2, Ang1-7, Mas and OPG expression in OVX animals. However, A-779 significantly eradicated the effects of losartan on RAS components and RANKL/OPG expression. Thus, Ang1-7 are involved in the osteo-preservative effects of losartan via Mas receptor, which may add therapeutic value to this well-known antihypertensive agent. Copyright © 2017 Elsevier B.V. All rights reserved.

Limitations of Single Slice Dynamic Contrast Enhanced MR in Pharmacokinetic Modeling of Bone Sarcomas

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Toms, Andoni P. (Dept. of Radiology, The Norfolk and Norwich Univ. Hospital, Norwich, Norfolk (United Kingdom)); White, Lawrence M.; Bleakney, Robert R. (Dept. of Medical Imaging, Mount Sinai Hospital, Toronto, ON (Canada)); Kandel, Rita (Dept. of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON (Canada)); Noseworthy, Michael (Health Sciences Centre, Faculty of Health Sciences, McMaster Univ., Hamilton, ON (Canada)); Lee, Shepstone (Institute of Health, Univ. of East Anglia, Norwich, Norfolk (United Kingdom)); Blackstein, Martin E. (Dept. of Oncology, Mount Sinai Hospital, Toronto, ON (Canada)); Wunder, Jay (Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto, ON (Canada))

2009-06-15

Background: Single slice dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) appears to provide perfusion data about sarcomas in vivo that correlate with tumor necrosis on equivalent pathological sections. However, sarcomas are heterogeneous and therefore single slice DCE-MRI may not correlate with total tumor necrosis. Purpose: To determine whether changes in pharmacokinetic modeling of DCE-MRI, during chemotherapy for primary bone sarcomas correlated with histological measures of total tumor necrosis. Material and Methods: Twelve patients with appendicular primary bone sarcomas were included in the study. Each patient had DCE-MRI before, and after completion, of pre-operative chemotherapy. The mean arterial slope (A), endothelial permeability coefficient (Ktrans), and extravascular extracellular volume (Ve) were derived from each data set using a modified two compartment pharmacokinetic model. Total tumor necrosis rates were compared with changes in A, Ktrans, and Ve. Results: Six patients had total tumor necrosis of =90% and six had a measure of <90%. The median percentage changes in A, Ktrans, and Ve for the =90% necrosis group were -52.5% (-83 to 6), -66% (-82 to 26), and 23.5% (-26 to 40), respectively. For the <90% necrosis group, A = - 35% (-75 to 132), Ktrans= - 53 (-66 to 149) and Ve= - 14.5% (-42 to 40). One patient with >90% necrosis had increases in all three measures. Comparison of the two groups generated P-values of 0.699 for A, 0.18 for Ktrans, and 0.31 for Ve. Conclusion: There was no statistically significant correlation between changes in pharmacokinetic perfusion parameters and total tumor necrosis. When using single slice DCE-MRI heterogeneous histology of primary bone sarcomas and repair mediated angiogenesis might both be confounding factors

Exercise enhance the ectopic bone formation of calcium phosphate biomaterials in muscles of mice.

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Cheng, Lijia; Yan, Shuo; Zhu, Jiang; Cai, Peiling; Wang, Ting; Shi, Zheng

2017-08-01

To investigate whether exercise can enhance ectopic bone formation of calcium phosphate (Ca-P) biomaterials in muscles of mice. Firstly, ten transient receptor potential vanilloid subfamily member 1 (TRPV1) knockout mice (group KO) and ten C57BL/6 mice (group WT) were randomly chosen, 10μg Ca-P biomaterials were implanted into the thigh muscle pouch of each mouse which was far away from femur; after that, all animals were kept in open field for free exploration 5min, and the movement time and distance were automatically analyzed. Ten weeks later, the Ca-P samples were harvested for histological staining and immunochemistry. Secondly, the Ca-P biomaterials were implanted into the thigh muscle pouch of C57BL/6 mice the same as previous operation, and then randomly divided into two groups: running group and non-running group (n=10); in running group, all mice run 1h as a speed of 6m/h in a treadmill for 10weeks. Ten weeks later, the blood was collected to detect the interleukin-4 (IL-4) and IL-12 levels by enzyme linked immunosorbent assay (ELISA), and the samples were harvested for histological staining. In groups KO and WT, both the movement time and distance were significant higher in group KO than that in group WT (Pstronger athletic ability of mice, causing better osteoinductivity of Ca-P biomaterials both in TRPV1 -/- mice and running mice; according to this, we want to offer a proposal to patients who suffer from bone defects and artificial bone transplantation: do moderate exercise, don't convalesce all the time. Copyright © 2017 Elsevier B.V. All rights reserved.

RECENT ADVANCES IN PATHO-BIOLOGY OF MYELOMA BONE DISEASE: CLINICOPATHOLOGY AND LITERATURE OF REVIEW

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Lohit Kumar

2016-03-01

Full Text Available Bone disease is a hallmark of multiple myeloma, presenting as lytic lesions associated with bone pain, pathological fractures requiring surgery and/or radiation to bone, spinal cord compression and hypercalcaemia. Increased osteoclastic activity unaccompanied by a compensatory increase in osteoblast function, leading to enhanced bone resorption results in bone disease. The interaction of plasma cells with the bone marrow microenvironment has been shown to play a vital role. Also, interactions of myeloma cells with osteoclasts enhance myeloma growth and survival, and thereby create a vicious cycle leading to extensive bone destruction and myeloma cell expansion.

Complications of bone tumors after multimodal therapy

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Shapeero, L.G., E-mail: lshapeero@usuhs.edu [Department of Radiology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Bone and Soft Tissue Program, United States Military Cancer Institute, 6900 Georgia Ave, NW, Washington, DC 20307 (United States); Poffyn, B. [Department of Orthopaedic Surgery, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); De Visschere, P.J.L. [Department of Radiology and Magnetic Resonance/MR-1K12 IB, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Sys, G. [Department of Orthopaedic Surgery, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Uyttendaele, D. [Department of Radiology and Magnetic Resonance/MR-1K12 IB, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Vanel, D. [Department of Radiology, Rizzoli Institute, 40136 Bologna (Italy); Forsyth, R. [Department of Pathology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Verstraete, K.L. [Department of Radiology and Magnetic Resonance/MR-1K12 IB, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium)

2011-01-15

Purpose: To define and compare the complications of bone tumors after resection, extracorporeal irradiation and re-implantation, with or without radiotherapy. Materials and methods: Eighty patients (40 males and 40 females, ages 4-77 years) with 61 malignant and 19 benign bone tumors were evaluated for local and distant complications after treatment. Two groups of patients were studied: (1) 53 patients had resection without (43 patients) or with external beam radiotherapy (RadRx) (10 patients) and (2) 27 patients underwent extracorporeal irradiation and re-implantation without (22 patients) or with RadRx (5 patients). Patient follow-up varied from 1 month to 13.63 years with mean follow-up of 4.7 years. Imaging studies included bone and chest radiography, spin echo T1- and T2-weighted (or STIR) magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), computed tomography (CT) for thoracic and abdominopelvic metastases and 3-phase technetium-99m-labeled-methylene-diphosphonate (Tc99m MDP) scintigraphy for bone metastases. Results: DCE-MRI differentiated the rapidly enhancing recurrences, residual tumors and metastases from the slowly enhancing inflammation, and the non-enhancing seromas and fibrosis. Recurrences, metastases (mainly to lung and bone), and seromas were greater than twice as frequent in patients after resection than after ECCRI. Although 11.3% of post-resection patients had residual tumor, no ECRRI-treated patient had residual tumor. In contrast, after ECRRI, infection was almost three times as frequent and aseptic loosening twice as frequent as compared with the post-resection patients. Bones treated with RadRx and/or ECRRI showed increased prevalence of fractures and osteoporosis. In addition, muscle inflammation was more common in the externally irradiated patient as compared with the patient who did not receive this therapy. However, another soft tissue complication, heterotopic ossification, was rare in the

Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation.

Science.gov (United States)

Taipaleenmäki, Hanna; Bjerre Hokland, Lea; Chen, Li; Kauppinen, Sakari; Kassem, Moustapha

2012-03-01

Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional and post-transcriptional mechanisms. Recently, a novel class of regulatory factors termed micro-RNAs (miRNAs) has been identified as playing an important role in the regulation of many aspects of osteoblast biology including proliferation, differentiation, metabolism and apoptosis. Also, preliminary data from animal disease models suggest that targeting miRNAs in bone can be a novel approach to increase bone mass. This review highlights the current knowledge of miRNA biology and their role in bone formation and discusses their potential use in future therapeutic applications for metabolic bone diseases.

Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using {sup 18F} FDG PET/CT and {sup 99mT}c HDP Bone Scintigraphy: Characteristics of Soft Tissue Formation

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Seo, Hyo Jung; Choi, Yun Jung; Kim, Hyun Jeong; Jeong, Youg Hyu; Cho, Arthur; Lee, Jae Hoon; Yun, Mijin; Choi, Hye Jin; Lee, Jong Doo; Kang, Won Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

2011-09-15

Bone metastasis from hepatocellular carcinoma (HCC) can present with soft tissue formation, resulting in oncologic emergency. Contrast enhanced FDG PET/CT and bone scintigraphy were compared to evaluate characteristics of bone metastases with of without soft tissue formation from HCC. of 4,151 patients with HCC, 263 patients had bone metastases. Eighty five patients with bone metastasis from HCC underwent contrast enhanced FDG PET/CT. Fifty four of the enrolled subjects had recent {sup 99mT}c HDP bone scintigraphy available for comparison. Metastatic bone lesions were identified with visual inspection on FDG PET/CT, and maximum standardized uptake value (SUVmax) was used for the quantitative analysis. Confirmation of bone metastasis was based on histopathology, combined imaging modalities, or serial follow up studies. Forty seven patients (55%) presented with soft tissue formation, while the remaining 38 patients presented without soft tissue formation. Frequent sites of bone metastases from HCC were the spine (39%), pelvis (19%), and rib cage (14%). The soft tissue formation group had more frequent bone pain (77 vs. 37%, p<0.0001), higher SUVmax (6.02 vs. 3.52, p<0.007), and higher incidence of photon defect in bone scintigraphy (75 vs. 0%) compared to the non soft tissue formation group. FDG PET/CT had higher detection rate for bone metastasis than bone scintigraphy both in lesion based analysis (98 vs. 53%, p=0.0015) and in patient based analysis (100 vs. 80%, p<0.001). Bone metastasis from HCC showed a high incidence of soft tissue formation requiring emergency treatment. Although the characteristic findings for soft tissue formation such as photon defect in bone scintigraphy are helpful in detection, overall detectability of bone metastasis is higher in FDG PET/CT. Contrast enhanced PET/CT will be useful in finding and delineating soft tissue forming bone metastasis from HCC.

Increased chemotaxis and activity of circulatory myeloid progenitor cells may contribute to enhanced osteoclastogenesis and bone loss in the C57BL/6 mouse model of collagen-induced arthritis.

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Ikić Matijašević, M; Flegar, D; Kovačić, N; Katavić, V; Kelava, T; Šućur, A; Ivčević, S; Cvija, H; Lazić Mosler, E; Kalajzić, I; Marušić, A; Grčević, D

2016-12-01

Our study aimed to determine the functional activity of different osteoclast progenitor (OCP) subpopulations and signals important for their migration to bone lesions, causing local and systemic bone resorption during the course of collagen-induced arthritis in C57BL/6 mice. Arthritis was induced with chicken type II collagen (CII), and assessed by clinical scoring and detection of anti-CII antibodies. We observed decreased trabecular bone volume of axial and appendicular skeleton by histomorphometry and micro-computed tomography as well as decreased bone formation and increased bone resorption rate in arthritic mice in vivo. In the affected joints, bone loss was accompanied with severe osteitis and bone marrow hypercellularity, coinciding with the areas of active osteoclasts and bone erosions. Flow cytometry analysis showed increased frequency of putative OCP cells (CD3 - B220 - NK1.1 - CD11b -/lo CD117 + CD115 + for bone marrow and CD3 - B220 - NK1.1 - CD11b + CD115 + Gr-1 + for peripheral haematopoietic tissues), which exhibited enhanced differentiation potential in vitro. Moreover, the total CD11b + population was expanded in arthritic mice as well as CD11b + F4/80 + macrophage, CD11b + NK1.1 + natural killer cell and CD11b + CD11c + myeloid dendritic cell populations in both bone marrow and peripheral blood. In addition, arthritic mice had increased expression of tumour necrosis factor-α, interleukin-6, CC chemokine ligand-2 (Ccl2) and Ccl5, with increased migration and differentiation of circulatory OCPs in response to CCL2 and, particularly, CCL5 signals. Our study characterized the frequency and functional properties of OCPs under inflammatory conditions associated with arthritis, which may help to clarify crucial molecular signals provided by immune cells to mediate systemically enhanced osteoresorption. © 2016 British Society for Immunology.

Extracorporeal shockwave enhanced regeneration of fibrocartilage in a delayed tendon-bone insertion repair model.

Science.gov (United States)

Chow, Dick Ho Kiu; Suen, Pui Kit; Huang, Le; Cheung, Wing-Hoi; Leung, Kwok-Sui; Ng, Chun; Shi, San Qiang; Wong, Margaret Wan Nar; Qin, Ling

2014-04-01

Fibrous tissue is often formed in delayed healing of tendon bone insertion (TBI) instead of fibrocartilage. Extracorporeal shockwave (ESW) provides mechanical cues and upregulates expression of fibrocartilage-related makers and cytokines. We hypothesized that ESW would accelerate fibrocartilage regeneration at the healing interface in a delayed TBI healing model. Partial patellectomy with shielding at the TBI interface was performed on 32 female New Zealand White Rabbits for establishing this delayed TBI healing model. The rabbits were separated into the control and ESW group for evaluations at postoperative week 8 and 12. Shielding was removed at week 4 and a single ESW treatment was applied at week 6. Fibrocartilage regeneration was evaluated histomorphologically and immunohistochemically. Vickers hardness of the TBI matrix was measured by micro-indentation. ESW group showed higher fibrocartilage area, thickness, and proteoglycan deposition than the control in week 8 and 12. ESW increased expression of SOX9 and collagen II significantly in week 8 and 12, respectively. ESW group showed a gradual transition of hardness from bone to fibrocartilage to tendon, and had a higher Vickers hardness than the control group at week 12. In conclusion, ESW enhanced fibrocartilage regeneration at the healing interface in a delayed TBI healing model. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Glucocorticoid Signaling and Bone Biology.

Science.gov (United States)

Komori, T

2016-11-01

Since glucocorticoids remain an effective therapeutic option for the treatment of many inflammatory and autoimmune diseases, glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis. Fractures may occur in as many as 30-50% of patients receiving chronic glucocorticoid therapy. Under physiological conditions, glucocorticoids are required for normal bone development due to their regulation of osteoblast differentiation, possibly via the Wnt/β-catenin pathway and TSC22D3. However, serum levels of endogenous corticosterone are elevated in aged mice and glucocorticoids exert negative effects on the survival of osteoblasts and osteocytes as well as angiogenesis. Glucocorticoid treatments impair bone formation and enhance bone resorption. Excess glucocorticoids induce osteoblast and osteocyte apoptosis by increasing pro-apoptotic molecules, reactive oxygen species, and endoplasmic reticulum stress and suppressing the Wnt/β-catenin pathway. Autophagy protects osteocytes from glucocorticoid-induced apoptosis, but passed some threshold, the process of autophagy leads the cells to apoptosis. Excess glucocorticoids impair osteoblastogenesis by inducing Wnt antagonists, including Dkk1, Sost, and sFRP-1. However, the findings are controversial and the involvement of Wnt antagonists requires further study. Excess glucocorticoids reduce the phosphorylation of Akt and GSK3β, which enhances the degradation of β-catenin. Excess glucocorticoids have been shown to modulate the expression of miRNAs, including miR-29a, miR-34a-5p, and miR-199a-5p, which regulate the proliferation and differentiation of osteoblast lineage cells. Excess glucocorticoids also enhance bone resorption by reducing OPG expression, increasing Rankl expression and reactive oxygen species, and prolonging the life span of osteoclasts; however, they also suppress the bone-degrading capacity of osteoclasts by disturbing the organization of the cytoskeleton. © Georg Thieme Verlag KG

Bone compaction enhances fixation of weightbearing titanium implants

DEFF Research Database (Denmark)

Kold, Søren; Rahbek, Ole; Vestermark, Marianne

2005-01-01

are weightbearing, the effects of compaction on weightbearing implants were examined. The hypothesis was that compaction would increase implant fixation compared with conventional drilling. Porous-coated titanium implants were inserted bilaterally into the weightbearing portion of the femoral condyles of dogs....... In each dog, one knee had the implant cavity prepared with drilling, and the other knee was prepared with compaction. Eight dogs were euthanized after 2 weeks, and eight dogs were euthanized after 4 weeks. Femoral condyles from an additional eight dogs represented Time 0. Compacted specimens had higher...... bone-implant contact and periimplant bone density at 0 and 2 weeks, but not at 4 weeks. A biphasic response of compaction was found with a pushout test, as compaction increased ultimate shear strength and energy absorption at 0 and 4 weeks, but not at 2 weeks. This biphasic response indicates...

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.

The effects of bone marrow aspirate, bone graft, and collagen composites on fixation of titanium implants

DEFF Research Database (Denmark)

Babiker, Hassan; Ding, Ming; Sandri, Monica

2012-01-01

Replacement of extensive local bone loss especially in revision joint arthroplasty and spine fusion is a significant clinical challenge. Allograft and autograft have been considered as gold standards for bone replacement. However, there are several disadvantages such as donor site pain, bacterial...... contamination, and non union as well as the potential risk of disease transmission. Hydroxyapatite and collagen composites (HA/Collagen) have the potential in mimicking and replacing skeletal bones. This study attempted to determine the effects of newly developed HA/Collagen-composites with and without bone...... marrow aspirate (BMA) on enhancement of bone implant fixation. Method: Titanium alloy implants were inserted into bilateral femoral condyles of eight skeletally mature sheep, four implants per sheep. The implant had a circumferential gap of 2 mm. The gap was filled with: HA/Collagen; HA...

Handball Practice Enhances Bone Mass in Specific Sites Among Prepubescent Boys.

Science.gov (United States)

Missawi, Kawther; Zouch, Mohamed; Chakroun, Yosra; Chaari, Hamada; Tabka, Zouhair; Bouajina, Elyès

2016-01-01

This investigation's purpose is to focus on the effects of practicing handball for at least 2 yr on bone acquisition among prepubescent boys. One hundred prepubescent boys aged 10.68 ± 0.85 yr were divided into 2 groups: 50 handball players (HP group) and 50 controls (C group). Bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) were evaluated by using dual-photon X-ray absorptiometry on the whole body, lumbar spine (L2-L4), legs, arms, femoral necks, hips and radiuses. Results showed greater values of BMD in both right and left femoral neck and total hip in handball players than in controls. In addition, handball players had higher values of legs and right total hip BMC than controls without any obvious variation of BA measurement in all sites between groups. All results of the paired t-test displayed an obviously marked variation of bone mass parameters between the left and right sides in the trained group without any marked variation among controls. Data showed an increased BMD of the supporting sites between the left and the right leg among handball players. However, "BMC" results exhibited higher values in the right than in the left total hip, and in the right total radius than in the left correspondent site. In addition, differences in the "BA" measurements were observed in the left total hip and in the right arm. Specific bone sites are markedly stimulated by handball training in prepubescent boys. Copyright © 2016 International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Cadmium accelerates bone loss in ovariectomized mice and fetal rat limb bones in culture

International Nuclear Information System (INIS)

Bhattacharyya, M.H.; Whelton, B.D.; Stern, P.H.; Peterson, D.P.

1988-01-01

Loss of bone mineral after ovariectomy was studied in mice exposed to dietary cadmium at 0.25, 5, or 50 ppm. Results show that dietary cadmium at 50 ppm increased bone mineral loss to a significantly greater extent in ovariectomized mice than in sham-operated controls. These results were obtained from two studies, one in which skeletal calcium content was determined 6 months after ovariectomy and a second in which 45 Ca release from 45 Ca-prelabeled bones was measured immediately after the start of dietary cadmium exposure. Furthermore, experiments with 45 Ca-prelabeled fetal rat limb bones in culture demonstrated that Cd at 10 nM in the medium, a concentration estimated to be in the plasma of mice exposed to 50 ppm dietary Cd, strikingly increased bone resorption. These in vitro results indicate that cadmium may enhance bone mineral loss by a direct action on bone. Results of the in vivo studies are consistent with a significant role of cadmium in the etiology of Itai-Itai disease among postmenopausal women in Japan and may in part explain the increased risk of postmenopausal osteoporosis among women who smoke

Bio-composites composed of a solid free-form fabricated polycaprolactone and alginate-releasing bone morphogenic protein and bone formation peptide for bone tissue regeneration.

Science.gov (United States)

Kim, MinSung; Jung, Won-Kyo; Kim, GeunHyung

2013-11-01

Biomedical scaffolds should be designed with highly porous three-dimensional (3D) structures that have mechanical properties similar to the replaced tissue, biocompatible properties, and biodegradability. Here, we propose a new composite composed of solid free-form fabricated polycaprolactone (PCL), bone morphogenic protein (BMP-2) or bone formation peptide (BFP-1), and alginate for bone tissue regeneration. In this study, PCL was used as a mechanical supporting component to enhance the mechanical properties of the final biocomposite and alginate was used as the deterring material to control the release of BMP-2 and BFP-1. A release test revealed that alginate can act as a good release control material. The in vitro biocompatibilities of the composites were examined using osteoblast-like cells (MG63) and the alkaline phosphatase (ALP) activity and calcium deposition were assessed. The in vitro test results revealed that PCL/BFP-1/Alginate had significantly higher ALP activity and calcium deposition than the PCL/BMP-2/Alginate composite. Based on these findings, release-controlled BFP-1 could be a good growth factor for enhancement of bone tissue growth and the simple-alginate coating method will be a useful tool for fabrication of highly functional biomaterials through release-control supplementation.

Enhanced In Vivo Bone and Blood Vessel Formation by Iron Oxide and Silica Doped 3D Printed Tricalcium Phosphate Scaffolds.

Science.gov (United States)

Bose, Susmita; Banerjee, Dishary; Robertson, Samuel; Vahabzadeh, Sahar

2018-05-04

Calcium phosphate (CaP) ceramics show significant promise towards bone graft applications because of the compositional similarity to inorganic materials of bone. With 3D printing, it is possible to create ceramic implants that closely mimic the geometry of human bone and can be custom-designed for unusual injuries or anatomical sites. The objective of the study was to optimize the 3D-printing parameters for the fabrication of scaffolds, with complex geometry, made from synthesized tricalcium phosphate (TCP) powder. This study was also intended to elucidate the mechanical and biological effects of the addition of Fe +3 and Si +4 in TCP implants in a rat distal femur model for 4, 8, and 12 weeks. Doped with Fe +3 and Si +4 TCP scaffolds with 3D interconnected channels were fabricated to provide channels for micronutrients delivery and improved cell-material interactions through bioactive fixation. Addition of Fe +3 into TCP enhanced early-stage new bone formation by increasing type I collagen production. Neovascularization was observed in the Si +4 doped samples after 12 weeks. These findings emphasize that the additive manufacturing of scaffolds with complex geometry from synthesized ceramic powder with modified chemistry is feasible and may serve as a potential candidate to introduce angiogenic and osteogenic properties to CaPs, leading to accelerated bone defect healing.

Bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions.

Science.gov (United States)

Khan, Wasim S; Adesida, Adetola B; Tew, Simon R; Lowe, Emma T; Hardingham, Timothy E

2010-06-01

Bone marrow-derived mesenchymal stem cells are a potential source of cells for the repair of articular cartilage defects. Hypoxia has been shown to improve chondrogenesis in some cells. In this study, bone marrow-derived stem cells were characterized and the effects of hypoxia on chondrogenesis investigated. Adherent bone marrow colony-forming cells were characterized for stem cell surface epitopes, and then cultured as cell aggregates in chondrogenic medium under normoxic (20% oxygen) or hypoxic (5% oxygen) conditions. The cells stained strongly for markers of adult mesenchymal stem cells, and a high number of cells were also positive for the pericyte marker 3G5. The cells showed a chondrogenic response in cell aggregate cultures and, in lowered oxygen, there was increased matrix accumulation of proteoglycan, but less cell proliferation. In hypoxia, there was increased expression of key transcription factor SOX6, and of collagens II and XI, and aggrecan. Pericytes are a candidate stem cell in many tissue, and our results show that bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5. The response to chondrogenic culture in these cells was enhanced by lowered oxygen tension. This has important implications for tissue engineering applications of bone marrow-derived stem cells. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Effect of nephrotoxic drugs on the development of radiation nephropathy after bone marrow transplantation

International Nuclear Information System (INIS)

Lawton, C.A.; Fish, B.L.; Moulder, J.E.

1994-01-01

Chronic renal failure is a significant cause of late morbidity in bone marrow transplant patients whose conditioning regimen includes total body irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow transplant nephropathy), but it may not be the only cause. These studies use a rat syngeneic bone marrow transplant model to determine whether nephrotoxic agents used in conjunction with bone marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy. Rats received 11-17 Gy TBI in six fractions over 3 days followed by syngeneic bone marrow transplant. In conjunction with the bone marrow transplants, animals received either no drugs, cyclosporine, amphotericin, gentamicin, or busulfan. Drugs were given in schedules analogous to their use in clinical bone marrow transplantation. Drug doses were chosen so that the drug regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6 months with periodic renal function tests. Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused late morbidity that appeared to be due to neurological problems, but did not enhance radiation nephropathy. Busulfan resulted in a significant enhancement of radiation nephropathy. Of the nephrotoxins used in conjunction with bone marrow transplantation only radiation and busulfan were found to be risk factors for bone marrow transplant nephropathy. 34 refs., 4 figs., 2 tabs

A feasibility study for in vitro evaluation of fixation between prosthesis and bone with bone marrow-derived mesenchymal stem cells.

Science.gov (United States)

Morita, Yusuke; Yamasaki, Kenichi; Hattori, Koji

2010-10-01

It is difficult to quantitatively evaluate adhesive strength between an implant and the neighboring bone using animal experiments, because the degree of fixation of an implant depends on differences between individuals and the clearance between the material and the bone resulting from surgical technique. A system was designed in which rat bone marrow cells were used to quantitatively evaluate the adhesion between titanium alloy plates and bone plates in vitro. Three kinds of surface treatment were used: a sand-blasted surface, a titanium-sprayed surface and a titanium-sprayed surface coated with hydroxyapatite. Bone marrow cells obtained from rat femora were seeded on the titanium alloy plates, and the cells were cultured between the titanium alloy plates and the bone plates sliced from porcine ilium for 2 weeks. After cultivation, adhesive strength was measured using a tensile test, after which DNA amount and Alkaline phosphatase activity were measured. The seeded cells accelerated adhesion of the titanium alloy plate to the bone plate. Adhesive strength of the titanium-sprayed surface was lower than that of the sand-blasted surface because of lower initial contact area, although there was no difference in Alkaline phosphatase activity between two surface treatments. A hydroxyapatite coating enhanced adhesive strength between the titanium alloy palate and the bone plate, as well as enhancing osteogenic differentiation of bone marrow cells. It is believed that this novel experimental method can be used to simultaneously evaluate the osteogenic differentiation and the adhesive strength of an implant during in vitro cultivation. 2010 Elsevier Ltd. All rights reserved.

Investigation of the optimal timing for chondrogenic priming of MSCs to enhance osteogenic differentiation in vitro as a bone tissue engineering strategy.

Science.gov (United States)

Freeman, F E; Haugh, M G; McNamara, L M

2016-04-01

Recent in vitro tissue engineering approaches have shown that chondrogenic priming of human bone marrow mesenchymal stem cells (MSCs) can have a positive effect on osteogenesis in vivo. However, whether chondrogenic priming is an effective in vitro bone regeneration strategy is not yet known. In particular, the appropriate timing for chondrogenic priming in vitro is unknown albeit that in vivo cartilage formation persists for a specific period before bone formation. The objective of this study is to determine the optimum time for chondrogenic priming of MSCs to enhance osteogenic differentiation by MSCs in vitro. Pellets derived from murine and human MSCs were cultured in six different media groups: two control groups (chondrogenic and osteogenic) and four chondrogenic priming groups (10, 14, 21 and 28 days priming). Biochemical analyses (Hoechst, sulfate glycosaminoglycan (sGAG), Alkaline Phosphate (ALP), calcium), histology (Alcian Blue, Alizarin Red) and immunohistochemistry (collagen types I, II and X) were performed on the samples at specific times. Our results show that after 49 days the highest amount of sGAG production occurred in MSCs chondrogenically primed for 21 days and 28 days. Moreover we found that chondrogenic priming of MSCs in vitro for specific amounts of time (14 days, 21 days) can have optimum influence on their mineralization capacity and can produce a construct that is mineralized throughout the core. Determining the optimum time for chondrogenic priming to enhance osteogenic differentiation in vitro provides information that might lead to a novel regenerative treatment for large bone defects, as well as addressing the major limitation of core degradation and construct failure. Copyright © 2013 John Wiley & Sons, Ltd.

Increased resistance during jump exercise does not enhance cortical bone formation.

Science.gov (United States)

Boudreaux, Ramon D; Swift, Joshua M; Gasier, Heath G; Wiggs, Michael P; Hogan, Harry A; Fluckey, James D; Bloomfield, Susan A

2014-01-01

This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cortical bone of the tibia and femur mid-diaphyses. Sprague-Dawley rats (male, 6 months old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15), or cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE for 5 wk. Load in the HRE group was progressively increased from 80 g added to a weighted vest (50 repetitions) to 410 g (16 repetitions). The LRE rats completed the same protocol as the HRE group (same number of repetitions), with only a 30-g vest applied. Low- and high-load jump RE resulted in 6%-11% higher cortical bone mineral content and cortical bone area compared with controls, as determined by in vivo peripheral quantitative computed tomography measurements. In the femur, however, only LRE demonstrated improvements in cortical volumetric bone mineral density (+11%) and cross-sectional moment of inertia (+20%) versus the CC group. The three-point bending to failure revealed a marked increase in tibial maximum force (25%-29%), stiffness (19%-22%), and energy to maximum force (35%-55%) and a reduction in elastic modulus (-11% to 14%) in both LRE and HRE compared with controls. Dynamic histomorphometry assessed at the tibia mid-diaphysis determined that both LRE and HRE resulted in 20%-30% higher periosteal mineralizing surface versus the CC group. Mineral apposition rate and bone formation rate were significantly greater in animals in the LRE group (27%, 39%) than those in the HRE group. These data demonstrate that jump training with minimal loading is equally, and sometimes more, effective at augmenting cortical bone integrity compared with overload training in skeletally mature rats.

Celecoxib enhances radiation response of secondary bone tumors of a human non-small cell lung cancer via antiangiogenesis in vivo

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Klenke, Frank Michael [Bern Univ. (Switzerland). Dept. of Orthopedic Surgery; Abdollahi, Amir [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Tufts Univ. School of Medicine, Boston, MA (United States). Center of Cancer Systems Biology; Bischof, Marc; Huber, Peter E. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Gebhard, Martha-Maria [Heidelberg Univ. (Germany). Dept. of Experimental Surgery; Ewerbeck, Volker [Heidelberg Univ. (Germany). Dept. of Orthopedic Surgery; Sckell, Axel [Charite Univ. Medical Center, Berlin (Germany). Dept. of Orthopedic, Trauma and Reconstructive Surgery

2011-01-15

Purpose: Cyclooxygenase-2 (COX-2) inhibitors mediate a systemic antitumor activity via antiangiogenesis and seem to enhance the response of primary tumors to radiation. Radiosensitizing effects of COX-2 inhibition have not been reported for bone metastases. Therefore, the aim of this study was the investigation of the radiosensitizing effects of the selective COX-2 inhibitor celecoxib in secondary bone tumors of a non-small cell lung carcinoma in vivo. Materials and Methods: Human A549 lung carcinomas were implanted into a cranial window preparation in male SCID mice (n = 24). Animals were treated with either celecoxib or radiation (7 Gy single photon dose) alone or a combination of celecoxib and radiation, respectively. Untreated animals served as controls. The impact of radiation and COX-2 inhibition on angiogenesis, microcirculation, and tumor growth was analyzed over 28 days by means of intravital microscopy and histological methods. Results: Monotherapies with radiation as well as celecoxib had significant antitumor effects compared to untreated controls. Both therapies reduced tumor growth and vascularization to a similar extent. The simultaneous administration of celecoxib and radiation further enhanced the antitumor and antiangiogenic effects of single-beam radiation. With the combined treatment approach, tumor vascularization and tumor size were decreased by 57% and 51%, respectively, as compared to monotherapy with radiation. Conclusion: The combined application of radiation therapy and COX-2 inhibition showed synergistic effects concerning the inhibition of tumor growth and tumor angiogenesis. Therefore, the combination of radiation with COX-2 inhibitor therapy represents a promising approach to improve the therapeutic efficacy of radiotherapy of bone metastases. (orig.)

PIXE analysis showed that the preirradiation enhanced recovery of bone marrow elements after challenging irradiation in C57BL/6N Mice

International Nuclear Information System (INIS)

Matsuda, Y.; Yonezawa, M.; Nishiyama, F.

2000-01-01

Priming X-irradiation with 0.3-0.5 Gy induces radio-resistance in C57BL/6 strain of mice 2 weeks afterward. Elements in the bone marrow, sampled 11 days after challenging exposure to 5.0 Gy, were determined by PIXE. The challenging irradiation decreased Mg, P, S, K, Ca and Zn as well as dried bone marrow weight. The pre-irradiation enhanced recovery of these levels, indicating stimulated recovery of the metabolism int he tissue. Fe in both control (without pre-irradiation) and experimental groups increased to about twice the original value, showing elevated hemoglobin synthesis after challenging exposure. In previous studies we have reported that recovery of peripheral blood cell counts after sub-lethal irradiation was enhanced by the pre-irradiation. Further, study on accumulation of p53 and Bax proteins, which lead to apoptotic cell death, revealed that the pre-irradiation significantly suppressed accumulation of these proteins in the spleen after challenging irradiation with 3 Gy. These results and our present study suggest that the pre-irradiation decreased the spleen cell death, and favored re-growth of the spleen cells, resulting in stimulated recovery of metabolism for hematopoiesis in the bone marrow as well as in the spleen after challenging high dose irradiation. Stimulated recovery of Mg, P, S, K, Ca and Zn levels might indicate the importance of these elements in hematopoiesis. (author)

Engraftment and bone mass are enhanced by PTHrP 1-34 in ectopically transplanted vertebrae (vossicle model) and can be non-invasively monitored with bioluminescence and fluorescence imaging.

Science.gov (United States)

Hildreth, Blake Eason; Williams, Michelle M; Dembek, Katarzyna A; Hernon, Krista M; Rosol, Thomas J; Toribio, Ramiro E

2015-12-01

Evidence exists that parathyroid hormone-related protein (PTHrP) 1-34 may be more anabolic in bone than parathyroid hormone 1-34. While optical imaging is growing in popularity, scant information exists on the relationships between traditional bone imaging and histology and bioluminescence (BLI) and fluorescence (FLI) imaging. We aimed to evaluate the effects of PTHrP 1-34 on bone mass and determine if relationships existed between radiographic and histologic findings in bone and BLI and FLI indices. Vertebrae (vossicles) from mice coexpressing luciferase and green fluorescent protein were implanted subcutaneously into allogenic nude mice. Transplant recipients were treated daily with saline or PTHrP 1-34 for 4 weeks. BLI, FLI, radiography, histology, and µCT of the vossicles were performed over time. PTHrP 1-34 increased bioluminescence the most after 2 weeks, fluorescence at all time points, and decreased the time to peak bioluminescence at 4 weeks (P ≤ 0.027), the latter of which suggesting enhanced engraftment. PTHrP 1-34 maximized vertebral body volume at 4 weeks (P bone observed histologically increased in both groups at 2 and 4 weeks (P ≤ 0.002); however, PTHrP 1-34 exceeded time-matched controls (P ≤ 0.044). A positive linear relationship existed between the percentage of trabecular bone and (1) total bioluminescence (r = 0.595; P = 0.019); (2) total fluorescence (r = 0.474; P = 0.074); and (3) max fluorescence (r = 0.587; P = 0.021). In conclusion, PTHrP 1-34 enhances engraftment and bone mass, which can be monitored non-invasively by BLI and FLI.

Enhanced mechanical properties and biocompatibility of novel hydroxyapatite/TOPAS hybrid composite for bone tissue engineering applications

Energy Technology Data Exchange (ETDEWEB)

Ain, Qurat Ul [Department of Materials Engineering, School of Chemical and Materials Engineering, National University of Sciences and Technology, H-12, Islamabad (Pakistan); Khan, Ahmad Nawaz, E-mail: ahmad.nawaz@scme.nust.edu.pk [Department of Materials Engineering, School of Chemical and Materials Engineering, National University of Sciences and Technology, H-12, Islamabad (Pakistan); Nabavinia, Mahboubeh [Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA (United States); Mujahid, Mohammad [Department of Materials Engineering, School of Chemical and Materials Engineering, National University of Sciences and Technology, H-12, Islamabad (Pakistan)

2017-06-01

The bioactivity and mechanical properties of hybrid composites of hydroxyapatite (HA) in cyclic olefinic copolymer (COC) also known commercially as TOPAS are investigated, first time, for regeneration and repair of the bone tissues. HA is synthesized to obtain the spherically shaped nanoparticles in the size range of 60 ± 20 nm. Various concentrations of HA ranging from 1 to 30 wt% are dispersed in TOPAS using sodium dodecyl sulfate (SDS) coupling agent for better dispersion and interaction of hydrophilic HA with hydrophobic TOPAS. Scanning electron microscope shows the uniform dispersion of HA ≤ 10 wt% in TOPAS and at higher concentrations > 10 wt%, agglomeration occurs in the hybrid composites. Tunable mechanical properties are achieved as the compressive modulus and strength are increased around 140% from 6.4 to 15.3 MPa and 185% from 0.26 to 0.74 MPa, respectively. Such increase in the mechanical properties of TOPAS is attributed to the anchoring of the polymer chains in the vicinity of HA nanoparticles owing to better dispersion and interfacial interactions. In comparison to neat TOPAS, hybrid composites of TOPAS/HA promoted the cell adhesion and proliferation significantly. The cell density and proliferation of TOPAS/HA hybrid composites is enhanced 9 and 3 folds, respectively, after 1 day culturing in preosteoblasts cells. Moreover, the morphology of cells changed from spherical to flattened spread morphology demonstrating clearly the migration of the cells for the formation of interconnected cellular network. Additionally, very few dead cells are found in hybrid composites showing their cytocompatibility. Overall, the hybrid composites of TOPAS/HA exhibited superior strength and stiffness along with enhanced cytocompatibility for bone tissue engineering applications. - Highlights: • TOPAS/HA hybrid composites exhibited enhanced mechanical properties owing to better dispersion and interaction of HA. • Without affecting the degradation rate, the

Enhanced mechanical properties and biocompatibility of novel hydroxyapatite/TOPAS hybrid composite for bone tissue engineering applications

International Nuclear Information System (INIS)

Ain, Qurat Ul; Khan, Ahmad Nawaz; Nabavinia, Mahboubeh; Mujahid, Mohammad

2017-01-01

The bioactivity and mechanical properties of hybrid composites of hydroxyapatite (HA) in cyclic olefinic copolymer (COC) also known commercially as TOPAS are investigated, first time, for regeneration and repair of the bone tissues. HA is synthesized to obtain the spherically shaped nanoparticles in the size range of 60 ± 20 nm. Various concentrations of HA ranging from 1 to 30 wt% are dispersed in TOPAS using sodium dodecyl sulfate (SDS) coupling agent for better dispersion and interaction of hydrophilic HA with hydrophobic TOPAS. Scanning electron microscope shows the uniform dispersion of HA ≤ 10 wt% in TOPAS and at higher concentrations > 10 wt%, agglomeration occurs in the hybrid composites. Tunable mechanical properties are achieved as the compressive modulus and strength are increased around 140% from 6.4 to 15.3 MPa and 185% from 0.26 to 0.74 MPa, respectively. Such increase in the mechanical properties of TOPAS is attributed to the anchoring of the polymer chains in the vicinity of HA nanoparticles owing to better dispersion and interfacial interactions. In comparison to neat TOPAS, hybrid composites of TOPAS/HA promoted the cell adhesion and proliferation significantly. The cell density and proliferation of TOPAS/HA hybrid composites is enhanced 9 and 3 folds, respectively, after 1 day culturing in preosteoblasts cells. Moreover, the morphology of cells changed from spherical to flattened spread morphology demonstrating clearly the migration of the cells for the formation of interconnected cellular network. Additionally, very few dead cells are found in hybrid composites showing their cytocompatibility. Overall, the hybrid composites of TOPAS/HA exhibited superior strength and stiffness along with enhanced cytocompatibility for bone tissue engineering applications. - Highlights: • TOPAS/HA hybrid composites exhibited enhanced mechanical properties owing to better dispersion and interaction of HA. • Without affecting the degradation rate, the

Novel Therapy for Bone Regeneration in Large Segmental Defects

Science.gov (United States)

2017-12-01

Nanohydrox- yapatite- coated electrospun poly(L-lactide) nanofibers enhance osteogenic differentiation of stem cells and induce ectopic bone formation... Bone Regeneration in a Large Animal Critical Sized Defect Model, Second Annual Symposium on Cell Therapy and Regenerative Medicine, 2016 4...osteogenic cells and growth factors demonstrated success in facilitating bone regeneration in these cases. However, due to the lack of mechanical property

Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.

Science.gov (United States)

Das, Anusuya; Segar, Claire E; Chu, Yihsuan; Wang, Tiffany W; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C; Cui, Quanjun; Botchwey, Edward A

2015-09-01

Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Direct lentiviral-cyclooxygenase 2 application to the tendon-bone interface promotes osteointegration and enhances return of the pull-out tensile strength of the tendon graft in a rat model of biceps tenodesis.

Directory of Open Access Journals (Sweden)

Charles H Rundle

Full Text Available This study sought to determine if direct application of the lentiviral (LV-cyclooxygenase 2 (COX2 vector to the tendon-bone interface would promote osteointegration of the tendon graft in a rat model of biceps tenodesis. The LV-COX2 gene transfer strategy was chosen for investigation because a similar COX2 gene transfer strategy promoted bony bridging of the fracture gap during bone repair, which involves similar histologic transitions that occur in osteointegration. Briefly, a 1.14-mm diameter tunnel was drilled in the mid-groove of the humerus of adult Fischer 344 rats. The LV-COX2 or βgal control vector was applied directly into the bone tunnel and onto the end of the tendon graft, which was then pulled into the bone tunnel. A poly-L-lactide pin was press-fitted into the tunnel as interference fixation. Animals were sacrificed at 3, 5, or 8 weeks for histology analysis of osteointegration. The LV-COX2 gene transfer strategy enhanced neo-chondrogenesis at the tendon-bone interface but with only marginal effect on de novo bone formation. The tendon-bone interface of the LV-COX2-treated tenodesis showed the well-defined tendon-to-fibrocartilage-to-bone histologic transitions that are indicative of osteointegration of the tendon graft. The LV-COX2 in vivo gene transfer strategy also significantly enhanced angiogenesis at the tendon-bone interface. To determine if the increased osteointegration was translated into an improved pull-out mechanical strength property, the pull-out tensile strength of the LV-COX2-treated tendon grafts was determined with a pull-out mechanical testing assay. The LV-COX2 strategy yielded a significant improvement in the return of the pull-out strength of the tendon graft after 8 weeks. In conclusion, the COX2-based in vivo gene transfer strategy enhanced angiogenesis, osteointegration and improved return of the pull-out strength of the tendon graft. Thus, this strategy has great potential to be developed into an

Magnetic resonance imaging of the bone marrow

International Nuclear Information System (INIS)

Baur-Melnyk, Andrea

2013-01-01

The first book devoted to MRI of the bone marrow. Describes the MRI appearances of normal bone marrows and the full range of bone marrow disorders. Discusses the role of advanced MRI techniques and contrast enhancement. On account of its unrivalled imaging capabilities and sensitivity, magnetic resonance imaging (MRI) is considered the modality of choice for the investigation of physiologic and pathologic processes affecting the bone marrow. This book describes the MRI appearances of both the normal bone marrow, including variants, and the full range of bone marrow disorders. Detailed discussion is devoted to malignancies, including multiple myeloma, lymphoma, chronic myeloproliferative disorders, leukemia, and bone metastases. Among the other conditions covered are benign and malignant compression fractures, osteonecrosis, hemolytic anemia, Gaucher's disease, bone marrow edema syndrome, trauma, and infective and non-infective inflammatory disease. Further chapters address the role of MRI in assessing treatment response, the use of contrast media, and advanced MRI techniques. Magnetic Resonance Imaging of the Bone Marrow represents an ideal reference for both novice and experienced practitioners.

Magnetic resonance imaging of the bone marrow

Energy Technology Data Exchange (ETDEWEB)

Baur-Melnyk, Andrea (ed.) [Klinikum der Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie

2013-08-01

The first book devoted to MRI of the bone marrow. Describes the MRI appearances of normal bone marrows and the full range of bone marrow disorders. Discusses the role of advanced MRI techniques and contrast enhancement. On account of its unrivalled imaging capabilities and sensitivity, magnetic resonance imaging (MRI) is considered the modality of choice for the investigation of physiologic and pathologic processes affecting the bone marrow. This book describes the MRI appearances of both the normal bone marrow, including variants, and the full range of bone marrow disorders. Detailed discussion is devoted to malignancies, including multiple myeloma, lymphoma, chronic myeloproliferative disorders, leukemia, and bone metastases. Among the other conditions covered are benign and malignant compression fractures, osteonecrosis, hemolytic anemia, Gaucher's disease, bone marrow edema syndrome, trauma, and infective and non-infective inflammatory disease. Further chapters address the role of MRI in assessing treatment response, the use of contrast media, and advanced MRI techniques. Magnetic Resonance Imaging of the Bone Marrow represents an ideal reference for both novice and experienced practitioners.

Exposure to Low-Dose X-Ray Radiation Alters Bone Progenitor Cells and Bone Microarchitecture.

Science.gov (United States)

Lima, Florence; Swift, Joshua M; Greene, Elisabeth S; Allen, Matthew R; Cunningham, David A; Braby, Leslie A; Bloomfield, Susan A

2017-10-01

Exposure to high-dose ionizing radiation during medical treatment exerts well-documented deleterious effects on bone health, reducing bone density and contributing to bone growth retardation in young patients and spontaneous fracture in postmenopausal women. However, the majority of human radiation exposures occur in a much lower dose range than that used in the radiation oncology clinic. Furthermore, very few studies have examined the effects of low-dose ionizing radiation on bone integrity and results have been inconsistent. In this study, mice were irradiated with a total-body dose of 0.17, 0.5 or 1 Gy to quantify the early (day 3 postirradiation) and delayed (day 21 postirradiation) effects of radiation on bone microarchitecture and bone marrow stromal cells (BMSCs). Female BALBc mice (4 months old) were divided into four groups: irradiated (0.17, 0.5 and 1 Gy) and sham-irradiated controls (0 Gy). Micro-computed tomography analysis of distal femur trabecular bone from animals at day 21 after exposure to 1 Gy of X-ray radiation revealed a 21% smaller bone volume (BV/TV), 22% decrease in trabecular numbers (Tb.N) and 9% greater trabecular separation (Tb.Sp) compared to sham-irradiated controls (P X-rays, whereas osteoclastogenesis was enhanced. A better understanding of the effects of radiation on osteoprogenitor cell populations could lead to more effective therapeutic interventions that protect bone integrity for individuals exposed to low-dose ionizing radiation.

Micro/Nano Structural Tantalum Coating for Enhanced Osteogenic Differentiation of Human Bone Marrow Stem Cells.

Science.gov (United States)

Ding, Ding; Xie, Youtao; Li, Kai; Huang, Liping; Zheng, Xuebin

2018-04-03

Recently, tantalum has been attracting much attention for its anticorrosion resistance and biocompatibility, and it has been widely used in surface modification for implant applications. To improve its osteogenic differentiation of human bone marrow stem cells (hBMSCs), a micro/nano structure has been fabricated on the tantalum coating surface through the combination of anodic oxidation and plasma spraying method. The morphology, composition, and microstructure of the modified coating were comprehensively studied by employing scanning electron microscopy (SEM), X-ray diffraction (XRD) as well as transmission electron microscopy (TEM). The effects of hierarchical structures as well as micro-porous structure of tantalum coating on the behavior for human bone marrow stem cells (hBMSCs) were evaluated and compared at both cellular and molecular levels in vitro. The experimental results show that a hierarchical micro/nano structure with Ta₂O₅ nanotubes spread onto a micro-scale tantalum coating has been fabricated successfully, which is confirmed to promote cell adhesion and spreading. Besides, the hierarchical micro/nano tantalum coating can provide 1.5~2.1 times improvement in gene expression, compared with the micro-porous tantalum coating. It demonstrates that it can effectively enhance the proliferation and differentiation of hBMSCs in vitro.

Micro/Nano Structural Tantalum Coating for Enhanced Osteogenic Differentiation of Human Bone Marrow Stem Cells

Directory of Open Access Journals (Sweden)

Ding Ding

2018-04-01

Full Text Available Recently, tantalum has been attracting much attention for its anticorrosion resistance and biocompatibility, and it has been widely used in surface modification for implant applications. To improve its osteogenic differentiation of human bone marrow stem cells (hBMSCs, a micro/nano structure has been fabricated on the tantalum coating surface through the combination of anodic oxidation and plasma spraying method. The morphology, composition, and microstructure of the modified coating were comprehensively studied by employing scanning electron microscopy (SEM, X-ray diffraction (XRD as well as transmission electron microscopy (TEM. The effects of hierarchical structures as well as micro-porous structure of tantalum coating on the behavior for human bone marrow stem cells (hBMSCs were evaluated and compared at both cellular and molecular levels in vitro. The experimental results show that a hierarchical micro/nano structure with Ta2O5 nanotubes spread onto a micro-scale tantalum coating has been fabricated successfully, which is confirmed to promote cell adhesion and spreading. Besides, the hierarchical micro/nano tantalum coating can provide 1.5~2.1 times improvement in gene expression, compared with the micro-porous tantalum coating. It demonstrates that it can effectively enhance the proliferation and differentiation of hBMSCs in vitro.

Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

International Nuclear Information System (INIS)

Hirata, Eri; Takita, Hiroko; Watari, Fumio; Yokoyama, Atsuro; Ménard-Moyon, Cécilia; Venturelli, Enrica; Bianco, Alberto

2013-01-01

Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF–CNT) showed the same effect as FGF alone. In addition, FGF–CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF–CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF–CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications. (paper)

Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

Science.gov (United States)

Hirata, Eri; Ménard-Moyon, Cécilia; Venturelli, Enrica; Takita, Hiroko; Watari, Fumio; Bianco, Alberto; Yokoyama, Atsuro

2013-11-01

Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF-CNT) showed the same effect as FGF alone. In addition, FGF-CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF-CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF-CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications.

Parathyroid hormone related to bone regeneration in grafted and nongrafted tooth extraction sockets in rats.

Science.gov (United States)

Kuroshima, Shinichiro; Al-Salihi, Zeina; Yamashita, Junro

2013-02-01

The quality and quantity of bone formed in tooth extraction sockets impact implant therapy. Therefore, the establishment of a new approach to enhance bone formation and to minimize bone resorption is important for the success of implant therapy. In this study, we investigated whether intermittent parathyroid hormone (PTH) therapy enhanced bone formation in grafted sockets. Tooth extractions of the maxillary first molars were performed in rats, and the sockets were grafted with xenograft. Intermittent PTH was administered either for 7 days before extractions, for 14 days after extractions, or both. The effect of PTH therapy on bone formation in the grafted sockets was assessed using microcomputed tomography at 14 days after extractions. PTH therapy for 7 days before extractions was not effective to augment bone fill, whereas PTH therapy for 14 days after operation significantly augmented bone formation in the grafted sockets. Intermittent PTH therapy starting right after tooth extractions significantly enhanced bone fill in the grafted sockets, suggesting that PTH therapy can be a strong asset for the success of the ridge preservation procedure.

Micro-computed tomography assessment of human alveolar bone: bone density and three-dimensional micro-architecture.

Science.gov (United States)

Kim, Yoon Jeong; Henkin, Jeffrey

2015-04-01

Micro-computed tomography (micro-CT) is a valuable means to evaluate and secure information related to bone density and quality in human necropsy samples and small live animals. The aim of this study was to assess the bone density of the alveolar jaw bones in human cadaver, using micro-CT. The correlation between bone density and three-dimensional micro architecture of trabecular bone was evaluated. Thirty-four human cadaver jaw bone specimens were harvested. Each specimen was scanned with micro-CT at resolution of 10.5 μm. The bone volume fraction (BV/TV) and the bone mineral density (BMD) value within a volume of interest were measured. The three-dimensional micro architecture of trabecular bone was assessed. All the parameters in the maxilla and the mandible were subject to comparison. The variables for the bone density and the three-dimensional micro architecture were analyzed for nonparametric correlation using Spearman's rho at the significance level of p architecture parameters were consistently higher in the mandible, up to 3.3 times greater than those in the maxilla. The most linear correlation was observed between BV/TV and BMD, with Spearman's rho = 0.99 (p = .01). Both BV/TV and BMD were highly correlated with all micro architecture parameters with Spearman's rho above 0.74 (p = .01). Two aspects of bone density using micro-CT, the BV/TV and BMD, are highly correlated with three-dimensional micro architecture parameters, which represent the quality of trabecular bone. This noninvasive method may adequately enhance evaluation of the alveolar bone. © 2013 Wiley Periodicals, Inc.

Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation.

Science.gov (United States)

Huang, Cynthia; Das, Anusuya; Barker, Daniel; Tholpady, Sunil; Wang, Tiffany; Cui, Quanjun; Ogle, Roy; Botchwey, Edward

2012-03-01

Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm(3), respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

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.

Application of semiquantitative parameters of bone scintigraphy in diabetic patients

International Nuclear Information System (INIS)

Bokhchelyan, Kh.; Klisarova, A.; Koeva, L.; Pranchev, L.; Tranulov, G.

1997-01-01

The aim of the study is to introduce semiquantitative indicators, contributing to early detection and dynamic measurement of the degree of bone metabolism in the foot of diabetic patients. Ten diabetics (3 women and 7 men) and 20 controls (10 women and 10 men) are included in the study. All patients are subjected to bone scintigraphy, clinical and biochemical investigation. Data are obtained pointing to enhanced and disproportional fixation of the radionuclide in symmetrical zones of the foot. The results are interpreted with a special reference to the extent of metabolic control and complications of the diabetic condition. Enhanced bone metabolism in the foot of the diabetic patients examined was established. Semiquantitative parameters enabling early detection and dynamic measurement of bone metabolism in the diabetic foot are practically implemented

Three-Dimensional Bio-Printed Scaffold Sleeves With Mesenchymal Stem Cells for Enhancement of Tendon-to-Bone Healing in Anterior Cruciate Ligament Reconstruction Using Soft-Tissue Tendon Graft.

Science.gov (United States)

Park, Sin Hyung; Choi, Yeong-Jin; Moon, Sang Won; Lee, Byung Hoon; Shim, Jin-Hyung; Cho, Dong-Woo; Wang, Joon Ho

2018-01-01

To investigate the efficacy of the insertion of 3-dimensional (3D) bio-printed scaffold sleeves seeded with mesenchymal stem cells (MSCs) to enhance osteointegration between the tendon and tunnel bone in anterior cruciate ligament (ACL) reconstruction in a rabbit model. Scaffold sleeves were fabricated by 3D bio-printing. Before ACL reconstruction, MSCs were seeded into the scaffold sleeves. ACL reconstruction with hamstring tendon was performed on both legs of 15 adult rabbits (aged 12 weeks). We implanted 15 bone tunnels with scaffold sleeves with MSCs and implanted another 15 bone tunnels with scaffold sleeves without MSCs before passing the graft. The specimens were harvested at 4, 8, and 12 weeks. H&E staining, immunohistochemical staining of type II collagen, and micro-computed tomography of the tunnel cross-sectional area were evaluated. Histologic assessment was conducted with a histologic scoring system. In the histologic assessment, a smooth bone-to-tendon transition through broad fibrocartilage formation was identified in the treatment group, and the interface zone showed abundant type II collagen production on immunohistochemical staining. Bone-tendon healing histologic scores were significantly higher in the treatment group than in the control group at all time points. Micro-computed tomography at 12 weeks showed smaller tibial (control, 9.4 ± 0.9 mm 2 ; treatment, 5.8 ± 2.9 mm 2 ; P = .044) and femoral (control, 9.6 ± 2.9 mm 2 ; treatment, 6.0 ± 1.0 mm 2 ; P = .03) bone-tunnel areas in the treated group than in the control group. The 3D bio-printed scaffold sleeve with MSCs exhibited excellent results in osteointegration enhancement between the tendon and tunnel bone in ACL reconstruction in a rabbit model. If secure biological healing between the tendon graft and tunnel bone can be induced in the early postoperative period, earlier, more successful rehabilitation may be facilitated. Three-dimensional bio-printed scaffold sleeves with

Inhibiting actin depolymerization enhances osteoblast differentiation and bone formation in human stromal stem cells

DEFF Research Database (Denmark)

Chen, Li; Shi, Kaikai; Frary, Charles

2015-01-01

Remodeling of the actin cytoskeleton through actin dynamics is involved in a number of biological processes, but its role in human stromal (skeletal) stem cells (hMSCs) differentiation is poorly understood. In the present study, we demonstrated that stabilizing actin filaments by inhibiting gene...... expression of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) in hMSCs, enhanced cell viability and differentiation into osteoblastic cells (OB) in vitro, as well as heterotopic bone formation in vivo. Similarly, treating hMSC with Phalloidin, which is known to stabilize...... polymerized actin filaments, increased hMSCs viability and OB differentiation. Conversely, Cytocholasin D, an inhibitor of actin polymerization, reduced cell viability and inhibited OB differentiation of hMSC. At a molecular level, preventing Cofilin phosphorylation through inhibition of LIM domain kinase 1...

Efficiently engineered cell sheet using a complex of polyethylenimine–alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation

Science.gov (United States)

Jin, Han; Zhang, Kai; Qiao, Chunyan; Yuan, Anliang; Li, Daowei; Zhao, Liang; Shi, Ce; Xu, Xiaowei; Ni, Shilei; Zheng, Changyu; Liu, Xiaohua; Yang, Bai; Sun, Hongchen

2014-01-01

Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine–alginate (PEI–al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI–al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI–al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration. PMID:24855355

Compacted cancellous bone has a spring-back effect

DEFF Research Database (Denmark)

Kold, S; Bechtold, JE; Ding, Ming

2003-01-01

A new surgical technique, compaction, has been shown to improve implant fixation. It has been speculated that the enhanced implant fixation with compaction could be due to a spring-back effect of compacted bone. However, such an effect has yet to be shown. Therefore we investigated in a canine mo....... Thus we found a spring-back effect of compacted bone, which may be important for increasing implant fixation by reducing initial gaps between the implant and bone....

Development and Testing of X-Ray Imaging-Enhanced Poly-L-Lactide Bone Screws.

Directory of Open Access Journals (Sweden)

Wei-Jen Chang

Full Text Available Nanosized iron oxide particles exhibit osteogenic and radiopaque properties. Thus, iron oxide (Fe3O4 nanoparticles were incorporated into a biodegradable polymer (poly-L-lactic acid, PLLA to fabricate a composite bone screw. This multifunctional, 3D printable bone screw was detectable on X-ray examination. In this study, mechanical tests including three-point bending and ultimate tensile strength were conducted to evaluate the optimal ratio of iron oxide nanoparticles in the PLLA composite. Both injection molding and 3D printing techniques were used to fabricate the PLLA bone screws with and without the iron oxide nanoparticles. The fabricated screws were implanted into the femoral condyles of New Zealand White rabbits. Bone blocks containing the PLLA screws were resected 2 and 4 weeks after surgery. Histologic examination of the surrounding bone and the radiopacity of the iron-oxide-containing PLLA screws were evaluated. Our results indicated that addition of iron oxide nanoparticles at 30% significantly decreased the ultimate tensile stress properties of the PLLA screws. The screws with 20% iron oxide exhibited strong radiopacity compared to the screws fabricated without the iron oxide nanoparticles. Four weeks after surgery, the average bone volume of the iron oxide PLLA composite screws was significantly greater than that of PLLA screws without iron oxide. These findings suggested that biodegradable and X-ray detectable PLLA bone screws can be produced by incorporation of 20% iron oxide nanoparticles. Furthermore, these screws had significantly greater osteogenic capability than the PLLA screws without iron oxide.

Bone marrow concentrate promotes bone regeneration with a suboptimal-dose of rhBMP-2.

Science.gov (United States)

Egashira, Kazuhiro; Sumita, Yoshinori; Zhong, Weijian; I, Takashi; Ohba, Seigo; Nagai, Kazuhiro; Asahina, Izumi

2018-01-01

Bone marrow concentrate (BMC), which is enriched in mononuclear cells (MNCs) and platelets, has recently attracted the attention of clinicians as a new optional means for bone engineering. We previously reported that the osteoinductive effect of bone morphogenetic protein-2 (BMP-2) could be enhanced synergistically by co-transplantation of peripheral blood (PB)-derived platelet-rich plasma (PRP). This study aims to investigate whether BMC can effectively promote bone formation induced by low-dose BMP-2, thereby reducing the undesirable side-effects of BMP-2, compared to PRP. Human BMC was obtained from bone marrow aspirates using an automated blood separator. The BMC was then seeded onto β-TCP granules pre-adsorbed with a suboptimal-dose (minimum concentration to induce bone formation at 2 weeks in mice) of recombinant human (rh) BMP-2. These specimens were transplanted subcutaneously to the dorsal skin of immunodeficient-mice and the induction of ectopic bone formation was assessed 2 and 4 weeks post-transplantation. Transplantations of five other groups [PB, PRP, platelet-poor plasma (PPP), bone marrow aspirate (BM), and BM-PPP] were employed as experimental controls. Then, to clarify the effects on vertical bone augmentation, specimens from the six groups were transplanted for on-lay placement on the craniums of mice. The results indicated that BMC, which contained an approximately 2.5-fold increase in the number of MNCs compared to PRP, could accelerate ectopic bone formation until 2 weeks post-transplantation. On the cranium, the BMC group promoted bone augmentation with a suboptimal-dose of rhBMP-2 compared to other groups. Particularly in the BMC specimens harvested at 4 weeks, we observed newly formed bone surrounding the TCP granules at sites far from the calvarial bone. In conclusion, the addition of BMC could reduce the amount of rhBMP-2 by one-half via its synergistic effect on early-phase osteoinduction. We propose here that BMC transplantation

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.

Combined Treatment of Alendronate and Low-Intensity Pulsed Ultrasound (LIPUS Increases Bone Mineral Density at the Cancellous Bone Osteotomy Site in Aged Rats: A Preliminary Study.

Directory of Open Access Journals (Sweden)

H Aonuma

2011-12-01

Full Text Available Introduction: During fracture healing, alendronate encourages callus volume by inhibiting bone resorption, whereas low-intensity pulsed ultrasound (LIPUS enhances bone regeneration by promoting an anabolic response. Methods: In the present study, 9-month-old Sprague-Dawley rats, with a unilateral proximal tibial osteotomy, were treated with alendronate (daily, 1 g/kg plus sham-LIPUS (n = 14, saline plus LIPUS (20 min/day (n = 18, alendronate plus LIPUS (n = 16, or saline plus sham- LIPUS as a control (n = 13 for 4 weeks. The rats were then examined for changes in bone mineral density (BMD during metaphyseal bone repair. Results: The combined therapy signi cantly increased BMD at the osteotomy site at 4 weeks (p < 0.001 compared with the control, without affecting the contralateral, non-osteotomized tibia. Both alendronate and LIPUS alone also exerted a positive, albeit less, effect on BMD in the affected limb (p < 0.001 and p = 0.006, respectively. Conclusions: Alendronate and LIPUS cooperate to enhance BMD during metaphyseal bone healing. Keywords: LIPUS, bisphosphonate, bone mineral density.

Small intestinal submucosa: A potential osteoconductive and osteoinductive biomaterial for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Li, Mei [Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211 (China); Ningbo Medical Science Research Institute, Ningbo, Zhejiang 315020 (China); Zhang, Chi; Cheng, Mengjie; Gu, Qiaoqiao [Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211 (China); Zhao, Jiyuan, E-mail: zhaojiyuan@nbu.edu.cn [Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211 (China)

2017-06-01

SIS is an acellular, naturally occurring collagenous extracellular matrix (ECM) material with various bioactive factors, which broadly applied in tissue engineering in clinic. Several studies have applied SIS in bone tissue engineering to enhance bone regeneration in animal models. However, the mechanism was rarely investigated. The aim of the current study was to investigate the osteoconductivity and osteoinductivity of SIS scaffold to bone regeneration systematically and the potential mechanism. Our results showed that SIS scaffold with excellent biocompatibility was beneficial for cell attachment, proliferation, migration and osteogenic differentiation of various cells contributing to bone repair. In mouse calvarial defect model, bone regeneration was significantly enhanced in the defects implanted with SIS scaffolds, along with the up-regulation of BMP-2 and CD31 expression. Accordingly, ID-1, the downstream target gene of BMPs, was increased in BMSCs cultured on SIS scaffolds. The results of this study suggest that SIS scaffold is a potential osteoconductive and osteoinductive biomaterial which plays multiple roles to various cells during process of bone regeneration. - Highlights: • SIS facilitates cell adhesion of BMSCs, osteoblasts and fibroblasts. • SIS promotes cell proliferation of osteoblasts and fibroblasts. • SIS promotes osteogenic differentiation of BMSCs and osteoblasts via BMP-2 pathway. • Synergistic effects of SIS to multiple cells enhance bone regeneration in vivo.

Small intestinal submucosa: A potential osteoconductive and osteoinductive biomaterial for bone tissue engineering

International Nuclear Information System (INIS)

Li, Mei; Zhang, Chi; Cheng, Mengjie; Gu, Qiaoqiao; Zhao, Jiyuan

2017-01-01

SIS is an acellular, naturally occurring collagenous extracellular matrix (ECM) material with various bioactive factors, which broadly applied in tissue engineering in clinic. Several studies have applied SIS in bone tissue engineering to enhance bone regeneration in animal models. However, the mechanism was rarely investigated. The aim of the current study was to investigate the osteoconductivity and osteoinductivity of SIS scaffold to bone regeneration systematically and the potential mechanism. Our results showed that SIS scaffold with excellent biocompatibility was beneficial for cell attachment, proliferation, migration and osteogenic differentiation of various cells contributing to bone repair. In mouse calvarial defect model, bone regeneration was significantly enhanced in the defects implanted with SIS scaffolds, along with the up-regulation of BMP-2 and CD31 expression. Accordingly, ID-1, the downstream target gene of BMPs, was increased in BMSCs cultured on SIS scaffolds. The results of this study suggest that SIS scaffold is a potential osteoconductive and osteoinductive biomaterial which plays multiple roles to various cells during process of bone regeneration. - Highlights: • SIS facilitates cell adhesion of BMSCs, osteoblasts and fibroblasts. • SIS promotes cell proliferation of osteoblasts and fibroblasts. • SIS promotes osteogenic differentiation of BMSCs and osteoblasts via BMP-2 pathway. • Synergistic effects of SIS to multiple cells enhance bone regeneration in vivo.

Enhanced bone formation in electrospun poly(L-lactic-co-glycolic acid)–tussah silk fibroin ultrafine nanofiber scaffolds incorporated with graphene oxide

International Nuclear Information System (INIS)

Shao, Weili; He, Jianxin; Sang, Feng; Wang, Qian; Chen, Li; Cui, Shizhong; Ding, Bin

2016-01-01

To engineer bone tissue, it is necessary to provide a biocompatible, mechanically robust scaffold. In this study, we fabricated an ultrafine nanofiber scaffold by electrospinning a blend of poly(L-lactic-co-glycolic acid), tussah silk fibroin, and graphene oxide (GO) and characterized its morphology, biocompatibility, mechanical properties, and biological activity. The data indicate that incorporation of 10 wt.% tussah silk and 1 wt.% graphene oxide into poly(L-lactic-co-glycolic acid) nanofibers significantly decreased the fiber diameter from 280 to 130 nm. Furthermore, tussah silk and graphene oxide boosted the Young's modulus and tensile strength by nearly 4-fold and 3-fold, respectively, and significantly enhanced adhesion, proliferation in mouse mesenchymal stem cells and functionally promoted biomineralization-relevant alkaline phosphatase (ALP) and mineral deposition. The results indicate that composite nanofibers could be excellent and versatile scaffolds for bone tissue engineering. - Highlights: • GO-doped PLGA–tussah silk fibroin ultrafine nanofibers with diameter of about 130 nm were fabricated by electrospinning. • Incorporation of 10 wt.% tussah silk to the PLGA nanofibers accelerates osteoblast differentiation and formation of new bone. • Mechanical properties of composite nanofiber mats had been significantly improved after embedding with GO nanosheets. • Nanostructured composite scaffolds effectively accelerate mesenchymal stem cells differentiation and formation of new bone.

Enhanced bone formation in electrospun poly(L-lactic-co-glycolic acid)–tussah silk fibroin ultrafine nanofiber scaffolds incorporated with graphene oxide

Energy Technology Data Exchange (ETDEWEB)

Shao, Weili [Key Laboratory of Advanced Textile Composites (Ministry of Education), Institute of Textile Composites, Tianjin Polytechnic University, Tianjin 300387 (China); Henan Provincial Key Laboratory of Functional Textile Materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); He, Jianxin, E-mail: hejianxin771117@163.com [Henan Provincial Key Laboratory of Functional Textile Materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); Sang, Feng [Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000 (China); Wang, Qian [Henan Provincial Key Laboratory of Functional Textile Materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); Chen, Li [Key Laboratory of Advanced Textile Composites (Ministry of Education), Institute of Textile Composites, Tianjin Polytechnic University, Tianjin 300387 (China); Cui, Shizhong [Key Laboratory of Advanced Textile Composites (Ministry of Education), Institute of Textile Composites, Tianjin Polytechnic University, Tianjin 300387 (China); Henan Provincial Key Laboratory of Functional Textile Materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); Ding, Bin [Henan Provincial Key Laboratory of Functional Textile Materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201600 (China)

2016-05-01

To engineer bone tissue, it is necessary to provide a biocompatible, mechanically robust scaffold. In this study, we fabricated an ultrafine nanofiber scaffold by electrospinning a blend of poly(L-lactic-co-glycolic acid), tussah silk fibroin, and graphene oxide (GO) and characterized its morphology, biocompatibility, mechanical properties, and biological activity. The data indicate that incorporation of 10 wt.% tussah silk and 1 wt.% graphene oxide into poly(L-lactic-co-glycolic acid) nanofibers significantly decreased the fiber diameter from 280 to 130 nm. Furthermore, tussah silk and graphene oxide boosted the Young's modulus and tensile strength by nearly 4-fold and 3-fold, respectively, and significantly enhanced adhesion, proliferation in mouse mesenchymal stem cells and functionally promoted biomineralization-relevant alkaline phosphatase (ALP) and mineral deposition. The results indicate that composite nanofibers could be excellent and versatile scaffolds for bone tissue engineering. - Highlights: • GO-doped PLGA–tussah silk fibroin ultrafine nanofibers with diameter of about 130 nm were fabricated by electrospinning. • Incorporation of 10 wt.% tussah silk to the PLGA nanofibers accelerates osteoblast differentiation and formation of new bone. • Mechanical properties of composite nanofiber mats had been significantly improved after embedding with GO nanosheets. • Nanostructured composite scaffolds effectively accelerate mesenchymal stem cells differentiation and formation of new bone.

Dry bone histology : technicalities, diagnostic value and new applications

NARCIS (Netherlands)

Boer, Hans Henk de

2014-01-01

This thesis presents an easy, rapid and inexpensive supplement to the well-known method of Maat et al. (2001). This new method allows for the histochemical staining of dry bone material, enhancing the visibility of important hallmarks of dry bone histomorphology. In addition, this thesis provides a

Diffusion and perfusion imaging of bone marrow

International Nuclear Information System (INIS)

Biffar, Andreas; Dietrich, Olaf; Sourbron, Steven; Duerr, Hans-Roland; Reiser, Maximilian F.; Baur-Melnyk, Andrea

2010-01-01

In diffusion-weighted magnetic resonance imaging (DWI), the observed MRI signal intensity is attenuated by the self-diffusion of water molecules. DWI provides information about the microscopic structure and organization of a biological tissue, since the extent and orientation of molecular motion is influenced by these tissue properties. The most common method to measure perfusion in the body using MRI is T1-weighted dynamic contrast enhancement (DCE-MRI). The analysis of DCE-MRI data allows determining the perfusion and permeability of a biological tissue. DWI as well as DCE-MRI are established techniques in MRI of the brain, while significantly fewer studies have been published in body imaging. In recent years, both techniques have been applied successfully in healthy bone marrow as well as for the characterization of bone marrow alterations or lesions; e.g., DWI has been used in particular for the differentiation of benign and malignant vertebral compression fractures. In this review article, firstly a short introduction to diffusion-weighted and dynamic contrast-enhanced MRI is given. Non-quantitative and quantitative approaches for the analysis of DWI and semiquantitative and quantitative approaches for the analysis of DCE-MRI are introduced. Afterwards a detailed overview of the results of both techniques in healthy bone marrow and their applications for the diagnosis of various bone-marrow pathologies, like osteoporosis, bone tumors, and vertebral compression fractures are described.

Function of Matrix IGF-1 in Coupling Bone Resorption and Formation

Science.gov (United States)

Crane, Janet L.; Cao, Xu

2013-01-01

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space and time dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of MSCs and HSCs and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis. PMID:24068256

Function of matrix IGF-1 in coupling bone resorption and formation.

Science.gov (United States)

Crane, Janet L; Cao, Xu

2014-02-01

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore, understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space- and time-dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of mesenchymal stem cells and hematopoietic stem cells and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis.

Melatonin: Bone Metabolism in Oral Cavity

Directory of Open Access Journals (Sweden)

Fanny López-Martínez

2012-01-01

Full Text Available Throughout life, bone tissue undergoes a continuous process of resorption and formation. Melatonin, with its antioxidant properties and its ability to detoxify free radicals, as suggested by Conconi et al. (2000 may interfere in the osteoclast function and thereby inhibit bone resorption, as suggested by Schroeder et al. (1981. Inhibition of bone resorption may be enhanced by a reaction of indoleamine in osteoclastogenesis. That it has been observed melatonin, at pharmacological doses, decrease bone mass resorption by suppressing through down regulation of the RANK-L, as suggested by Penarrocha Diago et al. (2005 and Steflik et al. (1994. These data point an osteogenic effect towards that may be of melatonin of clinical importance, as it could be used as a therapeutic agent in situations in which would be advantageous bone formation, such as in the treatment of fractures or osteoporosis or their use as, a bioactive surface on implant as suggested by Lissoni et al. (1991.

Enhanced mechanical properties and biocompatibility of novel hydroxyapatite/TOPAS hybrid composite for bone tissue engineering applications.

Science.gov (United States)

Ain, Qurat Ul; Khan, Ahmad Nawaz; Nabavinia, Mahboubeh; Mujahid, Mohammad

2017-06-01

The bioactivity and mechanical properties of hybrid composites of hydroxyapatite (HA) in cyclic olefinic copolymer (COC) also known commercially as TOPAS are investigated, first time, for regeneration and repair of the bone tissues. HA is synthesized to obtain the spherically shaped nanoparticles in the size range of 60±20nm. Various concentrations of HA ranging from 1 to 30wt% are dispersed in TOPAS using sodium dodecyl sulfate (SDS) coupling agent for better dispersion and interaction of hydrophilic HA with hydrophobic TOPAS. Scanning electron microscope shows the uniform dispersion of HA≤10wt% in TOPAS and at higher concentrations >10wt%, agglomeration occurs in the hybrid composites. Tunable mechanical properties are achieved as the compressive modulus and strength are increased around 140% from 6.4 to 15.3MPa and 185% from 0.26 to 0.74MPa, respectively. Such increase in the mechanical properties of TOPAS is attributed to the anchoring of the polymer chains in the vicinity of HA nanoparticles owing to better dispersion and interfacial interactions. In comparison to neat TOPAS, hybrid composites of TOPAS/HA promoted the cell adhesion and proliferation significantly. The cell density and proliferation of TOPAS/HA hybrid composites is enhanced 9 and 3 folds, respectively, after 1day culturing in preosteoblasts cells. Moreover, the morphology of cells changed from spherical to flattened spread morphology demonstrating clearly the migration of the cells for the formation of interconnected cellular network. Additionally, very few dead cells are found in hybrid composites showing their cytocompatibility. Overall, the hybrid composites of TOPAS/HA exhibited superior strength and stiffness along with enhanced cytocompatibility for bone tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Cell Fate and Differentiation of Bone Marrow Mesenchymal Stem Cells

Directory of Open Access Journals (Sweden)

Shoichiro Kokabu

2016-01-01

Full Text Available Osteoblasts and bone marrow adipocytes originate from bone marrow mesenchymal stem cells (BMMSCs and there appears to be a reciprocal relationship between adipogenesis and osteoblastogenesis. Alterations in the balance between adipogenesis and osteoblastogenesis in BMMSCs wherein adipogenesis is increased relative to osteoblastogenesis are associated with decreased bone quality and quantity. Several proteins have been reported to regulate this reciprocal relationship but the exact nature of the signals regulating the balance between osteoblast and adipocyte formation within the bone marrow space remains to be determined. In this review, we focus on the role of Transducin-Like Enhancer of Split 3 (TLE3, which was recently reported to regulate the balance between osteoblast and adipocyte formation from BMMSCs. We also discuss evidence implicating canonical Wnt signalling, which plays important roles in both adipogenesis and osteoblastogenesis, in regulating TLE3 expression. Currently, there is demand for new effective therapies that target the stimulation of osteoblast differentiation to enhance bone formation. We speculate that reducing TLE3 expression or activity in BMMSCs could be a useful approach towards increasing osteoblast numbers and reducing adipogenesis in the bone marrow environment.

Decision tree analysis as a supplementary tool to enhance histomorphological differentiation when distinguishing human from non-human cranial bone in both burnt and unburnt states: A feasibility study.

Science.gov (United States)

Simmons, T; Goodburn, B; Singhrao, S K

2016-01-01

This feasibility study was undertaken to describe and record the histological characteristics of burnt and unburnt cranial bone fragments from human and non-human bones. Reference series of fully mineralized, transverse sections of cranial bone, from all variables and specimen states, were prepared by manual cutting and semi-automated grinding and polishing methods. A photomicrograph catalogue reflecting differences in burnt and unburnt bone from human and non-humans was recorded and qualitative analysis was performed using an established classification system based on primary bone characteristics. The histomorphology associated with human and non-human samples was, for the main part, preserved following burning at high temperature. Clearly, fibro-lamellar complex tissue subtypes, such as plexiform or laminar primary bone, were only present in non-human bones. A decision tree analysis based on histological features provided a definitive identification key for distinguishing human from non-human bone, with an accuracy of 100%. The decision tree for samples where burning was unknown was 96% accurate, and multi-step classification to taxon was possible with 100% accuracy. The results of this feasibility study strongly suggest that histology remains a viable alternative technique if fragments of cranial bone require forensic examination in both burnt and unburnt states. The decision tree analysis may provide an additional but vital tool to enhance data interpretation. Further studies are needed to assess variation in histomorphology taking into account other cranial bones, ontogeny, species and burning conditions. © The Author(s) 2015.

Photoacoustic and ultrasound characterization of bone composition

Science.gov (United States)

Lashkari, Bahman; Yang, Lifeng; Liu, Lixian; Tan, Joel W. Y.; Mandelis, Andreas

2015-02-01

This study examines the sensitivity and specificity of backscattered ultrasound (US) and backscattering photoacoustic (PA) signals for bone composition variation assessment. The conventional approach in the evaluation of bone health relies on measurement of bone mineral density (BMD). Although, a crucial and probably the most important parameter, BMD is not the only factor defining the bone health. New trends in osteoporosis research, also pursue the changes in collagen content and cross-links with bone diseases and aging. Therefore, any non-invasive method that can assess any of these parameters can improve the diagnostic tools and also can help with the biomedical studies on the diseases themselves. Our previous studies show that both US and PA are responsive to changes in the BMD, PA is, in addition, sensitive to changes in the collagen content of the bone. Measurements were performed on bone samples before and after mild demineralization and decollagenization at the exact same points. Results show that combining both modalities can enhance the sensitivity and specificity of diagnostic tool.

Bone morphogenetic protein-2 and bone therapy: successes and pitfalls.

Science.gov (United States)

Poon, Bonnie; Kha, Tram; Tran, Sally; Dass, Crispin R

2016-02-01

Bone morphogenetic proteins (BMPs), more specifically BMP-2, are being increasingly used in orthopaedic surgery due to advanced research into osteoinductive factors that may enhance and improve bone therapy. There are many areas in therapy that BMP-2 is being applied to, including dental treatment, open tibial fractures, cancer and spinal surgery. Within these areas of treatment, there are many reports of successes and pitfalls. This review explores the use of BMP-2 and its successes, pitfalls and future prospects in bone therapy. The PubMed database was consulted to compile this review. With successes in therapy, there were descriptions of a more rapid healing time with no signs of rejection or infection attributed to BMP-2 treatment. Pitfalls included BMP-2 'off-label' use, which lead to various adverse effects. Our search highlighted that optimising treatment with BMP-2 is a direction that many researchers are exploring, with areas of current research interest including concentration and dose of BMP-2, carrier type and delivery. © 2015 Royal Pharmaceutical Society.

Pullulan microcarriers for bone tissue regeneration

Energy Technology Data Exchange (ETDEWEB)

Aydogdu, Hazal [Middle East Technical University, Department of Biomedical Engineering, Ankara 06800 (Turkey); Keskin, Dilek [Middle East Technical University, Department of Biomedical Engineering, Ankara 06800 (Turkey); Middle East Technical University, Department of Engineering Sciences, Ankara 06800 (Turkey); METU BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Ankara 06800 (Turkey); Baran, Erkan Turker, E-mail: erkanturkerbaran@gmail.com [METU BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Ankara 06800 (Turkey); Tezcaner, Aysen, E-mail: tezcaner@metu.edu.tr [Middle East Technical University, Department of Biomedical Engineering, Ankara 06800 (Turkey); Middle East Technical University, Department of Engineering Sciences, Ankara 06800 (Turkey); METU BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Ankara 06800 (Turkey)

2016-06-01

Microcarrier systems offer a convenient way to repair bone defects as injectable cell carriers that can be applied with small incisions owing to their small size and spherical shape. In this study, pullulan (PULL) microspheres were fabricated and characterized as cell carriers for bone tissue engineering applications. PULL was cross-linked by trisodium trimetaphosphate (STMP) to enhance the stability of the microspheres. Improved cytocompatibility was achieved by silk fibroin (SF) coating and biomimetic mineralization on the surface by incubating in simulated body fluid (SBF). X-ray diffraction (XRD), scanning electron microscopy (SEM) and fluorescent microscopy analysis confirmed biomimetic mineralization and SF coating on microspheres. The degradation analysis revealed that PULL microspheres had a slow degradation rate with 8% degradation in two weeks period indicating that the microspheres would support the formation of new bone tissue. Furthermore, the mechanical tests showed that the microspheres had a high mechanical stability that was significantly enhanced with the biomimetic mineralization. In vitro cell culture studies with SaOs-2 cells showed that cell viability was higher on SF and SBF coated microspheres on 7th day compared to PULL ones under dynamic conditions. Alkaline phosphatase activity was higher for SF coated microspheres in comparison to uncoated microspheres when dynamic culture condition was applied. The results suggest that both organic and inorganic surface modifications can be applied on PULL microspheres to prepare a biocompatible microcarrier system with suitable properties for bone tissue engineering. - Highlights: • Porous PULL microspheres were prepared as cell carrier for the first time. • Mineralization on the microspheres improved their mechanical properties. • Mineralization and SF coating enhanced cell proliferation on PULL microspheres.

Pullulan microcarriers for bone tissue regeneration

International Nuclear Information System (INIS)

Aydogdu, Hazal; Keskin, Dilek; Baran, Erkan Turker; Tezcaner, Aysen

2016-01-01

Microcarrier systems offer a convenient way to repair bone defects as injectable cell carriers that can be applied with small incisions owing to their small size and spherical shape. In this study, pullulan (PULL) microspheres were fabricated and characterized as cell carriers for bone tissue engineering applications. PULL was cross-linked by trisodium trimetaphosphate (STMP) to enhance the stability of the microspheres. Improved cytocompatibility was achieved by silk fibroin (SF) coating and biomimetic mineralization on the surface by incubating in simulated body fluid (SBF). X-ray diffraction (XRD), scanning electron microscopy (SEM) and fluorescent microscopy analysis confirmed biomimetic mineralization and SF coating on microspheres. The degradation analysis revealed that PULL microspheres had a slow degradation rate with 8% degradation in two weeks period indicating that the microspheres would support the formation of new bone tissue. Furthermore, the mechanical tests showed that the microspheres had a high mechanical stability that was significantly enhanced with the biomimetic mineralization. In vitro cell culture studies with SaOs-2 cells showed that cell viability was higher on SF and SBF coated microspheres on 7th day compared to PULL ones under dynamic conditions. Alkaline phosphatase activity was higher for SF coated microspheres in comparison to uncoated microspheres when dynamic culture condition was applied. The results suggest that both organic and inorganic surface modifications can be applied on PULL microspheres to prepare a biocompatible microcarrier system with suitable properties for bone tissue engineering. - Highlights: • Porous PULL microspheres were prepared as cell carrier for the first time. • Mineralization on the microspheres improved their mechanical properties. • Mineralization and SF coating enhanced cell proliferation on PULL microspheres.

Bisphosphonates enhance bacterial adhesion and biofilm formation on bone hydroxyapatite.

Science.gov (United States)

Kos, Marcin; Junka, Adam; Smutnicka, Danuta; Szymczyk, Patrycja; Gluza, Karolina; Bartoszewicz, Marzenna

2015-07-01

Because of the suspicion that bisphosphonates enhance bacterial colonization, this study evaluated adhesion and biofilm formation by Streptococcus mutans 25175, Staphylococcus aureus 6538, and Pseudomonas aeruginosa 14454 reference strains on hydroxyapatite coated with clodronate, pamidronate, or zoledronate. Bacterial strains were cultured on bisphosphonate-coated and noncoated hydroxyapatite discs. After incubation, nonadhered bacteria were removed by centrifugation. Biofilm formation was confirmed by scanning electron microscopy. Bacterial colonization was estimated using quantitative cultures compared by means with Kruskal-Wallis and post-hoc Student-Newman-Keuls tests. Modeling of the interactions between bisphosphonates and hydroxyapatite was performed using the Density Functional Theory method. Bacterial colonization of the hydroxyapatite discs was significantly higher for all tested strains in the presence of bisphosphonates vs. Adherence in the presence of pamidronate was higher than with other bisphosphonates. Density Functional Theory analysis showed that the protonated amine group of pamidronate, which are not present in clodronate or zoledronate, forms two additional hydrogen bonds with hydroxyapatite. Moreover, the reactive cationic amino group of pamidronate may attract bacteria by direct electrostatic interaction. Increased bacterial adhesion and biofilm formation can promote osteomyelitis, cause failure of dental implants or bisphosphonate-coated joint prostheses, and complicate bone surgery in patients on bisphosphonates. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Enhanced osteogenesis of β-tricalcium phosphate reinforced silk fibroin scaffold for bone tissue biofabrication.

Science.gov (United States)

Lee, Dae Hoon; Tripathy, Nirmalya; Shin, Jae Hun; Song, Jeong Eun; Cha, Jae Geun; Min, Kyung Dan; Park, Chan Hum; Khang, Gilson

2017-02-01

Scaffolds, used for tissue regeneration are important to preserve their function and morphology during tissue healing. Especially, scaffolds for bone tissue engineering should have high mechanical properties to endure load of bone. Silk fibroin (SF) from Bombyx mori silk cocoon has potency as a type of biomaterials in the tissue engineering. β-tricalcium phosphate (β-TCP) as a type of bioceramics is also critical as biomaterials for bone regeneration because of its biocompatibility, osteoconductivity, and mechanical strength. The aim of this study was to fabricate three-dimensional SF/β-TCP scaffolds and access its availability for bone grafts through in vitro and in vivo test. The scaffolds were fabricated in each different ratios of SF and β-TCP (100:0, 75:25, 50:50, 25:75). The characterizations of scaffolds were conducted by FT-IR, compressive strength, porosity, and SEM. The in vitro and in vivo tests were carried out by MTT, ALP, RT-PCR, SEM, μ-CT, and histological staining. We found that the SF/β-TCP scaffolds have high mechanical strength and appropriate porosity for bone tissue engineering. The study showed that SF/β-TCP (75:25) scaffold exhibited the highest osteogenesis compared with other scaffolds. The results suggested that SF/β-TCP (75:25) scaffold can be applied as one of potential bone grafts for bone tissue engineering. Copyright © 2016. Published by Elsevier B.V.

Serum albumin coating of demineralized bone matrix results in stronger new bone formation.

Science.gov (United States)

Horváthy, Dénes B; Vácz, Gabriella; Szabó, Tamás; Szigyártó, Imola C; Toró, Ildikó; Vámos, Boglárka; Hornyák, István; Renner, Károly; Klára, Tamás; Szabó, Bence T; Dobó-Nagy, Csaba; Doros, Attila; Lacza, Zsombor

2016-01-01

Blood serum fractions are hotly debated adjuvants in bone replacement therapies. In the present experiment, we coated demineralized bone matrices (DBM) with serum albumin and investigated stem cell attachment in vitro and bone formation in a rat calvaria defect model. In the in vitro experiments, we observed that significantly more cells adhere to the serum albumin coated DBMs at every time point. In vivo bone formation with albumin coated and uncoated DBM was monitored biweekly by computed tomography until 11 weeks postoperatively while empty defects served as controls. By the seventh week, the bone defect in the albumin group was almost completely closed (remaining defect 3.0 ± 2.3%), while uncoated DBM and unfilled control groups still had significant defects (uncoated: 40.2 ± 9.1%, control: 52.4 ± 8.9%). Higher density values were also observed in the albumin coated DBM group. In addition, the serum albumin enhanced group showed significantly higher volume of newly formed bone in the microCT analysis and produced significantly higher breaking force and stiffness compared to the uncoated grafts (peak breaking force: uncoated: 15.7 ± 4 N, albumin 46.1 ± 11 N). In conclusion, this investigation shows that implanting serum albumin coated DBM significantly reduces healing period in nonhealing defects and results in mechanically stronger bone. These results also support the idea that serum albumin coating provides a convenient milieu for stem cell function, and a much improved bone grafting success can be achieved without the use of exogenous stem cells. © 2015 Wiley Periodicals, Inc.

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.

Mechanochemical synthesis evaluation of nanocrystalline bone-derived bioceramic powder using for bone tissue engineering

Directory of Open Access Journals (Sweden)

Amirsalar Khandan

2014-01-01

Full Text Available Introduction: Bone tissue engineering proposes a suitable way to regenerate lost bones. Different materials have been considered for use in bone tissue engineering. Hydroxyapatite (HA is a significant success of bioceramics as a bone tissue repairing biomaterial. Among different bioceramic materials, recent interest has been risen on fluorinated hydroxyapatites, (FHA, Ca 10 (PO 4 6 F x (OH 2−x . Fluorine ions can promote apatite formation and improve the stability of HA in the biological environments. Therefore, they have been developed for bone tissue engineering. The aim of this study was to synthesize and characterize the FHA nanopowder via mechanochemical (MC methods. Materials and Methods: Natural hydroxyapatite (NHA 95.7 wt.% and calcium fluoride (CaF 2 powder 4.3 wt.% were used for synthesis of FHA. MC reaction was performed in the planetary milling balls using a porcelain cup and alumina balls. Ratio of balls to reactant materials was 15:1 at 400 rpm rotation speed. The structures of the powdered particles formed at different milling times were evaluated by X-ray diffraction (XRD, scanning electron microscopy (SEM and transmission electron microscopy (TEM. Results: Fabrication of FHA from natural sources like bovine bone achieved after 8 h ball milling with pure nanopowder. Conclusion: F− ion enhances the crystallization and mechanical properties of HA in formation of bone. The produced FHA was in nano-scale, and its crystal size was about 80-90 nm with sphere distribution in shape and size. FHA powder is a suitable biomaterial for bone tissue engineering.

The Mechanical Properties and Biometrical Effect of 3D Preformed Titanium Membrane for Guided Bone Regeneration on Alveolar Bone Defect

Directory of Open Access Journals (Sweden)

So-Hyoun Lee

2017-01-01

Full Text Available The purpose of this study is to evaluate the effect of three-dimensional preformed titanium membrane (3D-PFTM to enhance mechanical properties and ability of bone regeneration on the peri-implant bone defect. 3D-PFTMs by new mechanically compressive molding technology and manually shaped- (MS- PFTMs by hand manipulation were applied in artificial peri-implant bone defect model for static compressive load test and cyclic fatigue load test. In 12 implants installed in the mandibular of three beagle dogs, six 3D-PFTMs, and six collagen membranes (CM randomly were applied to 2.5 mm peri-implant buccal bone defect with particulate bone graft materials for guided bone regeneration (GBR. The 3D-PFTM group showed about 7.4 times higher mechanical stiffness and 5 times higher fatigue resistance than the MS-PFTM group. The levels of the new bone area (NBA, %, the bone-to-implant contact (BIC, %, distance from the new bone to the old bone (NB-OB, %, and distance from the osseointegration to the old bone (OI-OB, % were significantly higher in the 3D-PFTM group than the CM group (p<.001. It was verified that the 3D-PFTM increased mechanical properties which were effective in supporting the space maintenance ability and stabilizing the particulate bone grafts, which led to highly efficient bone regeneration.

Surface modification of implants in long bone.

Science.gov (United States)

Förster, Yvonne; Rentsch, Claudia; Schneiders, Wolfgang; Bernhardt, Ricardo; Simon, Jan C; Worch, Hartmut; Rammelt, Stefan

2012-01-01

Coatings of orthopedic implants are investigated to improve the osteoinductive and osteoconductive properties of the implant surfaces and thus to enhance periimplant bone formation. By applying coatings that mimic the extracellular matrix a favorable environment for osteoblasts, osteoclasts and their progenitor cells is provided to promote early and strong fixation of implants. It is known that the early bone ongrowth increases primary implant fixation and reduces the risk of implant failure. This review presents an overview of coating titanium and hydroxyapatite implants with components of the extracellular matrix like collagen type I, chondroitin sulfate and RGD peptide in different small and large animal models. The influence of these components on cells, the inflammation process, new bone formation and bone/implant contact is summarized.

What Is Breast in the Bone?

Science.gov (United States)

Shemanko, Carrie S; Cong, Yingying; Forsyth, Amanda

2016-10-22

The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at a site of secondary metastasis. Prolactin is a pleiotropic peptide hormone and cytokine that is secreted from the pituitary gland, as well as from normal and cancerous breast cells. Experimental and epidemiologic data suggest that prolactin is associated with mammary gland development, and also the increased risk of breast tumors and metastatic disease in postmenopausal women. Breast cancer spreads to the bone in approximately 70% of cases with advanced breast cancer. Despite treatment, new bone metastases will still occur in 30%-50% of patients. Only 20% of patients with bone metastases survive five years after the diagnosis of bone metastasis. The breast cancer cells in the bone microenvironment release soluble factors that engage osteoclasts and/or osteoblasts and result in bone breakdown. The breakdown of the bone matrix, in turn, enhances the proliferation of the cancer cells, creating a vicious cycle. Recently, it was shown that prolactin accelerated the breast cancer cell-mediated osteoclast differentiation and bone breakdown by the regulation of breast cancer-secreted proteins. Interestingly, prolactin has the potential to affect multiple proteins that are involved in both breast development and likely bone metastasis, as well. Prolactin has normal bone homeostatic roles and, combined with the natural "recycling" of proteins in different tissues that can be used for breast development and function, or in bone function, increases the impact of prolactin signaling in breast cancer bone metastases. Thus, this review will focus on the role of prolactin in breast development, bone homeostasis and in breast cancer to bone metastases, covering the molecular aspects of the vicious cycle.

Cyclic hydrostatic pressure stimulates enhanced bone development in the foetal chick femur in vitro.

Science.gov (United States)

Henstock, J R; Rotherham, M; Rose, J B; El Haj, A J

2013-04-01

Mechanical loading of bone and cartilage in vivo results in the generation of cyclic hydrostatic forces as bone compression is transduced to fluid pressure in the canalicular network and the joint synovium. It has therefore been suggested that hydrostatic pressure is an important stimulus by which osteochondral cells and their progenitors sense and respond to mechanical loading in vivo. In this study, hydrostatic pressure regimes of 0-279kPa at 0.005-2Hz were applied to organotypically cultured ex vivo chick foetal femurs (e11) for 1hour per day in a custom designed bioreactor for 14days and bone formation assessed by X-ray microtomography and qualified by histology. We found that the mineralised portion of the developing femur cultured under any cyclic hydrostatic pressure regime was significantly larger and/or denser than unstimulated controls but that constant (non-cycling) hydrostatic pressure had no effect on bone growth. Further experiments showed that the increase in bone formation was directly proportional to stimulation frequency (R(2)=0.917), but independent of the magnitude of the pressure applied, whilst even very low frequencies of stimulation (0.005Hz) had significant effects on bone growth. Expression of Type-II collagen in both epiphyses and diaphysis was significantly upregulated (1.48-fold and 1.95-fold respectively), together with osteogenic genes (osteonectin and osteopontin) and the osteocyte maturation marker CD44. This work demonstrates that cyclic hydrostatic pressure promotes bone growth and mineralisation in a developmental model and supports the hypothesis that hydrostatic forces play an important role in regulating bone growth and remodelling in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

Locally delivered ethyl-2,5-dihydroxybenzoate using 3D printed bone implant for promotion of bone regeneration in a osteoporotic animal model

Directory of Open Access Journals (Sweden)

B-J Kwon

2018-01-01

Full Text Available Osteoporosis is a disease characterized by low bone mass, most commonly caused by an increase in bone resorption that is not matched by sufficient bone formation. The most common complications of postmenopausal osteoporosis are bone-related defects and fractures. Fracture healing is a multifactorial bone regeneration process, influenced by both biological and mechanical factors related to age, osteoporosis and stability of the osteosynthesis. During the treatment of bone defects in osteoporotic conditions, imbalanced bone remodeling is the leading cause for implant failure. To overcome these problems, ethyl-2,5-dihydroxybenzoate (E-2,5-DHB, a drug that promotes bone formation and inhibits bone resorption, was used. E-2,5-DHB-incorporating titanium (Ti implants using poly(lactic-co-glycolic acid (PLGA coating for local delivery of E-2,5-DHB were developed and the effects on bone healing of femoral defects were evaluated in an osteoporotic model. The release of E-2,5-DHB resulted in decreased bone resorption and increased bone formation around the implant. Thus, it was confirmed that, in the osteoporotic model, bone healing was increased and implant fixation was enhanced. These results suggested that E-2,5-DHB-coated Ti implants have great potential as an ultimate local drug delivery system for bone tissue scaffolds.

Bone marker gene expression in calvarial bones: different bone microenvironments.

Science.gov (United States)

Al-Amer, Osama

2017-12-01

In calvarial mice, mesenchymal stem cells (MSCs) differentiate into osteoprogenitor cells and then differentiate into osteoblasts that differentiate into osteocytes, which become embedded within the bone matrix. In this case, the cells participating in bone formation include MSCs, osteoprogenitor cells, osteoblasts and osteocytes. The calvariae of C57BL/KaLwRijHsD mice consist of the following five bones: two frontal bones, two parietal bones and one interparietal bone. This study aimed to analyse some bone marker genes and bone related genes to determine whether these calvarial bones have different bone microenvironments. C57BL/KaLwRijHsD calvariae were carefully excised from five male mice that were 4-6 weeks of age. Frontal, parietal, and interparietal bones were dissected to determine the bone microenvironment in calvariae. Haematoxylin and eosin staining was used to determine the morphology of different calvarial bones under microscopy. TaqMan was used to analyse the relative expression of Runx2, OC, OSX, RANK, RANKL, OPG, N-cadherin, E-cadherin, FGF2 and FGFR1 genes in different parts of the calvariae. Histological analysis demonstrated different bone marrow (BM) areas between the different parts of the calvariae. The data show that parietal bones have the smallest BM area compared to frontal and interparietal bones. TaqMan data show a significant increase in the expression level of Runx2, OC, OSX, RANKL, OPG, FGF2 and FGFR1 genes in the parietal bones compared with the frontal and interparietal bones of calvariae. This study provides evidence that different calvarial bones, frontal, parietal and interparietal, contain different bone microenvironments.

Bone marrow edema pattern identification in patients with lytic bone lesions using digital subtraction angiography-like bone subtraction on large-area detector computed tomography.

Science.gov (United States)

Gondim Teixeira, Pedro Augusto; Hossu, Gabriela; Lecocq, Sophie; Razeto, Marco; Louis, Matthias; Blum, Alain

2014-03-01

The objective of this study was to evaluate the performance of digital subtraction angiography (DSA)-like bone subtraction with 2 different registration methods for the identification of bone marrow edema pattern (BMEP) in patients with lytic bone lesions, using magnetic resonance imaging as the criterion standard. Fifty-five patients with a lytic bone lesion were included in this prospective study with approval from the ethics committee. All patients underwent magnetic resonance imaging and low-dose computed tomographic (CT) perfusion after signing an informed consent. Two CT volumes were used for bone subtraction, which was performed with 2 different algorithms (rigid and nonrigid). Enhancement at the nonlytic bone marrow was considered as a sign of BMEP. Two readers evaluated the images blindly. The presence of BMEP on bone-subtracted CT images was evaluated subjectively and quantitatively. Image quality was assessed. Magnetic resonance imaging was used as the criterion standard. Using a rigid registration method, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CT with DSA-like bone subtraction BMEP was 77%, 100%, 100%, 68%, and 85%, respectively. The interobserver agreement was good (κ, 0.782). Image quality was better using a nonrigid registration. With this algorithm, artifacts interfered with image interpretation in only 5% of cases. However, there was a noticeable drop in sensitivity and negative predictive value when a nonrigid algorithm was used: 56% and 52%, respectively. The interobserver agreement was average with a nonrigid subtraction algorithm. Computed tomography with DSA-like bone subtraction is sensitive and highly specific for the identification of BMEP associated with lytic bone lesions. Rigid registering should be preferred, but nonrigid algorithms can be used as a second option when artifacts interfere with image interpretation.

Nanotechnology in bone tissue engineering.

Science.gov (United States)

Walmsley, Graham G; McArdle, Adrian; Tevlin, Ruth; Momeni, Arash; Atashroo, David; Hu, Michael S; Feroze, Abdullah H; Wong, Victor W; Lorenz, Peter H; Longaker, Michael T; Wan, Derrick C

2015-07-01

Nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering. Current limitations in regenerative strategies include impaired cellular proliferation and differentiation, insufficient mechanical strength of scaffolds, and inadequate production of extrinsic factors necessary for efficient osteogenesis. Here we review several major areas of research in nanotechnology with potential implications in bone regeneration: 1) nanoparticle-based methods for delivery of bioactive molecules, growth factors, and genetic material, 2) nanoparticle-mediated cell labeling and targeting, and 3) nano-based scaffold construction and modification to enhance physicochemical interactions, biocompatibility, mechanical stability, and cellular attachment/survival. As these technologies continue to evolve, ultimate translation to the clinical environment may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases. Traditionally, the reconstruction of bony defects has relied on the use of bone grafts. With advances in nanotechnology, there has been significant development of synthetic biomaterials. In this article, the authors provided a comprehensive review on current research in nanoparticle-based therapies for bone tissue engineering, which should be useful reading for clinicians as well as researchers in this field. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Enhancement of distribution of dermal multipotent stem cells to bone marrow in rats of total body irradiation by platelet-derived growth factor-AA treatment

International Nuclear Information System (INIS)

Zong Zhaowen; Ren Yongchuan; Shen Yue; Chen Yonghua; Ran Xinze; Shi Chunmeng; Cheng Tianmin

2011-01-01

Objective: To observe whether dermal multipotent stem cells (dMSCs) treated with platelet-derived growth factor-AA (PDGF-AA) could distribute more frequently to the bone marrow in rats of total body irradiation (TBI). Methods: Male dMSCs were isolated and 10 μg/L PDGF-AA was added to the culture medium and further cultured for 2 h. Then the expression of tenascin-C were examined by Western blot, and the migration ability of dMSCs was assessed in transwell chamber. The pre-treated dMSCs were transplanted by tail vein injection into female rats administered with total body irradiation, and 2 weeks after transplantation, real-time PCR was employed to measure the amount of dMSCs in bone marrow. Non-treated dMSCs served as control.Results PDGF-AA treatment increased the expression of tenascin-C in dMSCs, made (1.79 ± 0.13) × 10 5 cells migrate to the lower chamber under the effect of bone marrow extract, and distributed to bone marrow in TBI rats, significantly more than (1.24 ± 0.09) ×10 5 in non-treated dMSCs (t=8.833, P<0.01). Conclusions: PDGF-AA treatment could enhance the migration ability of dMSCs and increase the amount of dMSCs in bone marrow of TBI rats after transplantation. (authors)

Interstitial ultrasound ablation of tumors within or adjacent to bone: Contributions of preferential heating at the bone surface

Science.gov (United States)

Scott, Serena J.; Prakash, Punit; Salgaonkar, Vasant; Jones, Peter D.; Cam, Richard N.; Han, Misung; Rieke, Viola; Burdette, E. Clif; Diederich, Chris J.

2013-02-01

Preferential heating of bone due to high ultrasound attenuation may enhance thermal ablation performed with cathetercooled interstitial ultrasound applicators in or near bone. At the same time, thermally and acoustically insulating cortical bone may protect sensitive structures nearby. 3D acoustic and biothermal transient finite element models were developed to simulate temperature and thermal dose distributions during catheter-cooled interstitial ultrasound ablation near bone. Experiments in ex vivo tissues and tissue-mimicking phantoms were performed to validate the models and to quantify the temperature profiles and ablated volumes for various distances between the interstitial applicator and the bone surface. 3D patient-specific models selected to bracket the range of clinical usage were developed to investigate what types of tumors could be treated, applicator configurations, insertion paths, safety margins, and other parameters. Experiments show that preferential heating at the bone surface decreases treatment times compared to when bone is absent and that all tissue between an applicator and bone can be ablated when they are up to 2 cm apart. Simulations indicate that a 5-7 mm safety margin of normal bone is needed to protect (thermal dose tumors 1.0-3.8 cm (L) and 1.3-3.0 cm (D) near or within bone were ablated (thermal dose > 240 CEM43°C) within 10 min without damaging the nearby spinal cord, lungs, esophagus, trachea, or major vasculature. Preferential absorption of ultrasound by bone may provide improved localization, faster treatment times, and larger treatment zones in tumors in and near bone compared to other heating modalities.

Enhancing Bone Accretion Using Short-Duration, Low-Level Mechanical Vibrations

National Research Council Canada - National Science Library

Judex, tefan

2004-01-01

The etiology of the stress fractyre syndrome is incompetely understood but it is clear that skeletons with high peak bone quantity and quality will be better pretected against incurring this crippling condition...

Report on 2012 ISN Nexus symposium: 'Bone and the kidney'

DEFF Research Database (Denmark)

Drüeke, Tilman B; Olgaard, Klaus

2013-01-01

aspects of the bone-kidney axis was open to all participants. The numerous lectures given at the symposium addressed current knowledge and recent advances in kidney and bone physiology, as well as the pathogenesis, diagnosis, and therapy of CKD-MBD, inspired by the intention to enhance the translation...... in the fascinating world of the many hormones and factors involved in mineral homeostasis, bone disease, and vascular calcification of patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). The possibility of exchanging cutting-edge insights and discussing clinically relevant information on all...

Clinical assessment of bone quality of human extraction sockets after conversion with growth factors.

Science.gov (United States)

Ntounis, Athanasios; Geurs, Nico; Vassilopoulos, Philip; Reddy, Michael

2015-01-01

The study was conducted to evaluate the effect of mineralized freeze-dried bone allograft (FDBA), alone or in combination with growth factors in extraction sockets, on subjective assessment of bone quality during implant placement. Forty-one patients whose treatment plan involved extraction of anterior or premolar teeth were randomized into four groups: Group 1, collagen plug (control); Group 2, FDBA/β-tricalcium phosphate (β-TCP)/collagen plug; Group 3, FDBA/β-TCP/platelet-rich plasma (PRP)/collagen plug; Group 4, FDBA/β-TCP/recombinant human platelet-derived growth factor BB (rhPDGF-BB)/collagen plug. After 8 weeks of healing, implants were placed. The clinicians assessed bone quality according to the Misch classification. A benchtop calibration exercise test was conducted to evaluate agreement and accuracy of operators in recognizing different bone qualities. Differences were analyzed using one-way analysis of variance (ANOVA) or chi-square tests for continuous and categorical data. Pairwise comparisons were tested using least squares means (LS means). Spearman correlation coefficients were used to evaluate the relationship of bone growth with potential confounders. P .05). Inclusion of bone grafting is associated with a shift from D4 quality to D3 quality bone. Inclusion of PRP in bone grafting eliminates the incidence of D4 bone, establishing D3 and D2 quality bone as prevalent (56% vs. 42%, respectively). Inclusion of rhPDGF-BB and β-TCP in combination with the bone grafting has the same effect, although D2 quality is less prevalent. When compared to sockets grafted with FDBA/β-TCP/collagen plug alone, the sockets with growth factors demonstrated fewer residual bone graft particles. (1) Inclusion of bone grafting enhanced bone quality as assessed during implant placement. (2) Overall inclusion of PRP and rhPDGF-BB enhanced subjective bone quality, eliminating incidence of D4 quality in human extraction sockets. (3) The use of PRP or rhPDGF-BB may

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

quotient values in Ag-PIII groups were higher than that in the SLA group. In addition, all the Ag-PIII groups, compared to the SLA-group, exhibited enhanced new bone formation, bone mineral density, and trabecular pattern. With regard to osteogenic indicators, the implants treated with Ag-PIII for 30 minutes and 60 minutes, with the diameter of the Ag NPs ranging from 5–25 nm, were better than those treated with Ag-PIII for 90 minutes, with the Ag NPs diameter out of that range. These results suggest that Ag-PIII technique can reduce the mobility of Ag NPs and enhance the osseointegration of SLA surfaces and have the potential for future use. Keywords: surface modification, micro/nanostructure, silver, ion implantation, osseointegration

Dopaminergic enhancement of cellular adhesion in bone marrow derived mesenchymal stem cells (MSCs).

Science.gov (United States)

Chen, Si; Bai, Bing; Lee, Dong Joon; Diachina, Shannon; Li, Yina; Wong, Sing Wai; Wang, Zhengyan; Tseng, Henry C; Ko, Ching-Chang

2017-08-01

Dopamine (DA) is a well-known neurotransmitter and critical element in the mussel adhesive protein that has gained increasing attention for its role in cellular growth enhancement in biomaterials, including cellular adhesion improvement. As the mechanism underlying this remains unclear, the objective of this study was to explore the effects of DA on the adhesion properties of bone marrow derived rat mesenchymal stem cells (rMSCs) using an hydroxyapatite gelatin nanocomposite biomaterial and to test whether the effects are mediated through various endogenously expressed DA receptors. Primary rMSCs were pretreated with D1-like antagonist, D2-like antagonist, or a combination of these antagonists followed by treatment with 50 μM DA and cellular adhesion quantification at 0.5, 1, 2 and 4 hours post DA addition. DA was found to increase rMSC adhesion and spreading at the 0.5 hour time-point and the dopaminergic effect on cell adhesion was partially blocked by DA antagonists. In addition, the D1-like and D2-like antagonists appeared to have a similar effect on rMSCs. Immunofluorescent staining indicated that the rMSC spreading area was significantly increased in the DA treated group versus the control group. Treatment of the D1-like DA antagonists with DA revealed that the actin filaments of rMSCs could not connect the membrane with the nucleus. In summary, DA was found to enhance early rMSC adhesion partially via DA receptor activation.

Hot-boning enhances cook yield of boneless skinless chicken thighs.

Science.gov (United States)

Zhuang, H; Bowker, B C; Buhr, R J; Brambila, G Sanchez

2014-06-01

Three experiments were conducted to evaluate the effects of postmortem deboning time on cook yield of boneless skinless chicken thighs. In experiment 1, chicken thigh meat was deboned at 0.75 (hot-bone), 2, and 24 h postmortem (PM) and trimmed to obtain mainly iliotibialis muscle. Samples were cooked directly from a frozen state. Cook yield of the muscle was significantly influenced by PM deboning time. Hot-boned thighs exhibited a 7% greater cook yield than the samples deboned at 24 h. In experiment 2, boneless skinless chicken thighs were deboned at 0.3, 2, and 24 h PM and cooked directly from a fresh, never-frozen state at 24 h PM. Cook yield of the hot-boned thighs was significantly higher than those of the 2 and 24 h deboned samples, which did not differ from each other. In experiment 3, whole legs (thigh + drumstick) were cut from the carcass backbone at 0.3 (hot-cut), 2, and 24 h PM. Thighs were separated from the legs (drumsticks) at either the same time the whole legs were removed from the carcasses or at 24 h PM. Intact thighs (bone in) were cooked fresh at 24 h PM. Color of fresh thigh muscles, cook yield, and Warner-Bratzler shear force of cooked samples were measured. Cook yield of the thighs cut from the backbone before chilling was significantly higher than those cut from the carcasses at 2 and 24 h PM, which did not differ from each other. The PM time at which intact thighs were separated from the leg (drumstick) did not influence cook yield. These results demonstrate that postmortem deboning time can significantly affect cook yield of boneless skinless chicken thigh products. Deboning chicken thighs after chilling reduces the cook yield. Differences in the cook yield of thighs may also result from the removal of whole chicken legs from the carcass backbone. Poultry Science Association Inc.

ECM Decorated Electrospun Nanofiber for Improving Bone Tissue Regeneration

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Yong Fu

2018-03-01

Full Text Available Optimization of nanofiber surface properties can lead to enhanced tissue regeneration outcomes in the context of bone tissue engineering. Herein, we developed a facile strategy to decorate elctrospun nanofibers using extracellular matrix (ECM in order to improve their performance for bone tissue engineering. Electrospun PLLA nanofibers (PLLA NF were seeded with MC3T3-E1 cells and allowed to grow for two weeks in order to harvest a layer of ECM on nanofiber surface. After decellularization, we found that ECM was successfully preserved on nanofiber surface while maintaining the nanostructure of electrospun fibers. ECM decorated on PLLA NF is biologically active, as evidenced by its ability to enhance mouse bone marrow stromal cells (mBMSCs adhesion, support cell proliferation and promote early stage osteogenic differentiation of mBMSCs. Compared to PLLA NF without ECM, mBMSCs grown on ECM/PLLA NF exhibited a healthier morphology, faster proliferation profile, and more robust osteogenic differentiation. Therefore, our study suggests that ECM decoration on electrospun nanofibers could serve as an efficient approach to improving their performance for bone tissue engineering.

Advanced imaging of the musculoskeletal system: Standard, three-dimensional, and contrast-enhanced CT and MR imaging, and quantitative bone densitometry

International Nuclear Information System (INIS)

Resnick, D.; Sartoris, D.J.

1987-01-01

This course reviews the application of advanced imaging techniques to a broad spectrum of musculoskeletal disorders. The indications for and utility of standard CT in both the axial and the appendicular skeleton is explored. The combined use of CT with air and contrast arthrography at sites including the hip, knee, and shoulder is discussed. A summary of the proved and potential applications of MR imaging in osseous, articular, bone marrow, and soft-tissue disorders is provided. The utility of intraarticular contrast agents in enhancing the diagnostic capabilities of MR imaging for disorders of hyaline cartilage and and fibrocartilage is demonstrated. The advantages of multiplanar reformation and three-dimensional image reconstruction of cross-sectional imaging data are described in conjunction with the fundamental technological principles of these strategies. Accepted methods as well as investigative techniques for the diagnosis and follow-up of metabolic bone disease are contrasted with regard to relative indications, advantages, and limitations

Mesenchymal stem cells overexpressing Ihh promote bone repair.

Science.gov (United States)

Zou, Shasha; Chen, Tingting; Wang, Yanan; Tian, Ruhui; Zhang, Lingling; Song, Pingping; Yang, Shi; Zhu, Yong; Guo, Xizhi; Huang, Yiran; Li, Zheng; Kan, Lixin; Hu, Hongliang

2014-10-28

Indian hedgehog (Ihh) signaling pathway is known to play key roles in various aspects of normal endochondral bone development. This study tested the potential roles of high Ihh signaling in the context of injury-induced bone regeneration. A rabbit tibia defect model was established to test the effects of the implant of Ihh/mesenchymal stem cells (MSCs)/scaffold complex. Computed tomography (CT), gross observation, and standard histological and immunohistological techniques were used to evaluate the effectiveness of the treatment. In vitro studies with MSCs and C3H10T1/2 cells were also employed to further understand the cellular and molecular mechanisms. We found that the implanted Ihh/MSCs/scaffold complex promoted bone repair. Consistently, in vitro study found that Ihh induced the upregulation of chondrocytic, osteogenic, and vascular cell markers, both in C3H10T1/2 cells and MSCs. Our study has demonstrated that high Ihh signaling in a complex with MSCs enhanced bone regeneration effectively in a clinically relevant acute injury model. Even though the exact underlying mechanisms are still far from clear, our primary data suggested that enhanced chondrogenesis, osteogenesis, and angiogenesis of MSCs at least partially contribute to the process. This study not only has implications for basic research of MSCs and Ihh signaling pathway but also points to the possibility of direct application of this specific paradigm to clinical bone repair.

Electrospun composites of PHBV/pearl powder for bone repairing

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Jingjing Bai

2015-08-01

Full Text Available Electrospun fiber has highly structural similarity with natural bone extracelluar matrix (ECM. Many researches about fabricating organic–inorganic composite materials have been carried out in order to mimic the natural composition of bone and enhance the biocompatibility of materials. In this work, pearl powder was added to the poly (3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV and the composite nanofiber scaffold was prepared by electrospinning. Mineralization ability of the composite scaffolds can be evaluated by analyzing hydroxyapatite (HA formation on the surface of nanofiber scaffolds. The obtained composite nanofiber scaffolds showed an enhanced mineralization capacity due to incorporation of pearl powder. The HA formed amount of the composite scaffolds was raised as the increase of pearl powder in composite scaffolds. Therefore, the prepared PHBV/pearl composite nanofiber scaffolds would be a promising candidate as an osteoconductive composite material for bone repairing.

Characterization of Bone Marrow Mononuclear Cells on Biomaterials for Bone Tissue Engineering In Vitro

Science.gov (United States)

Verboket, René; Kontradowitz, Kerstin; Oppermann, Elsie; Brune, Jan C.; Nau, Christoph; Meier, Simon; Bonig, Halvard; Marzi, Ingo; Seebach, Caroline

2015-01-01

Bone marrow mononuclear cells (BMCs) are suitable for bone tissue engineering. Comparative data regarding the needs of BMC for the adhesion on biomaterials and biocompatibility to various biomaterials are lacking to a large extent. Therefore, we evaluated whether a surface coating would enhance BMC adhesion and analyze the biocompatibility of three different kinds of biomaterials. BMCs were purified from human bone marrow aspirate samples. Beta tricalcium phosphate (β-TCP, without coating or coated with fibronectin or human plasma), demineralized bone matrix (DBM), and bovine cancellous bone (BS) were assessed. Seeding efficacy on β-TCP was 95% regardless of the surface coating. BMC demonstrated a significantly increased initial adhesion on DBM and β-TCP compared to BS. On day 14, metabolic activity was significantly increased in BMC seeded on DBM in comparison to BMC seeded on BS. Likewise increased VEGF-synthesis was observed on day 2 in BMC seeded on DBM when compared to BMC seeded on BS. The seeding efficacy of BMC on uncoated biomaterials is generally high although there are differences between these biomaterials. Beta-TCP and DBM were similar and both superior to BS, suggesting either as suitable materials for spatial restriction of BMC used for regenerative medicine purposes in vivo. PMID:25802865

Characterization of bone marrow mononuclear cells on biomaterials for bone tissue engineering in vitro.

Science.gov (United States)

Henrich, Dirk; Verboket, René; Schaible, Alexander; Kontradowitz, Kerstin; Oppermann, Elsie; Brune, Jan C; Nau, Christoph; Meier, Simon; Bonig, Halvard; Marzi, Ingo; Seebach, Caroline

2015-01-01

Bone marrow mononuclear cells (BMCs) are suitable for bone tissue engineering. Comparative data regarding the needs of BMC for the adhesion on biomaterials and biocompatibility to various biomaterials are lacking to a large extent. Therefore, we evaluated whether a surface coating would enhance BMC adhesion and analyze the biocompatibility of three different kinds of biomaterials. BMCs were purified from human bone marrow aspirate samples. Beta tricalcium phosphate (β-TCP, without coating or coated with fibronectin or human plasma), demineralized bone matrix (DBM), and bovine cancellous bone (BS) were assessed. Seeding efficacy on β-TCP was 95% regardless of the surface coating. BMC demonstrated a significantly increased initial adhesion on DBM and β-TCP compared to BS. On day 14, metabolic activity was significantly increased in BMC seeded on DBM in comparison to BMC seeded on BS. Likewise increased VEGF-synthesis was observed on day 2 in BMC seeded on DBM when compared to BMC seeded on BS. The seeding efficacy of BMC on uncoated biomaterials is generally high although there are differences between these biomaterials. Beta-TCP and DBM were similar and both superior to BS, suggesting either as suitable materials for spatial restriction of BMC used for regenerative medicine purposes in vivo.

Characterization of Bone Marrow Mononuclear Cells on Biomaterials for Bone Tissue Engineering In Vitro

Directory of Open Access Journals (Sweden)

Dirk Henrich

2015-01-01

Full Text Available Bone marrow mononuclear cells (BMCs are suitable for bone tissue engineering. Comparative data regarding the needs of BMC for the adhesion on biomaterials and biocompatibility to various biomaterials are lacking to a large extent. Therefore, we evaluated whether a surface coating would enhance BMC adhesion and analyze the biocompatibility of three different kinds of biomaterials. BMCs were purified from human bone marrow aspirate samples. Beta tricalcium phosphate (β-TCP, without coating or coated with fibronectin or human plasma, demineralized bone matrix (DBM, and bovine cancellous bone (BS were assessed. Seeding efficacy on β-TCP was 95% regardless of the surface coating. BMC demonstrated a significantly increased initial adhesion on DBM and β-TCP compared to BS. On day 14, metabolic activity was significantly increased in BMC seeded on DBM in comparison to BMC seeded on BS. Likewise increased VEGF-synthesis was observed on day 2 in BMC seeded on DBM when compared to BMC seeded on BS. The seeding efficacy of BMC on uncoated biomaterials is generally high although there are differences between these biomaterials. Beta-TCP and DBM were similar and both superior to BS, suggesting either as suitable materials for spatial restriction of BMC used for regenerative medicine purposes in vivo.

Enhancement of Tendon–Bone Healing for Anterior Cruciate Ligament (ACL Reconstruction Using Bone Marrow-Derived Mesenchymal Stem Cells Infected with BMP-2

Directory of Open Access Journals (Sweden)

Shiyi Chen

2012-10-01

Full Text Available At present, due to the growing attention focused on the issue of tendon–bone healing, we carried out an animal study of the use of genetic intervention combined with cell transplantation for the promotion of this process. Here, the efficacy of bone marrow stromal cells infected with bone morphogenetic protein-2 (BMP-2 on tendon–bone healing was determined. A eukaryotic expression vector containing the BMP-2 gene was constructed and bone marrow-derived mesenchymal stem cells (bMSCs were infected with a lentivirus. Next, we examined the viability of the infected cells and the mRNA and protein levels of BMP-2-infected bMSCs. Gastrocnemius tendons, gastrocnemius tendons wrapped by bMSCs infected with the control virus (bMSCs+Lv-Control, and gastrocnemius tendons wrapped by bMSCs infected with the recombinant BMP-2 virus (bMSCs+Lv-BMP-2 were used to reconstruct the anterior cruciate ligament (ACL in New Zealand white rabbits. Specimens from each group were harvested four and eight weeks postoperatively and evaluated using biomechanical and histological methods. The bMSCs were infected with the lentivirus at an efficiency close to 100%. The BMP-2 mRNA and protein levels in bMSCs were significantly increased after lentiviral infection. The bMSCs and BMP-2-infected bMSCs on the gastrocnemius tendon improved the biomechanical properties of the graft in the bone tunnel; specifically, bMSCs infected with BMP-2 had a positive effect on tendon–bone healing. In the four-week and eight-week groups, bMSCs+Lv-BMP-2 group exhibited significantly higher maximum loads of 29.3 ± 7.4 N and 45.5 ± 11.9 N, respectively, compared with the control group (19.9 ± 6.4 N and 21.9 ± 4.9 N (P = 0.041 and P = 0.001, respectively. In the eight-week groups, the stiffness of the bMSCs+Lv-BMP-2 group (32.5 ± 7.3 was significantly higher than that of the bMSCs+Lv-Control group (22.8 ± 7.4 or control groups (12.4 ± 6.0 (p = 0.036 and 0.001, respectively. Based on the

Effects of different loading patterns on the trabecular bone morphology of the proximal femur using adaptive bone remodeling.

Science.gov (United States)

Banijamali, S Mohammad Ali; Oftadeh, Ramin; Nazarian, Ara; Goebel, Ruben; Vaziri, Ashkan; Nayeb-Hashemi, Hamid

2015-01-01

In this study, the changes in the bone density of human femur model as a result of different loadings were investigated. The model initially consisted of a solid shell representing cortical bone encompassing a cubical network of interconnected rods representing trabecular bone. A computationally efficient program was developed that iteratively changed the structure of trabecular bone by keeping the local stress in the structure within a defined stress range. The stress was controlled by either enhancing existing beam elements or removing beams from the initial trabecular frame structure. Analyses were performed for two cases of homogenous isotropic and transversely isotropic beams.Trabecular bone structure was obtained for three load cases: walking, stair climbing and stumbling without falling. The results indicate that trabecular bone tissue material properties do not have a significant effect on the converged structure of trabecular bone. In addition, as the magnitude of the loads increase, the internal structure becomes denser in critical zones. Loading associated with the stumbling results in the highest density;whereas walking, considered as a routine daily activity, results in the least internal density in different regions. Furthermore, bone volume fraction at the critical regions of the converged structure is in good agreement with previously measured data obtained from combinations of dual X-ray absorptiometry (DXA) and computed tomography (CT). The results indicate that the converged bone architecture consisting of rods and plates are consistent with the natural bone morphology of the femur. The proposed model shows a promising means to understand the effects of different individual loading patterns on the bone density.

Magnetic resonance imaging aspects of giant-cell tumours of bone

International Nuclear Information System (INIS)

Pereira, Helcio Mendoncça; Marchiori, Edson; Severo, Alessandro

2014-01-01

This study aimed to describe the magnetic resonance imaging (MRI) features of giant-cell tumours of bone. We analysed the clinical and MRI features of patients diagnosed with giant-cell tumours of bone confirmed by histopathology at our institution between 2010 and 2012. The peak incidence was between the second and third decades of life. There was no gender predominance. The most frequent locations were the knee and wrist. Pain and swelling were the prevailing symptoms. Fifty-one per cent of the patients were found to have associated secondary aneurysmal bone cysts on histopathology. On MRI, lesions demonstrated signal intensity equal to that of skeletal muscle on T1-weighted images and low signal intensity on T2-weighted images in 90% of cases. In gadolinium-enhanced T1-weighted images, 76.6% of cases demonstrated heterogeneous enhancement. We observed cystic components involving more than 50% of the lesion in 17 cases (56.6%). There was extra-osseous involvement in 13 cases (43.3%). MRI offers a valuable diagnostic tool for giant-cell tumours of bone. Contrast-enhanced MRI can distinguish between cystic and solid components of the tumour. MRI is also the imaging modality of choice for evaluation of soft-tissue involvement, offering a complete preoperative diagnosis.

Ozone Treatment of Alveolar Bone in the Cape Chacma Baboon Does Not Enhance Healing Following Trauma

OpenAIRE

Kotze, Marthinus; Bütow, Kürt-W; Olorunju, Steve A.; Kotze, Harry F.

2013-01-01

In the international literature, the role of Ozone (O3) in the advancement in alveolar bone healing in the absence of bone pathology was not tested before. The purpose of this study was to evaluate alveolar bone regeneration after a bone defect was created and treated with a single topical administration of O3. Alveolar bone defects were created on five healthy chacma baboons. One side of the maxilla and mandible was topically treated with a single treatment of an O3/O2 mixture (3,5–4 % O3), ...

Enhanced bone formation in electrospun poly(L-lactic-co-glycolic acid)-tussah silk fibroin ultrafine nanofiber scaffolds incorporated with graphene oxide.

Science.gov (United States)

Shao, Weili; He, Jianxin; Sang, Feng; Wang, Qian; Chen, Li; Cui, Shizhong; Ding, Bin

2016-05-01

To engineer bone tissue, it is necessary to provide a biocompatible, mechanically robust scaffold. In this study, we fabricated an ultrafine nanofiber scaffold by electrospinning a blend of poly(L-lactic-co-glycolic acid), tussah silk fibroin, and graphene oxide (GO) and characterized its morphology, biocompatibility, mechanical properties, and biological activity. The data indicate that incorporation of 10 wt.% tussah silk and 1 wt.% graphene oxide into poly(L-lactic-co-glycolic acid) nanofibers significantly decreased the fiber diameter from 280 to 130 nm. Furthermore, tussah silk and graphene oxide boosted the Young's modulus and tensile strength by nearly 4-fold and 3-fold, respectively, and significantly enhanced adhesion, proliferation in mouse mesenchymal stem cells and functionally promoted biomineralization-relevant alkaline phosphatase (ALP) and mineral deposition. The results indicate that composite nanofibers could be excellent and versatile scaffolds for bone tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells.

Science.gov (United States)

Salamanna, Francesca; Borsari, Veronica; Brogini, Silvia; Giavaresi, Gianluca; Parrilli, Annapaola; Cepollaro, Simona; Cadossi, Matteo; Martini, Lucia; Mazzotti, Antonio; Fini, Milena

2016-11-22

One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively. Bone tissue discarded from total hip replacement surgery was cultured in a rolling apparatus system in a normoxic or hypoxic environment. Gene expression profile, protein levels, histological, immunohistochemical and four-dimensional (4D) micro-CT analyses showed a noticeable specificity of breast and prostate cancer cells for bone colonization and ingrowth, thus highlighting the species-specific and sex-specific osteotropism and the need to widen the current knowledge on cancer-bone metastasis spread in human bone tissues. The results of this study support the application of this model in preclinical studies on bone metastases and also follow the 3R principles, the guiding principles, aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes.

Osteogenic protein-1 increases the fixation of implants grafted with morcellised bone allograft and ProOsteon bone substitute: an experimental study in dogs

DEFF Research Database (Denmark)

Jensen, T B; Overgaard, S; Lind, M

2007-01-01

Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules...... (ProOsteon) would improve the incorporation of bone and implant fixation. We also compared the response to using ProOsteon alone against bone allograft used in isolation. We implanted two non-weight-bearing hydroxyapatite-coated implants into each proximal humerus of six dogs, with each implant...... surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1. After three...

Thrombospondin-2 Influences the Proportion of Cartilage and Bone During Fracture Healing

OpenAIRE

Taylor, Douglas K; Meganck, Jeffrey A; Terkhorn, Shawn; Rajani, Rajiv; Naik, Amish; O'Keefe, Regis J; Goldstein, Steven A; Hankenson, Kurt D

2009-01-01

Thrombospondin-2 (TSP2) is a matricellular protein with increased expression during growth and regeneration. TSP2-null mice show accelerated dermal wound healing and enhanced bone formation. We hypothesized that bone regeneration would be enhanced in the absence of TSP2. Closed, semistabilized transverse fractures were created in the tibias of wildtype (WT) and TSP2-null mice. The fractures were examined 5, 10, and 20 days after fracture using ?CT, histology, immunohistochemistry, quantitativ...

Hybrid approach of ventricular assist device and autologous bone marrow stem cells implantation in end-stage ischemic heart failure enhances myocardial reperfusion

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Khayat Andre

2011-01-01

Full Text Available Abstract We challenge the hypothesis of enhanced myocardial reperfusion after implanting a left ventricular assist device together with bone marrow mononuclear stem cells in patients with end-stage ischemic cardiomyopathy. Irreversible myocardial loss observed in ischemic cardiomyopathy leads to progressive cardiac remodelling and dysfunction through a complex neurohormonal cascade. New generation assist devices promote myocardial recovery only in patients with dilated or peripartum cardiomyopathy. In the setting of diffuse myocardial ischemia not amenable to revascularization, native myocardial recovery has not been observed after implantation of an assist device as destination therapy. The hybrid approach of implanting autologous bone marrow stem cells during assist device implantation may eventually improve native cardiac function, which may be associated with a better prognosis eventually ameliorating the need for subsequent heart transplantation. The aforementioned hypothesis has to be tested with well-designed prospective multicentre studies.

Enhanced osteogenic differentiation and bone regeneration of poly(lactic-co-glycolic acid) by graphene via activation of PI3K/Akt/GSK-3β/β-catenin signal circuit.

Science.gov (United States)

Wu, Xiaowei; Zheng, Shang; Ye, Yuanzhou; Wu, Yuchen; Lin, Kaili; Su, Jiansheng

2018-05-01

The reconstruction of bone defects by guiding autologous bone tissue regeneration with artificial biomaterials is a potential strategy in the area of bone tissue engineering. The development of new polymers with good biocompatibility, favorable mechanical properties, and osteoinductivity is of vital importance. Graphene and its derivatives have attracted extensive interests due to the exceptional physiochemical and biological properties of graphene. In this study, poly(lactic-co-glycolic acid) (PLGA) films incorporated by graphene nanoplates were fabricated. The results indicated that the incorporation of proper graphene nanoplates into poly(lactic-co-glycolic acid) film could enhance the adhesion and proliferation of rat bone marrow-derived mesenchymal stem cells (rBMSCs). The augmentation of alkaline phosphatase activity, calcium mineral deposition, and the expression level of osteogenic-related genes of rBMSCs on the composite films were observed. Moreover, the incorporation of graphene might activate the PI3K/Akt/GSK-3β/β-catenin signaling pathway, which appeared to be the mechanism behind the osteoinductive properties of graphene. Moreover, the in vivo furcation defect implantation results revealed better guiding bone regeneration properties in the graphene-incorporated group. Thus, we highlight this graphene-incorporated film as a promising platform for the growth and osteogenic differentiation of BMSCs that can achieve application in bone regeneration.

Callus formation in bone fractures combined with brain injury in rat

Directory of Open Access Journals (Sweden)

Yu-Ping Chen

2017-01-01

Full Text Available Objective: The objective of this study was to determine the speed of bony union and the serum levels of biomarkers in the setting of bone fractures combined with brain injury. Materials and Methods: In this study, Sprague–Dawley rats were randomized into four groups: sham, brain injury, bone fracture, and bone fracture plus brain injury groups. The serum levels of biochemical markers, namely, nerve growth factor (NGF, Wnt-3a, Dickkopf-related protein-1, receptor-activator of NF-κB ligand, and adrenocorticotropic hormone (ACTH, were measured on the days 1, 3, 7, and 14 following injury. Bony union was evaluated using radiographs every week for 6 weeks. Results: Compared with the brain injury group and bone fracture group, the radiographs of the bone fracture plus brain injury group revealed enhanced callus formations in week 2. From week 3, the callus formation did not differ significantly among the groups. The serum levels of the biomarkers varied at different time points. The serum levels of NGF on days 1 and 3, Wnt-3a on days 3 and 14, and ACTH on days 1, 3, and 7 were significantly higher in the bone fracture plus brain injury group than in the bone fracture group. Conclusions: Brain injury increases callus formation in simultaneous bone fracture. Considering the time point, early NGF, Wnt-3a, and ACTH elevation might be associated with early callus formation enhancement. The results indicate that these brain injury-induced biomarkers might play crucial role in accelerating bone healing.

Rapid prototyping technology and its application in bone tissue engineering.

Science.gov (United States)

Yuan, Bo; Zhou, Sheng-Yuan; Chen, Xiong-Sheng

Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction. Autografts and allografts have been used in clinical application for some time, but they have disadvantages. With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques, the results of bone surgery may not be ideal. This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair. Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering, enhancing bone tissue regeneration in terms of mechanical strength, pore geometry, and bioactive factors, and overcoming some of the disadvantages of conventional technologies. This review focuses on the basic principles and characteristics of various fabrication technologies, such as stereolithography, selective laser sintering, and fused deposition modeling, and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering. In the near future, the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects.

Rapid prototyping technology and its application in bone tissue engineering*

Science.gov (United States)

YUAN, Bo; ZHOU, Sheng-yuan; CHEN, Xiong-sheng

2017-01-01

Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction. Autografts and allografts have been used in clinical application for some time, but they have disadvantages. With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques, the results of bone surgery may not be ideal. This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair. Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering, enhancing bone tissue regeneration in terms of mechanical strength, pore geometry, and bioactive factors, and overcoming some of the disadvantages of conventional technologies. This review focuses on the basic principles and characteristics of various fabrication technologies, such as stereolithography, selective laser sintering, and fused deposition modeling, and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering. In the near future, the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects. PMID:28378568

Scaling of Haversian canal surface area to secondary osteon bone volume in ribs and limb bones.

Science.gov (United States)

Skedros, John G; Knight, Alex N; Clark, Gunnar C; Crowder, Christian M; Dominguez, Victoria M; Qiu, Shijing; Mulhern, Dawn M; Donahue, Seth W; Busse, Björn; Hulsey, Brannon I; Zedda, Marco; Sorenson, Scott M

2013-06-01

Studies of secondary osteons in ribs have provided a great deal of what is known about remodeling dynamics. Compared with limb bones, ribs are metabolically more active and sensitive to hormonal changes, and receive frequent low-strain loading. Optimization for calcium exchange in rib osteons might be achieved without incurring a significant reduction in safety factor by disproportionally increasing central canal size with increased osteon size (positive allometry). By contrast, greater mechanical loads on limb bones might favor reducing deleterious consequences of intracortical porosity by decreasing osteon canal size with increased osteon size (negative allometry). Evidence of this metabolic/mechanical dichotomy between ribs and limb bones was sought by examining relationships between Haversian canal surface area (BS, osteon Haversian canal perimeter, HC.Pm) and bone volume (BV, osteonal wall area, B.Ar) in a broad size range of mature (quiescent) osteons from adult human limb bones and ribs (modern and medieval) and various adult and subadult non-human limb bones and ribs. Reduced major axis (RMA) and least-squares (LS) regressions of HC.Pm/B.Ar data show that rib and limb osteons cannot be distinguished by dimensional allometry of these parameters. Although four of the five rib groups showed positive allometry in terms of the RMA slopes, nearly 50% of the adult limb bone groups also showed positive allometry when negative allometry was expected. Consequently, our results fail to provide clear evidence that BS/BV scaling reflects a rib versus limb bone dichotomy whereby calcium exchange might be preferentially enhanced in rib osteons. Copyright © 2013 Wiley Periodicals, Inc.

Using the Enhanced Daily Load Stimulus Model to Quantify the Mechanical Load and Bone Mineral Density Changes Experienced by Crew Members on the International Space Station

Science.gov (United States)

Genc, K. O.; Gopalakrishnan, R.; Kuklis, M. M.; Maender, C. C.; Rice, A. J.; Cavanagh, P. R.

2009-01-01

Despite the use of exercise countermeasures during long-duration space missions, bone mineral density (BMD) and predicted bone strength of astronauts continue to show decreases in the lower extremities and spine. This site-specific bone adaptation is most likely caused by the effects of microgravity on the mechanical loading environment of the crew member. There is, therefore, a need to quantify the mechanical loading experienced on Earth and on-orbit to define the effect of a given "dose" of loading on bone homeostasis. Gene et al. recently proposed an enhanced DLS (EDLS) model that, when used with entire days of in-shoe forces, takes into account recently developed theories on the importance of factors such as saturation, recovery, and standing and their effects on the osteogenic response of bone to daily physical activity. This algorithm can also quantify the tinting and type of activity (sit/unload, stand, walk, run or other loaded activity) performed throughout the day. The purpose of the current study was to use in-shoe force measurements from entire typical work days on Earth and on-orbit in order to quantify the type and amount of loading experienced by crew members. The specific aim was to use these measurements as inputs into the EDLS model to determine activity timing/type and the mechanical "dose" imparted on the musculoskeletal system of crew members and relate this dose to changes in bone homeostasis.

Efficiently engineered cell sheet using a complex of polyethylenimine–alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation

Directory of Open Access Journals (Sweden)

Jin H

2014-05-01

Full Text Available Han Jin,1 Kai Zhang,2 Chunyan Qiao,1 Anliang Yuan,1 Daowei Li,1 Liang Zhao,1 Ce Shi,1 Xiaowei Xu,1 Shilei Ni,1 Changyu Zheng,3 Xiaohua Liu,4 Bai Yang,2 Hongchen Sun11Department of Pathology, School of Stomatology, Jilin University, Changchun, People’s Republic of China; 2State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, People’s Republic of China; 3Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA; 4Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX, USAAbstract: Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2 gene-engineered cell sheet using a complex of polyethylenimine–alginate (PEI–al nanocomposites plus human BMP-2 complementary(cDNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI–al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI�

Potential of Osteoblastic Cells Derived from Bone Marrow and Adipose Tissue Associated with a Polymer/Ceramic Composite to Repair Bone Tissue.

Science.gov (United States)

Freitas, Gileade P; Lopes, Helena B; Almeida, Adriana L G; Abuna, Rodrigo P F; Gimenes, Rossano; Souza, Lucas E B; Covas, Dimas T; Beloti, Marcio M; Rosa, Adalberto L

2017-09-01

One of the tissue engineering strategies to promote bone regeneration is the association of cells and biomaterials. In this context, the aim of this study was to evaluate if cell source, either from bone marrow or adipose tissue, affects bone repair induced by osteoblastic cells associated with a membrane of poly(vinylidene-trifluoroethylene)/barium titanate (PVDF-TrFE/BT). Mesenchymal stem cells (MSC) were isolated from rat bone marrow and adipose tissue and characterized by detection of several surface markers. Also, both cell populations were cultured under osteogenic conditions and it was observed that MSC from bone marrow were more osteogenic than MSC from adipose tissue. The bone repair was evaluated in rat calvarial defects implanted with PVDF-TrFE/BT membrane and locally injected with (1) osteoblastic cells differentiated from MSC from bone marrow, (2) osteoblastic cells differentiated from MSC from adipose tissue or (3) phosphate-buffered saline. Luciferase-expressing osteoblastic cells derived from bone marrow and adipose tissue were detected in bone defects after cell injection during 25 days without difference in luciferin signal between cells from both sources. Corroborating the in vitro findings, osteoblastic cells from bone marrow combined with the PVDF-TrFE/BT membrane increased the bone formation, whereas osteoblastic cells from adipose tissue did not enhance the bone repair induced by the membrane itself. Based on these findings, it is possible to conclude that, by combining a membrane with cells in this rat model, cell source matters and that bone marrow could be a more suitable source of cells for therapies to engineer bone.

Rapid Osteogenic Enhancement of Stem Cells in Human Bone Marrow Using a Glycogen-Synthease-Kinase-3-Beta Inhibitor Improves Osteogenic Efficacy In Vitro and In Vivo.

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Clough, Bret H; Zeitouni, Suzanne; Krause, Ulf; Chaput, Christopher D; Cross, Lauren M; Gaharwar, Akhilesh K; Gregory, Carl A

2018-04-01

Non-union defects of bone are a major problem in orthopedics, especially for patients with a low healing capacity. Fixation devices and osteoconductive materials are used to provide a stable environment for osteogenesis and an osteogenic component such as autologous human bone marrow (hBM) is then used, but robust bone formation is contingent on the healing capacity of the patients. A safe and rapid procedure for improvement of the osteoanabolic properties of hBM is, therefore, sought after in the field of orthopedics, especially if it can be performed within the temporal limitations of the surgical procedure, with minimal manipulation, and at point-of-care. One way to achieve this goal is to stimulate canonical Wingless (cWnt) signaling in bone marrow-resident human mesenchymal stem cells (hMSCs), the presumptive precursors of osteoblasts in bone marrow. Herein, we report that the effects of cWnt stimulation can be achieved by transient (1-2 hours) exposure of osteoprogenitors to the GSK3β-inhibitor (2'Z,3'E)-6-bromoindirubin-3'-oxime (BIO) at a concentration of 800 nM. Very-rapid-exposure-to-BIO (VRE-BIO) on either hMSCs or whole hBM resulted in the long-term establishment of an osteogenic phenotype associated with accelerated alkaline phosphatase activity and enhanced transcription of the master regulator of osteogenesis, Runx2. When VRE-BIO treated hBM was tested in a rat spinal fusion model, VRE-BIO caused the formation of a denser, stiffer, fusion mass as compared with vehicle treated hBM. Collectively, these data indicate that the VRE-BIO procedure may represent a rapid, safe, and point-of-care strategy for the osteogenic enhancement of autologous hBM for use in clinical orthopedic procedures. Stem Cells Translational Medicine 2018;7:342-353. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

MR findings of chondroblastoma with emphasis on enhancement pattern

International Nuclear Information System (INIS)

Oh, Kyung Joong; Go, Sung Hye; Lee, Gyung Kyu; Kim, Jung Eun; Choi, Jung A; Park, Chang Min; Choi, Seung Hong; Kang, Heung Sik; Ahn, Jung Mo; Kim, Sung Moon

2003-01-01

To analyze the MR findings of chondroblastoma and peritumoral bone marrow, focussing on the enhancement pattern. Enhanced MR images obtained from 23 patients with pathologically proven chondroblastoma were retrospectively reviewed by three radiologists. The enhancement pattern was classified as one of three types: homogeneous, heterogeneous, or peripheral rim, while peritumoral bone marrow enhancement was assigned one of four grades. Correlation between the enhancement pattern and T2 signal intensity of a tumor was analyzed by fisher's exact test. The enhancement pattern was homogeneous in ten cases, heterogeneous in six, and involved the peripheral rim in seven. In 11 cases, peritumoral bone marrow enhancement was observed. Among the ten instances of homogeneous enhancement the signal intensity seen at T2W1 was homogeneously iso or low in six cases, homogeneously high in two, and heterogeneous in two. Among the seven cases in which three was peripheral rim enhancement, the signal intensity observed at T2W1 was homogeneously high in three, fluid-fluid level in three, and homogeneously iso or low in one. At MR imaging, chondroblastoma shows variable signal intensities and enhancement patterns. The peripheral rim enhancement observed at T2W1 correlated with homogeneously high signal intensity or fluid-fluid levels

MR findings of chondroblastoma with emphasis on enhancement pattern

Energy Technology Data Exchange (ETDEWEB)

Oh, Kyung Joong; Go, Sung Hye; Lee, Gyung Kyu; Kim, Jung Eun; Choi, Jung A; Park, Chang Min; Choi, Seung Hong; Kang, Heung Sik [Seoul National University College of Medicine, Seoul (Korea, Republic of); Ahn, Jung Mo [Samsung Medical Center, Seoul (Korea, Republic of); Kim, Sung Moon [Asan Medical Center, Seoul (Korea, Republic of)

2003-03-01

To analyze the MR findings of chondroblastoma and peritumoral bone marrow, focussing on the enhancement pattern. Enhanced MR images obtained from 23 patients with pathologically proven chondroblastoma were retrospectively reviewed by three radiologists. The enhancement pattern was classified as one of three types: homogeneous, heterogeneous, or peripheral rim, while peritumoral bone marrow enhancement was assigned one of four grades. Correlation between the enhancement pattern and T2 signal intensity of a tumor was analyzed by fisher's exact test. The enhancement pattern was homogeneous in ten cases, heterogeneous in six, and involved the peripheral rim in seven. In 11 cases, peritumoral bone marrow enhancement was observed. Among the ten instances of homogeneous enhancement the signal intensity seen at T2W1 was homogeneously iso or low in six cases, homogeneously high in two, and heterogeneous in two. Among the seven cases in which three was peripheral rim enhancement, the signal intensity observed at T2W1 was homogeneously high in three, fluid-fluid level in three, and homogeneously iso or low in one. At MR imaging, chondroblastoma shows variable signal intensities and enhancement patterns. The peripheral rim enhancement observed at T2W1 correlated with homogeneously high signal intensity or fluid-fluid levels.

Bone Growth, Mechanical Stimulus and IGF-1

National Research Council Canada - National Science Library

Gilsanz, Vicente

2006-01-01

... in the weight bearing skeleton of young adult females with low bone density. Ultimately, this information could be of great benefit to enhance musculoskeletal development and decrease the risk for stress fractures in military recruits...

Interleukin-1β modulates endochondral ossification by human adult bone marrow stromal cells

Directory of Open Access Journals (Sweden)

M Mumme

2012-09-01

Full Text Available Inflammatory cytokines present in the milieu of the fracture site are important modulators of bone healing. Here we investigated the effects of interleukin-1β (IL-1β on the main events of endochondral bone formation by human bone marrow mesenchymal stromal cells (BM-MSC, namely cell proliferation, differentiation and maturation/remodelling of the resulting hypertrophic cartilage. Low doses of IL-1β (50 pg/mL enhanced colony-forming units-fibroblastic (CFU-f and -osteoblastic (CFU-o number (up to 1.5-fold and size (1.2-fold in the absence of further supplements and glycosaminoglycan accumulation (1.4-fold upon BM-MSC chondrogenic induction. In osteogenically cultured BM-MSC, IL-1β enhanced calcium deposition (62.2-fold and BMP-2 mRNA expression by differential activation of NF-κB and ERK signalling. IL-1β-treatment of BM-MSC generated cartilage resulted in higher production of MMP-13 (14.0-fold in vitro, mirrored by an increased accumulation of the cryptic cleaved fragment of aggrecan, and more efficient cartilage remodelling/resorption after 5 weeks in vivo (i.e., more TRAP positive cells and bone marrow, less cartilaginous areas, resulting in the formation of mature bone and bone marrow after 12 weeks. In conclusion, IL-1β finely modulates early and late events of the endochondral bone formation by BM-MSC. Controlling the inflammatory environment could enhance the success of therapeutic approaches for the treatment of fractures by resident MSC and as well as improve the engineering of implantable tissues.

Quinoline compound KM11073 enhances BMP-2-dependent osteogenic differentiation of C2C12 cells via activation of p38 signaling and exhibits in vivo bone forming activity.

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Seung-hwa Baek

Full Text Available Recombinant human bone morphogenetic protein (rhBMP-2 has been approved by the FDA for clinical application, but its use is limited due to high cost and a supra-physiological dose for therapeutic efficacy. Therefore, recent studies have focused on the generation of new therapeutic small molecules to induce bone formation or potentiate the osteogenic activity of BMP-2. Here, we show that [4-(7-chloroquinolin-4-yl piperazino][1-phenyl-5-(trifluoromethyl-1H-pyrazol-4-yl]methanone (KM11073 strongly enhances the BMP-2-stimulated induction of alkaline phosphatase (ALP, an early phase biomarker of osteoblast differentiation, in bi-potential mesenchymal progenitor C2C12 cells. The KM11073-mediated ALP induction was inhibited by the BMP antagonist noggin, suggesting that its osteogenic activity occurs via BMP signaling. In addition, a pharmacological inhibition study suggested the involvement of p38 activation in the osteogenic action of KM11073 accompanied by enhanced expression of BMP-2, -6, and -7 mRNA. Furthermore, the in vivo osteogenic activity of KM11073 was confirmed in zebrafish and mouse calvarial bone formation models, suggesting the possibility of its single use for bone formation. In conclusion, the combination of rhBMP-2 with osteogenic small molecules could reduce the use of expensive rhBMP-2, mitigating the undesirable side effects of its supra-physiological dose for therapeutic efficacy. Moreover, due to their inherent physical properties, small molecules could represent the next generation of regenerative medicine.

Igfbp2 Deletion in Ovariectomized Mice Enhances Energy Expenditure but Accelerates Bone Loss.

Science.gov (United States)

DeMambro, Victoria E; Le, Phuong T; Guntur, Anyonya R; Maridas, David E; Canalis, Ernesto; Nagano, Kenichi; Baron, Roland; Clemmons, David R; Rosen, Clifford J

2015-11-01

Previously, we reported sexually dimorphic bone mass and body composition phenotypes in Igfbp2(-/-) mice (-/-), where male mice exhibited decreased bone and increased fat mass, whereas female mice displayed increased bone but no changes in fat mass. To investigate the interaction between IGF-binding protein (IGFBP)-2 and estrogen, we subjected Igfbp2 -/- and +/+ female mice to ovariectomy (OVX) or sham surgery at 8 weeks of age. At 20 weeks of age, mice underwent metabolic cage analysis and insulin tolerance tests before killing. At harvest, femurs were collected for microcomputed tomography, serum for protein levels, brown adipose tissue (BAT) and inguinal white adipose tissue (IWAT) adipose depots for histology, gene expression, and mitochondrial respiration analysis of whole tissue. In +/+ mice, serum IGFBP-2 dropped 30% with OVX. In the absence of IGFBP-2, OVX had no effect on preformed BAT; however, there was significant "browning" of the IWAT depot coinciding with less weight gain, increased insulin sensitivity, lower intraabdominal fat, and increased bone loss due to higher resorption and lower formation. Likewise, after OVX, energy expenditure, physical activity and BAT mitochondrial respiration were decreased less in the OVX-/- compared with OVX+/+. Mitochondrial respiration of IWAT was reduced in OVX+/+ yet remained unchanged in OVX-/- mice. These changes were associated with significant increases in Fgf21 and Foxc2 expression, 2 proteins known for their insulin sensitizing and browning of WAT effects. We conclude that estrogen deficiency has a profound effect on body and bone composition in the absence of IGFBP-2 and may be related to changes in fibroblast growth factor 21.

MR imaging of edema accompanying benign and malignant bone tumors

International Nuclear Information System (INIS)

Kroon, H.M.; Bloem, J.L.; Holscher, H.C.; Woude, H.J. van der; Reijnierse, M.; Taminiau, A.H.M.

1994-01-01

To evaluate the incidence, quantity, and presentation of intra- and extraosseous edema accompanying benign and malignant primary bone lesions, the magnetic resonance (MR) studies of 63 consecutive patients with histologically proven primary bone tumors were reviewed. MR scans were assessed for the presence and quantity of marrow and soft tissue edema and correlated with preoperative findings, resected specimens and follow-up data. The signal intensity and enhancement of tumor and edema prior to and after intravenous administration (if any) of gadolinium-labled diethylene triamine pentaacetate (Gd-DTPA) was analyzed. Marrow edema was encountered adjacent to 8 of 39 maglinant tumors and 14 of 24 benign lesions. Soft tissue edema was found accompanying 28 of 39 malignancies and 10 of 24 benign disorders. On enhanced T1-weighted MR images tumor and edema were difficult to differentiate. Tumor inhomogeneity made this differentiation easier on T2-weighted sequences. In 36 patients the contrast medium Gd-DTPA was used. Edema was present in 27 of these patients and the respective enhancement of tumor and edema could be compared. Edema always enhanced homogeneously, and in most cases it enhanced to a similar degree as or more than tumor. Marrow and, more specifically, soft tissue edema is a frequent finding adjacent to primary bone tumors. The mere presence and quantity of marrow and soft tissue edema are unreliable indicators of the biologic potential of a lesion. Unenhanced MR scans cannot always differentiate between tumor and edema, but the administration of Gd-DTPA is of assistance in differentiating tumor from edema. Awareness of marrow and/or soft tissue edema adjacent to bone lesions is of importance because edema can be a pitfall in the diagnostic work-up and staging prior to biopsy or surgery. (orig.)

Bone Marrow Stromal Cells Contribute to Bone Formation Following Infusion into Femoral Cavities of a Mouse Model of Osteogenesis Imperfecta

Science.gov (United States)

Li, Feng; Wang, Xujun; Niyibizi, Christopher

2010-01-01

Currently, there are conflicting data in literature regarding contribution of bone marrow stromal cells (BMSCs) to bone formation when the cells are systemically delivered in recipient animals. To understand if BMSCs contribute to bone cell phenotype and bone formation in osteogenesis imperfecta bones (OI), MSCs marked with GFP were directly infused into the femurs of a mouse model of OI (oim). The contribution of the cells to the cell phenotype and bone formation was assessed by histology, immunohistochemistry and biomechanical loading of recipient bones. Two weeks following infusion of BMSCs, histological examination of the recipient femurs demonstrated presence of new bone when compared to femurs injected with saline which showed little or no bone formation. The new bone contained few donor cells as demonstrated by GFP fluorescence. At six weeks following cell injection, new bone was still detectable in the recipient femurs but was enhanced by injection of the cells suspended in pepsin solublized type I collagen. Immunofluorescence and immunohistochemical staining showed that donor GFP positive cells in the new bone were localized with osteocalcin expressing cells suggesting that the cells differentiated into osteoblasts in vivo. Biomechanical loading to failure in thee point bending, revealed that, femurs infused with BMSCs in PBS or in soluble type I collagen were biomechanically stronger than those injected with PBS or type I collagen alone. Taken together, the results indicate that transplanted cells differentiated into osteoblasts in vivo and contributed to bone formation in vivo; we also speculate that donor cells induced differentiation or recruitment of endogenous cells to initiate reparative process at early stages following transplantation. PMID:20570757

Effect of occlusal (mechanical) stimulus on bone remodelling in rat mandibular condyle.

Science.gov (United States)

Gazit, D; Ehrlich, J; Kohen, Y; Bab, I

1987-09-01

Mechanical load influences the remodelling of skeletal tissues. In the mandibular condyle, occlusal alterations and the consequent mechanical stimulus induce changes in chondrocytes and cartilage mineralization. In the present study we quantified in the mandibular condyle the effect of occlusal interference on remodelling of the subchondral bone. Computerized histomorphometry after 5-21-day exposure to the influence of a unilateral occlusal splint revealed an increased rate of trabecular remodelling, consisting of enhancement in osteoblast and osteoclast numbers and activities. The bone formation parameters reached their high values on Days 5 or 9 and remained stable thereafter. Bone resorption showed a gradual increase throughout the experimental period. These results further characterize the temporomandibular joint reaction to occlusal alterations. It is suggested that the present increase in bone turnover together with the known enhancement in chondrogenesis are part of a process of functional adaptation in response to mechanical stimulus.

Advances in allogenic bone graft processing and usage: preparation and evaluation of chitosan-demineralized cancellous bone powder composite scaffolds as a bone graft substitute

International Nuclear Information System (INIS)

Yongyudh Vajaradul

2008-01-01

Full text: Demineralized bone matrix (DBM) is currently used by surgeons. It usually exists as a lyophilized powder which is difficult to handle and operated. In this study, we try to improve these disadvantages by combining DBM with a biomaterial. It focuses on a natural biodegradable polymer, chitosan, to act as a temporary matrix for bone growth that easily prepare in any size and shape by using tissue engineering knowledge to get a proper temporary matrix. Thus, the development of chitosan-demineralized bone powder composite scaffold is an alternative way. Polymeric scaffold has been demonstrated to have great potential for tissue engineering because the scaffold or three dimension (3D) construct provides the necessary support for cells to proliferate, extracellular matrix deposition and vascularization of neo-tissue. Moreover, chitosan, a natural cationic polymer which its structural is similar to extracellular matrix glycosaminoblycans, is biodegradable, biocompatible, non-antigenic and biofunctional. It can enhance osteoblast cells proliferation and mineral matrix deposition in culture. The first study was to fabricate and analyze composite scaffold composed of either chitosan-demineralized cancellous bone powders or chitosan-demineralized cancellous cartilage bone powders in a ratio 50:50 and 70:30 w/w (chitosan : bone powders) based on physical properties composing of average pore diameter, mechanical integrity and swelling property. Secondly, scaffolds were evaluated in term of biological properties composing of their ability to support neo osteogenesis, including assessments of cell attachment and viability, cell morphology, and the biosynthesis of extracellular matrix. Results indicated that chitosan-demineralized cancellous bone powder composite scaffolds possessing an interconnecting, porous structure could be easily created through a simple freezing and lyophilization process. (Author)

Enhanced bioactivity and osseointegration of PEEK with accelerated neutral atom beam technology.

Science.gov (United States)

Khoury, Joseph; Maxwell, Melissa; Cherian, Raymond E; Bachand, James; Kurz, Arthur C; Walsh, Michael; Assad, Michel; Svrluga, Richard C

2017-04-01

Polyetheretherketone (PEEK) is growing in popularity for orthopedic, spinal, and trauma applications but has potential significant limitations in use. PEEK is biocompatible, similar in elasticity to bone, and radiolucent, but is inert and therefore does not integrate well with bone. Current efforts are focusing on increasing the bioactivity of PEEK with surface modifications to improve the bone-implant interface. We used a novel Accelerated Neutral Atom Beam (ANAB) technology to enhance the bioactivity of PEEK. Human osteoblast-like cells seeded on ANAB-treated PEEK result in significantly enhanced proliferation compared with control PEEK. Cells grown on ANAB-treated PEEK increase osteogenic expression of ALPL (1.98-fold, p PEEK implants resulted in enhanced bone-in-contact by 3.09-fold (p PEEK has the potential to enhance its bioactivity, leading to bone formation and significantly decreasing osseointegration time of orthopedic and spinal implants. ANAB treatment, therefore, may significantly enhance the performance of PEEK medical implants and lead to improved clinical outcomes. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 531-543, 2017. © 2015 Wiley Periodicals, Inc.

Malignant transformation of a unicameral bone cyst in a cat.

Science.gov (United States)

Berger, Björn; Brühschwein, Andreas; Eddicks, Lina; Meyer-Lindenberg, Andrea

2016-04-01

A unicameral bone cyst in the proximal humerus of a 3-year-old Norwegian forest cat was diagnosed by dynamic contrast-enhanced magnetic resonance imaging, surgical exploration, and histopathology. Surgical curettage and incorporation of bone cement led to full recovery. An osteosarcoma developed at the surgical site 17 months later. Thoracic radiographs showed pulmonary lesions consistent with metastasis.

Age changes in human bone: an overview

Energy Technology Data Exchange (ETDEWEB)

Sharpe, W.D.

1977-12-03

The human skeleton steadily changes structure and mass during life because of a variety of internal and external factors. Extracellular substance and bone cells get old, characteristic structural remodeling occurs with age and these age-related changes are important in the discrimination between pathological and physiological changes. Perhaps 20 percent of the bone mass is lost between the fourth and the ninth decades, osteoblasts function less efficiently and gradual loss of bone substance is enhanced by delayed mineralization of an increased surface area of thin and relatively less active osteoid seams. After the fifth decade, osteoclasia and the number of Howship's lacunae increase, and with age, the number of large osteolytic osteocytes increases as the number of small osteocytes declines and empty osteocyte lacunae become more common. The result is greater liability to fracture and diminished healing or replacement of injured bone.

Application of a novel bone osteotomy plate leads to reduction in heat-induced bone tissue necrosis in sheep.

Science.gov (United States)

Bekić, Marijo; Davila, Slavko; Hrskanović, Mato; Bekić, Marijana; Seiwerth, Sven; Erdeljić, Viktorija; Capak, Darko; Butković, Vladimir

2008-12-01

Previous studies have shown substantial effect thermal damage can have on new bone formation following osteotomy. In this study we evaluated the extent of thermal damage which occurs in four different methods of osteotomy and the effects it can have on bone healing. We further wanted to test whether a special osteotomy plate we constructed can lead to diminished heat generation during osteotomy and enhanced bone healing. The four methods evaluated included osteotomy performed by chisel, a newly constructed osteotomy plate, Gigly and oscillating saw. Twelve adult sheep underwent osteotomy performed on both tibiae. Bone fragments were stabilized using a fixation plate. Callus size was assessed using standard radiographs. Densitometry and histological evaluation were performed at 8 weeks following osteotomy. Temperature measurements were performed both in vivo during the operation, and ex vivo on explanted tibiae. The defects healed without complications and showed typical course of secondary fracture healing with callus ingrowth into the osteotomy gap. Radiographic examination of bone healing showed a tendency towards more callus formation in bones osteotomized using Gigly and oscillating saw, but this difference lacked significance. Use of Gigly and oscillating saw elicited much higher temperatures at the bone cortex surface, which subsequently lead to slightly impaired bone healing according to histological analysis. BMD was equal among all bones. In conclusion, the time required for complete healing of the defect differed depended greatly on the instruments used. The newly constructed osteotomy plate showed best results based on histological findings of capillary and osteoblast density.

Enhanced Bone Tissue Regeneration by Porous Gelatin Composites Loaded with the Chinese Herbal Decoction Danggui Buxue Tang.

Directory of Open Access Journals (Sweden)

Wen-Ling Wang

Full Text Available Danggui Buxue Tang (DBT is a traditional Chinese herbal decoction containing Radix Astragali and Radix Angelicae sinensis. Pharmacological results indicate that DBT can stimulate bone cell proliferation and differentiation. The aim of the study was to investigate the efficacy of adding DBT to bone substitutes on bone regeneration following bone injury. DBT was incorporated into porous composites (GGT made from genipin-crosslinked gelatin and β-triclacium phosphates as bone substitutes (GGTDBT. The biological response of mouse calvarial bone to these composites was evaluated by in vivo imaging systems (IVIS, micro-computed tomography (micro-CT, and histology analysis. IVIS images revealed a stronger fluorescent signal in GGTDBT-treated defect than in GGT-treated defect at 8 weeks after implantation. Micro-CT analysis demonstrated that the level of repair from week 4 to 8 increased from 42.1% to 71.2% at the sites treated with GGTDBT, while that increased from 33.2% to 54.1% at GGT-treated sites. These findings suggest that the GGTDBT stimulates the innate regenerative capacity of bone, supporting their use in bone tissue regeneration.

Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation.

Science.gov (United States)

Blouin, Stéphane; Fratzl-Zelman, Nadja; Glorieux, Francis H; Roschger, Paul; Klaushofer, Klaus; Marini, Joan C; Rauch, Frank

2017-09-01

In contrast to "classical" forms of osteogenesis imperfecta (OI) types I to IV, caused by a mutation in COL1A1/A2, OI type V is due to a gain-of-function mutation in the IFITM5 gene, encoding the interferon-induced transmembrane protein 5, or bone-restricted interferon-inducible transmembrane (IFITM)-like protein (BRIL). Its phenotype distinctly differs from OI types I to IV by absence of blue sclerae and dentinogenesis imperfecta, by the occurrence of ossification disorders such as hyperplastic callus and forearm interosseous membrane ossification. Little is known about the impact of the mutation on bone tissue/material level in untreated and bisphosphonate-treated patients. Therefore, investigations of transiliac bone biopsy samples from a cohort of OI type V children (n = 15, 8.7 ± 4 years old) untreated at baseline and a subset (n = 8) after pamidronate treatment (2.6 years in average) were performed. Quantitative backscattered electron imaging (qBEI) was used to determine bone mineralization density distribution (BMDD) as well as osteocyte lacunar density. The BMDD of type V OI bone was distinctly shifted toward a higher degree of mineralization. The most frequently occurring calcium concentration (CaPeak) in cortical (Ct) and cancellous (Cn) bone was markedly increased (+11.5%, +10.4%, respectively, p < 0.0001) compared to healthy reference values. Treatment with pamidronate resulted in only a slight enhancement of mineralization. The osteocyte lacunar density derived from sectioned bone area was elevated in OI type V Ct and Cn bone (+171%, p < 0.0001; +183.3%, p < 0.01; respectively) versus controls. The high osteocyte density was associated with an overall immature primary bone structure ("mesh-like") as visualized by polarized light microscopy. In summary, the bone material from OI type V patients is hypermineralized, similar to other forms of OI. The elevated osteocyte lacunar density in connection with lack of regular 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...

Influence of Contrast Media on Bone Mineral Density (BMD) Measurements from Routine Contrast-Enhanced MDCT Datasets using a Phantom-less BMD Measurement Tool.

Science.gov (United States)

Toelly, Andrea; Bardach, Constanze; Weber, Michael; Gong, Rui; Lai, Yanbo; Wang, Pei; Guo, Yulin; Kirschke, Jan; Baum, Thomas; Gruber, Michael

2017-06-01

Aim  To evaluate the differences in phantom-less bone mineral density (BMD) measurements in contrast-enhanced routine MDCT scans at different contrast phases, and to develop an algorithm for calculating a reliable BMD value. Materials and Methods  112 postmenopausal women from the age of 40 to 77 years (mean age: 57.31 years; SD 9.61) who underwent a clinically indicated MDCT scan, consisting of an unenhanced, an arterial, and a venous phase, were included. A retrospective analysis of the BMD values of the Th12 to L4 vertebrae in each phase was performed using a commercially available phantom-less measurement tool. Results  The mean BMD value in the unenhanced MDCT scans was 79.76 mg/cm³ (SD 31.20), in the arterial phase it was 85.09 mg/cm³ (SD 31.61), and in the venous phase it was 86.18 mg/cm³ (SD 31.30). A significant difference (p Influence of Contrast Media on Bone Mineral Density (BMD) Measurements from Routine Contrast-Enhanced MDCT Datasets using a Phantom-less BMD Measurement Tool. Fortschr Röntgenstr 2017; 189: 537 - 543. © Georg Thieme Verlag KG Stuttgart · New York.

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.

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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.

Biocompatibility of calcium phosphate bone cement with optimised mechanical properties: an in vivo study.

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Palmer, Iwan; Nelson, John; Schatton, Wolfgang; Dunne, Nicholas J; Buchanan, Fraser; Clarke, Susan A

2016-12-01

This work establishes the in vivo performance of modified calcium phosphate bone cements for vertebroplasty of spinal fractures using a lapine model. A non-modified calcium phosphate bone cement and collagen-calcium phosphate bone cements composites with enhanced mechanical properties, utilising either bovine collagen or collagen from a marine sponge, were compared to a commercial poly(methyl methacrylate) cement. Conical cement samples (8 mm height × 4 mm base diameter) were press-fit into distal femoral condyle defects in New Zealand White rabbits and assessed after 5 and 10 weeks. Bone apposition and tartrate-resistant acid phosphatase activity around cements were assessed. All implants were well tolerated, but bone apposition was higher on calcium phosphate bone cements than on poly(methyl methacrylate) cement. Incorporation of collagen showed no evidence of inflammatory or immune reactions. Presence of positive tartrate-resistant acid phosphatase staining within cracks formed in calcium phosphate bone cements suggested active osteoclasts were present within the implants and were actively remodelling within the cements. Bone growth was also observed within these cracks. These findings confirm the biological advantages of calcium phosphate bone cements over poly(methyl methacrylate) and, coupled with previous work on enhancement of mechanical properties through collagen incorporation, suggest collagen-calcium phosphate bone cement composite may offer an alternative to calcium phosphate bone cements in applications where low setting times and higher mechanical stability are important.

Effect of platelet-rich plasma combined with demineralised bone matrix on bone healing in rabbit ulnar defects.

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Galanis, Vasilios; Fiska, Alice; Kapetanakis, Stylianos; Kazakos, Konstantinos; Demetriou, Thespis

2017-09-01

This study evaluates the effect of autologous platelet-rich plasma (PRP) combined with xenogeneic demineralised bone matrix (DBM) on bone healing of critical-size ulnar defects (2-2.5 times the ulnar diameter) in New Zealand White rabbits. Critical-size defects were created unilaterally in the ulna of 36 rabbits, while keeping the contralateral limb intact. They were divided into three groups. In Group A, the defect was filled with autologous PRP and in Group B, with autologous PRP combined with DBM; in Group C, the defect remained empty. The rabbits were euthanised 12 weeks postoperatively. Radiological, biomechanical and histological assessments were carried out and statistical analysis of the results was performed. Group B had significantly higher radiological and histological scores than Groups A and C. Defects in Group B showed significant new bone formation, whereas there was minimal or no new bone formation in Groups A and C. Only specimens in Group B showed macroscopic bone union. Biomechanical evaluation of the treated and intact contralateral limbs in Group B showed significant differences. In this study, statistically significant enhancement of bone healing was found in critical-size defects treated with PRP and DBM, as shown by radiological findings, gross assessment, and biomechanical and histopathological results. Defects in the two other groups remained unbridged. Therefore, PRP was effective only when it was used in combination with a bone graft. Copyright: © Singapore Medical Association

Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

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Yibin Kang

2016-06-01

Full Text Available Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1 in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.

Ag-loaded MgSrFe-layered double hydroxide/chitosan composite scaffold with enhanced osteogenic and antibacterial property for bone engineering tissue.

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Cao, Dandan; Xu, Zhengliang; Chen, Yixuan; Ke, Qinfei; Zhang, Changqing; Guo, Yaping

2018-02-01

Bone tissue engineering scaffolds for the reconstruction of large bone defects should simultaneously promote osteogenic differentiation and avoid postoperative infection. Herein, we develop, for the first time, Ag-loaded MgSrFe-layered double hydroxide/chitosan (Ag-MgSrFe/CS) composite scaffold. This scaffold exhibits three-dimensional interconnected macroporous structure with a pore size of 100-300 μm. The layered double hydroxide nanoplates in the Ag-MgSrFe/CS show lateral sizes of 200-400 nm and thicknesses of ∼50 nm, and the Ag nanoparticles with particle sizes of ∼20 nm are uniformly dispersed on the scaffold surfaces. Human bone marrow-derived mesenchymal stem cells (hBMSCs) present good adhesion, spreading, and proliferation on the Ag-MgSrFe/CS composite scaffold, suggesting that the Ag and Sr elements in the composite scaffold have no toxicity to hBMSCs. When compared with MgFe/CS composite scaffold, the Ag-MgSrFe/CS composite scaffold has better osteogenic property. The released Sr 2+ ions from the composite scaffold enhance the alkaline phosphatase activity of hBMSCs, promote the extracellular matrix mineralization, and increase the expression levels of osteogenic-related RUNX2 and BMP-2. Moreover, the Ag-MgSrFe/CS composite scaffold possesses good antibacterial property because the Ag nanoparticles in the composite scaffold effectively prevent biofilm formation against S. aureus. Hence, the Ag-MgSrFe/CS composite scaffold with excellent osteoinductivity and antibacterial property has a great potential for bone tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 863-873, 2018. © 2017 Wiley Periodicals, Inc.

Bone Formation by Sheep Stem Cells in an Ectopic Mouse Model: Comparison of Adipose and Bone Marrow Derived Cells and Identification of Donor-Derived Bone by Antibody Staining

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Kristian Kjærgaard

2016-01-01

Full Text Available Background. Scaffolds for bone tissue engineering (BTE can be loaded with stem and progenitor cells (SPC from different sources to improve osteogenesis. SPC can be found in bone marrow, adipose tissue, and other tissues. Little is known about osteogenic potential of adipose-derived culture expanded, adherent cells (A-CEAC. This study compares in vivo osteogenic capacity between A-CEAC and bone marrow derived culture expanded, adherent cells (BM-CEAC. Method. A-CEAC and BM-CEAC were isolated from five female sheep and seeded on hydroxyapatite granules prior to subcutaneous implantation in immunodeficient mice. The doses of cells in the implants were 0.5 × 106, 1.0 × 106, or 1.5 × 106 A-CEAC and 0.5 × 106 BM-CEAC, respectively. After eight weeks, bone volume versus total tissue volume (BV/TV was quantified using histomorphometry. Origin of new bone was assessed using human vimentin (HVIM antibody staining. Results. BM-CEAC yielded significantly higher BV/TV than any A-CEAC group, and differences between A-CEAC groups were not statistically significant. HVIM antibody stain was successfully used to identify sheep cells in this model. Conclusion. A-CEAC and BM-CEAC were capable of forming bone, and BM-CEAC yielded significantly higher BV/TV than any A-CEAC group. In vitro treatment to enhance osteogenic capacity of A-CEAC is suggested for further research in ovine bone tissue engineering.

Conditioned medium from hypoxic bone marrow-derived mesenchymal stem cells enhances wound healing in mice.

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Lei Chen

Full Text Available Growing evidence indicates that bone marrow-derived mesenchymal stem cells (BM-MSCs enhance wound repair via paracrine. Because the extent of environmental oxygenation affects the innate characteristics of BM-MSCs, including their stemness and migration capacity, the current study set out to elucidate and compare the impact of normoxic and hypoxic cell-culture conditions on the expression and secretion of BM-MSC-derived paracrine molecules (e.g., cytokines, growth factors and chemokines that hypothetically contribute to cutaneous wound healing in vivo. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA analyses of normoxic and hypoxic BM-MSCs and their conditioned medium fractions showed that the stem cells expressed and secreted significantly higher amounts of basic fibroblast growth factor (bFGF,vascular endothelial growth factor A (VEGF-A interleukin 6 (IL-6 and interleukin 8 (IL-8 under hypoxic conditions. Moreover, hypoxic BM-MSC-derived conditioned medium (hypoCM vs. normoxic BM-MSC-derived conditioned medium (norCM or vehicle control medium significantly enhanced the proliferation of keratinocytes, fibroblasts and endothelial cells, the migration of keratinocytes, fibroblasts, endothelial cells and monocytes, and the formation of tubular structures by endothelial cells cultured on Matrigel matrix. Consistent with these in vitro results, skin wound contraction was significantly accelerated in Balb/c nude mice treated with topical hypoCM relative to norCM or the vehicle control. Notably increased in vivo cell proliferation, neovascularization as well as recruitment of inflammatory macrophages and evidently decreased collagen I, and collagen III were also found in the hypoCM-treated group. These findings suggest that BM-MSCs promote murine skin wound healing via hypoxia-enhanced paracrine.

MRI of degenerative bone marrow lesions in experimental osteoarthritis of canine knee joints

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Nolte-Ernsting, C.C.A. [Department of Diagnostic Radiology, University of Technology, Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany); Adam, G. [Department of Diagnostic Radiology, University of Technology, Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany); Buehne, M. [Department of Diagnostic Radiology, University of Technology, Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany); Prescher, A. [Department of Anatomy, University of Technology, Aachen (Germany); Guenther, R.W. [Department of Diagnostic Radiology, University of Technology, Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany)

1996-07-01

Objective. The objective of this study was to determine the value of MRI in the detection of degenerative bone marrow abnormalities in an animal osteoarthritis model. Design. In 10 dogs with experimentally induced unilateral osteoarthritis of the knee, MRI was performed using two-dimensional spin-echo (2D-SE) and three-dimensional gradient-echo (3D-GE) imaging. Contrast enhanced T1-weighted 2D-SE sequences were also obtained after injection of gadolinium-DTPA. The results were compared with the gross and histopathologic findings and with radiography. Results. Histopathologic specimens revealed 21 osteosclerotic lesions and 5 intraosseous cysts. On 2D-SE images, 24 of 26 lesions were detected, while 21 of 26 lesions were identified on 2D-GE sequences. Radiography, including conventional tomography, demonstrated 9 of 26 lesions. Regardless of the sequence weighting, all osteosclerotic lesions appeared hypointense on MRI. Signal loss in bone sclerosis resulted primarily from the reduction of intact fat marrow, the increased bone density being of secondary importance. Quantitative signal analysis allowed approximate estimation of the grade of sclerosis. On postcontrast images, sclerotic bone remained hypointense, although significant but non-specific enhancement relative to the normal fat marrow was observed. The extent of contrast enhancement did not correlate with the grade of osteosclerosis. All five cysts were readily diagnosed by MRI. Cysts displayed either central or marginal contrast enhancement within their cavities. Conclusions. MRI provides a sensitive method for the diagnosis of osteoarthritic bone abnormalities, allowing their differentiation from most non-degenerative subarticular lesions. (orig.). With 1 tab.

Titanium-Based Biomaterials for Preventing Stress Shielding between Implant Devices and Bone

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M. Niinomi

2011-01-01

Full Text Available β-type titanium alloys with low Young's modulus are required to inhibit bone atrophy and enhance bone remodeling for implants used to substitute failed hard tissue. At the same time, these titanium alloys are required to have high static and dynamic strength. On the other hand, metallic biomaterials with variable Young's modulus are required to satisfy the needs of both patients and surgeons, namely, low and high Young's moduli, respectively. In this paper, we have discussed effective methods to improve the static and dynamic strength while maintaining low Young's modulus for β-type titanium alloys used in biomedical applications. Then, the advantage of low Young's modulus of β-type titanium alloys in biomedical applications has been discussed from the perspective of inhibiting bone atrophy and enhancing bone remodeling. Further, we have discussed the development of β-type titanium alloys with a self-adjusting Young's modulus for use in removable implants.

Radiation-induced bone tumours in the guinea-pig

International Nuclear Information System (INIS)

Knowles, J.F.

1981-01-01

A remarkably high proportion of guinea-pigs given localized irradiations of 20 Gy x-rays developed bone tumours, 46% of all irradiated with 20 Gy and 86% of those that survived at least a year. Untreated controls were not included in the present experiment, but the authors refer to an earlier experiment using guinea-pigs from the same colony where no bone tumour occurred in 69 unirradiated animals followed for their natural life span i.e. up to 87 months. It is concluded that the author's strain of guinea-pig (details given in a previous paper, Int. J. Radiol. Biol., 40, 265) is particularly prone to radiation-induced bone tumours. Their possible value for investigating processes associated with radiation induction of bone tumours is further enhanced by their relatively large size and long life span (up to 7 years). (U.K.)

Osteoblast-targeted overexpression of TAZ increases bone mass in vivo.

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Jae-Yeon Yang

Full Text Available Osteoblasts are derived from mesenchymal progenitors. Differentiation to osteoblasts and adipocytes is reciprocally regulated. Transcriptional coactivator with a PDZ-binding motif (TAZ is a transcriptional coactivator that induces differentiation of mesenchymal cells into osteoblasts while blocking differentiation into adipocytes. To investigate the role of TAZ on bone metabolism in vivo, we generated transgenic mice that overexpress TAZ under the control of the procollagen type 1 promoter (Col1-TAZ. Whole body bone mineral density (BMD of 6- to 19-week-old Col-TAZ mice was 4% to 7% higher than that of their wild-type (WT littermates, whereas no difference was noticed in Col.1-TAZ female mice. Microcomputed tomography analyses of proximal tibiae at 16 weeks of age demonstrated a significant increase in trabecular bone volume (26.7% and trabecular number (26.6% with a reciprocal decrease in trabecular spacing (14.2% in Col1-TAZ mice compared with their WT littermates. In addition, dynamic histomorphometric analysis of the lumbar spine revealed increased mineral apposition rate (42.8% and the serum P1NP level was also significantly increased (53% in Col.1-TAZ mice. When primary calvaria cells were cultured in osteogenic medium, alkaline phosphatase (ALP activity was significantly increased and adipogenesis was significantly suppressed in Col1-TAZ mice compared with their WT littermates. Quantitative real-time polymerase chain reaction analyses showed that expression of collagen type 1, bone sialoprotein, osteocalcin, ALP, osterix, and Runx2 was significantly increased in calvaria cells from Col1-TAZ mice compared to their WT littermates. In vitro, TAZ enhanced Runx2-mediated transcriptional activity while suppressing the peroxisome proliferator-activated receptor gamma signaling pathway. TAZ also enhanced transcriptional activity from 3TP-Lux, which reflects transforming growth factor-beta (TGF-β-mediated signaling. In addition, TAZ enhanced TGF

Bone and fat connection in aging bone.

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Duque, Gustavo

2008-07-01

The fat and bone connection plays an important role in the pathophysiology of age-related bone loss. This review will focus on the age-induced mechanisms regulating the predominant differentiation of mesenchymal stem cells into adipocytes. Additionally, bone marrow fat will be considered as a diagnostic and therapeutic approach to osteoporosis. There are two types of bone and fat connection. The 'systemic connection', usually seen in obese patients, is hormonally regulated and associated with high bone mass and strength. The 'local connection' happens inside the bone marrow. Increasing amounts of bone marrow fat affect bone turnover through the inhibition of osteoblast function and survival and the promotion of osteoclast differentiation and activation. This interaction is regulated by paracrine secretion of fatty acids and adipokines. Additionally, bone marrow fat could be quantified using noninvasive methods and could be used as a therapeutic approach due to its capacity to transdifferentiate into bone without affecting other types of fat in the body. The bone and fat connection within the bone marrow constitutes a typical example of lipotoxicity. Additionally, bone marrow fat could be used as a new diagnostic and therapeutic approach for osteoporosis in older persons.

In Vivo Assessment of Bone Regeneration in Alginate/Bone ECM Hydrogels with Incorporated Skeletal Stem Cells and Single Growth Factors

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Gothard, David; Smith, Emma L.; Kanczler, Janos M.; Black, Cameron R.; Wells, Julia A.; Roberts, Carol A.; White, Lisa J.; Qutachi, Omar; Peto, Heather; Rashidi, Hassan; Rojo, Luis; Stevens, Molly M.; El Haj, Alicia J.; Rose, Felicity R. A. J.; Shakesheff, Kevin M.; Oreffo, Richard O. C.

2015-01-01

The current study has investigated the use of decellularised, demineralised bone extracellular matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation. Stro-1-enriched human bone marrow stromal cells were incorporated together with select growth factors including VEGF, TGF-β3, BMP-2, PTHrP and VitD3, to augment bone formation, and mixed with alginate for structural support. Growth factors were delivered through fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles. Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue assessed by micro-CT correlated with histologically assessed mineralised bone formation in all constructs. Exogenous growth factor addition did not enhance bone formation further compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone formation through degradation of intrinsic growth factors within the bone ECM component and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic growth factors led to altered bone formation. All constructs demonstrated extensive host tissue invasion and vascularisation aiding integration and implant longevity. The proposed hydrogel system functioned without the need for growth factor incorporation or an exogenous inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately, to form the tissue of choice through incorporation of select growth factors. PMID:26675008

Recombinant human bone morphogenetic protein-2 in the treatment of bone fractures

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Neil Ghodadra

2008-09-01

Full Text Available Neil Ghodadra, Kern SinghDepartment of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois, USAAbstract: Over one million fractures occur per year in the US and are associated with impaired healing increasing patient morbidity, stress, and economic costs. Despite improvements in surgical technique, internal fixation, and understanding of biologics, fracture healing is delayed or impaired in up to 4% of all fractures. Complications due to impaired fracture healing present therapeutic challenges to the orthopedic surgeon and often lead to chronic functional and psychological disability for the patient. As a result, it has become clinically desirable to augment mechanical fixation with biologic strategies in order to accelerate osteogenesis and promote successful arthrodesis. The discovery of bone morphogenic protein (BMP has been pivotal in understanding the biology of fracture healing and has been a source of intense clinical research as an adjunct to fracture treatment. Multiple in vitro and in vivo studies in animals have elucidated the complex biologic interactions between BMPs and cellular receptors and have convincingly demonstrated rhBMP-2 to be a safe, effective treatment option to enhance bone healing. Multiple clinical trials in trauma surgery have provided level 1 evidence for the use of rhBMP-2 as a safe and effective treatment of fractures. Human clinical trials have provided further insight into BMP-2 dosage, time course, carriers, and efficacy in fracture healing of tibial defects. These promising results have provided hope that a new biologic field of technology has emerged as a useful adjunct in the treatment of skeletal injuries and conditions.Keywords: bone morphogenic protein-2, bone fracture, bone healing

Contrast enhancement of bone imaging: use of a asymmetrical energy window of Tc99m MDP (133-145 keV)

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Elsaid, M.; Hommoud, S.; Shehab, F.; Elgazzar, A

2004-01-01

Objective: One of the major problems than can affect image quality of bone scan is poor target to non target ratio, due to scattered photons. The ideal Tc-99m energy spectrum is line shaped while the actual one is broader to include attenuated and scattered photons from the soft tissue. The air of this study is to evaluate the effect of asymmetrical 15% energy window of Tc-99m MDP setting at (133-154 keg) on the contrast of bone imaging in comparison to the commonly used 20% symmetrical energy window (126-154 keV). Methods: Sixty adult patients from those who are regularly referred to the clinic for bone scan were scanned twice, after intravenous injection of 925 Mbq (25mCi) of Tc-99m MDP, using 15% (133-154 keV) and 20% (126-154 keV) energy window respectively. Whole body scan was performed on 20 patients, 17 females and 3 males, with ages between 32-61 years. SPECT of the femurs were done on another 20 patients, 2 males and 18 females, with ages between 29-62 years. Planar images were acquired on 20 different patients 6 males and 14 females, with ages between 23-66 years. All technical parameters were kept the same for every group of patients. The acquisition time was recorded in case of the planar views and the count per projection was recorded for each SPECT study. Results: Our preliminary results shows that target to none target ratio were improved in all patients, using the 15% asymmetrical window, compared to the ratio obtained from imaging using the 200/o symmetrical window. The ratios wee increased by 12.4% in the planar images, 9.46% in SPECT images and 11.1% n the whole body images. The improvements in the planner images were on the expense of the acquisition time which increased by 31.1%. Conclusion: We conclude that the use of asymmetrical energy window of 15% (133-154 keV) will improve the image quality of bone scan by enhancing the contrast between bone and soft tissue. (authors)

Estradiol-loaded PLGA nanoparticles for improving low bone mineral density of cancellous bone caused by osteoporosis: Application of enhanced charged nanoparticles with iontophoresis.

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Takeuchi, Issei; Kobayashi, Shiori; Hida, Yukari; Makino, Kimiko

2017-07-01

Postmenopausal osteoporosis among older women, which occurs by an ovarian hormone deficiency, is one of the major public health problems. 17 β-estradiol (E2) is used to prevent and treat this disease as a drug of hormone replacement therapy. In oral administration, E2 is significantly affected by first-pass hepatic metabolism, and high dose administration must be needed to obtain drug efficacy. Therefore, alternative administration route is needed, and we have focused on the transdermal drug delivery system. In this study, we have prepared E2-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles for osteoporosis by using a combination of an antisolvent diffusion method with preferential solvation. The average particle diameter of the nanoparticles was 110.0±41.0nm and the surface charge number density was 82 times higher than that of conventional E2-loaded PLGA nanoparticles. Therapeutic evaluation of E2-loaded PLGA nanoparticles was carried out using ovariectomized female rats. Therapeutic efficacy was evaluated to measure bone mineral density of cancellous bone using an X-ray CT system. When the E2-loaded PLGA nanoparticles were administrated once a week, bone mineral density was significantly higher than that of the non-treated group at 60days after the start of treatment. Also, in the group administered this nanoparticle twice a week, the bone mineral density increased significantly at 45days after the start of treatment. From these results, it was revealed that E2-loaded PLGA nanoparticles with iontophoresis were useful to recover bone mineral density of cancellous bone, and it was also suggested that they extend the dosing interval of E2. Copyright © 2017 Elsevier B.V. All rights reserved.

MR imaging characteristics in primary lymphoma of bone with emphasis on non-aggressive appearance

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Heyning, Fenna H.; Kroon, Herman M.J.A.; Hogendoorn, Pancras C.W.; Taminiau, Antonie H.M.; Woude, Henk-Jan van der

2007-01-01

To assess the heterogeneity of magnetic resonance (MR) imaging characteristics in primary lymphoma of bone (PLB), in particular the non-aggressive appearance. In a retrospective study, MR imaging features were analyzed in 29 patients with histologically proven PLB. The following parameters were evaluated: tumor size, bone marrow and extension into soft tissues, signal characteristics of bone marrow and soft-tissue components, including enhancement, and involvement of cortical bone (complete disruption, focal destruction, permeative destruction and cortical thickening). PLB presented with extension into the soft tissue in 22 (76%) of 29 patients, was only subtle in three of these 22 patients, and was absent in seven patients. Signal intensity (SI) of the soft-tissue part was most frequently homogeneously isointense with muscle on T1-weighted images (90%) and high on T2-weighted images (91%). Enhancement was predominantly homogeneous and diffuse (82%). In 93% of patients cortical bone appeared abnormal: among those patients complete cortical disruption was seen in 28%, with extension into soft tissues in all but one patient; a permeative pattern of destruction was present in 52% of patients, 66% of these had an associated soft-tissue mass. Two patients with normal-appearing cortical bone had no extension into soft tissues. In two patients focal cortical destruction was noticed; in one patient cortical bone was homogeneously thickened, and in one patient PLB was selectively localized within the cortical bone. SI of the bone marrow tumor component was more frequently heterogeneous (in 54%), compared with the soft-tissue component, being high on T2-weighted images in 89%, intermediate in 7% and low in 4%. Similarly, enhancement was heterogeneous in 59%. The MR imaging appearance of PLB is variable. In 31% of PLB patients, the tumor was intra-osseous, with linear cortical signal abnormalities or even normal-appearing or thickened cortical bone without soft-tissue mass

Impact of Phosphorus-Based Food Additives on Bone and Mineral Metabolism.

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Gutiérrez, Orlando M; Luzuriaga-McPherson, Alexandra; Lin, Yiming; Gilbert, Linda C; Ha, Shin-Woo; Beck, George R

2015-11-01

Phosphorus-based food additives can substantially increase total phosphorus intake per day, but the effect of these additives on endocrine factors regulating bone and mineral metabolism is unclear. This study aimed to examine the effect of phosphorus additives on markers of bone and mineral metabolism. Design and Setting, and Participants: This was a feeding study of 10 healthy individuals fed a diet providing ∼1000 mg of phosphorus/d using foods known to be free of phosphorus additives for 1 week (low-additive diet), immediately followed by a diet containing identical food items; however, the foods contained phosphorus additives (additive-enhanced diet). Parallel studies were conducted in animals fed low- (0.2%) and high- (1.8%) phosphorus diets for 5 or 15 weeks. The changes in markers of mineral metabolism after each diet period were measured. Participants were 32 ± 8 years old, 30% male, and 70% black. The measured phosphorus content of the additive-enhanced diet was 606 ± 125 mg higher than the low-additive diet (P additive diet, consuming the additive-enhanced diet for 1 week significantly increased circulating fibroblast growth factor 23 (FGF23), osteopontin, and osteocalcin concentrations by 23, 10, and 11%, respectively, and decreased mean sclerostin concentrations (P foods can disturb bone and mineral metabolism in humans. The results of the animal studies suggest that this may compromise bone health.

Dynamic locking screw improves fixation strength in osteoporotic bone: an in vitro study on an artificial bone model.

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Pohlemann, Tim; Gueorguiev, Boyko; Agarwal, Yash; Wahl, Dieter; Sprecher, Christoph; Schwieger, Karsten; Lenz, Mark

2015-04-01

The novel dynamic locking screw (DLS) was developed to improve bone healing with locked-plate osteosynthesis by equalising construct stiffness at both cortices. Due to a theoretical damping effect, this modulated stiffness could be beneficial for fracture fixation in osteoporotic bone. Therefore, the mechanical behaviour of the DLS at the screw-bone interface was investigated in an artificial osteoporotic bone model and compared with conventional locking screws (LHS). Osteoporotic surrogate bones were plated with either a DLS or a LHS construct consisting of two screws and cyclically axially loaded (8,500 cycles, amplitude 420 N, increase 2 mN/cycle). Construct stiffness, relative movement, axial screw migration, proximal (P) and distal (D) screw pullout force and loosening at the bone interface were determined and statistically evaluated. DLS constructs exhibited a higher screw pullout force of P 85 N [standard deviation (SD) 21] and D 93 N (SD 12) compared with LHS (P 62 N, SD 28, p = 0.1; D 57 N, SD 25, p LHS (p = 0.01). DLS constructs showed significantly lower axial construct stiffness (403 N/mm, SD 21, p LHS (529 N/mm, SD 27; 0.8 mm, SD 0.04). Based on the model data, the DLS principle might also improve in vivo plate fixation in osteoporotic bone, providing enhanced residual holding strength and reducing screw cutout. The influence of pin-sleeve abutment still needs to be investigated.

Olives and Bone: A Green Osteoporosis Prevention Option

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Kok-Yong Chin

2016-07-01

Full Text Available Skeletal degeneration due to aging, also known as osteoporosis, is a major health problem worldwide. Certain dietary components confer protection to our skeletal system against osteoporosis. Consumption of olives, olive oil and olive polyphenols has been shown to improve bone health. This review aims to summarize the current evidence from cellular, animal and human studies on the skeletal protective effects of olives, olive oil and olive polyphenols. Animal studies showed that supplementation of olives, olive oil or olive polyphenols could improve skeletal health assessed via bone mineral density, bone biomechanical strength and bone turnover markers in ovariectomized rats, especially those with inflammation. The beneficial effects of olive oil and olive polyphenols could be attributed to their ability to reduce oxidative stress and inflammation. However, variations in the bone protective, antioxidant and anti-inflammatory effects between studies were noted. Cellular studies demonstrated that olive polyphenols enhanced proliferation of pre-osteoblasts, differentiation of osteoblasts and decreased the formation of osteoclast-like cells. However, the exact molecular pathways for its bone health promoting effects are yet to be clearly elucidated. Human studies revealed that daily consumption of olive oil could prevent the decline in bone mineral density and improve bone turnover markers. As a conclusion, olives, olive oil and its polyphenols are potential dietary interventions to prevent osteoporosis among the elderly.

Cordyceps sinensis health supplement enhances recovery from taxol-induced leukopenia.

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Liu, Wei-Chung; Chuang, Wei-Ling; Tsai, Min-Lung; Hong, Ji-Hong; McBride, William H; Chiang, Chi-Shiun

2008-04-01

This study aimed to evaluate the ability of the health food supplement Cordyceps sinensis (CS) to ameliorate suppressive effects of chemotherapy on bone marrow function as a model for cancer treatment. Mice were treated with Taxol (17 mg/kg body wt) one day before oral administration of a hot-water extract of CS (50 mg/kg daily) that was given daily for 3 weeks. White blood cell counts in peripheral blood of mice receiving Taxol were at 50% of normal levels on day 28 but had recovered completely in mice treated with CS. In vitro assays showed that CS enhanced the colony-forming ability of both granulocyte macrophage colony forming unit (GM-CFU) and osteogenic cells from bone marrow preparations and promoted the differentiation of bone marrow mesenchymal stromal cells into adipocytes, alkaline phosphatase-positive osteoblasts, and bone tissue. This result could be attributed to enhanced expression of Cbfa1 (core binding factor a) and BMP-2 (bone morphogenetic protein) with concurrent suppression of ODF (osteoclast differentiation factor/RANK [receptor activator of NF-kappaB]) ligand. In summary, CS enhances recovery of mice from leukopenia caused by Taxol treatment. It appears to do so by protecting both hematopoietic progenitor cells directly and the bone marrow stem cell niche through its effects on osteoblast differentiation.

Effect of Adipose Tissue-Derived Osteogenic and Endothelial Cells on Bone Allograft Osteogenesis and Vascularization in Critical-Sized Calvarial Defects

Science.gov (United States)

2012-05-10

1% peni - cillin/streptomycin, and 50 ng/mL recombinant rat VEGF-C (Promocell, Heidelberg, Germany). The media were changed every other day for 8...various animal models that have demonstrated an enhanced osteogenic effect after treating bone allografts with adipose tissue or bone marrow-derived... enhanced 1560 CORNEJO ET AL. performance of bone allografts using osteogenic differentiated adipose derived mesenchymal stem cells. Biomaterials 32, 8880

Evolutionary patterns of bone histology and bone compactness in xenarthran mammal long bones.

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Straehl, Fiona R; Scheyer, Torsten M; Forasiepi, Analía M; MacPhee, Ross D; Sánchez-Villagra, Marcelo R

2013-01-01

Bone microstructure reflects physiological characteristics and has been shown to contain phylogenetic and ecological signals. Although mammalian long bone histology is receiving increasing attention, systematic examination of the main clades has not yet been performed. Here we describe the long bone microstructure of Xenarthra based on thin sections representing twenty-two species. Additionally, patterns in bone compactness of humeri and femora are investigated. The primary bone tissue of xenarthran long bones is composed of a mixture of woven, parallel-fibered and lamellar bone. The vascular canals have a longitudinal, reticular or radial orientation and are mostly arranged in an irregular manner. Concentric rows of vascular canals and laminar organization of the tissue are only found in anteater bones. The long bones of adult specimens are marked by dense Haversian bone, a feature that has been noted for most groups of mammals. In the long bones of armadillos, secondary osteons have an oblique orientation within the three-dimensional bone tissue, thus resulting in their irregular shape when the bones are sectioned transversely. Secondary remodeling is generally more extensive in large taxa than in small taxa, and this could be caused by increased loading. Lines of arrested growth are assumed to be present in all specimens, but they are restricted to the outermost layer in bones of armadillos and are often masked by secondary remodeling in large taxa. Parameters of bone compactness show a pattern in the femur that separates Cingulata and Pilosa (Folivora and Vermilingua), with cingulates having a lower compactness than pilosans. In addition, cingulates show an allometric relationship between humeral and femoral bone compactness.

Evolutionary patterns of bone histology and bone compactness in xenarthran mammal long bones.

Directory of Open Access Journals (Sweden)

Fiona R Straehl

Full Text Available Bone microstructure reflects physiological characteristics and has been shown to contain phylogenetic and ecological signals. Although mammalian long bone histology is receiving increasing attention, systematic examination of the main clades has not yet been performed. Here we describe the long bone microstructure of Xenarthra based on thin sections representing twenty-two species. Additionally, patterns in bone compactness of humeri and femora are investigated. The primary bone tissue of xenarthran long bones is composed of a mixture of woven, parallel-fibered and lamellar bone. The vascular canals have a longitudinal, reticular or radial orientation and are mostly arranged in an irregular manner. Concentric rows of vascular canals and laminar organization of the tissue are only found in anteater bones. The long bones of adult specimens are marked by dense Haversian bone, a feature that has been noted for most groups of mammals. In the long bones of armadillos, secondary osteons have an oblique orientation within the three-dimensional bone tissue, thus resulting in their irregular shape when the bones are sectioned transversely. Secondary remodeling is generally more extensive in large taxa than in small taxa, and this could be caused by increased loading. Lines of arrested growth are assumed to be present in all specimens, but they are restricted to the outermost layer in bones of armadillos and are often masked by secondary remodeling in large taxa. Parameters of bone compactness show a pattern in the femur that separates Cingulata and Pilosa (Folivora and Vermilingua, with cingulates having a lower compactness than pilosans. In addition, cingulates show an allometric relationship between humeral and femoral bone compactness.

Selenium in bone health: roles in antioxidant protection and cell proliferation.

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Zeng, Huawei; Cao, Jay J; Combs, Gerald F

2013-01-10

Selenium (Se) is an essential trace element for humans and animals, and several findings suggest that dietary Se intake may be necessary for bone health. Such findings may relate to roles of Se in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Elucidation of the mechanisms by which Se supports these cellular processes can lead to a better understanding of the role of this nutrient in normal bone metabolism. This article reviews the current knowledge concerning the molecular functions of Se relevant to bone health.

Detection of bone marrow involvement in patients with cancer

International Nuclear Information System (INIS)

Federico, M.; Silingardi, V.; Wright, R.M.

1989-01-01

Current methods for the study of bone marrow to evaluate possible primary or metastatic cancers are reviewed. Bone marrow biopsy, radionuclide scan, computed tomography and magnetic resonance imaging (MRI) are analyzed with regard to their clinical usefulness at the time of diagnosis and during the course of the disease. Bone marrow biopsy is still the examination of choice not only in hematologic malignancies but also for tumors that metastasize into the marrow. Radionuclide scans are indicated for screening for skeletal metastases, except for those from thyroid carcinoma and multiple myeloma. Computed tomography is useful for cortical bone evaluation. MRI shows a high sensitivity in finding occult sites of disease in the marrow but its use has been restricted by high cost and limited availability. However, the future of MRI in bone marrow evaluation seems assured. MRI is alredy the method of choice for diagnosis of multiple myeloma, when radiography is negative, and for quantitative evaluation of lymphoma when a crucial therapeutic decision (i.e. bone marrow transplantation) must be made. Finally, methods are being developed that will enhance the sensitivity and specificity of MRI studies of bone marrow

Use of Gamma Correction Pinhole Bone Scans in Trauma

International Nuclear Information System (INIS)

Bahk, Youg Whee; Chung, Youg An; Park, Jung Mee

2012-01-01

99 mTc hydroxydiphosphonate (HDP) bone scanning is a classic metabolic nuclear imaging method and the most frequently performed examination. Clinically, it has long been cherished as an indispensable diagnostic screening tool and for monitoring of patients with bone, joint, and soft tissue diseases. The HDP bone scan, the pinhole scan in particular, is known for its ability to detect increased, decreased, or defective tracer uptake along with magnified anatomy. Unfortunately, however, the findings of such uptake changes are not specific in many traumatic bone disorders, especially when lesions are minute and complex. This study discusses the recently introduced gamma correction pinhole bone scan (GCPBS), emphasizing its usefulness in the diagnosis of traumatic bone diseases including occult fractures; and fish vertebra. Indeed, GCPBS can remarkably enhance the diagnostic feasibility of HDP pinhole bone scans by refining the topography, pathologic anatomy, and altered chemical profile of the traumatic diseases in question. The fine and precise depiction of anatomic and metabolic changes in these diseases has been shown to be unique to GCPBS, and they are not appreciated on conventional radiographs, multiple detector CT, or ultrasonographs. It is true that MR imaging can portray proton change, but understandably, it is a manifestation that is common to any bone disease

Deproteinized bovine bone functionalized with the slow delivery of BMP-2 for the repair of critical-sized bone defects in sheep.

Science.gov (United States)

Liu, Tie; Wu, Gang; Wismeijer, Daniel; Gu, Zhiyuan; Liu, Yuelian

2013-09-01

As an alternative to an autologous bone graft, deproteinized bovine bone (DBB) is widely used in the clinical dentistry. Although DBB provides an osteoconductive scaffold, it is not capable of enhancing bone regeneration because it is not osteoinductive. In order to render DBB osteoinductive, bone morphogenetic protein 2 (BMP-2) has previously been incorporated into a three dimensional reservoir (a biomimetic calcium phosphate coating) on DBB, which effectively promoted the osteogenic response by the slow delivery of BMP-2. The aim of this study was to investigate the therapeutic effectiveness of such coating on the DBB granules in repairing a large cylindrical bone defect (8 mm diameter, 13 mm depth) in sheep. Eight groups were randomly assigned to the bone defects: (i) no graft material; (ii) autologous bone; (iii) DBB only; (iv) DBB mixed with autologous bone; (v) DBB bearing adsorbed BMP-2; (vi) DBB bearing a coating but no BMP-2; (vii) DBB bearing a coating with adsorbed BMP-2; and (viii) DBB bearing a coating-incorporated depot of BMP-2. 4 and 8 weeks after implantation, samples were withdrawn for a histological and a histomorphometric analysis. Histological results confirmed the excellent biocompatibility and osteoconductivity of all the grafts tested. At 4 weeks, DBB mixed with autologous bone or functionalized with coating-incorporated BMP-2 showed more newly-formed bone than the other groups with DBB. At 8 weeks, the volume of newly-formed bone around DBB that bore a coating-incorporated depot of BMP-2 was greatest among the groups with DBB, and was comparable to the autologous bone group. The use of autologous bone and BMP-2 resulted in more bone marrow formation. Multinucleated giant cells were observed in the resorption process around DBB, whereas histomorphometric analysis revealed no significant degradation of DBB. In conclusion, it was shown that incorporating BMP-2 into the calcium phosphate coating of DBB induced strong bone formation around DBB

Immunological Enhancement of Interferon Alpha Treatment to Allogeneic Bone Marrow Transplantation in Irradiated Rats

International Nuclear Information System (INIS)

Hussein, E.M.; Abd El-Naby, Y.H.

2011-01-01

The Influence of the biological response modifiers: interferon alpha (IFN-α) and bone marrow transplantation (BMT) on stimulation of blood cell recovery and boosting the immunological response were investigated in this work. Male rats received BMT 3 h post total body ?-irradiation of 5 Gy and were injected with 10 units of IFN-α weekly for 5 weeks. Irradiation induced a significant decrease in blood parameters, reduced glutathione (GSH) as well as bone marrow lymphocyte count and viability. Immunological data revealed that tumour necrosis factor alpha (TNF-α) and interleukin-2 (IL-2) recorded a significant depression while lipid peroxidation (MDA) was conversely elevated. White blood cells (WBC), erythrocytes (RBC), haemoglobin (Hb), haematocrit (Hct), lymphocytes and GSH in irradiated animals receiving BMT and IFN-α, were significantly elevated, while MDA was significantly depressed as compared to the irradiated group. Bone marrow lymphocytic count and viability percentage were significantly increased while IL-2 and TNF-α were normalized. The curative action of IFN-α enforcing significant innate response could trigger and augment adaptive immune response by bone marrow transplantation. Such therapies boosting both components of immunity would be considered a potential strategy for irradiation treatment

Bone graft extenders and substitutes in the thoracolumbar spine.

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Arner, Justin W; Daffner, Scott D

2012-05-01

Autologous iliac crest bone graft remains the gold standard for lumbar fusion. The potential for complications has led to the development of alternative bone graft materials and enhancers, including autologous growth factors, demineralized bone matrix products, osteoinductive agents, and ceramic products. The current literature centers mainly on preclinical studies, which, further complicating the situation, evaluate these products in different clinical scenarios or surgical techniques. Autologous growth factors and demineralized bone matrix products have had promising results in preclinical studies, but few strong clinical studies have been conducted. Ceramic extenders were evaluated with other substances and had good but often inconsistent results. Bone morphogenetic proteins have been extensively studied and may have benefits as osteoinductive agents. Category comparisons are difficult to make, and there are differences even between products within the same category. The surgeon must be knowledgeable about products and their advantages, disadvantages, indications, contraindications, and possible applications so that they can make the best choice for each patient.

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

International Nuclear Information System (INIS)

Brady, Robert T.; O'Brien, Fergal J.; Hoey, David A.

2015-01-01

Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

Energy Technology Data Exchange (ETDEWEB)

Brady, Robert T. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); O' Brien, Fergal J. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Hoey, David A., E-mail: david.hoey@ul.ie [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); The Centre for Applied Biomedical Engineering Research, University of Limerick (Ireland); Materials & Surface Science Institute, University of Limerick (Ireland)

2015-03-27

Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

Angiographic findings of demineralised bone matrix grafts in femoral fracture repair in canines*

International Nuclear Information System (INIS)

Kumar, R.V.S.; Ramakrishna, O.

2000-01-01

Demineralised bone matrix implants and autogenous cancellous bone grafts were evaluated in femoral fracture repair with bone loss in canines, and compared to untreated animals. Angiograms were taken at 3,6,9 and 12 weeks post- operatively using conrary-420 as contrast medium. Early angiograms showed leakage of contrast medium into soft tissue. Grafted groups showed slight hypervascularity and enhanced capillary network. At 12 Weeks the same groups observed nearly normal persistent vascular supply. Early establishment of cortices continuity and draining of contrast medium via extraosseous veins was observed in demineralized bone matrix implanted groups

Bone tumor

Science.gov (United States)

Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

3D-Printed Bioactive Ca3SiO5 Bone Cement Scaffolds with Nano Surface Structure for Bone Regeneration.

Science.gov (United States)

Yang, Chen; Wang, Xiaoya; Ma, Bing; Zhu, Haibo; Huan, Zhiguang; Ma, Nan; Wu, Chengtie; Chang, Jiang

2017-02-22

Silicate bioactive materials have been widely studied for bone regeneration because of their eminent physicochemical properties and outstanding osteogenic bioactivity, and different methods have been developed to prepare porous silicate bioactive ceramics scaffolds for bone-tissue engineering applications. Among all of these methods, the 3D-printing technique is obviously the most efficient way to control the porous structure. However, 3D-printed bioceramic porous scaffolds need high-temperature sintering, which will cause volume shrinkage and reduce the controllability of the pore structure accuracy. Unlike silicate bioceramic, bioactive silicate cements such as tricalcium silicate (Ca 3 SiO 5 and C 3 S) can be self-set in water to obtain high mechanical strength under mild conditions. Another advantage of using C 3 S to prepare 3D scaffolds is the possibility of simultaneous drug loading. Herein, we, for the first time, demonstrated successful preparation of uniform 3D-printed C 3 S bone cement scaffolds with controllable 3D structure at room temperature. The scaffolds were loaded with two model drugs and showed a loading location controllable drug-release profile. In addition, we developed a surface modification process to create controllable nanotopography on the surface of pore wall of the scaffolds, which showed activity to enhance rat bone-marrow stem cells (rBMSCs) attachment, spreading, and ALP activities. The in vivo experiments revealed that the 3D-printed C 3 S bone cement scaffolds with nanoneedle-structured surfaces significantly improved bone regeneration, as compared to pure C 3 S bone cement scaffolds, suggesting that 3D-printed C 3 S bone cement scaffolds with controllable nanotopography surface are bioactive implantable biomaterials for bone repair.

Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury.

Science.gov (United States)

Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

2014-08-15

Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.

Osteogenesis and angiogenesis: The potential for engineering bone

Directory of Open Access Journals (Sweden)

JM Kanczler

2008-05-01

Full Text Available The repair of large bone defects remains a major clinical orthopaedic challenge. Bone is a highly vascularised tissue reliant on the close spatial and temporal connection between blood vessels and bone cells to maintain skeletal integrity. Angiogenesis thus plays a pivotal role in skeletal development and bone fracture repair. Current procedures to repair bone defects and to provide structural and mechanical support include the use of grafts (autologous, allogeneic or implants (polymeric or metallic. These approaches face significant limitations due to insufficient supply, potential disease transmission, rejection, cost and the inability to integrate with the surrounding host tissue.The engineering of bone tissue offers new therapeutic strategies to aid musculoskeletal healing. Various scaffold constructs have been employed in the development of tissue-engineered bone; however, an active blood vessel network is an essential pre-requisite for these to survive and integrate with existing host tissue. Combination therapies of stem cells and polymeric growth factor release scaffolds tailored to promote angiogenesis and osteogenesis are under evaluation and development actively to stimulate bone regeneration. An understanding of the cellular and molecular interactions of blood vessels and bone cells will enhance and aid the successful development of future vascularised bone scaffold constructs, enabling survival and integration of bioengineered bone with the host tissue. The role of angiogenic and osteogenic factors in the adaptive response and interaction of osteoblasts and endothelial cells during the multi step process of bone development and repair will be highlighted in this review, with consideration of how some of these key mechanisms can be combined with new developments in tissue engineering to enable repair and growth of skeletal fractures. Elucidation of the processes of angiogenesis, osteogenesis and tissue engineering strategies offer

Super bone scans on bone scintigraphy in patients with metastatic bone tumor

International Nuclear Information System (INIS)

Morita, Koichi; Fukunaga, Masao; Otsuka, Nobuaki

1988-01-01

Eight patients with malignant tumor (3 with gastric cancer, 4 with prostatic cancer, 1 with transitional cell carcinoma), which showed diffusely increased uptake of 99m Tc labelled phosphorous compound in axial skeleton (''Super Bone Scan'') on bone scintigraphy were clinically studied. No relationship with its histological type of the tumor was recognized. All cases revealed extremely high serum ALP concentration, which might reflect increased osteoblastic activity. Furthermore, on bone roentgenograms all cases showed predominantly osteosclerotic change in the metastatic bones, while some did locally osteolytic change. In three cases with gastric cancer, although they had diffuse skeletal metastases, two had no evidence of liver metastases. Thus, it seemed that clinical study of patients with ''Super Bone Scan'' was interesting to evaluate the mechanism of accumulation of 99m Tc labelled phosphorous compound to bone and bone metabolism, and the pathophysiology in the pathway of bone metastases. (author)

Three-dimensional poly (ε-caprolactone)/hydroxyapatite/collagen scaffolds incorporating bone marrow mesenchymal stem cells for the repair of bone defects

International Nuclear Information System (INIS)

Qi, Xin; Huang, Yinjun; Zhang, Jieyuan; Cao, Jiaqing; Jin, Xiangyun; Huang, Jinghuan; Li, Xiaolin; Wang, Ting; Han, Dan

2016-01-01

We previously demonstrated that three-dimensional (3D) hydroxyapatite (HAP)-collagen (COL)-coated poly(ε-caprolactone) (PCL) scaffolds (HAP-COL-PCL) possess appropriate nano-structures, surface roughness, and nutrients, providing a favorable environment for osteogenesis. However, the effect of using 3D HAP-COL-PCL scaffolds incorporating BMSCs for the repair of bone defects in rats has been not evaluated. 3D PCL scaffolds coated with HAP, collagen or HAP/COL and incorporating BMSCs were implanted into calvarial defects. At 12 weeks after surgery, the rats were sacrificed and crania were harvested to assess the bone defect repair using microcomputed tomography (micro-CT), histology, immunohistochemistry and sequential fluorescent labeling analysis. 3D micro-CT reconstructed images and quantitative analysis showed that HAP-COL-PCL groups possessed better bone-forming capacity than HAP-PCL groups or COL-PCL groups. Fluorescent labeling analysis revealed the percentage of tetracycline labeling, alizarin red labeling, and calcein labeling in HAP-COL-PCL groups were all greater than in the other two groups (P  <  0.05), and the result was confirmed by immunohistochemical staining and histological analysis of bone regeneration. This study demonstrates that 3D HAP-COL-PCL scaffolds incorporating BMSCs markedly enhance bone regeneration of bone defects in rats. (paper)

Aging and bone. X-ray bone densitometry

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Morita, Rikushi (Shiga Univ. of Medical Sciences, Otsu (Japan))

1994-01-01

Bone mass at all ages of the individuals is the integration of genetic factors, nutrition, physical exercise, hormonal environments, and other factors influencing the bone. It is also a measurable risk factor for osteoporosis which may subsequently cause bone fractures. Thus measuring bone mass is required to predict the probability of developing bone fractures subsequent to osteoporosis, and to diagnose osteoporosis, and to manage the osteoporosis patient. This paper discusses bone mineral measurements according to their characteristics and clinical application. Methodology for measuring bone mass has rapidly progressed during the past 15 years, which covers photodensitometry, photon absorptiometry (single energy X-ray absorptiometry and dual energy X-ray absorptiometry), quantitative CT, and ultrasound. These techniques have allowed noninvasive measurement of bone mineral density in any site of the skeleton with high accuracy and precision, although a single use of the technique cannot satisfy the complete clinical requirements. Thus the most appropriate method for measuring bone mineral density is important to monitor bone mass change and according to the specific site. (N.K.).

Aging and bone. X-ray bone densitometry

International Nuclear Information System (INIS)

Morita, Rikushi

1994-01-01

Bone mass at all ages of the individuals is the integration of genetic factors, nutrition, physical exercise, hormonal environments, and other factors influencing the bone. It is also a measurable risk factor for osteoporosis which may subsequently cause bone fractures. Thus measuring bone mass is required to predict the probability of developing bone fractures subsequent to osteoporosis, and to diagnose osteoporosis, and to manage the osteoporosis patient. This paper discusses bone mineral measurements according to their characteristics and clinical application. Methodology for measuring bone mass has rapidly progressed during the past 15 years, which covers photodensitometry, photon absorptiometry (single energy X-ray absorptiometry and dual energy X-ray absorptiometry), quantitative CT, and ultrasound. These techniques have allowed noninvasive measurement of bone mineral density in any site of the skeleton with high accuracy and precision, although a single use of the technique cannot satisfy the complete clinical requirements. Thus the most appropriate method for measuring bone mineral density is important to monitor bone mass change and according to the specific site. (N.K.)

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging of bone marrow in healthy individuals

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Hillengass, Jens (Dept. of Radiology, German Cancer Research Center, Heidelberg (Germany); Dept. of Hematology, Oncology and Rheumatology, Univ. of Heidelberg (Germany)), e-mail: j.hillengass@dkfz.de; Stieltjes, Bram (Dept. of Radiology, German Cancer Research Center, Heidelberg (Germany)); Baeuerle, Tobias (Dept. of Medical Physics in Radiology, German Cancer Research Center, Heidelberg (Germany)) (and others)

2011-04-15

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) displays microcirculation and permeability by application of contrast-media and diffusion-weighted imaging (DWI) is a tool for quantification of cellularity in the investigated area. Recently published examples cover breast cancer, CNS tumors, head and neck cancer, gastrointestinal cancer, prostate cancer as well as hematologic malignancies. Purpose: To investigated the influence of age, sex, and localization of the investigated region on findings of DCE-MRI and DWI. Material and Methods: DCE-MRI-parameters amplitude A and exchange rate constant kep as well as the DWI-parameter ADC of the bone marrow of the lumbar vertebral column of 30 healthy individuals covering the typical range of age of tumor patients were evaluated. ADC was calculated using b=0 and a maximal b value of either 400 or 750 s/mm2. Results: Amplitude A of DCE-MRI decreased with age (P = 0.01) and amplitude A, exchange rate constant kep as well as ADC based on b = 400 s/mm2 and b = 750 s/mm2, respectively, decreased significantly from the first to the fifth lumbar vertebra with P = 0.02, P = 0.05, P = 0.003, and P = 0.002, respectively. Conclusion: Quantitative parameters of functional imaging techniques in bone marrow are influenced by the age of the examined individual and the anatomical location of the investigated region

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging of bone marrow in healthy individuals

International Nuclear Information System (INIS)

Hillengass, Jens; Stieltjes, Bram; Baeuerle, Tobias

2011-01-01

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) displays microcirculation and permeability by application of contrast-media and diffusion-weighted imaging (DWI) is a tool for quantification of cellularity in the investigated area. Recently published examples cover breast cancer, CNS tumors, head and neck cancer, gastrointestinal cancer, prostate cancer as well as hematologic malignancies. Purpose: To investigated the influence of age, sex, and localization of the investigated region on findings of DCE-MRI and DWI. Material and Methods: DCE-MRI-parameters amplitude A and exchange rate constant kep as well as the DWI-parameter ADC of the bone marrow of the lumbar vertebral column of 30 healthy individuals covering the typical range of age of tumor patients were evaluated. ADC was calculated using b=0 and a maximal b value of either 400 or 750 s/mm2. Results: Amplitude A of DCE-MRI decreased with age (P = 0.01) and amplitude A, exchange rate constant kep as well as ADC based on b = 400 s/mm 2 and b = 750 s/mm 2 , respectively, decreased significantly from the first to the fifth lumbar vertebra with P = 0.02, P = 0.05, P = 0.003, and P = 0.002, respectively. Conclusion: Quantitative parameters of functional imaging techniques in bone marrow are influenced by the age of the examined individual and the anatomical location of the investigated region

Functional regeneration of ligament-bone interface using a triphasic silk-based graft.

Science.gov (United States)

Li, Hongguo; Fan, Jiabing; Sun, Liguo; Liu, Xincheng; Cheng, Pengzhen; Fan, Hongbin

2016-11-01

The biodegradable silk-based scaffold with unique mechanical property and biocompatibility represents a favorable ligamentous graft for tissue-engineering anterior cruciate ligament (ACL) reconstruction. However, the low efficiency of ligament-bone interface restoration barriers the isotropic silk graft to common ACL therapeutics. To enhance the regeneration of the silk-mediated interface, we developed a specialized stratification approach implementing a sequential modification on isotropic silk to constitute a triphasic silk-based graft in which three regions respectively referring to ligament, cartilage and bone layers of interface were divided, followed by respective biomaterial coating. Furthermore, three types of cells including bone marrow mesenchymal stem cells (BMSCs), chondrocytes and osteoblasts were respectively seeded on the ligament, cartilage and bone region of the triphasic silk graft, and the cell/scaffold complex was rolled up as a multilayered graft mimicking the stratified structure of native ligament-bone interface. In vitro, the trilineage cells loaded on the triphasic silk scaffold revealed a high proliferative capacity as well as enhanced differentiation ability into their corresponding cell lineage. 24 weeks postoperatively after the construct was implanted to repair the ACL defect in rabbit model, the silk-based ligamentous graft exhibited the enhancement of osseointegration detected by a robust pullout force and formation of three-layered structure along with conspicuously corresponding matrix deposition via micro-CT and histological analysis. These findings potentially broaden the application of silk-based ligamentous graft for ACL reconstruction and further large animal study. Copyright © 2016 Elsevier Ltd. All rights reserved.

Extraskeletal and intraskeletal new bone formation induced by demineralized bone matrix combined with bone marrow cells

International Nuclear Information System (INIS)

Lindholm, T.S.; Nilsson, O.S.; Lindholm, T.C.

1982-01-01

Dilutions of fresh autogenous bone marrow cells in combination with allogeneic demineralized cortical bone matrix were tested extraskeletally in rats using roentgenographic, histologic, and 45 Ca techniques. Suspensions of bone marrow cells (especially diluted 1:2 with culture media) combined with demineralized cortical bone seemed to induce significantly more new bone than did demineralized bone, bone marrow, or composite grafts with whole bone marrow, respectively. In a short-term spinal fusion experiment, demineralized cortical bone combined with fresh bone marrow produced new bone and bridged the interspace between the spinous processes faster than other transplantation procedures. The induction of undifferentiated host cells by demineralized bone matrix is further complemented by addition of autogenous, especially slightly diluted, bone marrow cells

Enhanced MRI in patients with facial palsy; Study of time-related enhancement

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Yanagida, Masahiro; Kato, Tsutomu; Ushiro, Koichi; Kitajiri, Masanori; Yamashita, Toshio; Kumazawa, Tadami; Tanaka, Yoshimasa (Kansai Medical School, Moriguchi, Osaka (Japan))

1991-03-01

We performed Gd-DTPA-enhanced magnetic resonance imaging (MRI) examinations at several stages in 40 patients with peripheral facial nerve palsy (Bell's palsy and Ramsay-Hunt syndrome). In 38 of the 40 patients, one and more enhanced region could be seen in certain portion of the facial nerve in the temporal bone on the affected side, whereas no enhanced regions were seen on the intact side. Correlations between the timing of the MRI examination and the location of the enhanced regions were analysed. In all 6 patients examined by MRI within 5 days after the onset of facial nerve palsy, enhanced regions were present in the meatal portion. In 3 of the 8 patients (38%) examined by MRI 6 to 10 days after the onset of facial palsy, enhanced areas were seen in both the meatal and labyrinthine portions. In 8 of the 9 patients (89%) tested 11 to 20 days after the onset of palsy, the vertical portion was enhanced. In the 12 patients examined by MRI 21 to 40 days after the onset of facial nerve palsy, the meatal portion was not enhanced while the labyrinthine portion, the horizontal portion and the vertical portion were enhanced in 5 (42%), 8 (67%) and 11 (92%), respectively. Enhancement in the vertical portion was observed in all 5 patients examined more than 41 days after the onset of facial palsy. These results suggest that the central portion of the facial nerve in the temporal bone tends to be enhanced in the early stage of facial nerve palsy, while the peripheral portion is enhanced in the late stage. These changes of Gd-DTPA enhanced regions in the facial nerve may suggest dromic degeneration of the facial nerve in peripheral facial nerve palsy. (author).

Bone Marrow Aspirate Concentrate versus Platelet Rich Plasma to Enhance Osseous Integration Potential for Osteochondral Allografts.

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Stoker, Aaron M; Baumann, Charles A; Stannard, James P; Cook, James L

2018-04-01

Fresh osteochondral allograft (OCA) transplantation is an attractive treatment option for symptomatic articular cartilage lesions in young, healthy patients. Since a lack of OCA bone integration can be a cause of treatment failure, methods for speeding and enhancing OCA bone integration to mitigate this potential complication are highly desirable. This study sought to determine and compare the potential of bone marrow aspirate concentrate (BMC) and leukoreduced platelet rich plasma (PRP) to repopulate the osseous portion of an OCA with cells and deliver osteogenic proteins. It was hypothesized that BMC would have significantly higher colony forming units (CFUs)/mL and seed the osseous portion of OCA with more cells than PRP. Finally, we hypothesized that the media of BMC and PRP treated OCAs would have significantly higher concentrations of osteogenic proteins compared with negative control OCAs. Cylindrical OCAs ( n  = 36) created from tissue stored for 21 days were treated with BMC ( n  = 12) or PRP ( n  = 12) obtained for 6 dogs, or left untreated as a negative control ( n  = 12). After treatment, OCAs were cultured for 7 or 14 days. Media were collected for analysis of osteogenic biomarker concentration. Samples of each BMC and PRP were tested for CFU concentration. On day 7 or 14, the grafts were assessed for cell surface adhesion and penetration using fluorescent microscopy. Significant differences in CFU and media biomarker concentration between the groups were determined using one-way analysis of variance (ANOVA) and Tukey's post-hoc test with the significance set at p  BMC had viable cells detectable on the osseous portion of the allografts at day 7 and 14 of culture. BMC samples had a significantly higher ( p  = 0.029) CFU/mL compared with PRP samples. At day 3 and/or 7 of culture, the concentration of several osteogenic proteins was significantly higher in both BMC and PRP samples. Autogenous BMC can be used to deliver both a cell

Constitutive activation of Gli2 impairs bone formation in postnatal growing mice.

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Kyu Sang Joeng

Full Text Available Indian hedgehog (Ihh signaling is indispensable for osteoblast differentiation during endochondral bone development in the mouse embryo. We have previously shown that the Gli2 transcription activator critically mediates Ihh function in osteoblastogenesis. To explore the possibility that activation of Hedgehog (Hh signaling may enhance bone formation, we generated mice that expressed a constitutively active form of Gli2 in the Osx-lineage cells. Unexpectedly, these mice exhibited severe osteopenia due to a marked decrease in osteoblast number and function, although bone resorption was not affected. Quantitative analyses of the molecular markers indicated that osteoblast differentiation was impaired in the mutant mouse. However, the osteoblast-lineage cells isolated from these mice exhibited more robust osteoblast differentiation than normal in vitro. Similarly, pharmacological stimulation of Hh signaling enhanced osteoblast differentiation from Osx-expressing cells isolated from the wild-type mouse. Thus, even though Hh signaling directly promotes osteoblast differentiation in vitro, constitutive activation of this pathway impairs bone formation in vivo, perhaps through an indirect mechanism.

Osteoprotegerin in bone metastases: mathematical solution to the puzzle.

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Marc D Ryser

Full Text Available Bone is a common site for cancer metastasis. To create space for their growth, cancer cells stimulate bone resorbing osteoclasts. Cytokine RANKL is a key osteoclast activator, while osteoprotegerin (OPG is a RANKL decoy receptor and an inhibitor of osteoclastogenesis. Consistently, systemic application of OPG decreases metastatic tumor burden in bone. However, OPG produced locally by cancer cells was shown to enhance osteolysis and tumor growth. We propose that OPG produced by cancer cells causes a local reduction in RANKL levels, inducing a steeper RANKL gradient away from the tumor and towards the bone tissue, resulting in faster resorption and tumor expansion. We tested this hypothesis using a mathematical model of nonlinear partial differential equations describing the spatial dynamics of OPG, RANKL, PTHrP, osteoclasts, tumor and bone mass. We demonstrate that at lower expression rates, tumor-derived OPG enhances the chemotactic RANKL gradient and osteolysis, whereas at higher expression rates OPG broadly inhibits RANKL and decreases osteolysis and tumor burden. Moreover, tumor expression of a soluble mediator inducing RANKL in the host tissue, such as PTHrP, is important for correct orientation of the RANKL gradient. A meta-analysis of OPG, RANKL and PTHrP expression in normal prostate, carcinoma and metastatic tissues demonstrated an increase in expression of OPG, but not RANKL, in metastatic prostate cancer, and positive correlation between OPG and PTHrP in metastatic prostate cancer. The proposed mechanism highlights the importance of the spatial distribution of receptors, decoys and ligands, and can be applied to other systems involving regulation of spatially anisotropic processes.

Exercise does not enhance aged bone's impaired response to artificial loading in C57Bl/6 mice.

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Meakin, Lee B; Udeh, Chinedu; Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

2015-12-01

Bones adapt their structure to their loading environment and so ensure that they become, and are maintained, sufficiently strong to withstand the loads to which they are habituated. The effectiveness of this process declines with age and bones become fragile fracturing with less force. This effect in humans also occurs in mice which experience age-related bone loss and reduced adaptation to loading. Exercise engenders many systemic and local muscular physiological responses as well as engendering local bone strain. To investigate whether these physiological responses influence bones' adaptive responses to mechanical strain we examined whether a period of treadmill exercise influenced the adaptive response to an associated period of artificial loading in young adult (17-week) and old (19-month) mice. After treadmill acclimatization, mice were exercised for 30 min three times per week for two weeks. Three hours after each exercise period, right tibiae were subjected to 40 cycles of non-invasive axial loading engendering peak strain of 2250 με. In both young and aged mice exercise increased cross-sectional muscle area and serum sclerostin concentration. In young mice it also increased serum IGF1. Exercise did not affect bone's adaptation to loading in any measured parameter in young or aged bone. These data demonstrate that a level of exercise sufficient to cause systemic changes in serum, and adaptive changes in local musculature, has no effect on bone's response to loading 3h later. This study provides no support for the beneficial effects of exercise on bone in the elderly being mediated by systemic or local muscle-derived effects rather than local adaptation to altered mechanical strain. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Cellular and molecular prerequisites for bone tissue engineering

NARCIS (Netherlands)

Siddappa, Ramakrishnaiah

2007-01-01

Recent advances in medicine and other biological disciplines have considerably enhanced the life expectancy of human and consequently, resulting in age related health problems including skeletal complications. In addition, bone substitute to regenerate fractures resulting from trauma, congenital and

Polymeric membranes for guided bone regeneration.

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Gentile, Piergiorgio; Chiono, Valeria; Tonda-Turo, Chiara; Ferreira, Ana M; Ciardelli, Gianluca

2011-10-01

In this review, different barrier membranes for guided bone regeneration (GBR) are described as a useful surgical technique to enhance bone regeneration in damaged alveolar sites before performing implants and fitting other dental appliances. The GBR procedure encourages bone regeneration through cellular exclusion and avoids the invasion of epithelial and connective tissues that grow at the defective site instead of bone tissue. The barrier membrane should satisfy various properties, such as biocompatibility, non-immunogenicity, non-toxicity, and a degradation rate that is long enough to permit mechanical support during bone formation. Other characteristics such as tissue integration, nutrient transfer, space maintenance and manageability are also of interest. In this review, various non-resorbable and resorbable commercially available membranes are described, based on expanded polytetrafluoroethylene, poly(lactic acid), poly(glycolic acid) and their copolymers. The polyester-based membranes are biodegradable, permit a single-stage procedure, and have higher manageability than non-resorbable membranes; however, they have shown poor biocompatibility. In contrast, membranes based on natural materials, such as collagen, are biocompatible but are characterized by poor mechanical properties and stability due to their early degradation. Moreover, new approaches are described, such as the use of multi-layered, graft-copolymer-based and composite membranes containing osteoconductive ceramic fillers as alternatives to conventional membranes. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The imaging findings of metastatic neuroblastoma in the craniofacial bone in children

International Nuclear Information System (INIS)

Bian Xin; Wang Zhenchang; Xian Junfang; Li Mei; Yan Fei; Chen Qinghua; Yang Bentao; Chang Qinglin; Tian Qichang; Liu Zhonglin

2009-01-01

Objective: To investigate the characteristic imaging findings of metastatic neuroblastoma in the craniofacial bone in children. Methods: Imaging findings in 12 patients with metastatic neuroblastoma in the craniofacial bone were analyzed retrospectively. Among them, 10 patients undenvent plain CT scan, 6 underwent MRI and 7 underwent whole body single-photon emission computed tomography bone scanning. Results: In the 10 patients with CT images, lytic bone destruction and soft tissue masses were found in 9 eases, in which periosteal reaction was observed in 8 patients with spiculated periosteal reaction in 3 patients. The remaining 1 patient didn't show any abnormalities on CT images but had abnormal findings in bone scanning. Six patients with MR images showed abnormal signal intensity in the bone marrow of the craniofacial bone and adjacent soft tissue masses. Postcontrast T 1 -weighted imaging in 5 patients demonstrated remarkable enhancement of the bone marrow and soft tissue masses. Bone scanning of 7 patients showed abnormal foci of increased radionuclide activity of the craniofacial bone in 7 patients and metastasis at other body parts in 6 patients. Conclusion: The metastatic neuroblastoma in the craniofacial bone has its characteristic imaging findings which are helpful for correct diagnosis. (authors)

Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche.

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Templeton, Zach S; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V; Tamaresis, John S; Bachmann, Michael H; Lee, Kitty; Maloney, William J; Contag, Christopher H; King, Bonnie L

2015-12-01

Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Histological and molecular-biological analyses of poly(3-hydroxybutyrate) (PHB) patches for enhancement of bone regeneration.

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Gredes, Tomasz; Gedrange, Tomasz; Hinüber, Claudia; Gelinsky, Michael; Kunert-Keil, Christiane

2015-05-01

Tissue engineered cell-seeded constructs with poly(3)hydroxybutyrate (PHB) induced ectopic bone formation after implantation into the back muscle of rats. The objective of our in vivo study was to evaluate the osteogenic potential of pure PHB patches in surgically created cranial defects. For this, PHB patches were analyzed after implantation in surgically created defects on the cranium of adult male rats. After healing periods of 4, 8 and 12 weeks, the bone tissue specimens containing PHB patches were processed and analyzed histologically as well as molecular-biologically. After 4 weeks, the PHB patches were completely embedded in connective tissue. Eight weeks after PHB insertion, bone regeneration proceeding from bearing bone was found in 50% of all treated animals, whereas all PHB treated cavities showed both bone formation and embedding of the patches in bone 12 weeks after surgery. Furthermore, all slices showed pronounced development of blood vessels. Histomorphometric analysis presented a regenerated bone mean value between 46.4 ± 16.1% and 54.2 ± 19.3% after 4-12 weeks of healing. Caveolin-1 staining in capillary-like structures showed a 1.16-1.38 fold increased expression in PHB treated defects compared to controls. Real-time RT-PCR analyses showed significantly lower expressions of Alpl, Col1a1 and VEGFA in cranium defects after treatment with PHB patches compared to untreated bony defects of the same cranium. Within the limits of the presented animal investigation, it could conclude that the tested PHB patches featured a good biocompatibility and an osteoconductive character. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

Physiological role of growth factors and bone morphogenetic proteins in osteogenesis and bone fracture healing: а review

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S. Sagalovsky

2015-01-01

Full Text Available The repair of large bone defects remains a major clinical orthopedic challenge. Bone regeneration and fracture healing is a complex physiological mechanisms regulated by a large number of biologically active molecules. Multiple factors regulate this cascade of molecular events, which affects different stages in the osteoblast and chondroblast lineage during such processes as migration, proliferation, chemotaxis, differentiation, inhibition, and extracellular protein synthesis. A recent review has focused on the mechanisms by which growth and differentiation factors regulate the fracture healing process. Rapid progress in skeletal cellular and molecular biology has led to identification of many signaling molecules associated with formation of skeletal tissues, including a large family of growth factors (transforming growth factor-β and bone morphogenetic proteins, fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, platelet-derived growth factor, cytokines and interleukins. There is increasing evidence indicating that they are critical regulators of cellular proliferation, differentiation, extracellular matrix biosynthesis and bone mineralization. A clear understanding of cellular and molecular pathways involved in fracture healing is not only critical for improvement of fracture treatments, but it may also enhance further our knowledge of mechanisms involved in skeletal growth and repair, as well as mechanisms of aging. This suggests that, in the future, they may play a major role in the treatment of bone disease and fracture repair.

Platelet-rich plasma for bone healing and regeneration.

Science.gov (United States)

Oryan, Ahmad; Alidadi, Soodeh; Moshiri, Ali

2016-01-01

Successful healing of large bone defects (LBDs) is a complicated phenomenon because the body's natural ability often fails to effectively repair the LBDs. New modalities should be utilized to increase the quality and accelerate bone healing. Platelet concentrates in different forms can be considered an attractive option for such purpose. Platelets as a natural source of growth factors, cytokines, and other micro and macromolecules are hypothesized to improve bone healing. This review has covered important concepts regarding platelet-rich plasma (PRP) including mechanisms of action, preparation protocols and their differences, and factors affecting the PRP efficacy during bone healing. In addition, the most recent studies in different levels which evaluated the role of PRP on bone repair has been reviewed and discussed to clarify the controversies and conflicts, and to illustrate a future prospective and directions for orthopedic surgeons to overcome current limitations and difficulties. As the efficacy of PRP is dependent on various factors, the outcome of PRP therapy is variable and unpredictable in orthopedic patients. Therefore, it is still too soon to suggest PRP as the first line treatment option in complicated bone injuries such as LBDs and nonunions. However, combination of PRP with natural and synthetic biomaterials can enhance the effectiveness of PRP.

Peritumoral bone marrow edema accompanying benign giant cell tumor

International Nuclear Information System (INIS)

Kim, Sung Hun; Park, Jeong Mi; Kim, Ji Yong; Gi, Won Hee; Sung, Mi Suk; Lee, Jae Mun; Shin, Kyung Sub

1998-01-01

To evaluate the frequency of peritumoral bone marrow(BM) edema accompanying benign giant cell tumor(GCT) of the appendicular bone by magnetic resonance(MR) imaging and to correlate MRI findings with those of plain radiography and bone scintigraphy. Eighteen cases of pathologically proven benign GCT of the appendicular bone were retrospectively analyzed using MR images, plain radiographs and bone scintigrams. A plain radiography was available in 15 cases, and a scintigram in six. Marrow edema was defined as peritumoral signal changes which were of homogeneous intermediate or low signal intensity(SI) onT1WI and high SI on T2WI, relative to the SI of normal BM, and homogeneous enhancement on Gd-DTPA -enhanced T1WI. The transition zone, sclerotic margin and aggressiveness of the lesion were assessed on the basis of plain radiographs. BM edema seen on MR images was correlated with plain radiographic and scintigraphic findings. 1. Peritumoral BM edema was seen on MR images in 10 of 18 cases (55.5%). 2. In 8 of 15 cases for which plain radiographs were available, MR imaging revealed BM edema. In six of these eight, transition zone was wide, while in two it was narrow. Six of seven patients without marrow edema showed a wide transition zone, and in one this was narrow. There was significant correlation between BM edema shown by MR imaging and the transition zone seen on plain radiographs (x 2 , p<0.05). But the aggressiveness shown by plain radiographs correlated only marginally while the presence of sclerotic rim did not correlate. 3. All six cases for which a bone scintigram was available showed an extended uptake pattern. In five of the six, MR imaging revealed edema. Peritumoral BM edema was frequently seen (55.5%) in the GCTs of appendicular bone; it was more often shown in association with a wide transition zone by plain radiographs.=20

Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

International Nuclear Information System (INIS)

Gilmour, Peter S.; O'Shea, Patrick J.; Fagura, Malbinder; Pilling, James E.; Sanganee, Hitesh; Wada, Hiroki; Courtney, Paul F.; Kavanagh, Stefan; Hall, Peter A.; Escott, K. Jane

2013-01-01

mineralisation produced by GSK-3 inhibition. • In rats, 3 GSK-3 inhibitors produced a unique serum bone turnover biomarker profile. • Enhanced bone formation was seen within 7 to 14 days of compound treatment in rats

An adaptation model for trabecular bone at different mechanical levels

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Lv Linwei

2010-07-01

Full Text Available Abstract Background Bone has the ability to adapt to mechanical usage or other biophysical stimuli in terms of its mass and architecture, indicating that a certain mechanism exists for monitoring mechanical usage and controlling the bone's adaptation behaviors. There are four zones describing different bone adaptation behaviors: the disuse, adaptation, overload, and pathologic overload zones. In different zones, the changes of bone mass, as calculated by the difference between the amount of bone formed and what is resorbed, should be different. Methods An adaptation model for the trabecular bone at different mechanical levels was presented in this study based on a number of experimental observations and numerical algorithms in the literature. In the proposed model, the amount of bone formation and the probability of bone remodeling activation were proposed in accordance with the mechanical levels. Seven numerical simulation cases under different mechanical conditions were analyzed as examples by incorporating the adaptation model presented in this paper with the finite element method. Results The proposed bone adaptation model describes the well-known bone adaptation behaviors in different zones. The bone mass and architecture of the bone tissue within the adaptation zone almost remained unchanged. Although the probability of osteoclastic activation is enhanced in the overload zone, the potential of osteoblasts to form bones compensate for the osteoclastic resorption, eventually strengthening the bones. In the disuse zone, the disuse-mode remodeling removes bone tissue in disuse zone. Conclusions The study seeks to provide better understanding of the relationships between bone morphology and the mechanical, as well as biological environments. Furthermore, this paper provides a computational model and methodology for the numerical simulation of changes of bone structural morphology that are caused by changes of mechanical and biological

Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment

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Vessella Robert L

2006-01-01

Full Text Available Abstract Background After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL, a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment. Methods Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis. Results ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone. Conclusion In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option.

Mechanical stimulation enhanced estrogen receptor expression and callus formation in diaphyseal long bone fracture healing in ovariectomy-induced osteoporotic rats.

Science.gov (United States)

Chow, S K H; Leung, K S; Qin, J; Guo, A; Sun, M; Qin, L; Cheung, W H

2016-10-01

Estrogen receptor (ER) in ovariectomy-induced osteoporotic fracture was reported to exhibit delayed expression. Mechanical stimulation enhanced ER-α expression in osteoporotic fracture callus at the tissue level. ER was also found to be required for the effectiveness of vibrational mechanical stimulation treatment in osteoporotic fracture healing. Estrogen receptor(ER) is involved in mechanical signal transduction in bone metabolism. Its expression was reported to be delayed in osteoporotic fracture healing. The purpose of this study was to investigate the roles played by ER during osteoporotic fracture healing enhanced with mechanical stimulation. Ovariectomy-induced osteoporotic SD rats that received closed femoral fractures were divided into five groups, (i) SHAM, (ii) SHAM-VT, (iii) OVX, (iv) OVX-VT, and (v) OVX-VT-ICI, where VT stands for whole-body vibration treatment and ICI for ER antagonization by ICI 182,780. Callus formation and gene expression were assessed at 2, 4, and 8 weeks postfracture. In vitro osteoblastic differentiation, mineralization, and ER-α expression were assessed. The delayed ER expression was found to be enhanced by vibration treatment. Callus formation enhancement was shown by callus morphometry and micro-CT analysis. Enhancement effects by vibration were partially abolished when ER was modulated by ICI 182,780, in terms of callus formation capacity at 2-4 weeks and ER gene and protein expression at all time points. In vitro, ER expression in osteoblasts was not enhanced by VT treatment, but osteoblastic differentiation and mineralization were enhanced under estrogen-deprived condition. When osteoblastic cells were modulated by ICI 182,780, enhancement effects of VT were eliminated. Vibration was able to enhance ER expression in ovariectomy-induced osteoporotic fracture healing. ER was essential in mechanical signal transduction and enhancement in callus formation effects during osteoporotic fracture healing enhanced by vibration

Bone Regeneration Using N-Methyl-2-pyrrolidone as an Enhancer for Recombinant Human Bone Morphogenetic Protein-2 in a Rabbit Sinus Augmentation Model.

Science.gov (United States)

Lim, Hyun-Chang; Thoma, Daniel S; Yoon, So-Ra; Cha, Jae-Kook; Lee, Jung-Seok; Jung, Ui-Won

2017-01-01

The aim of this study was to determine whether N-methyl-2-pyrrolidone (NMP) can decrease the dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) in sinus augmentation of rabbits. In each of 15 rabbits, 2 sinuses were randomly grafted using 1 of 3 treatment modalities: (i) biphasic calcium phosphate (BCP; control), (ii) rhBMP-2-coated BCP (BMP), or (iii) rhBMP-2-coated BCP soaked in NMP solution (BMP/NMP). The rabbits were sacrificed 2 weeks postoperatively. Histologic and histomorphometric analyses were performed. Bone formation in all groups was predominantly located close to the access window and the lateral walls. Newly formed bone within the total augmented area (NB TA ) was greatest in BMP/NMP (1.94 ± 0.69 mm 2 ), followed by BMP (1.50 ± 0.72 mm 2 ) and BCP (1.28 ± 0.52 mm 2 ) ( P > 0.05). In the center of the augmentation (NB ROI_C ) and the area close to the sinus membrane (NB ROI_M ), BMP/NMP produced the largest area of NB (NB ROI_C : 0.10 ± 0.11 mm 2 ; NB ROI_M : 0.17 ± 0.08 mm 2 ); the corresponding NB values for BCP were 0.05 ± 0.05 mm 2 and 0.08 ± 0.09 mm 2 , respectively ( P > 0.05 for all comparisons). The effect of NMP on bone regeneration was inconsistent between the specimens. Adding NMP as an adjunct to rhBMP-2-coated BCP produced inconsistent effects on bone regeneration, resulting in no significant benefit compared to controls.

Enhancing Quality of Life for Breast Cancer Patients with Bone Metastases

Science.gov (United States)

2008-04-01

paclitaxel. British Journal of Cancer 84:1126-34; 2001. 46. Jilka, R. L., Weinstein , R. S., Bellido, T., Roberson, P., Parfitt, A. M., and Manolagas...D., and Harvey , W. J. Correlation of neoplasms with incidence and localization of skeletal metastases: An analysis of 1,355 diphosphonate bone scans

The Effects of Bone Remodeling Inhibition by Alendronate on Three-Dimensional Microarchitecture of Subchondral Bone Tissues in Guinea Pig Primary Osteoarthrosis

DEFF Research Database (Denmark)

Ding, Ming

2008-01-01

We assessed whether increase of subchondral bone density enhances cartilage stress during impact loading, leading to progressive cartilage degeneration and accelerated osteoarthrosis (OA) progression. Sixty-six male guinea pigs were randomly divided into six groups. During a 9-week treatment period...

B lymphocyte "original sin" in the bone marrow enhances islet autoreactivity in type 1 diabetes-prone nonobese diabetic mice.

Science.gov (United States)

Henry-Bonami, Rachel A; Williams, Jonathan M; Rachakonda, Amita B; Karamali, Mariam; Kendall, Peggy L; Thomas, James W

2013-06-15

Effective central tolerance is required to control the large extent of autoreactivity normally present in the developing B cell repertoire. Insulin-reactive B cells are required for type 1 diabetes in the NOD mouse, because engineered mice lacking this population are protected from disease. The Cg-Tg(Igh-6/Igh-V125)2Jwt/JwtJ (VH125Tg) model is used to define this population, which is found with increased frequency in the periphery of NOD mice versus nonautoimmune C57BL/6 VH125Tg mice; however, the ontogeny of this disparity is unknown. To better understand the origins of these pernicious B cells, anti-insulin B cells were tracked during development in the polyclonal repertoire of VH125Tg mice. An increased proportion of insulin-binding B cells is apparent in NOD mice at the earliest point of Ag commitment in the bone marrow. Two predominant L chains were identified in B cells that bind heterologous insulin. Interestingly, Vκ4-57-1 polymorphisms that confer a CDR3 Pro-Pro motif enhance self-reactivity in VH125Tg/NOD mice. Despite binding circulating autoantigen in vivo, anti-insulin B cells transition from the parenchyma to the sinusoids in the bone marrow of NOD mice and enter the periphery unimpeded. Anti-insulin B cells expand at the site of autoimmune attack in the pancreas and correlate with increased numbers of IFN-γ-producing cells in the repertoire. These data identify the failure to cull autoreactive B cells in the bone marrow as the primary source of anti-insulin B cells in NOD mice and suggest that dysregulation of central tolerance permits their escape into the periphery to promote disease.

8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage.

Science.gov (United States)

Hoshino, Marie; Kaneko, Kotaro; Miyamoto, Yoichi; Yoshimura, Kentaro; Suzuki, Dai; Akaike, Takaaki; Sawa, Tomohiro; Ida, Tomoaki; Fujii, Shigemoto; Ihara, Hideshi; Tanaka, Junichi; Tsukuura, Risa; Chikazu, Daichi; Mishima, Kenji; Baba, Kazuyoshi; Kamijo, Ryutaro

2017-09-01

In endochondral ossification, growth of bones occurs at their growth plate cartilage. While it is known that nitric oxide (NO) synthases are required for proliferation of chondrocytes in growth plate cartilage and growth of bones, the precise mechanism by which NO facilitates these process has not been clarified yet. C-type natriuretic peptide (CNP) also positively regulate elongation of bones through expansion of the growth plate cartilage. Both NO and CNP are known to use cGMP as the second messenger. Recently, 8-nitro-cGMP was identified as a signaling molecule produced in the presence of NO in various types of cells. Here, we found that 8-nitro-cGMP is produced in proliferating chondrocytes in the growth plates, which was enhanced by CNP, in bones cultured ex vivo. In addition, 8-nitro-cGMP promoted bone growth with expansion of the proliferating zone as well as increase in the number of proliferating cells in the growth plates. 8-Nitro-cGMP also promoted the proliferation of chondrocytes in vitro. On the other hand, 8-bromo-cGMP enhanced the growth of bones with expansion of hypertrophic zone of the growth plates without affecting either the width of proliferating zone or proliferation of chondrocytes. These results indicate that 8-nitro-cGMP formed in growth plate cartilage accelerates chondrocyte proliferation and bone growth as a downstream molecule of NO. Copyright © 2017. Published by Elsevier Inc.

Evolutionary Patterns of Bone Histology and Bone Compactness in Xenarthran Mammal Long Bones

OpenAIRE

Straehl, Fiona; Scheyer, Torsten; Forasiepi, Analia Marta; Macphee, Ross; Sanchez-Villagra, Marcelo

2015-01-01

Bone microstructure reflects physiological characteristics and has been shown to contain phylogenetic and ecological signals. Although mammalian long bone histology is receiving increasing attention, systematic examination of the main clades has not yet been performed. Here we describe the long bone microstructure of Xenarthra based on thin sections representing twenty-two species. Additionally, patterns in bone compactness of humeri and femora are investigated. The primary bone tissue of xen...

Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans

DEFF Research Database (Denmark)

Aslan, Derya; Dahl Andersen, Mille; Gede, Lene Bjerring

2012-01-01

. However, development of the biochemical measurement of PTH in the 1980s led us to understand the regulation of PTH secretion and calcium metabolism which subsequently paved the way for the use of PTH as an anabolic treatment of osteoporosis as, when given intermittently, it has strong anabolic effects...... in bone. This could not have taken place without the basic understanding achieved by the biochemical measurements of PTH. The stimulatory effects of PTH on bone formation have been explained by the so-called ‘anabolic window’, which means that during PTH treatment, bone formation is in excess over bone...... resorption during the first 6–18 months. This is due to the following: (1) PTH up-regulates c-fos expression in bone cells, (2) IGF is essential for PTH's anabolic effect, (3) bone lining cells are driven to differentiate into osteoblasts, (4) mesenchymal stem cells adhesion to bone surface is enhanced, (5...

Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2

International Nuclear Information System (INIS)

Li Huiwu; Dai Kerong; Tang Tingting; Zhang Xiaoling; Yan Mengning; Lou Jueren

2007-01-01

In this study, we reported that the adipose-derived stromal cells (ADSCs) genetically modified by bone morphogenetic protein 2 (BMP-2) healed critical-sized canine ulnar bone defects. First, the osteogenic and adipogenic differentiation potential of the ADSCs derived from canine adipose tissue were demonstrated. And then the cells were modified by the BMP-2 gene and the expression and bone-induction ability of BMP-2 were identified. Finally, the cells modified by BMP-2 gene were applied to a β-tricalcium phosphate (TCP) carrier and implanted into ulnar bone defects in the canine model. After 16 weeks, radiographic, histological, and histomorphometry analysis showed that ADSCs modified by BMP-2 gene produced a significant increase of newly formed bone area and healed or partly healed all of the bone defects. We conclude that ADSCs modified by the BMP-2 gene can enhance the repair of critical-sized bone defects in large animals

Mechanistic aspects of fracture and R-curve behavior in elk antler bone

Energy Technology Data Exchange (ETDEWEB)

Launey, Maximilien E.; Chen, Po-Yu; McKittrick, Joanna; Ritchie, Robert O.

2009-11-23

Bone is an adaptative material that is designed for different functional requirements; indeed, bones have a variety of properties depending on their role in the body. To understand the mechanical response of bone requires the elucidation of its structure-function relationships. Here, we examine the fracture toughness of compact bone of elk antler which is an extremely fast growing primary bone designed for a totally different function than human (secondary) bone. We find that antler in the transverse (breaking) orientation is one of the toughest biological materials known. Its resistance to fracture is achieved during crack growth (extrinsically) by a combination of gross crack deflection/twisting and crack bridging via uncracked 'ligaments' in the crack wake, both mechanisms activated by microcracking primarily at lamellar boundaries. We present an assessment of the toughening mechanisms acting in antler as compared to human cortical bone, and identify an enhanced role of inelastic deformation in antler which further contributes to its (intrinsic) toughness.

Ibrutinib enhances IL-17 response by modulating the function of bone marrow derived dendritic cells.

Science.gov (United States)

Natarajan, Gayathri; Terrazas, Cesar; Oghumu, Steve; Varikuti, Sanjay; Dubovsky, Jason A; Byrd, John C; Satoskar, Abhay R

Ibrutinib (PCI-32765) is an irreversible dual Btk/Itk inhibitor shown to be effective in treating several B cell malignancies. However, limited studies have been conducted to study the effect of this drug on myeloid cell function. Hence, we studied the effect of ibrutinib treatment on TLR-4 mediated activation of bone marrow derived dendritic cell culture (DCs). Upon ibrutinib treatment, LPS-treated DCs displayed lower synthesis of TNF-α and nitric oxide (NO) and higher induction of IL-6, TGF-β, IL-10 and IL-18. While ibrutinib dampened MHC-II and CD86 expression on DCs, CD80 expression was upregulated. Further, ibrutinib-treated DCs promoted T cell proliferation and enhanced IL-17 production upon co-culture with nylon wool enriched T cells. Taken together, our results indicate that ibrutinib modulates TLR-4 mediated DC activation to promote an IL-17 response. We describe a novel mode of action for ibrutinib on DCs which should be explored to treat other forms of cancer besides B cell malignancies.

Metal deposition at the bone-cartilage interface in articular cartilage

Energy Technology Data Exchange (ETDEWEB)

Kaabar, W. [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom)], E-mail: w.kaabar@surrey.ac.uk; Daar, E.; Gundogdu, O.; Jenneson, P.M. [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Farquharson, M.J. [Department of Radiography, School of Allied Health Sciences, City University, London EC1V 0HB (United Kingdom); Webb, M.; Jeynes, C. [Surrey Ion Beam Centre, University of Surrey, Guildford GU2 7XH (United Kingdom); Bradley, D.A. [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom)

2009-03-15

There is a growing interest being shown in the changes occurring in elemental distribution at the bone-cartilage interface, the changes either being a result of mechanical damage or disease. In particular, such investigations have tended to concern the elemental alterations associated with the osteoarthritic wear and tear damage occurring to the cartilage and subchondral bone of synovial joints or that associated with disease processes such as rheumatic arthritis. Present studies examine sections of femoral head obtained from total hip replacement surgery, use being made of micro-proton-induced X-ray emission ({mu}-PIXE) and the Rutherford back scattering (RBS) techniques. Enhancements of Zn, Ca and P have been observed at the bone-cartilage interface. Further, the concentration of Zn in spongy bone underlying the subchondral surface of a section of the femoral head has been measured, obtaining 136 {mu}g g{sup -1} bone, the presence of Ca and P at the same position being 0.235 and 0.0451 g g{sup -1} bone, respectively. These values are slightly different to figures recently published by other authors using similar techniques.

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

Hydrogel/bioactive glass composites for bone regeneration applications: Synthesis and characterisation

International Nuclear Information System (INIS)

Killion, John A.; Kehoe, Sharon; Geever, Luke M.; Devine, Declan M.; Sheehan, Eoin; Boyd, Daniel; Higginbotham, Clement L.

2013-01-01

Due to the deficiencies of current commercially available biological bone grafts, alternative bone graft substitutes have come to the forefront of tissue engineering in recent times. The main challenge for scientists in manufacturing bone graft substitutes is to obtain a scaffold that has sufficient mechanical strength and bioactive properties to promote formation of new tissue. The ability to synthesise hydrogel based composite scaffolds using photopolymerisation has been demonstrated in this study. The prepared hydrogel based composites were characterised using techniques including Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray spectrometry (EDX), rheological studies and compression testing. In addition, gel fraction, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), porosity and swelling studies of the composites were carried out. It was found that these novel hydrogel bioglass composite formulations did not display the inherent brittleness that is typically associated with bioactive glass based bone graft materials and exhibited enhanced biomechanical properties compared to the polyethylene glycol hydrogel scaffolds along. Together, the combination of enhanced mechanical properties and the deposition of apatite on the surface of these hydrogel based composites make them an ideal candidate as bone graft substitutes in cancellous bone defects or low load bearing applications. Highlights: • Young's modulus increases with the addition of bioactive glasses. • Hydrogel based composites formed an apatite layer in simulated body fluid. • Storage modulus increases with addition of bioactive glasses. • Compressive strength is dependent on molecular weight and bioactive glass loading

Recombinant human bone morphogenetic protein induces bone formation

International Nuclear Information System (INIS)

Wang, E.A.; Rosen, V.; D'Alessandro, J.S.; Bauduy, M.; Cordes, P.; Harada, T.; Israel, D.I.; Hewick, R.M.; Kerns, K.M.; LaPan, P.; Luxenberg, D.P.; McQuaid, D.; Moutsatsos, I.K.; Nove, J.; Wozney, J.M.

1990-01-01

The authors have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 μg of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans

Bone tumors

International Nuclear Information System (INIS)

Unni, K.K.

1988-01-01

This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

ALVEOLAR BONE REGENERATION AFTER DEMINERALIZED FREEZE DRIED BONE ALOGRAFT (DFDBA BONE GRAFTING

Directory of Open Access Journals (Sweden)

Sri Oktawati

2006-04-01

Full Text Available Periodontal treatment by conventional way will result in healing repair, which easily cause recurrence. Modification of treatment should be done to get an effective result, that is the regeneration of alveolar bone and to reduce inflammation. The objective of this study is to determine the alveolar bone regeneration after using DFDBA (Demineralized Freeze Dried Bone Allograft. Quasi experimental designs with pre and post test method was used in this study. From 13 patients, 26 defects got conventional or regenerative treatment. The indicator of alveolar bone regenaration in bone height in radiographic appearance and level of osteocalsin in gingival crevicular fluid (GCF were checked before and after the treatment, then the changes that occurred were analyzed. The result of the research showed that alveolar bone regeneration only occurred to the group of regenerative treatment using DFDBA. The conclusion is the effective periodontal tissue regeneration occurred at regenerative treatment by using DFDBA, and the osteocalsin in GCF can be used as indicator of bone growth.

Bactericidal strontium-releasing injectable bone cements based on bioactive glasses.

Science.gov (United States)

Brauer, Delia S; Karpukhina, Natalia; Kedia, Gopal; Bhat, Aditya; Law, Robert V; Radecka, Izabela; Hill, Robert G

2013-01-06

Strontium-releasing injectable bone cements may have the potential to prevent implant-related infections through the bactericidal action of strontium, while enhancing bone formation in patients suffering from osteoporosis. A melt-derived bioactive glass (BG) series (SiO2–CaO–CaF2–MgO) with 0–50% of calcium substituted with strontium on a molar base were produced. By mixing glass powder, poly(acrylic acid) and water, cements were obtained which can be delivered by injection and set in situ, giving compressive strength of up to 35 MPa. Strontium release was dependent on BG composition with increasing strontium substitution resulting in higher concentrations in the medium. Bactericidal effects were tested on Staphylococcus aureus and Streptococcus faecalis; cell counts were reduced by up to three orders of magnitude over 6 days. Results show that bactericidal action can be increased through BG strontium substitution, allowing for the design of novel antimicrobial and bone enhancing cements for use in vertebroplasty or kyphoplasty for treating osteoporosis-related vertebral compression fractures.

The skeletal vascular system - Breathing life into bone tissue.

Science.gov (United States)

Stegen, Steve; Carmeliet, Geert

2017-08-26

During bone development, homeostasis and repair, a dense vascular system provides oxygen and nutrients to highly anabolic skeletal cells. Characteristic for the vascular system in bone is the serial organization of two capillary systems, each typified by specific morphological and physiological features. Especially the arterial capillaries mediate the growth of the bone vascular system, serve as a niche for skeletal and hematopoietic progenitors and couple angiogenesis to osteogenesis. Endothelial cells and osteoprogenitor cells interact not only physically, but also communicate to each other by secretion of growth factors. A vital angiogenic growth factor is vascular endothelial growth factor and its expression in skeletal cells is controlled by osteogenic transcription factors and hypoxia signaling, whereas the secretion of angiocrine factors by endothelial cells is regulated by Notch signaling, blood flow and possibly hypoxia. Bone loss and impaired fracture repair are often associated with reduced and disorganized blood vessel network and therapeutic targeting of the angiogenic response may contribute to enhanced bone regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Medial tibial pain: a dynamic contrast-enhanced MRI study.

Science.gov (United States)

Mattila, K T; Komu, M E; Dahlström, S; Koskinen, S K; Heikkilä, J

1999-09-01

The purpose of this study was to compare the sensitivity of different magnetic resonance imaging (MRI) sequences to depict periosteal edema in patients with medial tibial pain. Additionally, we evaluated the ability of dynamic contrast-enhanced imaging (DCES) to depict possible temporal alterations in muscular perfusion within compartments of the leg. Fifteen patients with medial tibial pain were examined with MRI. T1-, T2-weighted, proton density axial images and dynamic and static phase post-contrast images were compared in ability to depict periosteal edema. STIR was used in seven cases to depict bone marrow edema. Images were analyzed to detect signs of compartment edema. Region-of-interest measurements in compartments were performed during DCES and compared with controls. In detecting periosteal edema, post-contrast T1-weighted images were better than spin echo T2-weighted and proton density images or STIR images, but STIR depicted the bone marrow edema best. DCES best demonstrated the gradually enhancing periostitis. Four subjects with severe periosteal edema had visually detectable pathologic enhancement during DCES in the deep posterior compartment of the leg. Percentage enhancement in the deep posterior compartment of the leg was greater in patients than in controls. The fast enhancement phase in the deep posterior compartment began slightly slower in patients than in controls, but it continued longer. We believe that periosteal edema in bone stress reaction can cause impairment of venous flow in the deep posterior compartment. MRI can depict both these conditions. In patients with medial tibial pain, MR imaging protocol should include axial STIR images (to depict bone pathology) with T1-weighted axial pre and post-contrast images, and dynamic contrast enhanced imaging to show periosteal edema and abnormal contrast enhancement within a compartment.

Olive oil and vitamin D synergistically prevent bone loss in mice.

Directory of Open Access Journals (Sweden)

Camille Tagliaferri

Full Text Available As the Mediterranean diet (and particularly olive oil has been associated with bone health, we investigated the impact of extra virgin oil as a source of polyphenols on bone metabolism. In that purpose sham-operated (SH or ovariectomized (OVX mice were subjected to refined or virgin olive oil. Two supplementary OVX groups were given either refined or virgin olive oil fortified with vitamin D3, to assess the possible synergistic effects with another liposoluble nutrient. After 30 days of exposure, bone mineral density and gene expression were evaluated. Consistent with previous data, ovariectomy was associated with increased bone turnover and led to impaired bone mass and micro-architecture. The expression of oxidative stress markers were enhanced as well. Virgin olive oil fortified with vitamin D3 prevented such changes in terms of both bone remodeling and bone mineral density. The expression of inflammation and oxidative stress mRNA was also lower in this group. Overall, our data suggest a protective impact of virgin olive oil as a source of polyphenols in addition to vitamin D3 on bone metabolism through improvement of oxidative stress and inflammation.

From bone biology to bone analysis.

NARCIS (Netherlands)

Schoenau, E.; Saggese, G.; Peter, F.; Baroncelli, G.I.; Shaw, N.J.; Crabtree, N.J.; Zadik, Z.; Neu, C.M.; Noordam, C.; Radetti, G.; Hochberg, Z.