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Sample records for bone regeneration process

  1. Effectiveness of Russian current in bone regeneration process in rats

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    Renata Aparecida de Oliveira Lima

    Full Text Available Abstract Introduction: Russian current is an electric current of average frequency that is able to restore the properties of skeletal muscle at a low treatment cost. It is essential to know the effects of Russian current in bone tissue, since electromagnetic energy could be an efficient and low cost method to treat bone disorders. Objective: The aim of the study was to evaluate the effectiveness of Russian current in the consolidation of tibia fracture in adult rats. Methods: 24 adult male Albinus Wistar rats wereused. The animals were divided randomly into two groups: control group (CG, composed of 12 animals, and Intervention Group (IG consisting of 12 animals, both groups were submitted to osteotomy (proximal medial surface of the tibia. The IG underwent an electrical stimulation protocol with Russian current, while the CG did not undergo any kind of intervention. Euthanasia was performed in three animals of each group on the following days: 5, 10, 20, and 30 days of treatment. Results: The results suggested higher primary ossification, intense osteogenic activity, and increased thickness of the periosteum, characterizing more advanced ossification and a greater presence of trabecular bone marrow in rats in the group subjected to the treatment. In this way, we can assign one more beneficial effect to interventions with Russian current, for the treatment of postfracture rehabilitation. Conclusion: In both groups the bone tissue repair process occurred, but in the electrically stimulated group the osteogenesis process was more advanced.

  2. 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.

  3. Processing and characterization of biocomposites Poly (3-hydroxybutyrate) / hydroxyapatite for temporary support in bone regeneration

    International Nuclear Information System (INIS)

    Cardoso, Cyntia Esteves; Ferreira, Willian Hermogenes; Andrade, Cristina Tristao

    2011-01-01

    Composite materials like biopolymer / hydroxyapatite (HA) has been attracting the interest of researchers because of its applications in medicine. These materials have been used as temporary supports during the regeneration of bone tissue. In this work, poly (3-hydroxybutyrate) (PHB) was chosen as matrix because it has good processability and biocompatibility. The HA was obtained by precipitation from calcium hydroxide and phosphoric acid, varying the speed of dripping, the synthesis temperature and time of calcination. The techniques of infrared absorption spectroscopy and X-ray diffraction (XRD) were used to characterize the samples synthesized HA. The biocomposites were prepared in an internal mixer, with compositions PHB / HA varied. After processing, the biocomposites were ground, characterized by XRD analysis and the crystallinity index. The aim of this study was to examine the variables during the synthesis of HA and its thermal treatment in order to obtain a powder of HA using a simple technique and accessible, creating good properties for the biocomposites prepared. (author)

  4. [Guided bone regeneration: general survey].

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    Cosyn, Jan; De Bruyn, Hugo

    2009-01-01

    The principle of 'guided bone regeneration' was first described in 1988 on the basis of animal-experimental data. Six weeks after transmandibular defects had been created and protected by non-resorbable teflonmembranes, complete bone regeneration was found. The technique was based on the selective repopulation of the wound: every infiltration of cells outside the neighbouring bone tissue was prevented by the application of the membrane. Additional animal experiments showed that guided bone regeneration was a viable treatment option for local bone defects surrounding dental implants. Clinical practice, however, showed that premature membrane exposure was a common complication, which was responsible for a tremendous reduction in regenerated bone volume. In addition, a second surgical intervention was always necessary to remove the membrane. As a result, resorbable alternatives were developed. Since these are less rigid, bone fillers are usually used simultaneously. These comprise autogenous bone chips and bone substitutes from allogenic or xenogenic origine. Also alloplastic materials could be used for this purpose. Based on their characteristics this article provides an overview of the biomaterials that could be considered for guided bone regeneration. Specific attention goes to their application in clinical practice.

  5. Applications of Metals for Bone Regeneration

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    Kristina Glenske

    2018-03-01

    Full Text Available The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP-based substitute materials based on natural (allo- and xenografts and synthetic origins (alloplastic materials are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, as well as resorb in the time frame needed for complete regeneration up to the condition of restitution ad integrum. In this context, the modes of action of CaP-based substitute materials have been frequently investigated, where it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between new bone tissue formation and material degradation has not been found, until now. The addition of different substances such as collagen or growth factors and also of different cell types has already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are used differently as a basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue, playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designed for bone regeneration, with the aim to provide an overview of currently existing knowledge about the effects of metals in the field of bone regeneration.

  6. The potential of chitosan combined with chicken shank collagen as scaffold on bone defect regeneration process in Rattus norvegicus

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    Fitria Rahmitasari

    2016-12-01

    Full Text Available Background: In the field of dentistry, alveolar bone damage can be caused by periodontal disease, traumatic injury due to tooth extraction, cyst enucleation, and tumor surgery. One of the ways to regenerate the bone defect is using graft scaffold. Thus, combination of chitosan and collagen can stimulate osteogenesis. Purpose: The aim of this study was to examine the potential of chitosan combined with chicken shank collagen on bone defect regeneration process. Method: Twelve Rattus norvegicus were prepared as animal models in this research. A bone defect was intentionally created at both of the right and left femoral bones of the models. Next, 24 samples were divided into four groups, namely Group 1 using chitosan – collagen scaffold (50:50, Group 2 using chitosan collagen-scaffold (80:20, Group 3 using chitosan scaffold only, and Control Group using 3% CMC-Na. On 14th day, those animals were sacrificed, and histopathological anatomy examination was conducted to observe osteoclast cells. In addition, immunohistochemistry examination was also performed to observe RANKL expressions. Result: There was a significant difference in RANKL expressions among the groups, except between Group 3 using chitosan scaffold only and control group (p value > 0.05. The highest expression of RANKL was found in Group 1 with chitosan – collagen scaffold (50:50, followed by Group 2 with chitosan-collagen scaffold (80:20. Moreover, there was also a significant difference in osteoclast generation, except between Group 1 using chitosan – collagen scaffold (50:50 and Group 2 using chitosan-collagen scaffold (80:20, p value 0.05. Less osteoclast was found in the groups using chitosan – collagen scaffold (Group 1 and Group 2. Conclusion: Combination of chitosan and chicken shank collagen scaffold can improve regeneration process of bone defect in Rattus novergicus animals through increasing of RANKL expressions, and decreasing of osteoclast.

  7. Bone regeneration and stem cells

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    Arvidson, K; Abdallah, B M; Applegate, L A; Baldini, N; Cenni, E; Gomez-Barrena, E; Granchi, D; Kassem, M; Konttinen, Y T; Mustafa, K; Pioletti, D P; Sillat, T; Finne-Wistrand, A

    2011-01-01

    Abstract This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. PMID:21129153

  8. Bone regeneration and stem cells

    DEFF Research Database (Denmark)

    Arvidson, K; Abdallah, B M; Applegate, L A

    2011-01-01

    cells, use of platelet rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.......This invited review covers research areas of central importance for orthopedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and fetal stem cells, effects of sex steroids on mesenchymal stem...

  9. 'Pre-prosthetic use of poly(lactic-co-glycolic acid) membranes treated with oxygen plasma and TiO2 nanocomposite particles for guided bone regeneration processes'.

    Science.gov (United States)

    Castillo-Dalí, Gabriel; Castillo-Oyagüe, Raquel; Terriza, Antonia; Saffar, Jean-Louis; Batista-Cruzado, Antonio; Lynch, Christopher D; Sloan, Alastair J; Gutiérrez-Pérez, José-Luis; Torres-Lagares, Daniel

    2016-04-01

    Guided bone regeneration (GBR) processes are frequently necessary to achieve appropriate substrates before the restoration of edentulous areas. This study aimed to evaluate the bone regeneration reliability of a new poly-lactic-co-glycolic acid (PLGA) membrane after treatment with oxygen plasma (PO2) and titanium dioxide (TiO2) composite nanoparticles. Circumferential bone defects (diameter: 10mm; depth: 3mm) were created on the parietal bones of eight experimentation rabbits and were randomly covered with control membranes (Group 1: PLGA) or experimental membranes (Group 2: PLGA/PO2/TiO2). The animals were euthanized two months afterwards, and a morphologic study was then performed under microscope using ROI (region of interest) colour analysis. Percentage of new bone formation, length of mineralised bone formed in the grown defects, concentration of osteoclasts, and intensity of osteosynthetic activity were assessed. Comparisons among the groups and with the original bone tissue were made using the Kruskal-Wallis test. The level of significance was set in advance at a=0.05. The experimental group recorded higher values for new bone formation, mineralised bone length, and osteoclast concentration; this group also registered the highest osteosynthetic activity. Bone layers in advanced formation stages and low proportions of immature tissue were observed in the study group. The functionalised membranes showed the best efficacy for bone regeneration. The addition of TiO2 nanoparticles onto PLGA/PO2 membranes for GBR processes may be a promising technique to restore bone dimensions and anatomic contours as a prerequisite to well-supported and natural-appearing prosthetic rehabilitations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Nanostructured Mesoporous Silicas for Bone Tissue Regeneration

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    Isabel Izquierdo-Barba

    2008-01-01

    Full Text Available The research on the development of new biomaterials that promote bone tissue regeneration is receiving great interest by the biomedical scientific community. Recent advances in nanotechnology have allowed the design of materials with nanostructure similar to that of natural bone. These materials can promote new bone formation by inducing the formation of nanocrystalline apatites analogous to the mineral phase of natural bone onto their surfaces, i.e. they are bioactive. They also stimulate osteoblast proliferation and differentiation and, therefore, accelerate the healing processes. Silica-based ordered mesoporous materials are excellent candidates to be used as third generation bioceramics that enable the adsorption and local control release of biological active agents that promote bone regeneration. This local delivery capability together with the bioactive behavior of mesoporous silicas opens up promising expectations in the bioclinical field. In this review, the last advances in nanochemistry aimed at designing and tailoring the chemical and textural properties of mesoporous silicas for biomedical applications are described. The recent developed strategies to synthesize bioactive glasses with ordered mesopore arrangements are also summarized. Finally, a deep discussion about the influence of the textural parameters and organic modification of mesoporous silicas on molecules adsorption and controlled release is performed.

  11. Multimodal-3D imaging based on μMRI and μCT techniques bridges the gap with histology in visualization of the bone regeneration process.

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    Sinibaldi, R; Conti, A; Sinjari, B; Spadone, S; Pecci, R; Palombo, M; Komlev, V S; Ortore, M G; Tromba, G; Capuani, S; Guidotti, R; De Luca, F; Caputi, S; Traini, T; Della Penna, S

    2018-03-01

    Bone repair/regeneration is usually investigated through X-ray computed microtomography (μCT) supported by histology of extracted samples, to analyse biomaterial structure and new bone formation processes. Magnetic resonance imaging (μMRI) shows a richer tissue contrast than μCT, despite at lower resolution, and could be combined with μCT in the perspective of conducting non-destructive 3D investigations of bone. A pipeline designed to combine μMRI and μCT images of bone samples is here described and applied on samples of extracted human jawbone core following bone graft. We optimized the coregistration procedure between μCT and μMRI images to avoid bias due to the different resolutions and contrasts. Furthermore, we used an Adaptive Multivariate Clustering, grouping homologous voxels in the coregistered images, to visualize different tissue types within a fused 3D metastructure. The tissue grouping matched the 2D histology applied only on 1 slice, thus extending the histology labelling in 3D. Specifically, in all samples, we could separate and map 2 types of regenerated bone, calcified tissue, soft tissues, and/or fat and marrow space. Remarkably, μMRI and μCT alone were not able to separate the 2 types of regenerated bone. Finally, we computed volumes of each tissue in the 3D metastructures, which might be exploited by quantitative simulation. The 3D metastructure obtained through our pipeline represents a first step to bridge the gap between the quality of information obtained from 2D optical microscopy and the 3D mapping of the bone tissue heterogeneity and could allow researchers and clinicians to non-destructively characterize and follow-up bone regeneration. Copyright © 2017 John Wiley & Sons, Ltd.

  12. [Biocompatibility of poly-L-lactic acid/Bioglass-guided bone regeneration membranes processed with oxygen plasma].

    Science.gov (United States)

    Fang, Wei; Zeng, Shu-Guang; Gao, Wen-Feng

    2015-04-01

    To prepare and characterize a nano-scale fibrous hydrophilic poly-L-lactic acid/ Bioglass (PLLA/BG) composite membrane and evaluate its biocompatibility as a composite membrane for guiding bone regeneration (GBR). PLLA/BG-guided bone regeneration membrane was treated by oxygen plasma to improved its hydrophilicity. The growth of MG-63 osteoblasts on the membrane was observed using Hoechst fluorescence staining, and the biocompatibility of the membrane was evaluated by calculating the cells adhesion rate and proliferation rate. Osteogenesis of MG-63 cells was assessed by detecting alkaline phosphatase (ALP), and the formation of calcified nodules and cell morphology changes were observed using scanning electron microscope (SEM). The cell adhesion rates of PLLA/BG-guided bone regeneration membrane treated with oxygen plasma were (30.570±0.96)%, (47.27±0.78)%, and (66.78±0.69)% at 1, 3, and 6 h, respectively, significantly higher than those on PLLA membrane and untreated PLLA/BG membrane (Pmembranes increased with time, but highest on oxygen plasma-treated PLLA/BG membrane (Pplasma treatment of the PLLA/BG membrane promoted cell adhesion. The membranes with Bioglass promoted the matrix secretion of the osteoblasts. Under SEM, the formation of calcified nodules and spindle-shaped cell morphology were observed on oxygen plasma-treated PLLA/BG membrane. Oxygen plasma-treated PLLA/BG composite membrane has good biocompatibility and can promote adhesion, proliferation and osteogenesis of the osteoblasts.

  13. Dual-controlled release system of drugs for bone regeneration.

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    Kim, Yang-Hee; Tabata, Yasuhiko

    2015-11-01

    Controlled release systems have been noted to allow drugs to enhance their ability for bone regeneration. To this end, various biomaterials have been used as the release carriers of drugs, such as low-molecular-weight drugs, growth factors, and others. The drugs are released from the release carriers in a controlled fashion to maintain their actions for a long time period. Most research has been focused on the controlled release of single drugs to demonstrate the therapeutic feasibility. Controlled release of two combined drugs, so-called dual release systems, are promising and important for tissue regeneration. This is because the tissue regeneration process of bone formation is generally achieved by multiple bioactive molecules, which are produced from cells by other molecules. If two types of bioactive molecules, (i.e., drugs), are supplied in an appropriate fashion, the regeneration process of living bodies will be efficiently promoted. This review focuses on the bone regeneration induced by dual-controlled release of drugs. In this paper, various dual-controlled release systems of drugs aiming at bone regeneration are overviewed explaining the type of drugs and their release materials. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Regenerate augmentation with bone marrow concentrate after traumatic bone loss

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    Jan Gessmann

    2012-03-01

    Full Text Available Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22-64 with an average posttraumatic bone defect of 82.4 mm and concomitant risk factors (nicotine abuse, soft-tissue defects, obesity and/or circulatory disorders were treated with a modified Ilizarov external frame using an intramedullary cable transportation system. At the end of the distraction phase, each patient was treated with a percutaneously injection of autologous BMAC into the centre of the regenerate. The concentration factor was analysed using flow cytometry. The mean follow up after frame removal was 10 (4-15 months. With a mean healing index (HI of 36.9 d/cm, bony consolidation of the regenerate was achieved in all eight cases. The mean concentration factor of the bone marrow aspirate was 4.6 (SD 1.23. No further operations concerning the regenerate were needed and no adverse effects were observed with the BMAC procedure. This procedure can be used for augmentation of the regenerate in cases of segmental bone transport. Further studies with a larger number of patients and control groups are needed to evaluate a possible higher success rate and accelerating effects on regenerate healing.

  15. Carbon nanohorns accelerate bone regeneration in rat calvarial bone defect

    Energy Technology Data Exchange (ETDEWEB)

    Kasai, Takao; Iizuka, Tadashi; Kanamori, Takeshi; Yokoyama, Atsuro [Department of Oral Functional Prosthodontics, Division of Oral Functional Science, Graduate School of Dental Medicine, Hokkaido University, Kita 13, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8586 (Japan); Matsumura, Sachiko; Shiba, Kiyotaka [Division of Protein Engineering, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31, Ariake, koutou-ku, Tokyo 135-8550 (Japan); Yudasaka, Masako; Iijima, Sumio, E-mail: tkasai@den.hokudai.ac.jp [Nanotube Research Center, National Institute of Advanced Industrial Science and Technology, Central 5, 1-1-1, Higashi, Tsukuba, Ibaraki 305-8565 (Japan)

    2011-02-11

    A recent study showed that carbon nanohorns (CNHs) have biocompatibility and possible medical uses such as in drug delivery systems. It was reported that some kinds of carbon nanomaterials such as carbon nanotubes were useful for bone formation. However, the effect of CNHs on bone tissue has not been clarified. The purpose of this study was to evaluate the effect of CNHs on bone regeneration and their possible application for guided bone regeneration (GBR). CNHs dispersed in ethanol were fixed on a porous polytetrafluoroethylene membrane by vacuum filtration. Cranial defects were created in rats and covered by a membrane with/without CNHs. At two weeks, bone formation under the membrane with CNHs had progressed more than under that without CNHs and numerous macrophages were observed attached to CNHs. At eight weeks, there was no significant difference in the amount of newly formed bone between the groups and the appearance of macrophages was decreased compared with that at two weeks. Newly formed bone attached to some CNHs directly. These results suggest that macrophages induced by CNHs are related to bone regeneration. In conclusion, the present study indicates that CNHs are compatible with bone tissue and effective as a material for GBR.

  16. Calcium phosphate coatings for bone regeneration

    NARCIS (Netherlands)

    Yang, Liang

    2010-01-01

    As a novel approach to repair and regenerate damaged and degraded bone tissue, tissue engineering has recorded tremendous growth for the last thirty years. This is an emerging interdisciplinary field applying the principles of biology and engineering to the development of viable substitutes that

  17. Polymeric membranes for guided bone regeneration.

    Science.gov (United States)

    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.

  18. Guided bone regeneration : the influence of barrier membranes on bone grafts and bone defects

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    Gielkens, Pepijn Frans Marie

    2008-01-01

    Guided bone regeneration (GBR) can be described as the use of a barrier membrane to provide a space available for new bone formation in a bony defect. The barrier membrane protects the defect from in-growth of soft tissue cells and allows bone progenitor cells to develop bone within a blood clot

  19. 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.

  20. A novel osteogenesis technique: The expansible guided bone regeneration

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    Osama Zakaria

    2012-12-01

    Full Text Available Guided bone regeneration is a unique osteogenesis technique that requires a barrier membrane under periosteum to create space for bone regeneration. However, creating sizeable spaces is clinically not commonly feasible. A titanium plate and a thin silicone membrane were surgically layered on each calvaria of eight rabbits. Then, the periphery of the silicone membrane was fixed by a plastic ring to the underlying bone using titanium micro screws. After 1 week, a 5-mm-length titanium screw was used to elevate the titanium plate, which in turn elevated the silicone membrane together with overlying soft tissue in a rate of 1 mm/day for 5 days to create a secluded space. Animals were killed at 2 months (n = 4, group 1 and 4 months (n = 4, group 2 after the elevation. Histological and microradiographical analyses demonstrated creation of an amount of de novo bone formation (68.2 ± 22 mm3 in group 1 and 70.3 ± 14 mm3 in group 2 in the sizeable created spaces (207.1 ± 31 mm3 in group 1 and 202 ± 21 mm3 in group 2 without exposure of the device. This novel osteogenesis technique, “expansible guided bone regeneration,” created a substantial in vivo incubator without applying growth factors or osteoprogenitor cells. Creating a growing space over the secluded surface allowed the development of normal biological healing process occurring on the bone surface into a regenerative process, generating bone outside the genetically determined skeletal bone. This technique is a new tissue engineering approach stimulating endogenous tissue repair without applying cells or factors exogenously.

  1. Perkembangan Terkini Membran Guided Tissue Regeneration/Guided Bone Regeneration sebagai Terapi Regenerasi Jaringan Periodontal

    Directory of Open Access Journals (Sweden)

    Cindy Cahaya

    2015-06-01

    kombinasi prosedur-prosedur di atas, termasuk prosedur bedah restoratif yang berhubungan dengan rehabilitasi oral dengan penempatan dental implan. Pada tingkat selular, regenerasi periodontal adalah proses kompleks yang membutuhkan proliferasi yang terorganisasi, differensiasi dan pengembangan berbagai tipe sel untuk membentuk perlekatan periodontal. Rasionalisasi penggunaan guided tissue regeneration sebagai membran pembatas adalah menahan epitel dan gingiva jaringan pendukung, sebagai barrier membrane mempertahankan ruang dan gigi serta menstabilkan bekuan darah. Pada makalah ini akan dibahas sekilas mengenai 1. Proses penyembuhan terapi periodontal meliputi regenerasi, repair ataupun pembentukan perlekatan baru. 2. Periodontal spesific tissue engineering. 3. Berbagai jenis membran/guided tissue regeneration yang beredar di pasaran dengan keuntungan dan kerugian sekaligus karakteristik masing-masing membran. 4. Perkembangan membran terbaru sebagai terapi regenerasi penyakit periodontal. Tujuan penulisan untuk memberi gambaran masa depan mengenai terapi regenerasi yang menjanjikan sebagai perkembangan terapi penyakit periodontal.   Latest Development of Guided Tissue Regeneration and Guided Bone Regeneration Membrane as Regenerative Therapy on Periodontal Tissue. Periodontitis is a patological state which influences the integrity of periodontal system that could lead to the destruction of the periodontal tissue and end up with tooth loss. Currently, there are so many researches and efforts to regenerate periodontal tissue, not only to stop the process of the disease but also to reconstruct the periodontal tissue. Periodontal regenerative therapy aims at directing the growth of new bone, cementum and periodontal ligament on the affected teeth. Regenerative procedures consist of soft tissue graft, bone graft, roots biomodification, guided tissue regeneration and combination of the procedures, including restorative surgical procedure that is

  2. 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

  3. Bone-Inspired Spatially Specific Piezoelectricity Induces Bone Regeneration.

    Science.gov (United States)

    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.

  4. Individual differences in post radiation regeneration of the bone marrow in nonuniform irradiation (experimental investigation)

    International Nuclear Information System (INIS)

    Kalandarova, M.P.

    1980-01-01

    Reparative regeneration in bone marrow of sternum and iliac bone in each of 20 dogs was studied after single and two-time total X-ray irradiation. Extreme dose rates in bodies differed 5 and 8 times. It was shown that bone marrow repair did not depend on its composition before irradiation. Dogs whose bone narrow was rich of cellular elements before irradiation had both active and sharply reduced bone marrow regeneration after single and two-time irradiation in 0.75-1.45 Gy doses (sternum). Animals with a poor total cellular composition of bone marrow of sternum before irradiation also had differences in the course of reparative processes: in some of them they were considerably pronoUnced and in others bone marrow aplasia lasted for one month. IndiVidual differences in the bone marrow (iliac bone) irradiated with 1.85-3.2 Gy doses were less marked during the reparative regeneration

  5. Biomimetic approaches with smart interfaces for bone regeneration.

    Science.gov (United States)

    Sailaja, G S; Ramesh, P; Vellappally, Sajith; Anil, Sukumaran; Varma, H K

    2016-11-05

    A 'smart tissue interface' is a host tissue-biomaterial interface capable of triggering favourable biochemical events inspired by stimuli responsive mechanisms. In other words, biomaterial surface is instrumental in dictating the interface functionality. This review aims to investigate the fundamental and favourable requirements of a 'smart tissue interface' that can positively influence the degree of healing and promote bone tissue regeneration. A biomaterial surface when interacts synergistically with the dynamic extracellular matrix, the healing process become accelerated through development of a smart interface. The interface functionality relies equally on bound functional groups and conjugated molecules belonging to the biomaterial and the biological milieu it interacts with. The essential conditions for such a special biomimetic environment are discussed. We highlight the impending prospects of smart interfaces and trying to relate the design approaches as well as critical factors that determine species-specific functionality with special reference to bone tissue regeneration.

  6. Mathematical modeling in wound healing, bone regeneration and tissue engineering.

    Science.gov (United States)

    Geris, Liesbet; Gerisch, Alf; Schugart, Richard C

    2010-12-01

    The processes of wound healing and bone regeneration and problems in tissue engineering have been an active area for mathematical modeling in the last decade. Here we review a selection of recent models which aim at deriving strategies for improved healing. In wound healing, the models have particularly focused on the inflammatory response in order to improve the healing of chronic wound. For bone regeneration, the mathematical models have been applied to design optimal and new treatment strategies for normal and specific cases of impaired fracture healing. For the field of tissue engineering, we focus on mathematical models that analyze the interplay between cells and their biochemical cues within the scaffold to ensure optimal nutrient transport and maximal tissue production. Finally, we briefly comment on numerical issues arising from simulations of these mathematical models.

  7. 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

  8. Novel Therapy for Bone Regeneration in Large Segmental Defects

    Science.gov (United States)

    2017-12-01

    can maintain bone length and allow successfully regeneration in segmental defects. r 2006 Elsevier Ltd. All rights reserved. Keywords: Bone...pre- formed endothelial networks, as the MSCs can act as pericytes to the newly formed blood vessels. Pirraco et al. [159] also cultured ECs and...AWARD NUMBER: W81XWH-13-1-0407 TITLE: Novel Therapy for Bone Regeneration in Large Segmental Defects PRINCIPAL INVESTIGATOR: Melissa Kacena

  9. Bioceramics of apatites: an option for bone regeneration

    International Nuclear Information System (INIS)

    Arxer, Eliana Alves; Almeida Filho, Edson de; Guastaldi, Antonio Carlos

    2011-01-01

    The bioceramics of calcium phosphate called apatite, are widely used as material for bone replacement and regeneration, due to its similarity to the mineral component of bones and teeth. The apatites are biocompatible, bioactive and integrate with living tissue by the same active process of physiological bone remodeling. These bioceramics may be used in medical, dental and orthopedic applications. In this research, it was used the wet method for the synthesis of the powder and biomimetic method for coating the surface. The Solubility study was performed in the layer deposited, apatite, for possible application as a platform for inorganic drug delivery. The bioceramics were characterized by MEV, DRX, and EDS. The curves of solubility of apatite in coatings showed that the OCP phase had a higher rate of release in the short term (4 days) while the HA phase showed a gradual release throughout the experiment (16 days). (author)

  10. Stem cells applications in bone and tooth repair and regeneration: New insights, tools, and hopes.

    Science.gov (United States)

    Abdel Meguid, Eiman; Ke, Yuehai; Ji, Junfeng; El-Hashash, Ahmed H K

    2018-03-01

    The exploration of stem and progenitor cells holds promise for advancing our understanding of the biology of tissue repair and regeneration mechanisms after injury. This will also help in the future use of stem cell therapy for the development of regenerative medicine approaches for the treatment of different tissue-species defects or disorders such as bone, cartilages, and tooth defects or disorders. Bone is a specialized connective tissue, with mineralized extracellular components that provide bones with both strength and rigidity, and thus enable bones to function in body mechanical supports and necessary locomotion process. New insights have been added to the use of different types of stem cells in bone and tooth defects over the last few years. In this concise review, we briefly describe bone structure as well as summarize recent research progress and accumulated information regarding the osteogenic differentiation of stem cells, as well as stem cell contributions to bone repair/regeneration, bone defects or disorders, and both restoration and regeneration of bones and cartilages. We also discuss advances in the osteogenic differentiation and bone regeneration of dental and periodontal stem cells as well as in stem cell contributions to dentine regeneration and tooth engineering. © 2017 Wiley Periodicals, Inc.

  11. The role of vasculature in bone development, regeneration and proper systemic functioning.

    Science.gov (United States)

    Filipowska, Joanna; Tomaszewski, Krzysztof A; Niedźwiedzki, Łukasz; Walocha, Jerzy A; Niedźwiedzki, Tadeusz

    2017-08-01

    Bone is a richly vascularized connective tissue. As the main source of oxygen, nutrients, hormones, neurotransmitters and growth factors delivered to the bone cells, vasculature is indispensable for appropriate bone development, regeneration and remodeling. Bone vasculature also orchestrates the process of hematopoiesis. Blood supply to the skeletal system is provided by the networks of arteries and arterioles, having distinct molecular characteristics and localizations within the bone structures. Blood vessels of the bone develop through the process of angiogenesis, taking place through different, bone-specific mechanisms. Impaired functioning of the bone blood vessels may be associated with the occurrence of some skeletal and systemic diseases, i.e., osteonecrosis, osteoporosis, atherosclerosis or diabetes mellitus. When a disease or trauma-related large bone defects appear, bone grafting or bone tissue engineering-based strategies are required. However, a successful bone regeneration in both approaches largely depends on a proper blood supply. In this paper, we review the most recent data on the functions, molecular characteristics and significance of the bone blood vessels, with a particular emphasis on the role of angiogenesis and blood vessel functioning in bone development and regeneration, as well as the consequences of its impairment in the course of different skeletal and systemic diseases.

  12. Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits

    Directory of Open Access Journals (Sweden)

    Živadinović Milka

    2016-01-01

    Full Text Available Background/Aim. The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods. The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm, which were grafted with autogenous bone and β-tricalcium phosphate (n = 4 or served as unfilled controls (n = 4. After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results. Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53% compared with β-tricalcium phosphate (30%, (p < 0.030 and control (7%, (p < 0.000 groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p < 0.008. Conclusion. In the present

  13. In Vitro Comparative Study of Oxygen Plasma Treated Poly(Lactic⁻Co⁻Glycolic) (PLGA) Membranes and Supported Nanostructured Oxides for Guided Bone Regeneration Processes.

    Science.gov (United States)

    Torres-Lagares, Daniel; Castellanos-Cosano, Lizett; Serrera-Figallo, Maria-Angeles; López-Santos, Carmen; Barranco, Angel; Rodríguez-González-Elipe, Agustín; Gutierrez-Perez, Jose-Luis

    2018-05-08

    (1) Background: The use of physical barriers to prevent the invasion of gingival and connective tissue cells into bone cavities during the healing process is called guided bone regeneration. The objective of this in-vitro study was to compare the growth of human osteoblasts on Poly(Lactic⁻co⁻Glycolic) (PLGA) membranes modified with oxygen plasma and Hydroxyapatite (HA), silicon dioxide (SiO₂), and titanium dioxide (TiO₂) composite nanoparticles, respectively. (2) Methods: All the membranes received a common treatment with oxygen plasma and were subsequently treated with HA nanostructured coatings (n = 10), SiO₂ (n = 10) and TiO₂ (n = 10), respectively and a PLGA control membrane (n = 10). The assays were performed using the human osteoblast line MG-63 acquired from the Center for Scientific Instrumentation (CIC) from the University of Granada. The cell adhesion and the viability of the osteoblasts were analyzed by means of light-field microphotographs of each condition with the inverted microscope Axio Observer A1 (Carl Zeiss). For the determination of the mitochondrial energy balance, the MitoProbe™ JC-1 Assay Kit was employed. For the determination of cell growth and the morphology of adherent osteoblasts, two techniques were employed: staining with phalloidin-TRITC and staining with DAPI. (3) Results: The modified membranes that show osteoblasts with a morphology more similar to the control osteoblasts follow the order: PLGA/PO₂/HA > PLGA/PO₂/SiO₂ > PLGA/PO₂/TiO₂ > PLGA ( p membranes was observed as follows: PLGA/PO₂/SiO₂ > PLGA/PO₂/HA > PLGA/PO₂/TiO₂ > PLGA ( p membranes PLGA/PO₂/HA and PLGA/PO₂/SiO₂. (4) Conclusion: The membrane in which osteoblasts show characteristics more similar to the control osteoblasts is the PLGA/PO₂/HA, followed by the PLGA/PO₂/SiO₂.

  14. 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.

  15. In vivo bone regeneration using a novel porous bioactive composite

    Energy Technology Data Exchange (ETDEWEB)

    Xie En [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Hu Yunyu [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China)], E-mail: orth1@fmmn.edu.cn; Chen Xiaofeng [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Bai Xuedong; Li Dan [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Ren Li [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Zhang Ziru [Foreign Languages School, Northwest University Xi' an (China)

    2008-11-15

    Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications.

  16. In vivo bone regeneration using a novel porous bioactive composite

    International Nuclear Information System (INIS)

    Xie En; Hu Yunyu; Chen Xiaofeng; Bai Xuedong; Li Dan; Ren Li; Zhang Ziru

    2008-01-01

    Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications

  17. Bioactive Scaffolds for Regeneration of Cartilage and Subchondral Bone Interface

    Science.gov (United States)

    Deng, Cuijun; Zhu, Huiying; Li, Jiayi; Feng, Chun; Yao, Qingqiang; Wang, Liming; Chang, Jiang; Wu, Chengtie

    2018-01-01

    The cartilage lesion resulting from osteoarthritis (OA) always extends into subchondral bone. It is of great importance for simultaneous regeneration of two tissues of cartilage and subchondral bone. 3D-printed Sr5(PO4)2SiO4 (SPS) bioactive ceramic scaffolds may achieve the aim of regenerating both of cartilage and subchondral bone. We hypothesized that strontium (Sr) and silicon (Si) ions released from SPS scaffolds play a crucial role in osteochondral defect reconstruction. Methods: SPS bioactive ceramic scaffolds were fabricated by a 3D-printing method. The SEM and ICPAES were used to investigate the physicochemical properties of SPS scaffolds. The proliferation and maturation of rabbit chondrocytes stimulated by SPS bioactive ceramics were measured in vitro. The stimulatory effect of SPS scaffolds for cartilage and subchondral bone regeneration was investigated in vivo. Results: SPS scaffolds significantly stimulated chondrocyte proliferation, and SPS extracts distinctly enhanced the maturation of chondrocytes and preserved chondrocytes from OA. SPS scaffolds markedly promoted the regeneration of osteochondral defects. The complex interface microstructure between cartilage and subchondral bone was obviously reconstructed. The underlying mechanism may be related to Sr and Si ions stimulating cartilage regeneration by activating HIF pathway and promoting subchondral bone reconstruction through activating Wnt pathway, as well as preserving chondrocytes from OA via inducing autophagy and inhibiting hedgehog pathway. Conclusion: Our findings suggest that SPS scaffolds can help osteochondral defect reconstruction and well reconstruct the complex interface between cartilage and subchondral bone, which represents a promising strategy for osteochondral defect regeneration. PMID:29556366

  18. The application of nanomaterials in controlled drug delivery for bone regeneration.

    Science.gov (United States)

    Shi, Shuo; Jiang, Wenbao; Zhao, Tianxiao; Aifantis, Katerina E; Wang, Hui; Lin, Lei; Fan, Yubo; Feng, Qingling; Cui, Fu-zhai; Li, Xiaoming

    2015-12-01

    Bone regeneration is a complicated process that involves a series of biological events, such as cellular recruitment, proliferation and differentiation, and so forth, which have been found to be significantly affected by controlled drug delivery. Recently, a lot of research studies have been launched on the application of nanomaterials in controlled drug delivery for bone regeneration. In this article, the latest research progress in this area regarding the use of bioceramics-based, polymer-based, metallic oxide-based and other types of nanomaterials in controlled drug delivery for bone regeneration are reviewed and discussed, which indicates that the controlling drug delivery with nanomaterials should be a very promising treatment in orthopedics. Furthermore, some new challenges about the future research on the application of nanomaterials in controlled drug delivery for bone regeneration are described in the conclusion and perspectives part. Copyright © 2015 Wiley Periodicals, Inc.

  19. Bone regeneration potential of sub-microfibrous membranes with ...

    African Journals Online (AJOL)

    electrospinning. Cell viability, biocompatibility, and bone regeneration were measured. ... human mesenchymal stem cells (hMSCs) were grown on the ... In vivo biocompatibility test ..... biodegradability and drug release behavior of aliphatic.

  20. Bone regeneration with biomaterials and active molecules delivery.

    Science.gov (United States)

    D' Este, Matteo; Eglin, David; Alini, Mauro; Kyllonen, Laura

    2015-01-01

    The combination of biomaterials and drug delivery strategies is a promising avenue towards improved synthetic bone substitutes. With the delivery of active species biomaterials can be provided with the bioactivity they still lack for improved bone regeneration. Recently, a lot of research efforts have been put towards this direction. Biomaterials for bone regeneration have been supplemented with small or biological molecules for improved osteoprogenitor cell recruitment, osteoinductivity, anabolic or angiogenic response, regulation of bone metabolism and others. The scope of this review is to summarize the most recent results in this field.

  1. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration

    International Nuclear Information System (INIS)

    Xiao Caiwen; Zhou Huifang; Fu Yao; Gu Ping; Fan Xianqun; Liu Guangpeng; Zhang Peng; Hou Hongliang; Tang Tingting

    2011-01-01

    Bone graft substitutes with osteogenic factors alone often exhibit poor bone regeneration due to inadequate vascularization. Combined delivery of osteogenic and angiogenic factors from biodegradable scaffolds may enhance bone regeneration. We evaluated the effects of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), combined with natural coral scaffolds, on the repair of critical-sized bone defects in rabbit orbits. In vitro expanded rabbit bone marrow stromal cells (BMSCs) were transfected with human BMP2 and VEGF165 genes. Target protein expression and osteogenic differentiation were confirmed after gene transduction. Rabbit orbital defects were treated with a coral scaffold loaded with BMP2-transduced and VEGF-transduced BMSCs, BMP2-expressing BMSCs, VEGF-expressing BMSCs, or BMSCs without gene transduction. Volume and density of regenerated bone were determined by micro-computed tomography at 4, 8, and 16 weeks after implantation. Neovascularity, new bone deposition rate, and new bone formation were measured by immunostaining, tetracycline and calcein labelling, and histomorphometric analysis at different time points. The results showed that VEGF increased blood vessel formation relative to groups without VEGF. Combined delivery of BMP2 and VEGF increased new bone deposition and formation, compared with any single factor. These findings indicate that mimicking the natural bone development process by combined BMP2 and VEGF delivery improves healing of critical-sized orbital defects in rabbits.

  2. Strontium borate glass: potential biomaterial for bone regeneration.

    Science.gov (United States)

    Pan, H B; Zhao, X L; Zhang, X; Zhang, K B; Li, L C; Li, Z Y; Lam, W M; Lu, W W; Wang, D P; Huang, W H; Lin, K L; Chang, J

    2010-07-06

    Boron plays important roles in many life processes including embryogenesis, bone growth and maintenance, immune function and psychomotor skills. Thus, the delivery of boron by the degradation of borate glass is of special interest in biomedical applications. However, the cytotoxicity of borate glass which arises with the rapid release of boron has to be carefully considered. In this study, it was found that the incorporation of strontium into borate glass can not only moderate the rapid release of boron, but also induce the adhesion of osteoblast-like cells, SaOS-2, thus significantly increasing the cyto-compatibility of borate glass. The formation of multilayers of apatite with porous structure indicates that complete degradation is optimistic, and the spread of SaOS-2 covered by apatite to form a sandwich structure may induce bone-like tissue formation at earlier stages. Therefore, such novel strontium-incorporated borosilicate may act as a new generation of biomaterial for bone regeneration, which not only renders boron as a nutritious element for bone health, but also delivers strontium to stimulate formation of new bones.

  3. PREDICTION OF THE DURATION OF DISTRACTION REGENERATED BONE MATURATION

    Directory of Open Access Journals (Sweden)

    N. V. Tushina

    2012-01-01

    Full Text Available Aim of the study the characteristics of changes of serum biochemical parameters in dogs with delayed maturation of the distraction regenerate after surgical lengthening the leg bones by Ilizarov. The comparative analysis of biochemical changes in blood serum of animals with delayed regenerated bone osteogenesis after surgical leg bone lengthening according to Ilizarov has been made in the work. The development of persistent and marked hypocalcemia, significant accumulation of blood serum nonoxidized degradation products during limb bone surgical lengthening according to Ilizarov have been revealed to be adverse signs evidencing of the high probability of the disorder of further formation of the regenerated bone and its subsequent maturation at the stage of fixation.

  4. In Vitro Comparative Study of Oxygen Plasma Treated Poly(Lactic–Co–Glycolic (PLGA Membranes and Supported Nanostructured Oxides for Guided Bone Regeneration Processes

    Directory of Open Access Journals (Sweden)

    Daniel Torres-Lagares

    2018-05-01

    Full Text Available (1 Background: The use of physical barriers to prevent the invasion of gingival and connective tissue cells into bone cavities during the healing process is called guided bone regeneration. The objective of this in-vitro study was to compare the growth of human osteoblasts on Poly(Lactic–co–Glycolic (PLGA membranes modified with oxygen plasma and Hydroxyapatite (HA, silicon dioxide (SiO2, and titanium dioxide (TiO2 composite nanoparticles, respectively. (2 Methods: All the membranes received a common treatment with oxygen plasma and were subsequently treated with HA nanostructured coatings (n = 10, SiO2 (n = 10 and TiO2 (n = 10, respectively and a PLGA control membrane (n = 10. The assays were performed using the human osteoblast line MG-63 acquired from the Center for Scientific Instrumentation (CIC from the University of Granada. The cell adhesion and the viability of the osteoblasts were analyzed by means of light-field microphotographs of each condition with the inverted microscope Axio Observer A1 (Carl Zeiss. For the determination of the mitochondrial energy balance, the MitoProbe™ JC-1 Assay Kit was employed. For the determination of cell growth and the morphology of adherent osteoblasts, two techniques were employed: staining with phalloidin-TRITC and staining with DAPI. (3 Results: The modified membranes that show osteoblasts with a morphology more similar to the control osteoblasts follow the order: PLGA/PO2/HA > PLGA/PO2/SiO2 > PLGA/PO2/TiO2 > PLGA (p < 0.05. When analysing the cell viability, a higher percentage of viable cells bound to the membranes was observed as follows: PLGA/PO2/SiO2 > PLGA/PO2/HA > PLGA/PO2/TiO2 > PLGA (p < 0.05, with a better energy balance of the cells adhered to the membranes PLGA/PO2/HA and PLGA/PO2/SiO2. (4 Conclusion: The membrane in which osteoblasts show characteristics more similar to the control osteoblasts is the PLGA/PO2/HA, followed by the PLGA/PO2/SiO2.

  5. Guided Bone Regeneration in Long-Bone Defects with a Structural Hydroxyapatite Graft and Collagen Membrane

    Science.gov (United States)

    2013-01-01

    Original Articles Guided Bone Regeneration in Long-Bone Defects with a Structural Hydroxyapatite Graft and Collagen Membrane Teja Guda, PhD,1,2 John...Joint Surg Br 90-B, 1617, 2008. 6. Carlo Reis, E.C., Borges AaPB, Araujo, M.V.F., Mendes, V.C., Guan, L., and Davies, J.E. Periodontal regeneration...Regeneration of periodontal tissues: combinations of barrier membranes and grafting materials–biological foundation and preclinical evi- dence: a

  6. Post-irradiation thymocyte regeneration after bone marrow transplantation

    International Nuclear Information System (INIS)

    Boersma, W.; Betel, I.; Daculsi, R.; Westen, G. van der

    1981-01-01

    Growth kinetics of the donor-type thymus cell population after transplantation of bone marrow into irradiated syngeneic recipient mice is biphasic. During the first rapid phase of regeneration, lasting until day 19 after transplantation, the rate of development of the donor cells is independent of the number of bone marrow cells inoculated. The second slow phase is observed only when low numbers of bone marrow cells (2.5 x 10 4 ) are transplanted. The decrease in the rate of development is attributed to an efflux of donor cells from the thymus because, at the same time, the first immunologically competent cells are found in spleen. After bone marrow transplantation the regeneration of thymocyte progenitor cells in the marrow is delayed when compared to regeneration of CFUs. Therefore, regenerating marrow has a greatly reduced capacity to restore the thymus cell population. One week after transplantation of 3 x 10 6 cells, 1% of normal capacity of bone marrow is found. It is concluded that the regenerating thymus cells population after bone marrow transplantation is composed of the direct progeny of precursor cells in the inoculum. (author)

  7. Optimization of scaled-up chitosan microparticles for bone regeneration

    International Nuclear Information System (INIS)

    Jayasuriya, A Champa; Bhat, Archana

    2009-01-01

    The aim of this study was to scale-up and optimize the chitosan (CS) microparticles (MPs) from 1x batch (41-85 mg) to 4x batch (270-567 mg) to be used in bone regeneration. The MPs used in the present study were prepared by double emulsification technique using CS as a base material under physiologically friendly conditions throughout the process. Structural integrity of MPs was improved creating cross-links between amine groups in CS and phosphate groups in tripolyphosphate (TPP) which has been used as an ionic cross-linking agent. The cross-linking density was varied using different amounts of TPP to CS such as 0%, 8%, 32%, 64% and 110% (w/w). The CS MPs were approximately spherical in shape with a size of 30-50 μm according to scanning electron microscopy results. X-ray diffraction data revealed having TPP in the CS MPs. The evidence of ionic cross-links in the CS MPs was analyzed using Fourier Transform Infra Red. When we scaled-up the yield of MPs, we investigated that 64% TPP cross-linking density provided the best quality MPs. In addition, those MPs provided the yield from 75 mg to 310 mg when scaled up from 1x to 4x batch, respectively. The MPs developed have a great potential to be used as an injectable scaffold for bone regeneration including orthopedic and craniofacial applications using minimally invasive conditions compared with conventional three-dimensional scaffolds.

  8. Bone Regeneration from PLGA Micro-Nanoparticles.

    Science.gov (United States)

    Ortega-Oller, Inmaculada; Padial-Molina, Miguel; Galindo-Moreno, Pablo; O'Valle, Francisco; Jódar-Reyes, Ana Belén; Peula-García, Jose Manuel

    2015-01-01

    Poly-lactic-co-glycolic acid (PLGA) is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2). Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed.

  9. Production of new 3D scaffolds for bone tissue regeneration by rapid prototyping.

    Science.gov (United States)

    Fradique, R; Correia, T R; Miguel, S P; de Sá, K D; Figueira, D R; Mendonça, A G; Correia, I J

    2016-04-01

    The incidence of bone disorders, whether due to trauma or pathology, has been trending upward with the aging of the worldwide population. The currently available treatments for bone injuries are rather limited, involving mainly bone grafts and implants. A particularly promising approach for bone regeneration uses rapid prototyping (RP) technologies to produce 3D scaffolds with highly controlled structure and orientation, based on computer-aided design models or medical data. Herein, tricalcium phosphate (TCP)/alginate scaffolds were produced using RP and subsequently their physicochemical, mechanical and biological properties were characterized. The results showed that 60/40 of TCP and alginate formulation was able to match the compression and present a similar Young modulus to that of trabecular bone while presenting an adequate biocompatibility. Moreover, the biomineralization ability, roughness and macro and microporosity of scaffolds allowed cell anchoring and proliferation at their surface, as well as cell migration to its interior, processes that are fundamental for osteointegration and bone regeneration.

  10. Nanomechanical mapping of bone tissue regenerated by magnetic scaffolds.

    Science.gov (United States)

    Bianchi, Michele; Boi, Marco; Sartori, Maria; Giavaresi, Gianluca; Lopomo, Nicola; Fini, Milena; Dediu, Alek; Tampieri, Anna; Marcacci, Maurilio; Russo, Alessandro

    2015-01-01

    Nanoindentation can provide new insights on the maturity stage of regenerating bone. The aim of the present study was the evaluation of the nanomechanical properties of newly-formed bone tissue at 4 weeks from the implantation of permanent magnets and magnetic scaffolds in the trabecular bone of rabbit femoral condyles. Three different groups have been investigated: MAG-A (NdFeB magnet + apatite/collagen scaffold with magnetic nanoparticles directly nucleated on the collagen fibers during scaffold synthesis); MAG-B (NdFeB magnet + apatite/collagen scaffold later infiltrated with magnetic nanoparticles) and MAG (NdFeB magnet). The mechanical properties of different-maturity bone tissues, i.e. newly-formed immature, newly-formed mature and native trabecular bone have been evaluated for the three groups. Contingent correlations between elastic modulus and hardness of immature, mature and native bone have been examined and discussed, as well as the efficacy of the adopted regeneration method in terms of "mechanical gap" between newly-formed and native bone tissue. The results showed that MAG-B group provided regenerated bone tissue with mechanical properties closer to that of native bone compared to MAG-A or MAG groups after 4 weeks from implantation. Further, whereas the mechanical properties of newly-formed immature and mature bone were found to be fairly good correlated, no correlation was detected between immature or mature bone and native bone. The reported results evidence the efficacy of nanoindentation tests for the investigation of the maturity of newly-formed bone not accessible through conventional analyses.

  11. A tissue regeneration approach to bone and cartilage repair

    CERN Document Server

    Dunstan, Colin; Rosen, Vicki

    2015-01-01

    Reviewing exhaustively the current state of the art of tissue engineering strategies for regenerating bones and joints through the use of biomaterials, growth factors and stem cells, along with an investigation of the interactions between biomaterials, bone cells, growth factors and added stem cells and how together skeletal tissues can be optimised, this book serves to highlight the importance of biomaterials composition, surface topography, architectural and mechanical properties in providing support for tissue regeneration. Maximizing reader insights into the importance of the interplay of these attributes with bone cells (osteoblasts, osteocytes and osteoclasts) and cartilage cells (chondrocytes), this book also provides a detailed reference as to how key signalling pathways are activated. The contribution of growth factors to drive tissue regeneration and stem cell recruitment is discussed along with a review the potential and challenges of adult or embryonic mesenchymal stem cells to further enhance the...

  12. Osteostatin-coated porous titanium can improve early bone regeneration of cortical bone defects in rats

    NARCIS (Netherlands)

    Van Der Stok, Johan; Lozano, Daniel; Chai, Yoke Chin; Amin Yavari, Saber; Bastidas Coral, Angela P.; Verhaar, Jan A N; Gómez-Barrena, Enrique; Schrooten, Jan; Jahr, Holger; Zadpoor, Amir A.; Esbrit, Pedro; Weinans, Harrie

    2015-01-01

    A promising bone graft substitute is porous titanium. Porous titanium, produced by selective laser melting (SLM), can be made as a completely open porous and load-bearing scaffold that facilitates bone regeneration through osteoconduction. In this study, the bone regenerative capacity of porous

  13. Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitis.

    Science.gov (United States)

    Haze, Amir; Taylor, Angela L; Haegewald, Stefan; Leiser, Yoav; Shay, Boaz; Rosenfeld, Eli; Gruenbaum-Cohen, Yael; Dafni, Leah; Zimmermann, Bernd; Heikinheimo, Kristiina; Gibson, Carolyn W; Fisher, Larry W; Young, Marian F; Blumenfeld, Anat; Bernimoulin, Jean P; Deutsch, Dan

    2009-06-01

    Regeneration of mineralized tissues affected by chronic diseases comprises a major scientific and clinical challenge. Periodontitis, one such prevalent disease, involves destruction of the tooth-supporting tissues, alveolar bone, periodontal-ligament and cementum, often leading to tooth loss. In 1997, it became clear that, in addition to their function in enamel formation, the hydrophobic ectodermal enamel matrix proteins (EMPs) play a role in the regeneration of these periodontal tissues. The epithelial EMPs are a heterogeneous mixture of polypeptides encoded by several genes. It was not clear, however, which of these many EMPs induces the regeneration and what mechanisms are involved. Here we show that a single recombinant human amelogenin protein (rHAM(+)), induced in vivo regeneration of all tooth-supporting tissues after creation of experimental periodontitis in a dog model. To further understand the regeneration process, amelogenin expression was detected in normal and regenerating cells of the alveolar bone (osteocytes, osteoblasts and osteoclasts), periodontal ligament, cementum and in bone marrow stromal cells. Amelogenin expression was highest in areas of high bone turnover and activity. Further studies showed that during the first 2 weeks after application, rHAM(+) induced, directly or indirectly, significant recruitment of mesenchymal progenitor cells, which later differentiated to form the regenerated periodontal tissues. The ability of a single protein to bring about regeneration of all periodontal tissues, in the correct spatio-temporal order, through recruitment of mesenchymal progenitor cells, could pave the way for development of new therapeutic devices for treatment of periodontal, bone and ligament diseases based on rHAM(+).

  14. Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats

    Science.gov (United States)

    Gedrange, Tomasz

    2016-01-01

    The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen) and unmodified (PLA-wt, PCL-wt), were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions. PMID:27597965

  15. Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats.

    Science.gov (United States)

    Gredes, Tomasz; Kunath, Franziska; Gedrange, Tomasz; Kunert-Keil, Christiane

    2016-01-01

    The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen) and unmodified (PLA-wt, PCL-wt), were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions.

  16. Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats

    Directory of Open Access Journals (Sweden)

    Tomasz Gredes

    2016-01-01

    Full Text Available The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen and unmodified (PLA-wt, PCL-wt, were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions.

  17. Unbiased stereological methods used for the quantitative evaluation of guided bone regeneration

    DEFF Research Database (Denmark)

    Aaboe, Else Merete; Pinholt, E M; Schou, S

    1998-01-01

    The present study describes the use of unbiased stereological methods for the quantitative evaluation of the amount of regenerated bone. Using the principle of guided bone regeneration the amount of regenerated bone after placement of degradable or non-degradable membranes covering defects...

  18. Incomplete bone regeneration of rabbit calvarial defects using different membranes

    DEFF Research Database (Denmark)

    Aaboe, M; Pinholt, E M; Schou, S

    1998-01-01

    The present study describes the use of a degradable and a non-degradable material for guided bone regeneration. Forty rabbits were divided into 5 groups. Bicortical defects 15 mm in diameter were prepared in rabbit calvaria. A titanium microplate was placed over the defect to prevent collapse...

  19. Biomechanical, microvascular, and cellular factors promote muscle and bone regeneration.

    Science.gov (United States)

    Duda, Georg N; Taylor, William R; Winkler, Tobias; Matziolis, Georg; Heller, Markus O; Haas, Norbert P; Perka, Carsten; Schaser, Klaus-D

    2008-04-01

    It is becoming clear that the long-term outcome of complex bone injuries benefits from approaches that selectively target biomechanical, vascular, and cellular pathways. The typically held view of either biological or mechanical aspects of healing is oversimplified and does not correspond to clinical reality. The fundamental mechanisms of soft tissue regeneration most likely hold the key to understanding healing response.

  20. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration.

    Science.gov (United States)

    Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

    2013-01-01

    Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically.

  1. Manufacture of degradable polymeric scaffolds for bone regeneration.

    Science.gov (United States)

    Ge, Zigang; Jin, Zhaoxia; Cao, Tong

    2008-06-01

    Many innovative technology platforms for promoting bone regeneration have been developed. A common theme among these is the use of scaffolds to provide mechanical support and osteoconduction. Scaffolds can be either ceramic or polymer-based, or composites of both classes of material. Both ceramics and polymers have their own merits and drawbacks, and a better solution may be to synergize the advantageous properties of both materials within composite scaffolds. In this current review, after a brief introduction of the anatomy and physiology of bone, different strategies of fabricating polymeric scaffolds for bone regeneration, including traditional and solid free-form fabrication, are critically discussed and compared, while focusing on the advantages and disadvantages of individual techniques.

  2. Manufacture of degradable polymeric scaffolds for bone regeneration

    International Nuclear Information System (INIS)

    Ge Zigang; Jin Zhaoxia; Cao Tong

    2008-01-01

    Many innovative technology platforms for promoting bone regeneration have been developed. A common theme among these is the use of scaffolds to provide mechanical support and osteoconduction. Scaffolds can be either ceramic or polymer-based, or composites of both classes of material. Both ceramics and polymers have their own merits and drawbacks, and a better solution may be to synergize the advantageous properties of both materials within composite scaffolds. In this current review, after a brief introduction of the anatomy and physiology of bone, different strategies of fabricating polymeric scaffolds for bone regeneration, including traditional and solid free-form fabrication, are critically discussed and compared, while focusing on the advantages and disadvantages of individual techniques. (topical review)

  3. 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.

  4. Delivery of bone morphogenetic protein-2 and substance P using graphene oxide for bone regeneration

    Directory of Open Access Journals (Sweden)

    La WG

    2014-05-01

    Full Text Available Wan-Geun La,1 Min Jin,1 Saibom Park,1,2 Hee-Hun Yoon,1 Gun-Jae Jeong,1 Suk Ho Bhang,1 Hoyoung Park,1,2 Kookheon Char,1,2 Byung-Soo Kim1,31School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea; 2The National Creative Research Initiative Center for Intelligent Hybrids, Seoul National University, Seoul, Republic of Korea; 3Institute of Bioengineering, Institute of Chemical Processes, Engineering Research Institute, Seoul National University, Seoul, Republic of KoreaAbstract: In this study, we demonstrate that graphene oxide (GO can be used for the delivery of bone morphogenetic protein-2 (BMP-2 and substance P (SP, and that this delivery promotes bone formation on titanium (Ti implants that are coated with GO. GO coating on Ti substrate enabled a sustained release of BMP-2. BMP-2 delivery using GO-coated Ti exhibited a higher alkaline phosphatase activity in bone-forming cells in vitro compared with bare Ti. SP, which is known to recruit mesenchymal stem cells (MSCs, was co-delivered using Ti or GO-coated Ti to further promote bone formation. SP induced the migration of MSCs in vitro. The dual delivery of BMP-2 and SP using GO-coated Ti showed the greatest new bone formation on Ti implanted in the mouse calvaria compared with other groups. This approach may be useful to improve osteointegration of Ti in dental or orthopedic implants.Keywords: bone morphogenetic protein-2, bone regeneration, graphene oxides, stem cell recruitment, substance P

  5. The effect of carrier type on bone regeneration of demineralized bone matrix in vivo.

    Science.gov (United States)

    Tavakol, Shima; Khoshzaban, Ahad; Azami, Mahmoud; Kashani, Iraj Ragerdi; Tavakol, Hani; Yazdanifar, Mahbube; Sorkhabadi, Seyed Mahdi Rezayat

    2013-11-01

    Demineralized bone matrix (DBM) is a bone substitute biomaterial used as an excellent grafting material. Some factors such as carrier type might affect the healing potential of this material. The background data discuss the present status of the field: Albumin as a main protein in blood and carboxymethyl cellulose (CMC) were applied frequently in the DBM gels. We investigated the bone-repairing properties of 2 DBMs with different carriers. Bone regeneration in 3 groups of rat calvaria treated with DBM from the Iranian Tissue Bank Research and Preparation Center, DBM from Hans Biomed Corporation, and an empty cavity was studied. Albumin and CMC as carriers were used. The results of bone regeneration in the samples after 1, 4, and 8 weeks of implantation were compared. The block of the histologic samples was stained with hematoxylin and eosin, and the percentage area of bone formation was calculated using the histomorphometry method. The results of in vivo tests showed a significantly stronger new regenerated bone occupation in the DBM with albumin carrier compared with the one with CMC 8 weeks after the implantation. The 2 types of DBM had a significant difference in bone regeneration. This difference is attributed to the type of carriers. Albumin could improve mineralization and bioactivity compared with CMC.

  6. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

    Directory of Open Access Journals (Sweden)

    Gu W

    2013-06-01

    Full Text Available Wenyi Gu,1,2 Chengtie Wu,3 Jiezhong Chen,1 Yin Xiao1 1Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia; 2Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia; 3State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People's Republic of China Abstract: Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically. Keywords: nanoparticles, nanostructured scaffold, cancer bone metastasis, bone diseases, target drug delivery, bone regeneration

  7. Instructive function of surface structure of calcium phosphate ceramics in bone regeneration

    NARCIS (Netherlands)

    Zhang, Jingwei

    2016-01-01

    The incidence of patients which require spinal fusion or bone regeneration in large bone defects caused by trauma, tumors, tumor resection, infections or abnormal skeletal development, is on the rise. Traditionally, in both spinal fusion surgery and other bone regeneration approaches, bone grafts

  8. Demineralized Freeze-Dried Bovine Cortical Bone: Its Potential for Guided Bone Regeneration Membrane

    Directory of Open Access Journals (Sweden)

    David B. Kamadjaja

    2017-01-01

    Full Text Available Background. Bovine pericardium collagen membrane (BPCM had been widely used in guided bone regeneration (GBR whose manufacturing process usually required chemical cross-linking to prolong its biodegradation. However, cross-linking of collagen fibrils was associated with poorer tissue integration and delayed vascular invasion. Objective. This study evaluated the potential of bovine cortical bone collagen membrane for GBR by evaluating its antigenicity potential, cytotoxicity, immune and tissue response, and biodegradation behaviors. Material and Methods. Antigenicity potential of demineralized freeze-dried bovine cortical bone membrane (DFDBCBM was done with histology-based anticellularity evaluation, while cytotoxicity was analyzed using MTT Assay. Evaluation of immune response, tissue response, and biodegradation was done by randomly implanting DFDBCBM and BPCM in rat’s subcutaneous dorsum. Samples were collected at 2, 5, and 7 days and 7, 14, 21, and 28 days for biocompatibility and tissue response-biodegradation study, respectively. Result. DFDBCBM, histologically, showed no retained cells; however, it showed some level of in vitro cytotoxicity. In vivo study exhibited increased immune response to DFDBCBM in early healing phase; however, normal tissue response and degradation rate were observed up to 4 weeks after DFDBCBM implantation. Conclusion. Demineralized freeze-dried bovine cortical bone membrane showed potential for clinical application; however, it needs to be optimized in its biocompatibility to fulfill all requirements for GBR membrane.

  9. Bone regeneration performance of surface-treated porous titanium.

    Science.gov (United States)

    Amin Yavari, Saber; van der Stok, Johan; Chai, Yoke Chin; Wauthle, Ruben; Tahmasebi Birgani, Zeinab; Habibovic, Pamela; Mulier, Michiel; Schrooten, Jan; Weinans, Harrie; Zadpoor, Amir Abbas

    2014-08-01

    The large surface area of highly porous titanium structures produced by additive manufacturing can be modified using biofunctionalizing surface treatments to improve the bone regeneration performance of these otherwise bioinert biomaterials. In this longitudinal study, we applied and compared three types of biofunctionalizing surface treatments, namely acid-alkali (AcAl), alkali-acid-heat treatment (AlAcH), and anodizing-heat treatment (AnH). The effects of treatments on apatite forming ability, cell attachment, cell proliferation, osteogenic gene expression, bone regeneration, biomechanical stability, and bone-biomaterial contact were evaluated using apatite forming ability test, cell culture assays, and animal experiments. It was found that AcAl and AnH work through completely different routes. While AcAl improved the apatite forming ability of as-manufactured (AsM) specimens, it did not have any positive effect on cell attachment, cell proliferation, and osteogenic gene expression. In contrast, AnH did not improve the apatite forming ability of AsM specimens but showed significantly better cell attachment, cell proliferation, and expression of osteogenic markers. The performance of AlAcH in terms of apatite forming ability and cell response was in between both extremes of AnH and AsM. AcAl resulted in significantly larger volumes of newly formed bone within the pores of the scaffold as compared to AnH. Interestingly, larger volumes of regenerated bone did not translate into improved biomechanical stability as AnH exhibited significantly better biomechanical stability as compared to AcAl suggesting that the beneficial effects of cell-nanotopography modulations somehow surpassed the benefits of improved apatite forming ability. In conclusion, the applied surface treatments have considerable effects on apatite forming ability, cell attachment, cell proliferation, and bone ingrowth of the studied biomaterials. The relationship between these properties and the bone

  10. 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.

  11. 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.

  12. Histomorphological evaluation of Compound bone of Granulated Ricinus in bone regeneration in rabbits

    International Nuclear Information System (INIS)

    Mateus, Christiano Pavan; Chierice, Gilberto Orivaldo; Okamoto, Tetuo

    2011-01-01

    Histological evaluation is an effective method in the behavioral description of the qualitative and quantitative implanted materials. The research validated the performance of Compound bone of Granulated Ricinus on bone regeneration with the histomorphological analysis results. Were selected 30 rabbits, females, divided into 3 groups of 10 animals (G1, G2, G3) with a postoperative time of 45, 70 and 120 days respectively. Each animal is undergone 2 bone lesions in the ilium, one implemented in the material: Compound bone of Granulated Ricinus and the other for control. After the euthanasia, the iliac bone was removed, identified and subjected to histological procedure. The evaluation histological, histomorphological results were interpreted and described by quantitative and qualitative analysis based facts verified in the three experimental groups evaluating the rate of absorption of the material in the tissue regeneration, based on the neo-bone formation. The histomorphologic results classified as a material biocompatible and biologically active. Action in regeneration by bone resorption occurs slowly and gradually. Knowing the time and rate of absorption and neo-formation bone biomaterial, which can be determined in the bone segment applicable in the clinical surgical area.

  13. Antibacterial Membrane with a Bone-Like Structure for Guided Bone Regeneration

    Directory of Open Access Journals (Sweden)

    YuYuan Zhang

    2015-01-01

    Full Text Available An antibacterial membrane with a bone-like structure was developed for guided bone regeneration (GBR by mineralising acellular bovine pericardium (ABP and loading it with the antibiotic minocycline. The bovine pericardium (BP membrane was processed using physical and chemical methods to remove the cellular components and obtain ABP membranes. Then, the ABP membranes were biomimetically mineralised using a calcium phosphate-loaded agarose hydrogel system aided by electrophoresis. Minocycline was adsorbed to the mineralised ABP membrane, and the release profile in vitro was studied. The membranes were characterised through scanning electron microscopy, diffuse reflectance-Fourier transform infrared spectroscopy, and X-ray diffraction. Results showed that the ABP membrane had an asymmetric structure with a layer of densely arranged and irregularly aligned collagen fibrils. Collagen fibrils were calcified with the formation of intrafibrillar and interfibrillar hydroxyapatites similar to the bone structure. Minocycline was incorporated into the mineralised collagen membrane and could be released in vitro. This process endowed the membrane with an antibacterial property. This novel composite membrane offers promising applications in bioactive GBR.

  14. Bacterial Cellulose-Hydroxyapatite Nanocomposites for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    S. Saska

    2011-01-01

    Full Text Available The aim of this study was to develop and to evaluate the biological properties of bacterial cellulose-hydroxyapatite (BC-HA nanocomposite membranes for bone regeneration. Nanocomposites were prepared from bacterial cellulose membranes sequentially incubated in solutions of CaCl2 followed by Na2HPO4. BC-HA membranes were evaluated in noncritical bone defects in rat tibiae at 1, 4, and 16 weeks. Thermogravimetric analyses showed that the amount of the mineral phase was 40%–50% of the total weight. Spectroscopy, electronic microscopy/energy dispersive X-ray analyses, and X-ray diffraction showed formation of HA crystals on BC nanofibres. Low crystallinity HA crystals presented Ca/P a molar ratio of 1.5 (calcium-deficient HA, similar to physiological bone. Fourier transformed infrared spectroscopy analysis showed bands assigned to phosphate and carbonate ions. In vivo tests showed no inflammatory reaction after 1 week. After 4 weeks, defects were observed to be completely filled in by new bone tissue. The BC-HA membranes were effective for bone regeneration.

  15. LIVER AND BONE MARROW STEM/PROGENITOR CELLS AS REGULATORS OF REPARATIVE REGENERATION OF DAMAGED LIVER

    Directory of Open Access Journals (Sweden)

    А. V. Lundup

    2010-01-01

    Full Text Available In this review the modern information about effectiveness of liver insufficiency treatment by stem/ progenitor cells of liver (oval cells and bone marrow (hemopoietic cells and mesenchymal cells was presented. It is shown that medical action of these cells is referred on normalization of liver cell interaction and reorganization of processes of a reparative regeneration in damaged liver. It is believed that application of mesenchymal stromal cells from an autological bone marrow is the most perspective strategy. However, for definitive judgement about regenerative possibilities of the autological bone marrow cells it is necessary to carry out large-scale double blind clinical researches. 

  16. Alkali-free bioactive glasses for bone regeneration

    OpenAIRE

    Kapoor, Saurabh

    2014-01-01

    Bioactive glasses and glass-ceramics are a class of third generation biomaterials which elicit a special response on their surface when in contact with biological fluids, leading to strong bonding to living tissues. The purpose of the present study was to develop diopside based alkali-free bioactive glasses in order to achieve good sintering behaviour, high bioactivity, and a dissolution/ degradation rates compatible with the target applications in bone regeneration and tiss...

  17. Administration of RANKL boosts thymic regeneration upon bone marrow transplantation.

    Science.gov (United States)

    Lopes, Noella; Vachon, Hortense; Marie, Julien; Irla, Magali

    2017-06-01

    Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs), which result in delayed de novo thymopoiesis and a prolonged period of T-cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation (BMT). Here, we show that RANK ligand (RANKL) is upregulated in CD4 + thymocytes and lymphoid tissue inducer (LTi) cells during the early phase of thymic regeneration. Importantly, whereas RANKL neutralization alters TEC recovery after irradiation, ex vivo RANKL administration during BMT boosts the regeneration of TEC subsets including thymic epithelial progenitor-enriched cells, thymus homing of lymphoid progenitors, and de novo thymopoiesis. RANKL increases specifically in LTi cells, lymphotoxin α, which is critical for thymic regeneration. RANKL treatment, dependent on lymphotoxin α, is beneficial upon BMT in young and aged individuals. This study thus indicates that RANKL may be clinically useful to improve T-cell function recovery after BMT by controlling multiple facets of thymic regeneration. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  18. Histological evolution of the regenerate during bone transport: an experimental study in sheep.

    Science.gov (United States)

    López-Pliego, Esperanza Macarena; Giráldez-Sánchez, Miguel Ángel; Mora-Macías, Juan; Reina-Romo, Esther; Domínguez, Jaime

    2016-09-01

    Bone transport (BT) for segmentary bone defects is a well-known technique as it enables correction with new bone formation, which is similar to the previous bone. Despite the high number of experimental studies of distraction osteogenesis in bone lengthening, the types of ossification and histological changes that occur in the regenerate of the bone transport process remain controversial. The aim of this study is to provide the complete evolution of tissues and the types of ossification in the regenerate during the different phases of bone formation after BT until the end of the remodelling period. A histological study was performed using ten adult sheep that were submitted to BT. The types of ossification as well as the evolution of different tissues in the regenerate were determined using histomorphometry and inmunohistochemical studies. The evolution of trabeculae thickness, osteoblast and osteoclast densities, relationship between collagen types and changes in vascularization were also studied. Ossification was primarily intramembranous, with some focus of endochondral ossification in isolated animals. The cell counts showed a progression of cellular activity from the periphery to the centre, presenting the same progression as the growth of bone trabeculae, whose trabeculae thickness was quadrupled at the end of remodelling. Inmunohistochemical studies confirmed the prevalence of type I collagen and the ratio of the Type I/Type II collagen ratio was found to be 2.48. The percentages of the vascularized areas were proximally higher than distally in all animals, but distal zone obtained higher rates than the central region. Bone transport regenerate exhibits a centripetal ossification model and a mixed pattern with predominance of intramembranous over endochondral ossification. The data obtained resemble partially to those found in models of bone lengthening applied to large animals. This study provides a detailed structural characterization of the newly formed

  19. Osteoinductive recombinant silk fusion proteins for bone regeneration.

    Science.gov (United States)

    Dinjaski, Nina; Plowright, Robyn; Zhou, Shun; Belton, David J; Perry, Carole C; Kaplan, David L

    2017-02-01

    Protein polymers provide a unique opportunity for tunable designs of material systems due to the genetic basis of sequence control. To address the challenge of biomineralization interfaces with protein based materials, we genetically engineered spider silks to design organic-inorganic hybrid systems. The spider silk inspired domain (SGRGGLGGQG AGAAAAAGGA GQGGYGGLGSQGT) 15 served as an organic scaffold to control material stability and to allow multiple modes of processing, whereas the hydroxyapatite binding domain VTKHLNQISQSY (VTK), provided control over osteogenesis. The VTK domain was fused either to the N-, C- or both terminals of the spider silk domain to understand the effect of position on material properties and mineralization. The addition of the VTK domain to silk did not affect the physical properties of the silk recombinant constructs, but it had a critical role in the induction of biomineralization. When the VTK domain was placed on both the C- and N-termini the formation of crystalline hydroxyapatite was significantly increased. In addition, all of the recombinant proteins in film format supported the growth and proliferation of human mesenchymal stem cells (hMSCs). Importantly, the presence of the VTK domain enhanced osteoinductive properties up to 3-fold compared to the control (silk alone without VTK). Therefore, silk-VTK fusion proteins have been shown suitable for mineralization and functionalization for specific biomedical applications. Organic-inorganic interfaces are integral to biomaterial functions in many areas of repair and regeneration. Several protein polymers have been investigated for this purpose. Despite their success the limited options to fine-tune their material properties, degradation patterns and functionalize them for each specific biomedical application limits their application. Various studies have shown that the biological performance of such proteins can be improved by genetic engineering. The present study provides data

  20. Evolutionary Regeneration Model of Thought Process

    OpenAIRE

    Noboru, HOKKYO; Hitachi Energy Research Laboratory

    1982-01-01

    A preliminary attempt is made to understand the thought process and the evolution of the nervous system on the same footing as regeneration processes obeying certain recursive algebraic rules which possibly economize the information content of the increasingly complex structural-functional correlate of the evolving and thinking nervous system.

  1. Strategies for Controlled Delivery of Growth Factors and Cells for Bone Regeneration

    Science.gov (United States)

    Vo, Tiffany N.; Kasper, F. Kurtis; Mikos, Antonios G.

    2012-01-01

    The controlled delivery of growth factors and cells within biomaterial carriers can enhance and accelerate functional bone formation. The carrier system can be designed with preprogrammed release kinetics to deliver bioactive molecules in a localized, spatiotemporal manner most similar to the natural wound healing process. The carrier can also act as an extracellular matrix-mimicking substrate for promoting osteoprogenitor cellular infiltration and proliferation for integrative tissue repair. This review discusses the role of various regenerative factors involved in bone healing and their appropriate combinations with different delivery systems for augmenting bone regeneration. The general requirements of protein, cell and gene therapy are described, with elaboration on how the selection of materials, configurations and processing affects growth factor and cell delivery and regenerative efficacy in both in vitro and in vivo applications for bone tissue engineering. PMID:22342771

  2. A Therapeutic Potential for Marine Skeletal Proteins in Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Bruce Milthorpe

    2013-04-01

    Full Text Available A vital ingredient for engineering bone tissue, in the culture dish, is the use of recombinant matrix and growth proteins to help accelerate the growth of cultivated tissues into clinically acceptable quantities. The skeletal organic matrices of calcifying marine invertebrates are an untouched potential source of such growth inducing proteins. They have the advantage of being ready-made and retain the native state of the original protein. Striking evidence shows that skeleton building bone morphogenic protein-2/4 (BMP and transforming growth factor beta (TGF-β exist within various marine invertebrates such as, corals. Best practice mariculture and the latest innovations in long-term marine invertebrate cell cultivation can be implemented to ensure that these proteins are produced sustainably and supplied continuously. This also guarantees that coral reef habitats are not damaged during the collection of specimens. Potential proteins for bone repair, either extracted from the skeleton or derived from cultivated tissues, can be identified, evaluated and retrieved using chromatography, cell assays and proteomic methods. Due to the current evidence for bone matrix protein analogues in marine invertebrates, together with the methods established for their production and retrieval there is a genuine prospect that they can be used to regenerate living bone for potential clinical use.

  3. A Therapeutic Potential for Marine Skeletal Proteins in Bone Regeneration

    Science.gov (United States)

    Green, David W.; Padula, Matthew P.; Santos, Jerran; Chou, Joshua; Milthorpe, Bruce; Ben-Nissan, Besim

    2013-01-01

    A vital ingredient for engineering bone tissue, in the culture dish, is the use of recombinant matrix and growth proteins to help accelerate the growth of cultivated tissues into clinically acceptable quantities. The skeletal organic matrices of calcifying marine invertebrates are an untouched potential source of such growth inducing proteins. They have the advantage of being ready-made and retain the native state of the original protein. Striking evidence shows that skeleton building bone morphogenic protein-2/4 (BMP) and transforming growth factor beta (TGF-β) exist within various marine invertebrates such as, corals. Best practice mariculture and the latest innovations in long-term marine invertebrate cell cultivation can be implemented to ensure that these proteins are produced sustainably and supplied continuously. This also guarantees that coral reef habitats are not damaged during the collection of specimens. Potential proteins for bone repair, either extracted from the skeleton or derived from cultivated tissues, can be identified, evaluated and retrieved using chromatography, cell assays and proteomic methods. Due to the current evidence for bone matrix protein analogues in marine invertebrates, together with the methods established for their production and retrieval there is a genuine prospect that they can be used to regenerate living bone for potential clinical use. PMID:23574983

  4. Bone regeneration in cranioplasty and clinical complications in rabbits with alloxan-induced diabetes

    Directory of Open Access Journals (Sweden)

    Evanice Menezes Marçal Vieira

    2008-06-01

    Full Text Available This research evaluated the bone repair process in surgical defects created on the parietal bones of diabetic rabbits using the guided bone regeneration technique to observe the effects of alloxan in the induction of diabetes mellitus. Twenty-four adult rabbits were divided into three study groups: control (C, diabetic (D and diabetic associated to polytetrafluoroethylene (PTFE membrane (D-PTFE. For diabetes induction the animals received one dose of monohydrated alloxan (90 mg/kg by intravenous administration in the auricular or femoral vein. In group D-PTFE the membrane covered both the floor and the surface of the bone defect. In groups D and C, the bone defect was filled up with blood clot. The specimens were fixed in 10% formol and prepared for histomorphometric analysis. The results showed that the 90 mg/kg dose of monohydrate alloxan was sufficient to promote diabetes mellitus when administered in the auricular vein. Bone regeneration was slower in the diabetic group when compared with the control and diabetic-PTFE groups, but there was no significant statistical difference between the two experimental groups (D and D-PTFE. The oral and general clinical complications among the diabetics were weight loss, polyuria, polyphagia and severe chronic gingivitis.

  5. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

    Science.gov (United States)

    Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

    2013-01-01

    Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically. PMID:23836972

  6. Mechanical properties of a biodegradable bone regeneration scaffold

    Science.gov (United States)

    Porter, B. D.; Oldham, J. B.; He, S. L.; Zobitz, M. E.; Payne, R. G.; An, K. N.; Currier, B. L.; Mikos, A. G.; Yaszemski, M. J.

    2000-01-01

    Poly (Propylene Fumarate) (PPF), a novel, bulk erosion, biodegradable polymer, has been shown to have osteoconductive effects in vivo when used as a bone regeneration scaffold (Peter, S. J., Suggs, L. J., Yaszemski, M. J., Engel, P. S., and Mikos, A. J., 1999, J. Biomater. Sci. Polym. Ed., 10, pp. 363-373). The material properties of the polymer allow it to be injected into irregularly shaped voids in vivo and provide mechanical stability as well as function as a bone regeneration scaffold. We fabricated a series of biomaterial composites, comprised of varying quantities of PPF, NaCl and beta-tricalcium phosphate (beta-TCP), into the shape of right circular cylinders and tested the mechanical properties in four-point bending and compression. The mean modulus of elasticity in compression (Ec) was 1204.2 MPa (SD 32.2) and the mean modulus of elasticity in bending (Eb) was 1274.7 MPa (SD 125.7). All of the moduli were on the order of magnitude of trabecular bone. Changing the level of NaCl from 20 to 40 percent, by mass, did not decrease Ec and Eb significantly, but did decrease bending and compressive strength significantly. Increasing the beta-TCP from 0.25 g/g PPF to 0.5 g/g PPF increased all of the measured mechanical properties of PPF/NVP composites. These results indicate that this biodegradable polymer composite is an attractive candidate for use as a replacement scaffold for trabecular bone.

  7. Bone regeneration potential of sub-microfibrous membranes with ...

    African Journals Online (AJOL)

    Conclusion: The results indicate that biodegradable PCL sub-microfibrous membrane produced by electrospinning process seems to have excellent biocompatibility, and may be used as a scaffold for bone tissue engineering. Keywords: Biocompatibility, Hard tissue, Biomaterial availability, Bone remodeling, Polylactic acid, ...

  8. ECM Decorated Electrospun Nanofiber for Improving Bone Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    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.

  9. Strontium-rich injectable hybrid system for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Neves, Nuno, E-mail: nsmneves@gmail.com [Instituto de Investigação e Inovação em Saúde, Universidade do Porto (Portugal); INEB — Instituto de Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto (Portugal); FMUP — Faculdade de Medicina da Universidade do Porto, Departamento de Cirurgia, Serviço de Ortopedia, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Campos, Bruno B. [FCUP — Faculdade de Ciências da Universidade do Porto, Centro de Investigação em Química, Departamento de Química e Bioquímica, Rua do Campo Alegre 1021/1055, 4169-007 Porto (Portugal); Almeida, Isabel F.; Costa, Paulo C. [FFUP — Faculdade de Farmácia da Universidade do Porto, Laboratório de Tecnologia Farmacêutica, Departamento de Ciências do Medicamento, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto (Portugal); Cabral, Abel Trigo [FMUP — Faculdade de Medicina da Universidade do Porto, Departamento de Cirurgia, Serviço de Ortopedia, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); and others

    2016-02-01

    Current challenges in the development of scaffolds for bone regeneration include the engineering of materials that can withstand normal dynamic physiological mechanical stresses exerted on the bone and provide a matrix capable of supporting cell migration and tissue ingrowth. The objective of the present work was to develop and characterize a hybrid polymer–ceramic injectable system that consists of an alginate matrix crosslinked in situ in the presence of strontium (Sr), incorporating a ceramic reinforcement in the form of Sr-rich microspheres. The incorporation of Sr in the microspheres and in the vehicle relies on the growing evidence that Sr has beneficial effects in bone remodeling and in the treatment of osteopenic disorders and osteoporosis. Sr-rich porous hydroxyapatite microspheres with a uniform size and a mean diameter of 555 μm were prepared, and their compression strength and friability tested. A 3.5% (w/v) ultrapure sodium alginate solution was used as the vehicle and its in situ gelation was promoted by the addition of calcium (Ca) or Sr carbonate and Glucone-δ-lactone. Gelation times varied with temperature and crosslinking agent, being slower for Sr than for Ca, but adequate for injection in both cases. Injectability was evaluated using a device employed in vertebroplasty surgical procedures, coupled to a texture analyzer in compression mode. Compositions with 35% w of microspheres presented the best compromise between injectability and compression strength of the system, the force required to extrude it being lower than 100 N. Micro CT analysis revealed a homogeneous distribution of the microspheres inside the vehicle, and a mean inter-microspheres space of 220 μm. DMA results showed that elastic behavior of the hybrid is dominant over the viscous one and that the higher storage modulus was obtained for the 3.5%Alg–35%Sr-HAp-Sr formulation. - Highlights: • We developed a Sr rich viscoelastic hybrid system (alginate matrix crosslinked in

  10. Clinical and radiological studies upon a combined method for guided bone regeneration in experimental mandibular defects in dogs - a preliminary communication

    International Nuclear Information System (INIS)

    Borissov, I.; Uzunov, N.; Paskalev, M.

    2004-01-01

    The treated bone defects were compared clinically and radiologically. After a 3-month period of survey, the best results were obtained in the group treated with partially demineralized bone matrix, enzymatically processed and lyophilized dura mater and mucoperiosteal flap. The placement of titanium screw dental implants did not impair the guided bone regeneration, that was confirmed by their good osteointegration

  11. Effect of a novel load-bearing trabecular Nitinol scaffold on rabbit radius bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Gotman, Irena, E-mail: gotman@technion.ac.il; Gutmanas, Elazar Y., E-mail: gutmanas@technion.ac.il [Department of Materials Science and Engineering, Techion-Israel Institute of Technology, Haifa, 32000 Israel (Israel); National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Zaretzky, Asaph [The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 31096 Israel (Israel); Psakhie, Sergey G. [National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Institute of Strength Physics and Materials Science SB RAS, Tomsk, 634055 (Russian Federation)

    2015-10-27

    The research aim was to evaluate the bone regeneration capability of novel load-bearing NiTi alloy (Nitinol) scaffolds in a critical-size defect (CSD) model. High strength “trabecular Nitinol” scaffolds were prepared by PIRAC (Powder Immersion Reaction Assisted Coating) annealing of the highly porous Ni foam in Ti powder at 900°C. This was followed by PIRAC nitriding to mitigate the release of potentially toxic Ni ions. Scaffolds phase composition and microstructure were characterized by X-ray diffraction and scanning electron microscopy (SEM/EDS), and their mechanical properties were tested in compression. New Zealand white rabbits received bone defect in right radius and were divided in four groups randomly. In the control group, nothing was placed in the defect. In other groups, NiTi scaffolds were implanted in the defect: (i) as produced, (ii) loaded with bone marrow aspirate (BMA), and (iii) biomimetically CaP-coated. The animals were sacrificed after 12 weeks. The forelimbs with scaffolds were resected, fixed, sectioned and examined in SEM. New bone formation inside the scaffold was studied by EDS analysis and by the processing of backscattered electron images. Bone ingrowth into the scaffold was observed in all implant groups, mostly next to the ulna. New bone formation was strongly enhanced by BMA loading and biomimeatic CaP coating, the bone penetrating as much as 1–1.5 mm into the scaffold. The results of this preliminary study demonstrate that the newly developed high strength trabecular Nitinol scaffolds can be successfully used for bone regeneration in critical size defects.

  12. Bone Repair on Fractures Treated with Osteosynthesis, ir Laser, Bone Graft and Guided Bone Regeneration: Histomorfometric Study

    Science.gov (United States)

    dos Santos Aciole, Jouber Mateus; dos Santos Aciole, Gilberth Tadeu; Soares, Luiz Guilherme Pinheiro; Barbosa, Artur Felipe Santos; Santos, Jean Nunes; Pinheiro, Antonio Luiz Barbosa

    2011-08-01

    The aim of this study was to evaluate, through the analysis of histomorfometric, the repair of complete tibial fracture in rabbits fixed with osteosynthesis, treated or not with infrared laser light (λ780 nm, 50 mW, CW) associated or not to the use of hydroxyapatite and guided bone regeneration (GBR). Surgical fractures were created, under general anesthesia (Ketamina 0,4 ml/Kg IP and Xilazina 0,2 ml/Kg IP), on the dorsum of 15 Oryctolagus rabbits that were divided into 5 groups and maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet and had water ad libidum. On groups II, III, IV and V the fracture was fixed with wire osteosynthesis. Animals of groups III and V were grafted with hydroxyapatite and GBR technique used. Animals of groups IV and V were irradiated at every other day during two weeks (16 J/cm2, 4×4 J/cm2). Observation time was that of 30 days. After animal death (overdose of general anesthetics) the specimes were routinely processed to wax and underwent histological analysis by light microscopy. The histomorfometric analysis showed an increased bone neoformation, increased collagen deposition, less reabsorption and inflammation when laser was associated to the HATCP. It is concluded that IR laser light was able to accelerate fracture healing and the association with HATCP and GBR resulted on increased deposition of CHA.

  13. Mechanical Properties of 3d Scaffolds for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Deividas Mizeras

    2017-01-01

    Full Text Available One of the biggest challenges in modern tissue engineering is a creation 3D scaffolds for bone tissue regeneration. Until now, in order to restore bone defects are used various bone substitutes (autologous and allogeneic, however, their usage is limited because is required additional surgery, possible complications, also limited their use is associated with ethical point of view. In this work we aim to determine the mechanical properties of 3D printed PLA objects having various orientation woodpile microarchitectures. In this work we chose three different 3D microarchitectures: woodpile BCC (each layer consists of parallel logs which are rotated 90 deg every next layer, woodpile FCC (every layer is additionally shifted half of the period in respect to the previous parallel log layer and a rotating woodpile 60 deg (each layer is rotated 60 deg in respect to the previous one. Compressive and bending tests were carried out with TIRAtest2300 universal testing machine. We found that 60 deg rotating woodpile geometry had the highest mechanical values which were approximately about 3 times higher than the BCC or FCC microstructures.

  14. Regeneration of skull bones in adult rabbits after implantation of commercial osteoinductive materials and transplantation of a tissue-engineering construct.

    Science.gov (United States)

    Volkov, A V; Alekseeva, I S; Kulakov, A A; Gol'dshtein, D V; Shustrov, S A; Shuraev, A I; Arutyunyan, I V; Bukharova, T B; Rzhaninova, A A; Bol'shakova, G B; Grigor'yan, A S

    2010-10-01

    We performed a comparative study of reparative osteogenesis in rabbits with experimental critical defects of the parietal bones after implantation of commercial osteoinductive materials "Biomatrix", "Osteomatrix", "BioOss" in combination with platelet-rich plasma and transplantation of a tissue-engineering construct on the basis of autogenic multipotent stromal cells from the adipose tissue predifferentiated in osteogenic direction. It was found that experimental reparative osteogenesis is insufficiently stimulated by implantation materials and full-thickness trepanation holes were not completely closed. After transplantation of the studied tissue-engineering construct, the defect was filled with full-length bone regenerate (in the center of the regenerate and from the maternal bone) in contrast to control and reference groups, where the bone tissue was formed only on the side of the maternal bone. On day 120 after transplantation of the tissue-engineering construct, the percent of newly-formed bone tissue in the regenerate was 24% (the total percent of bone tissue in the regenerate was 39%), which attested to active incomplete regenerative process in contrast to control and reference groups. Thus, the study demonstrated effective regeneration of the critical defects of the parietal bones in rabbits 120 days after transplantation of the tissue-engineering construct in contrast to commercial osteoplastic materials for directed bone regeneration.

  15. The paradoxes in patterns and mechanism of bone marrow regeneration after irradiation. 1

    International Nuclear Information System (INIS)

    Scarantino, C.W.; Rubin, P.; Constine, L.S. III

    1984-01-01

    Bone marrow regeneration following irradiation has been largely studied as a dose-effect phenomenon, however, a large literature has simultaneously developed utilizing a wide variety of volumes, both in clinical studies and in experimental studies. Volume factors, more than dose, determine patterns of suppression and regeneration which have been documented by a variety of assay systems. Experimental evidence is presented which indicates that high dose irradiation to large volumes of bone marrow does not completely suppress bone marrow regeneration but results in a rapid compensatory response. Comparisons are made between the small and larger volumes at similar doses and indicate a greater overall compensatory response after the larger field irradiation, being more rapid in onset particularly after the 1000 rad dose. Although in-field regeneration of bone marrow occurs after single dose radiation to different volumes of bone marrow, experimental and clinical evidence from protracted conventional doses of irradiation to different volumes of bone marrow indicate significantly different response mechanisms. (Auth.)

  16. Electrospun PVA-PCL-HAB scaffold for craniofacial bone regeneration

    DEFF Research Database (Denmark)

    Prabha, Rahul; Kraft, David Christian Evar; Melsen, Birte

    2015-01-01

    -caprolactone (PCL)- triphasic bioceramic(HAB) scaffold to biomimic native tissue and we tested its ability to support osteogenic differentiation of stromal stem cells ( MSC) and its suitability for regeneration of craniofa- cial defects. Physiochemical characterizations of the scaffold, including con- tact angle...... body fluid immersed scaffold samples. Culturing human adult dental pulp stem cells (DPSC) and human bone marrow derived MSC seeded on PVA-PCL-HAB scaffold showed enhanced cell proliferation and in vitro osteoblastic differentiation. Cell-containing scaffolds were implanted subcutaneously in immune...... deficient mice. Histologic ex- amination of retrieved implant sections stained with H&E, Col- lagenType I and Human Vimentin antibody demonstrated that the cells survived in vivo in the implants for at least 8 weeks with evidence of osteoblastic differentiation and angiogenesis within the implants. Our...

  17. Preparation and Characterization of an Advanced Medical Device for Bone Regeneration

    OpenAIRE

    Dorati, Rossella; Colonna, Claudia; Genta, Ida; Bruni, Giovanna; Visai, Livia; Conti, Bice

    2013-01-01

    Tridimensional scaffolds can promote bone regeneration as a framework supporting the migration of cells from the surrounding tissue into the damaged tissue and as delivery systems for the controlled or prolonged release of cells, genes, and growth factors. The goal of the work was to obtain an advanced medical device for bone regeneration through coating a decellularized and deproteinized bone matrix of bovine origin with a biodegradable, biocompatible polymer, to improve the cell engraftment...

  18. Effect of the biodegradation rate controlled by pore structures in magnesium phosphate ceramic scaffolds on bone tissue regeneration in vivo.

    Science.gov (United States)

    Kim, Ju-Ang; Lim, Jiwon; Naren, Raja; Yun, Hui-Suk; Park, Eui Kyun

    2016-10-15

    P) scaffold by combination of the 3D printing process, self-setting reaction and salt-leaching technique, and first studied the effect of pore structures of bioceramic scaffolds on bone tissue regeneration through both in vitro and in vivo studies (rabbit calvarial model). The MgP scaffolds with higher porosity promoted more rapid biodegradation and enhanced new bone formation and remodeling activities at the same time. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  19. 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.

  20. Bioceramics of apatites: an option for bone regeneration; Bioceramica de apatitas: uma opcao para regeneracao ossea

    Energy Technology Data Exchange (ETDEWEB)

    Arxer, Eliana Alves; Almeida Filho, Edson de; Guastaldi, Antonio Carlos, E-mail: iarxer@iq.unesp.br [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Araraquara, SP (Brazil). Instituto de Quimica

    2011-07-01

    The bioceramics of calcium phosphate called apatite, are widely used as material for bone replacement and regeneration, due to its similarity to the mineral component of bones and teeth. The apatites are biocompatible, bioactive and integrate with living tissue by the same active process of physiological bone remodeling. These bioceramics may be used in medical, dental and orthopedic applications. In this research, it was used the wet method for the synthesis of the powder and biomimetic method for coating the surface. The Solubility study was performed in the layer deposited, apatite, for possible application as a platform for inorganic drug delivery. The bioceramics were characterized by MEV, DRX, and EDS. The curves of solubility of apatite in coatings showed that the OCP phase had a higher rate of release in the short term (4 days) while the HA phase showed a gradual release throughout the experiment (16 days). (author)

  1. Osteoblast Production by Reserved Progenitor Cells in Zebrafish Bone Regeneration and Maintenance.

    Science.gov (United States)

    Ando, Kazunori; Shibata, Eri; Hans, Stefan; Brand, Michael; Kawakami, Atsushi

    2017-12-04

    Mammals cannot re-form heavily damaged bones as in large fracture gaps, whereas zebrafish efficiently regenerate bones even after amputation of appendages. However, the source of osteoblasts that mediate appendage regeneration is controversial. Several studies in zebrafish have shown that osteoblasts are generated by dedifferentiation of existing osteoblasts at injured sites, but other observations suggest that de novo production of osteoblasts also occurs. In this study, we found from cell-lineage tracing and ablation experiments that a group of cells reserved in niches serves as osteoblast progenitor cells (OPCs) and has a significant role in fin ray regeneration. Besides regeneration, OPCs also supply osteoblasts for normal bone maintenance. We further showed that OPCs are derived from embryonic somites, as is the case with embryonic osteoblasts, and are replenished from mesenchymal precursors in adult zebrafish. Our findings reveal that reserved progenitors are a significant and complementary source of osteoblasts for zebrafish bone regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Xerogel Interfaced Nanofibers Stimulate Bone Regeneration Through the Activation of Integrin and Bone Morphogenetic Protein Pathways.

    Science.gov (United States)

    Lee, Yoo-Mi; Yun, Hyung-Mun; Lee, Hye-Young; Lim, Hyun-Chang; Lee, Hae-Hyoung; Kim, Hae-Won; Kim, Eun-Cheol

    2017-02-01

    A xerogel was interfaced onto biopolymer nanofibers though a core–shell electrospinning design for bone regeneration. The xerogel-interfaced biopolymer nanofibrous matrix was bioactive and highly hydrophilic, with a significant decrease in the water contact angle. The matrix showed excellent in vitro responses of primary osteoblasts in terms of adhesion, proliferation, and migration. Furthermore, the osteoblastic differentiation of cells, including alkaline phosphatase activity, mineralization, and gene expression, was significantly upregulated by the xerogel interface. In vivo animal tests in a critical-sized calvarial defect confirmed the new bone formation ability of the xerogel-surfaced nanofiber matrices. The underlying signaling mechanisms of the stimulation were implied to be integrin and bone morphogenetic protein (BMP) pathways, as demonstrated by the activation of integrin (α2β1) and downstream signaling molecules (FAK, paxillin, RhoA, MAPK, and NF-κB), as well as the BMPs and the downstream transcription factor Smad1/5/8. Taking these findings together, the xerogel-surfaced biopolymer nanofibers are proposed to be a promising scaffold candidate for bone regeneration.

  3. 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.

  4. Toward guided tissue and bone regeneration: morphology, attachment, proliferation, and migration of cells cultured on collagen barrier membranes. A systematic review.

    NARCIS (Netherlands)

    Behring, J.; Junker, R.; Walboomers, X.F.; Chessnut, B.; Jansen, J.A.

    2008-01-01

    Collagen barrier membranes are frequently used in both guided tissue regeneration (GTR) and guided bone regeneration (GBR). Collagen used for these devices is available from different species and is often processed to alter the properties of the final product. This is necessary because unprocessed

  5. 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...

  6. Bone Regeneration of Hydroxyapatite with Granular Form or Porous Scaffold in Canine Alveolar Sockets

    Science.gov (United States)

    JANG, SEOK JIN; KIM, SE EUN; HAN, TAE SUNG; SON, JUN SIK; KANG, SEONG SOO; CHOI, SEOK HWA

    2017-01-01

    This study was undertaken to assess bone regeneration using hydroxyapatite (HA). The primary focus was comparison of bone regeneration between granular HA (gHA) forms and porous HA (pHA) scaffold. The extracted canine alveolar sockets were divided with three groups: control, gHA and pHA. Osteogenic effect in the gHA and pHA groups showed bone-specific surface and bone mineral density to be significantly higher than that of the control group (psocket healing. For new bone formation during 8 weeks' post-implantation, HA with porous scaffold was superior to the granular form of HA. PMID:28438860

  7. The Components of Bone and What They Can Teach Us about Regeneration

    Directory of Open Access Journals (Sweden)

    Bach Quang Le

    2017-12-01

    Full Text Available The problem of bone regeneration has engaged both physicians and scientists since the beginning of medicine. Not only can bone heal itself following most injuries, but when it does, the regenerated tissue is often indistinguishable from healthy bone. Problems arise, however, when bone does not heal properly, or when new tissue is needed, such as when two vertebrae are required to fuse to stabilize adjacent spine segments. Despite centuries of research, such procedures still require improved therapeutic methods to be devised. Autologous bone harvesting and grafting is currently still the accepted benchmark, despite drawbacks for clinicians and patients that include limited amounts, donor site morbidity, and variable quality. The necessity for an alternative to this “gold standard” has given rise to a bone-graft and substitute industry, with its central conundrum: what is the best way to regenerate bone? In this review, we dissect bone anatomy to summarize our current understanding of its constituents. We then look at how various components have been employed to improve bone regeneration. Evolving strategies for bone regeneration are then considered.

  8. Bone regeneration effect after the addition of a vitamin complex in two bio ceramics

    International Nuclear Information System (INIS)

    Beolchi, Rafael da Silva

    2009-01-01

    One of the goals of the Biomaterials research is the development of devices that help bone regeneration. Two synthetic ceramics has been widely used with that purpose: hydroxyapatite (HAp) and beta tricalcium phosphate (β-TCP). In many situations it is desirable that the resorption rate of these materials by the body matches the bone growth rate. In these cases, the use of a mixture between the two phases is beneficial. The material resorption and bone growth are complexes physiological processes, influenced amongst other things by the inflammatory response of the surgical site. That being said, an exacerbated inflammatory response is potentially hazardous, since it may induce an increase of the oxidative stress due to the free radicals production. The free radicals attack causes, amongst other hazardous effects, the cell membrane degeneration which in turn may lead to cell necrosis and/or apoptosis within the surgical site. In this work, two ceramics were implanted in rats femora: β-TCP or the biphasic mixture of 60:40% in mass of HAp:β-TCP. The bone growth was assessed by both optical and fluorescence microscopy, using fluorescent bone markers. Moreover, it was also evaluated the effect of the presence of a vitamin complex, mediator of the inflammatory response. It was concluded that the pure β-TCP was more readily absorbed when compared with the mixture β-TCP-HAp, and there it was signs that the presence of the vitamin complex may have helped in a favorable way the bone neo formation. (author)

  9. Network-Based Method for Identifying Co- Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues.

    Science.gov (United States)

    Chen, Lei; Pan, Hongying; Zhang, Yu-Hang; Feng, Kaiyan; Kong, XiangYin; Huang, Tao; Cai, Yu-Dong

    2017-10-02

    Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein-protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method.

  10. Biodegradation, biocompatibility, and osteoconduction evaluation of collagen-nanohydroxyapatite cryogels for bone tissue regeneration.

    Science.gov (United States)

    Salgado, Christiane Laranjo; Grenho, Liliana; Fernandes, Maria Helena; Colaço, Bruno Jorge; Monteiro, Fernando Jorge

    2016-01-01

    Designing biomimetic biomaterials inspired by the natural complex structure of bone and other hard tissues is still a challenge nowadays. The control of the biomineralization process onto biomaterials should be evaluated before clinical application. Aiming at bone regeneration applications, this work evaluated the in vitro biodegradation and interaction between human bone marrow stromal cells (HBMSC) cultured on different collagen/nanohydroxyapatite cryogels. Cell proliferation, differentiation, morphology, and metabolic activity were assessed through different protocols. All the biocomposite materials allowed physiologic apatite deposition after incubation in simulated body fluid and the cryogel with the highest nanoHA content showed to have the highest mechanical strength (DMA). The study clearly showed that the highest concentration of nanoHA granules on the cryogels were able to support cell type's survival, proliferation, and individual functionality in a monoculture system, for 21 days. In fact, the biocomposites were also able to differentiate HBMSCs into osteoblastic phenotype. The composites behavior was also assessed in vivo through subcutaneous and bone implantation in rats to evaluate its tissue-forming ability and degradation rate. The cryogels Coll/nanoHA (30 : 70) promoted tissue regeneration and adverse reactions were not observed on subcutaneous and bone implants. The results achieved suggest that scaffolds of Coll/nanoHA (30 : 70) should be considered promising implants for bone defects that present a grotto like appearance with a relatively small access but a wider hollow inside. This material could adjust to small dimensions and when entering into the defect, it could expand inside and remain in close contact with the defect walls, thus ensuring adequate osteoconductivity. © 2015 Wiley Periodicals, Inc.

  11. Osteoimmunology: Influence of the Immune System on Bone Regeneration and Consumption.

    Science.gov (United States)

    Limmer, Andreas; Wirtz, Dieter C

    2017-06-01

    Background Stimulating bone regeneration is a central aim in orthopaedic and trauma surgery. Although the replacement of bone with artificial materials like cement or apatite helps to keep up bone stability, new bone often cannot be regenerated. Increasing research efforts have led to the clinical application of growth factors stimulating bone growth (e.g. bone morphogenic protein, BMP) and inhibitors preventing bone consumption (e.g. RANKL blocking antibodies). These factors mostly concentrate on stimulating osteoblast or preventing osteoclast activity. Current Situation It is widely accepted that osteoblasts and osteoclasts are central players in bone regeneration. This concept assumes that osteoblasts are responsible for bone growth while osteoclasts cause bone consumption by secreting matrix-degrading enzymes such as cathepsin K and matrix metalloproteinases (MMP). However, according to new research results, bone growth or consumption are not regulated by single cell types. It is rather the interaction of various cell types that regulates bone metabolism. While factors secreted by osteoblasts are essential for osteoclast differentiation and activation, factors secreted by activated osteoclasts are essential for osteoblast activity. In addition, recent research results imply that the influence of the immune system on bone metabolism has long been neglected. Factors secreted by macrophages or T cells strongly influence bone growth or degradation, depending on the bone microenvironment. Infections, sterile inflammation or tumour metastases not only affect bone cells directly, but also influence immune cells such as T cells indirectly. Furthermore, immune cells and bone are mechanistically regulated by similar factors such as cytokines, chemokines and transcription factors, suggesting that the definition of bone and immune cells has to be thought over. Outlook Bone and the immune system are regulated by similar mechanisms. These newly identified similarities

  12. Development of a Novel Degradation-Controlled Magnesium-Based Regeneration Membrane for Future Guided Bone Regeneration (GBR Therapy

    Directory of Open Access Journals (Sweden)

    Da-Jun Lin

    2017-11-01

    Full Text Available This study aimed to develop and evaluate the ECO-friendly Mg-5Zn-0.5Zr (ECO505 alloy for application in dental-guided bone regeneration (GBR. The microstructure and surface properties of biomedical Mg materials greatly influence anti-corrosion performance and biocompatibility. Accordingly, for the purpose of microstructure and surface modification, heat treatments and surface coatings were chosen to provide varied functional characteristics. We developed and integrated both an optimized solution heat-treatment condition and surface fluoride coating technique to fabricate a Mg-based regeneration membrane. The heat-treated Mg regeneration membrane (ARRm-H380 and duplex-treated regeneration membrane group (ARRm-H380-F24 h were thoroughly investigated to characterize the mechanical properties, as well as the in vitro corrosion and in vivo degradation behaviors. Significant enhancement in ductility and corrosion resistance for the ARRm-H380 was obtained through the optimized solid-solution heat treatment; meanwhile, the corrosion resistance of ARRm-H380-F24 h showed further improvement, resulting in superior substrate integrity. In addition, the ARRm-H380 provided the proper amount of Mg-ion concentration to accelerate bone growth in the early stage (more than 80% new bone formation. From a specific biomedical application point of view, these research results point out a successful manufacturing route and suggest that the heat treatment and duplex treatment could be employed to offer custom functional regeneration membranes for different clinical patients.

  13. Cartilage and bone cells do not participate in skeletal regeneration in Ambystoma mexicanum limbs.

    Science.gov (United States)

    McCusker, Catherine D; Diaz-Castillo, Carlos; Sosnik, Julian; Q Phan, Anne; Gardiner, David M

    2016-08-01

    The Mexican Axolotl is one of the few tetrapod species that is capable of regenerating complete skeletal elements in injured adult limbs. Whether the skeleton (bone and cartilage) plays a role in the patterning and contribution to the skeletal regenerate is currently unresolved. We tested the induction of pattern formation, the effect on cell proliferation, and contributions of skeletal tissues (cartilage, bone, and periosteum) to the regenerating axolotl limb. We found that bone tissue grafts from transgenic donors expressing GFP fail to induce pattern formation and do not contribute to the newly regenerated skeleton. Periosteum tissue grafts, on the other hand, have both of these activities. These observations reveal that skeletal tissue does not contribute to the regeneration of skeletal elements; rather, these structures are patterned by and derived from cells of non-skeletal connective tissue origin. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Alkali-free bioactive glasses for bone regeneration =

    Science.gov (United States)

    Kapoor, Saurabh

    Bioactive glasses and glass-ceramics are a class of third generation biomaterials which elicit a special response on their surface when in contact with biological fluids, leading to strong bonding to living tissues. The purpose of the present study was to develop diopside based alkali-free bioactive glasses in order to achieve good sintering behaviour, high bioactivity, and a dissolution/ degradation rates compatible with the target applications in bone regeneration and tissue engineering. Another aim was to understand the structure-property relationships in the investigated bioactive glasses. In this quest, various glass compositions within the Diopside (CaMgSi2O6) - Fluorapatite (Ca5(PO4)3F) - Tricalcium phosphate (3CaO•P2O5) system have been investigated. All the glasses were prepared by melt-quenching technique and characterized by a wide array of complementary characterization techniques. The glass-ceramics were produced by sintering of glass powders compacts followed by a suitable heat treatment to promote the nucleation and crystallization phenomena. Furthermore, selected parent glass compositions were doped with several functional ions and an attempt to understand their effects on the glass structure, sintering ability and on the in vitro bio-degradation and biomineralization behaviours of the glasses was made. The effects of the same variables on the devitrification (nucleation and crystallization) behaviour of glasses to form bioactive glass-ceramics were also investigated. Some of the glasses exhibited high bio-mineralization rates, expressed by the formation of a surface hydroxyapatite layer within 1-12 h of immersion in a simulated body fluid (SBF) solution. All the glasses showed relatively lower degradation rates in comparison to that of 45S5 Bioglass. Some of the glasses showed very good in vitro behaviour and the glasses co-doped with zinc and strontium showed an in vitro dose dependent behaviour. The as-designed bioactive glasses and glass

  15. Platelet-rich plasma, plasma rich in growth factors and simvastatin in the regeneration and repair of alveolar bone.

    Science.gov (United States)

    Rivera, César; Monsalve, Francisco; Salas, Juan; Morán, Andrea; Suazo, Iván

    2013-12-01

    Platelet preparations promote bone regeneration by inducing cell migration, proliferation and differentiation in the area of the injury, which are essential processes for regeneration. In addition, several studies have indicated that simvastatin (SIMV), widely used for the treatment of hypercholesterolemia, stimulates osteogenesis. The objective of this study was to evaluate the effects of treatment with either platelet-rich plasma (PRP) or plasma rich in growth factors (PRGF) in combination with SIMV in the regeneration and repair of alveolar bone. The jaws of Sprague Dawley rats (n=18) were subjected to rotary instrument-induced bone damage (BD). Animals were divided into six groups: BD/H 2 O (n=3), distilled water without the drug and alveolar bone damage; BD/H 2 O/PRP (n=3), BD and PRP; BD/H 2 O/PRGF (n=3), BD and PRGF; BD/SIMV (n=3), BD and water with SIMV; BD/SIMV/PRP (n=3), BD, PRP and SIMV; and BD/SIMV/PRGF (n=3), BD, PRGF and SIMV. Conventional histological analysis (hematoxylin and eosin staining) revealed that the BD/SIMV group showed indicators for mature bone tissue, while the BD/SIMV/PRP and BD/SIMV/PRGF groups showed the coexistence of indicators for mature and immature bone tissue, with no statistical differences between the platelet preparations. Simvastatin did not improve the effect of platelet-rich plasma and plasma rich in growth factors. It was not possible to determine which platelet preparation produced superior effects.

  16. Decellularization and Delipidation Protocols of Bovine Bone and Pericardium for Bone Grafting and Guided Bone Regeneration Procedures.

    Directory of Open Access Journals (Sweden)

    Chiara Gardin

    Full Text Available The combination of bone grafting materials with guided bone regeneration (GBR membranes seems to provide promising results to restore bone defects in dental clinical practice. In the first part of this work, a novel protocol for decellularization and delipidation of bovine bone, based on multiple steps of thermal shock, washes with detergent and dehydration with alcohol, is described. This protocol is more effective in removal of cellular materials, and shows superior biocompatibility compared to other three methods tested in this study. Furthermore, histological and morphological analyses confirm the maintenance of an intact bone extracellular matrix (ECM. In vitro and in vivo experiments evidence osteoinductive and osteoconductive properties of the produced scaffold, respectively. In the second part of this study, two methods of bovine pericardium decellularization are compared. The osmotic shock-based protocol gives better results in terms of removal of cell components, biocompatibility, maintenance of native ECM structure, and host tissue reaction, in respect to the freeze/thaw method. Overall, the results of this study demonstrate the characterization of a novel protocol for the decellularization of bovine bone to be used as bone graft, and the acquisition of a method to produce a pericardium membrane suitable for GBR applications.

  17. Bioinspired, biomimetic, double-enzymatic mineralization of hydrogels for bone regeneration with calcium carbonate

    DEFF Research Database (Denmark)

    Lopez-Heredia, Marco A.; Łapa, Agata; Mendes, Ana Carina Loureiro

    2017-01-01

    Hydrogels are popular materials for tissue regeneration. Incorporation of biologically active substances, e.g. enzymes, is straightforward. Hydrogel mineralization is desirable for bone regeneration. Here, hydrogels of Gellan Gum (GG), a biocompatible polysaccharide, were mineralized biomimetically...... of osteoblast-like cells....

  18. The use of titanium plates for bone regeneration with root form implants: a case report.

    Science.gov (United States)

    Maksoud, M A

    1999-01-01

    In reconstruction of the partially and totally edentulous ridges that have bony defects due to old trauma or longstanding atrophy, it is necessary to reconstruct both the width and height of the alveolar ridge. This clinical case report covers bone regeneration prior to implant placement to achieve an aesthetic and functional base for prosthetic restoration. The focus of this report will be on bone regeneration, which does not depend on the utilization of a barrier membrane.

  19. Biomimetic mineralization of recombinant collagen type I derived protein to obtain hybrid matrices for bone regeneration.

    Science.gov (United States)

    Ramírez-Rodríguez, Gloria Belén; Delgado-López, José Manuel; Iafisco, Michele; Montesi, Monica; Sandri, Monica; Sprio, Simone; Tampieri, Anna

    2016-11-01

    Understanding the mineralization mechanism of synthetic protein has recently aroused great interest especially in the development of advanced materials for bone regeneration. Herein, we propose the synthesis of composite materials through the mineralization of a recombinant collagen type I derived protein (RCP) enriched with RGD sequences in the presence of magnesium ions (Mg) to closer mimic bone composition. The role of both RCP and Mg ions in controlling the precipitation of the mineral phase is in depth evaluated. TEM and X-ray powder diffraction reveal the crystallization of nanocrystalline apatite (Ap) in all the evaluated conditions. However, Raman spectra point out also the precipitation of amorphous calcium phosphate (ACP). This amorphous phase is more evident when RCP and Mg are at work, indicating the synergistic role of both in stabilizing the amorphous precursor. In addition, hybrid matrices are prepared to tentatively address their effectiveness as scaffolds for bone tissue engineering. SEM and AFM imaging show an homogeneous mineral distribution on the RCP matrix mineralized in presence of Mg, which provides a surface roughness similar to that found in bone. Preliminary in vitro tests with pre-osteoblast cell line show good cell-material interaction on the matrices prepared in the presence of Mg. To the best of our knowledge this work represents the first attempt to mineralize recombinant collagen type I derived protein proving the simultaneous effect of the organic phase (RCP) and Mg on ACP stabilization. This study opens the possibility to engineer, through biomineralization process, advanced hybrid matrices for bone regeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Autogenous bone particle/titanium fiber composites for bone regeneration in a rabbit radius critical-size defect model.

    Science.gov (United States)

    Xie, Huanxin; Ji, Ye; Tian, Qi; Wang, Xintao; Zhang, Nan; Zhang, Yicai; Xu, Jun; Wang, Nanxiang; Yan, Jinglong

    2017-11-01

    To explore the effects of autogenous bone particle/titanium fiber composites on repairing segmental bone defects in rabbits. A model of bilateral radial bone defect was established in 36 New Zealand white rabbits which were randomly divided into 3 groups according to filling materials used for bilaterally defect treatment: in group C, 9 animal bone defect areas were prepared into simple bilateral radius bone defect (empty sham) as the control group; 27 rabbits were used in groups ABP and ABP-Ti. In group ABP, left defects were simply implanted with autogenous bone particles; meanwhile, group ABP-Ti animals had right defects implanted with autogenous bone particle/titanium fiber composites. Animals were sacrificed at 4, 8, and 12 weeks, respectively, after operation. Micro-CT showed that group C could not complete bone regeneration. Bone volume to tissue volume values in group ABP-Ti were better than group ABP. From histology and histomorphometry Groups ABP and ABP-Ti achieved bone repair, the bone formation of group ABP-Ti was better. The mechanical strength of group ABP-Ti was superior to that of other groups. These results confirmed the effectiveness of autologous bone particle/titanium fiber composites for promoting bone regeneration and mechanical strength.

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

    Science.gov (United States)

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

    2012-01-01

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

  2. Mesenchymal Stem Cells as a Potent Cell Source for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Elham Zomorodian

    2012-01-01

    Full Text Available While small bone defects heal spontaneously, large bone defects need surgical intervention for bone transplantation. Autologous bone grafts are the best and safest strategy for bone repair. An alternative method is to use allogenic bone graft. Both methods have limitations, particularly when bone defects are of a critical size. In these cases, bone constructs created by tissue engineering technologies are of utmost importance. Cells are one main component in the manufacture of bone construct. A few cell types, including embryonic stem cells (ESCs, adult osteoblast, and adult stem cells, can be used for this purpose. Mesenchymal stem cells (MSCs, as adult stem cells, possess characteristics that make them good candidate for bone repair. This paper discusses different aspects of MSCs that render them an appropriate cell type for clinical use to promote bone regeneration.

  3. Boon and Bane of Inflammation in Bone Tissue Regeneration and Its Link with Angiogenesis.

    Science.gov (United States)

    Schmidt-Bleek, Katharina; Kwee, Brian J; Mooney, David J; Duda, Georg N

    2015-08-01

    Delayed healing or nonhealing of bone is an important clinical concern. Although bone, one of the two tissues with scar-free healing capacity, heals in most cases, healing is delayed in more than 10% of clinical cases. Treatment of such delayed healing condition is often painful, risky, time consuming, and expensive. Tissue healing is a multistage regenerative process involving complex and well-orchestrated steps, which are initiated in response to injury. At best, these steps lead to scar-free tissue formation. At the onset of healing, during the inflammatory phase, stationary and attracted macrophages and other immune cells at the fracture site release cytokines in response to injury. This initial reaction to injury is followed by the recruitment, proliferation, and differentiation of mesenchymal stromal cells, synthesis of extracellular matrix proteins, angiogenesis, and finally tissue remodeling. Failure to heal is often associated with poor revascularization. Since blood vessels mediate the transport of circulating cells, oxygen, nutrients, and waste products, they appear essential for successful healing. The strategy of endogenous regeneration in a tissue such as bone is interesting to analyze since it may represent a blueprint of successful tissue formation. This review highlights the interdependency of the time cascades of inflammation, angiogenesis, and tissue regeneration. A better understanding of these inter-relations is mandatory to early identify patients at risk as well as to overcome critical clinical conditions that limit healing. Instead of purely tolerating the inflammatory phase, modulations of inflammation (immunomodulation) might represent a valid therapeutic strategy to enhance angiogenesis and foster later phases of tissue regeneration.

  4. Strontium borate glass: potential biomaterial for bone regeneration

    OpenAIRE

    Pan, H. B.; Zhao, X. L.; Zhang, X.; Zhang, K. B.; Li, L. C.; Li, Z. Y.; Lam, W. M.; Lu, W. W.; Wang, D. P.; Huang, W. H.; Lin, K. L.; Chang, J.

    2009-01-01

    Boron plays important roles in many life processes including embryogenesis, bone growth and maintenance, immune function and psychomotor skills. Thus, the delivery of boron by the degradation of borate glass is of special interest in biomedical applications. However, the cytotoxicity of borate glass which arises with the rapid release of boron has to be carefully considered. In this study, it was found that the incorporation of strontium into borate glass can not only moderate the rapid relea...

  5. Acceleration of biomimetic mineralization to apply in bone regeneration

    International Nuclear Information System (INIS)

    Jayasuriya, A Champa; Shah, Chiragkumar; Ebraheim, Nabil A; Jayatissa, Ahalapitiya H

    2008-01-01

    The delivery of growth factors and therapeutic drugs into bone defects is a major clinical challenge. Biomimetically prepared bone-like mineral (BLM) containing a carbonated apatite layer can be used to deliver growth factors and drugs in a controlled manner. In the conventional biomimetic process, BLM can be deposited on the biodegradable polymer surfaces by soaking them in simulated body fluid (SBF) for 16 days or more. The aim of this study was to accelerate the biomimetic process of depositing BML in the polymer surfaces. We accelerated the deposition of mineral on 3D poly(lactic-co-glycolic acid) (PLGA) porous scaffolds to 36-48 h by modifying the biomimetic process parameters and applying surface treatments to PLGA scaffolds. The BLM was coated on scaffolds after surface treatments followed by incubation at 37 0 C in 15 ml of 5x SBF. We characterized the BLM created using the accelerated biomineralization process with wide angle x-ray diffraction (XRD), Fourier transform infrared (FTIR) microscopy, and scanning electron microscopy (SEM). The FTIR and XRD analyses of mineralized scaffolds show similarities between biomimetically prepared BLM, and bone bioapatite and carbonated apatite. We also found that the BLM layer on the surface of scaffolds was stable even after 21 days immersed in Tris buffered saline and cell culture media. This study suggests that BLM was stable for at least 3 weeks in both media, and therefore, BLM has a potential for use as a carrier for biological molecules for localized release applications as well as bone tissue engineering applications

  6. Cells responding to surface structure of calcium phosphate ceramics for bone regeneration.

    Science.gov (United States)

    Zhang, Jingwei; Sun, Lanying; Luo, Xiaoman; Barbieri, Davide; de Bruijn, Joost D; van Blitterswijk, Clemens A; Moroni, Lorenzo; Yuan, Huipin

    2017-11-01

    Surface structure largely affects the inductive bone-forming potential of calcium phosphate (CaP) ceramics in ectopic sites and bone regeneration in critical-sized bone defects. Surface-dependent osteogenic differentiation of bone marrow stromal cells (BMSCs) partially explained the improved bone-forming ability of submicron surface structured CaP ceramics. In this study, we investigated the possible influence of surface structure on different bone-related cells, which may potentially participate in the process of improved bone formation in CaP ceramics. Besides BMSCs, the response of human brain vascular pericytes (HBVP), C2C12 (osteogenic inducible cells), MC3T3-E1 (osteogenic precursors), SV-HFO (pre-osteoblasts), MG63 (osteoblasts) and SAOS-2 (mature osteoblasts) to the surface structure was evaluated in terms of cell proliferation, osteogenic differentiation and gene expression. The cells were cultured on tricalcium phosphate (TCP) ceramics with either micron-scaled surface structure (TCP-B) or submicron-scaled surface structure (TCP-S) for up to 14 days, followed by DNA, alkaline phosphatase (ALP) and quantitative polymerase chain reaction gene assays. HBVP were not sensitive to surface structure with respect to cell proliferation and osteogenic differentiation, but had downregulated angiogenesis-related gene expression (i.e. vascular endothelial growth factor) on TCP-S. Without additional osteogenic inducing factors, submicron-scaled surface structure enhanced ALP activity and osteocalcin gene expression of human (h)BMSCs and C2C12 cells, favoured the proliferation of MC3T3-E1, MG63 and SAOS-2, and increased ALP activity of MC3T3-E1 and SV-HFO. The results herein indicate that cells with osteogenic potency (either osteogenic inducible cells or osteogenic cells) could be sensitive to surface structure and responded to osteoinductive submicron-structured CaP ceramics in cell proliferation, ALP production or osteogenic gene expression, which favour bone

  7. Comparative Efficacies of Collagen-Based 3D Printed PCL/PLGA/?-TCP Composite Block Bone Grafts and Biphasic Calcium Phosphate Bone Substitute for Bone Regeneration

    OpenAIRE

    Hwang, Kyoung-Sub; Choi, Jae-Won; Kim, Jae-Hun; Chung, Ho Yun; Jin, Songwan; Shim, Jin-Hyung; Yun, Won-Soo; Jeong, Chang-Mo; Huh, Jung-Bo

    2017-01-01

    The purpose of this study was to compare bone regeneration and space maintaining ability of three-dimensional (3D) printed bone grafts with conventional biphasic calcium phosphate (BCP). After mixing polycaprolactone (PCL), poly (lactic-co-glycolic acid) (PLGA), and ?-tricalcium phosphate (?-TCP) in a 4:4:2 ratio, PCL/PLGA/?-TCP particulate bone grafts were fabricated using 3D printing technology. Fabricated particulate bone grafts were mixed with atelocollagen to produce collagen-based PCL/P...

  8. New nano-hydroxyapatite in bone defect regeneration: A histological study in rats.

    Science.gov (United States)

    Kubasiewicz-Ross, Paweł; Hadzik, Jakub; Seeliger, Julia; Kozak, Karol; Jurczyszyn, Kamil; Gerber, Hanna; Dominiak, Marzena; Kunert-Keil, Christiane

    2017-09-01

    Many types of bone substitute materials are available on the market. Researchers are refining new bone substitutes to make them comparable to autologous grafting materials in treatment of bone defects. The purpose of the study was to evaluate the osseoconductive potential and bone defect regeneration in rat calvaria bone defects treated with new synthetic nano-hydroxyapatite. The study was performed on 30 rats divided into 5 equal groups. New preproduction of experimental nano-hydroxyapatite material by NanoSynHap (Poznań, Poland) was tested and compared with commercially available materials. Five mm critical size defects were created and filled with the following bone grafting materials: 1) Geistlich Bio-Oss ® ; 2) nano-hydroxyapatite+β-TCP; 3) nano-hydroxyapatite; 4) nano-hydroxyapatite+collagen membrane. The last group served as controls without any augmentation. Bone samples from calvaria were harvested for histological and micro-ct evaluation after 8 weeks. New bone formation was observed in all groups. Histomorphometric analysis revealed an amount of regenerated bone between 34.2 and 44.4% in treated bone defects, whereas only 13.0% regenerated bone was found in controls. Interestingly, in group 3, no significant particles of the nano-HA material were found. In contrast, residual bone substitute material could be detected in all other test groups. Micro-CT study confirmed the results of the histological examinations. The new nano-hydroxyapatite provides comparable results to other grafts in the field of bone regeneration. Copyright © 2017 Elsevier GmbH. All rights reserved.

  9. Engineering bone regeneration with novel cell-laden hydrogel microfiber-injectable calcium phosphate scaffold

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yang [Department of Prosthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong (China); Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD 21201 (United States); Zhang, Chi [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041 (China); Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD 21201 (United States); Wang, Ping, E-mail: dentistping@gmail.com [Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD 21201 (United States); Wang, Lin [Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD 21201 (United States); VIP Integrated Department, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130011 (China); Bao, Chunyun [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041 (China); Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD 21201 (United States); Weir, Michael D.; Reynolds, Mark A. [Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD 21201 (United States); Ren, Ke [Department of Neural and Pain Sciences, School of Dentistry, Program in Neuroscience, University of Maryland, Baltimore, MD 21201 (United States); Zhao, Liang, E-mail: lzhaonf@126.com [Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD 21201 (United States); Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515 (China); and others

    2017-06-01

    Cell-based tissue engineering is promising to create living functional tissues for bone regeneration. The implanted cells should be evenly distributed in the scaffold, be fast-released to the defect and maintain high viability in order to actively participate in the regenerative process. Herein, we report an injectable calcium phosphate cement (CPC) scaffold containing cell-encapsulating hydrogel microfibers with desirable degradability that could deliver cells in a timely manner and maintain cell viability. Microfibers were synthesized using partially-oxidized alginate with various concentrations (0–0.8%) of fibrinogen to optimize the degradation rate of the alginate-fibrin microfibers (Alg-Fb MF). A fibrin concentration of 0.4% in Alg-Fb MF resulted in the greatest enhancement of cell migration, release and proliferation. Interestingly, a significant amount of cell–cell contact along the long-axis of the microfibers was established in Alg-0.4%Fb MF as early as day 2. The injectable tissue engineered construct for bone reconstruct was fabricated by mixing the fast-degradable Alg-0.4%Fb MF with CPC paste at 1:1 volume ratio. In vitro study showed that cells re-collected from the construct maintained good viability and osteogenic potentials. In vivo study demonstrated that the hBMSC-encapsulated CPC-MF tissue engineered construct displayed a robust capacity for bone regeneration. At 12 weeks after implantation, osseous bridge in the rat mandibular defect was observed in CPC-MF-hBMSCs group with a new bone area fraction of (42.1 ± 7.8) % in the defects, which was > 3-fold that of the control group. The novel tissue-engineered construct presents an excellent prospect for a wide range of dental, craniofacial and orthopedic applications. - Highlights: • Microfibers protected cells during CPC mixing and injection, and supported the viability, migration and differentiation of encapsulated cells. • Cells re-collected from the construct maintained good viability

  10. Engineering bone regeneration with novel cell-laden hydrogel microfiber-injectable calcium phosphate scaffold

    International Nuclear Information System (INIS)

    Song, Yang; Zhang, Chi; Wang, Ping; Wang, Lin; Bao, Chunyun; Weir, Michael D.; Reynolds, Mark A.; Ren, Ke; Zhao, Liang

    2017-01-01

    Cell-based tissue engineering is promising to create living functional tissues for bone regeneration. The implanted cells should be evenly distributed in the scaffold, be fast-released to the defect and maintain high viability in order to actively participate in the regenerative process. Herein, we report an injectable calcium phosphate cement (CPC) scaffold containing cell-encapsulating hydrogel microfibers with desirable degradability that could deliver cells in a timely manner and maintain cell viability. Microfibers were synthesized using partially-oxidized alginate with various concentrations (0–0.8%) of fibrinogen to optimize the degradation rate of the alginate-fibrin microfibers (Alg-Fb MF). A fibrin concentration of 0.4% in Alg-Fb MF resulted in the greatest enhancement of cell migration, release and proliferation. Interestingly, a significant amount of cell–cell contact along the long-axis of the microfibers was established in Alg-0.4%Fb MF as early as day 2. The injectable tissue engineered construct for bone reconstruct was fabricated by mixing the fast-degradable Alg-0.4%Fb MF with CPC paste at 1:1 volume ratio. In vitro study showed that cells re-collected from the construct maintained good viability and osteogenic potentials. In vivo study demonstrated that the hBMSC-encapsulated CPC-MF tissue engineered construct displayed a robust capacity for bone regeneration. At 12 weeks after implantation, osseous bridge in the rat mandibular defect was observed in CPC-MF-hBMSCs group with a new bone area fraction of (42.1 ± 7.8) % in the defects, which was > 3-fold that of the control group. The novel tissue-engineered construct presents an excellent prospect for a wide range of dental, craniofacial and orthopedic applications. - Highlights: • Microfibers protected cells during CPC mixing and injection, and supported the viability, migration and differentiation of encapsulated cells. • Cells re-collected from the construct maintained good viability

  11. Articular Cartilage Increases Transition Zone Regeneration in Bone-tendon Junction Healing

    Science.gov (United States)

    Qin, Ling; Lee, Kwong Man; Leung, Kwok Sui

    2008-01-01

    The fibrocartilage transition zone in the direct bone-tendon junction reduces stress concentration and protects the junction from failure. Unfortunately, bone-tendon junctions often heal without fibrocartilage transition zone regeneration. We hypothesized articular cartilage grafts could increase fibrocartilage transition zone regeneration. Using a goat partial patellectomy repair model, autologous articular cartilage was harvested from the excised distal third patella and interposed between the residual proximal two-thirds bone fragment and tendon during repair in 36 knees. We evaluated fibrocartilage transition zone regeneration, bone formation, and mechanical strength after repair at 6, 12, and 24 weeks and compared them with direct repair. Autologous articular cartilage interposition resulted in more fibrocartilage transition zone regeneration (69.10% ± 14.11% [mean ± standard deviation] versus 8.67% ± 7.01% at 24 weeks) than direct repair at all times. There was no difference in the amount of bone formation and mechanical strength achieved. Autologous articular cartilage interposition increases fibrocartilage transition zone regeneration in bone-tendon junction healing, but additional research is required to ascertain the mechanism of stimulation and to establish the clinical applicability. PMID:18987921

  12. Self-fitting shape memory polymer foam inducing bone regeneration: A rabbit femoral defect study.

    Science.gov (United States)

    Xie, Ruiqi; Hu, Jinlian; Hoffmann, Oskar; Zhang, Yuanchi; Ng, Frankie; Qin, Tingwu; Guo, Xia

    2018-04-01

    Although tissue engineering has been attracted greatly for healing of critical-sized bone defects, great efforts for improvement are still being made in scaffold design. In particular, bone regeneration would be enhanced if a scaffold precisely matches the contour of bone defects, especially if it could be implanted into the human body conveniently and safely. In this study, polyurethane/hydroxyapatite-based shape memory polymer (SMP) foam was fabricated as a scaffold substrate to facilitate bone regeneration. The minimally invasive delivery and the self-fitting behavior of the SMP foam were systematically evaluated to demonstrate its feasibility in the treatment of bone defects in vivo. Results showed that the SMP foam could be conveniently implanted into bone defects with a compact shape. Subsequently, it self-matched the boundary of bone defects upon shape-recovery activation in vivo. Micro-computed tomography determined that bone ingrowth initiated at the periphery of the SMP foam with a constant decrease towards the inside. Successful vascularization and bone remodeling were also demonstrated by histological analysis. Thus, our results indicate that the SMP foam demonstrated great potential for bone regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Accelerated craniofacial bone regeneration through dense collagen gel scaffolds seeded with dental pulp stem cells

    Science.gov (United States)

    Chamieh, Frédéric; Collignon, Anne-Margaux; Coyac, Benjamin R.; Lesieur, Julie; Ribes, Sandy; Sadoine, Jérémy; Llorens, Annie; Nicoletti, Antonino; Letourneur, Didier; Colombier, Marie-Laure; Nazhat, Showan N.; Bouchard, Philippe; Chaussain, Catherine; Rochefort, Gael Y.

    2016-12-01

    Therapies using mesenchymal stem cell (MSC) seeded scaffolds may be applicable to various fields of regenerative medicine, including craniomaxillofacial surgery. Plastic compression of collagen scaffolds seeded with MSC has been shown to enhance the osteogenic differentiation of MSC as it increases the collagen fibrillary density. The aim of the present study was to evaluate the osteogenic effects of dense collagen gel scaffolds seeded with mesenchymal dental pulp stem cells (DPSC) on bone regeneration in a rat critical-size calvarial defect model. Two symmetrical full-thickness defects were created (5 mm diameter) and filled with either a rat DPSC-containing dense collagen gel scaffold (n = 15), or an acellular scaffold (n = 15). Animals were imaged in vivo by microcomputer tomography (Micro-CT) once a week during 5 weeks, whereas some animals were sacrificed each week for histology and histomorphometry analysis. Bone mineral density and bone micro-architectural parameters were significantly increased when DPSC-seeded scaffolds were used. Histological and histomorphometrical data also revealed significant increases in fibrous connective and mineralized tissue volume when DPSC-seeded scaffolds were used, associated with expression of type I collagen, osteoblast-associated alkaline phosphatase and osteoclastic-related tartrate-resistant acid phosphatase. Results demonstrate the potential of DPSC-loaded-dense collagen gel scaffolds to benefit of bone healing process.

  14. Bone Tissue Engineering and Regeneration: From Discovery to the Clinic—An Overview

    OpenAIRE

    O'Keefe, Regis J.; Mao, Jeremy

    2011-01-01

    A National Institutes of Health sponsored workshop “Bone Tissue Engineering and Regeneration: From Discovery to the Clinic” gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineerin...

  15. Evaluation of the Effect of Plasma Rich in Growth Factors (PRGF) on Bone Regeneration

    OpenAIRE

    Paknejad, M.; Shayesteh, Y. Soleymani; Yaghobee, S.; Shariat, S.; Dehghan, M.; Motahari, P.

    2012-01-01

    Objective: Reconstruction methods are an essential prerequisite for functional rehabilitation of the stomatognathic system. Plasma rich in growth factors (PRGF) offers a new and potentially useful adjunct to bone substitute materials in bone reconstructive surgery. This study was carried out to investigate the influence of PRGF and fibrin membrane on regeneration of bony defects with and without deproteinized bovine bone mineral (DBBM) on rabbit calvaria. Materials and Methods: Twelve New Zea...

  16. Evaluation of the Effect of Plasma Rich in Growth Factors (PRGF) on Bone Regeneration

    OpenAIRE

    M. Paknejad; Y. Soleymani Shayesteh; S. Yaghobee; S. Shariat; M. Dehghan; P. Motahari

    2012-01-01

    Objective: Reconstruction methods are an essential prerequisite for functional rehabilitation of the stomatognathic system. Plasma rich in growth factors (PRGF) offers a new and potentially useful adjunct to bone substitute materials in bone reconstructive surgery. This study was carried out to investigate the influ-ence of PRGF and fibrin membrane on regeneration of bony defects with and without deproteinized bovine bone mineral (DBBM) on rabbit calvaria. Materials and Methods: Twelve New Ze...

  17. Hard tissue regeneration using bone substitutes: an update on innovations in materials.

    Science.gov (United States)

    Sarkar, Swapan Kumar; Lee, Byong Taek

    2015-05-01

    Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues.

  18. Bone tissue engineering and regeneration: from discovery to the clinic--an overview.

    Science.gov (United States)

    O'Keefe, Regis J; Mao, Jeremy

    2011-12-01

    A National Institutes of Health sponsored workshop "Bone Tissue Engineering and Regeneration: From Discovery to the Clinic" gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineering, similar to that for other tissues and organs, requires integration of multiple disciplines such as cell biology, stem cells, developmental and molecular biology, biomechanics, biomaterials science, and immunology and transplantation science. Although each of the research areas has undergone enormous advances in last decade, the translation to clinical care and the development of tissue engineering composites to replace human tissues has been limited. Bone, similar to other tissue and organs, has complex structure and functions and requires exquisite interactions between cells, matrices, biomechanical forces, and gene and protein regulatory factors for sustained function. The process of engineering bone, thus, requires a comprehensive approach with broad expertise. Although in vitro and preclinical animal studies have been pursued with a large and diverse collection of scaffolds, cells, and biomolecules, the field of bone tissue engineering remains fragmented up to the point that a clear translational roadmap has yet to emerge. Translation is particularly important for unmet clinical needs such as large segmental defects and medically compromised conditions such as tumor removal and infection sites. Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics. © Mary Ann Liebert, Inc.

  19. Bone Tissue Engineering and Regeneration: From Discovery to the Clinic—An Overview

    Science.gov (United States)

    2011-01-01

    A National Institutes of Health sponsored workshop “Bone Tissue Engineering and Regeneration: From Discovery to the Clinic” gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineering, similar to that for other tissues and organs, requires integration of multiple disciplines such as cell biology, stem cells, developmental and molecular biology, biomechanics, biomaterials science, and immunology and transplantation science. Although each of the research areas has undergone enormous advances in last decade, the translation to clinical care and the development of tissue engineering composites to replace human tissues has been limited. Bone, similar to other tissue and organs, has complex structure and functions and requires exquisite interactions between cells, matrices, biomechanical forces, and gene and protein regulatory factors for sustained function. The process of engineering bone, thus, requires a comprehensive approach with broad expertise. Although in vitro and preclinical animal studies have been pursued with a large and diverse collection of scaffolds, cells, and biomolecules, the field of bone tissue engineering remains fragmented up to the point that a clear translational roadmap has yet to emerge. Translation is particularly important for unmet clinical needs such as large segmental defects and medically compromised conditions such as tumor removal and infection sites. Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics. PMID:21902614

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

    Science.gov (United States)

    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.

  1. Thermal processing of bone: in vitro response of mesenchymal cells to bone-conditioned medium.

    Science.gov (United States)

    Sawada, K; Caballé-Serrano, J; Schuldt Filho, G; Bosshardt, D D; Schaller, B; Buser, D; Gruber, R

    2015-08-01

    The autoclaving, pasteurization, and freezing of bone grafts to remove bacteria and viruses, and for preservation, respectively, is considered to alter biological properties during graft consolidation. Fresh bone grafts release paracrine-like signals that are considered to support tissue regeneration. However, the impact of the autoclaving, pasteurization, and freezing of bone grafts on paracrine signals remains unknown. Therefore, conditioned medium was prepared from porcine cortical bone chips that had undergone thermal processing. The biological properties of the bone-conditioned medium were assessed by examining the changes in expression of target genes in oral fibroblasts. The data showed that conditioned medium obtained from bone chips that had undergone pasteurization and freezing changed the expression of adrenomedullin, pentraxin 3, BTB/POZ domain-containing protein 11, interleukin 11, NADPH oxidase 4, and proteoglycan 4 by at least five-fold in oral fibroblasts. Bone-conditioned medium obtained from autoclaved bone chips, however, failed to change the expression of the respective genes. Also, when bone-conditioned medium was prepared from fresh bone chips, autoclaving blocked the capacity of bone-conditioned medium to modulate gene expression. These in vitro results suggest that pasteurization and freezing of bone grafts preserve the release of biologically active paracrine signals, but autoclaving does not. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. Magnetic forces and magnetized biomaterials provide dynamic flux information during bone regeneration.

    Science.gov (United States)

    Russo, Alessandro; Bianchi, Michele; Sartori, Maria; Parrilli, Annapaola; Panseri, Silvia; Ortolani, Alessandro; Sandri, Monica; Boi, Marco; Salter, Donald M; Maltarello, Maria Cristina; Giavaresi, Gianluca; Fini, Milena; Dediu, Valentin; Tampieri, Anna; Marcacci, Maurilio

    2016-03-01

    The fascinating prospect to direct tissue regeneration by magnetic activation has been recently explored. In this study we investigate the possibility to boost bone regeneration in an experimental defect in rabbit femoral condyle by combining static magnetic fields and magnetic biomaterials. NdFeB permanent magnets are implanted close to biomimetic collagen/hydroxyapatite resorbable scaffolds magnetized according to two different protocols . Permanent magnet only or non-magnetic scaffolds are used as controls. Bone tissue regeneration is evaluated at 12 weeks from surgery from a histological, histomorphometric and biomechanical point of view. The reorganization of the magnetized collagen fibers under the effect of the static magnetic field generated by the permanent magnet produces a highly-peculiar bone pattern, with highly-interconnected trabeculae orthogonally oriented with respect to the magnetic field lines. In contrast, only partial defect healing is achieved within the control groups. We ascribe the peculiar bone regeneration to the transfer of micro-environmental information, mediated by collagen fibrils magnetized by magnetic nanoparticles, under the effect of the static magnetic field. These results open new perspectives on the possibility to improve implant fixation and control the morphology and maturity of regenerated bone providing "in site" forces by synergically combining static magnetic fields and biomaterials.

  3. Maxillary Bone Regeneration Based on Nanoreservoirs Functionalized ε-Polycaprolactone Biomembranes in a Mouse Model of Jaw Bone Lesion

    Directory of Open Access Journals (Sweden)

    Marion Strub

    2018-01-01

    Full Text Available Current approaches of regenerative therapies constitute strategies for bone tissue reparation and engineering, especially in the context of genetical diseases with skeletal defects. Bone regeneration using electrospun nanofibers’ implant has the following objectives: bone neoformation induction with rapid healing, reduced postoperative complications, and improvement of bone tissue quality. In vivo implantation of polycaprolactone (PCL biomembrane functionalized with BMP-2/Ibuprofen in mouse maxillary defects was followed by bone neoformation kinetics evaluation using microcomputed tomography. Wild-Type (WT and Tabby (Ta mice were used to compare effects on a normal phenotype and on a mutant model of ectodermal dysplasia (ED. After 21 days, no effect on bone neoformation was observed in Ta treated lesion (4% neoformation compared to 13% in the control lesion. Between the 21st and the 30th days, the use of biomembrane functionalized with BMP-2/Ibuprofen in maxillary bone lesions allowed a significant increase in bone neoformation peaks (resp., +8% in mutant Ta and +13% in WT. Histological analyses revealed a neoformed bone with regular trabecular structure, areas of mineralized bone inside the membrane, and an improved neovascularization in the treated lesion with bifunctionalized membrane. In conclusion, PCL functionalized biomembrane promoted bone neoformation, this effect being modulated by the Ta bone phenotype responsible for an alteration of bone response.

  4. Extracellular matrix scaffolds for cartilage and bone regeneration

    NARCIS (Netherlands)

    Benders, K.E.M.; van Weeren, P.R.; Badylak, S.F.; Saris, Daniël B.F.; Dhert, W.J.A.; Malda, J.

    2013-01-01

    Regenerative medicine approaches based on decellularized extracellular matrix (ECM) scaffolds and tissues are rapidly expanding. The rationale for using ECM as a natural biomaterial is the presence of bioactive molecules that drive tissue homeostasis and regeneration. Moreover, appropriately

  5. A review of the effects of dietary silicon intake on bone homeostasis and regeneration.

    Science.gov (United States)

    Rodella, L F; Bonazza, V; Labanca, M; Lonati, C; Rezzani, R

    2014-11-01

    Increasing evidences suggest that dietary Silicon (Si) intake, is positively correlated with bone homeostasis and regeneration, representing a potential and valid support for the prevention and improvement of bone diseases, like osteoporosis. This review, aims to provide the state of art of the studies performed until today, in order to investigate and clarify the beneficial properties and effects of silicates, on bone metabolism. We conducted a systematic literature search up to March 2013, using two medical databases (Pubmed and the Cochrane Library), to review the studies about Si consumption and bone metabolism. We found 45 articles, but 38 were specifically focused on Si studies. RESULTS showed a positive relationship between dietary Si intake and bone regeneration.

  6. JAW CYSTS AND GUIDED BONE REGENERATION (a late complication after enucleation

    Directory of Open Access Journals (Sweden)

    Hristina Lalabonova

    2013-10-01

    Full Text Available Maxillary jaw bone possesses a high regenerative capacity. Yet sometimes the defects enucleation of jaw cysts leaves may regenerate only partially or not at all. For this reason some researchers advise treatment of the residual cavities after cystectomy using bone regeneration stimulation methods. We report a case of an atypical complication after enucleation of a maxillary cyst manifesting itself eight years after the initial treatment. The symptoms the patient reported were at first periodic sweating on the left sides of face and head. This was followed by a piercing pain in the left palpebral fissure radiating to the middle of the palate and felt in the left cheekbone, left eye and left supraorbital ridge. The patient has a history of maxillary cysts recurring three times and of three operations she had 20, 12 and 8 years previously. The multiple recurrences of the cysts after their enucleation indicates poor regenerative capacity of the body which resulted in the formation of cicatricial tissue. It is most probably this tissue that was responsible for the disruption of the nerve conduction capacity which can account for the reported symptoms. We filled the cavity with bone graft material which boosted the bone structure regeneration. Although maxillary jaws possess high regenerative capacity we advise the use of guided bone regeneration in cases of large bone defects that usually occur after enucleation of jaw cysts.

  7. Electrospun three dimensional scaffolds for bone tissue regeneration

    OpenAIRE

    Paşcu, Elena Irina

    2013-01-01

    Bone is a complex and highly specialized form of connective tissue which acts as the main supporting organ of the body. It is hard and dynamic by its nature, with a unique combination of organic and inorganic elements embedded in a fibrous extracellular matrix (ECM), onto which cells attach, proliferate and differentiate. When bone repair mechanisms fail, due to infection or defect magnitude, bone formation can be stimulated with the use of autologous bone grafts or donor allografts. However,...

  8. Bone regeneration: molecular and cellular interactions with calcium phospate ceramics

    NARCIS (Netherlands)

    Barrère, F.; van Blitterswijk, Clemens; de Groot, K.

    2006-01-01

    Calcium phosphate bioceramics are widely used in orthopedic and dental applications and porous scaffolds made of them are serious candidates in the field of bone tissue engineering. They have superior properties for the stimulation of bone formation and bone bonding, both related to the specific

  9. PATHOHISTOLOGICAL INVESTIGATION ON THE INFLUENCE OF INTRACANAL MEDICATION ON THE REGENERATION OF JAW BONE

    Directory of Open Access Journals (Sweden)

    Anatoliy Borysenko

    2012-12-01

    Full Text Available The results of histological investigation on the influence of the proposed drug composition (metronidazole, enterosgel (Sigma, alflutop (Biotehnos S.A., Romania for experimental mandible bone defect regeneration in rats were presented. The high efficiency and osteoregenerative properties of this paste were shown, and its significant clinical efficiency for temporary placement into the root canals in the treatment of chronic apical periodontitis, for stimulating regeneration of the damaged periapical tissues, was assessed.

  10. 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.

  11. Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

    Science.gov (United States)

    Henkel, Jan; Woodruff, Maria A.; Epari, Devakara R.; Steck, Roland; Glatt, Vaida; Dickinson, Ian C.; Choong, Peter F. M.; Schuetz, Michael A.; Hutmacher, Dietmar W.

    2013-01-01

    The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental “origin” require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts. PMID:26273505

  12. Current Progress in Bioactive Ceramic Scaffolds for Bone Repair and Regeneration

    Science.gov (United States)

    Gao, Chengde; Deng, Youwen; Feng, Pei; Mao, Zhongzheng; Li, Pengjian; Yang, Bo; Deng, Junjie; Cao, Yiyuan; Shuai, Cijun; Peng, Shuping

    2014-01-01

    Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration. PMID:24646912

  13. Comparative analysis of guided bone regeneration using autogenous tooth bone graft material with and without resorbable membrane

    Directory of Open Access Journals (Sweden)

    Ji-Young Lee

    2013-09-01

    Conclusion: Both groups showed clinically acceptable bone regeneration without any eventful complications. Within the limitation of this study, we can carefully conclude that the use of resorbable membrane is not a critical factor in GBR when using AutoBT.

  14. An Overview of Long Noncoding RNAs Involved in Bone Regeneration from Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Shuping Peng

    2018-01-01

    Full Text Available Bone regeneration is very important for the recovery of some diseases including osteoporosis and bone fracture trauma. It is a multiple-step- and multiple-gene-involved complex process, including the matrix secretion and calcium mineralization by osteoblasts differentiated from mesenchymal stem cells (MSCs and the absorption of calcium and phosphorus by osteoclasts differentiated from hematopoietic stem cells. Long noncoding RNAs (lncRNAs are a family of transcripts longer than 200 nt without or with very low protein-coding potential. Recent studies have demonstrated that lncRNAs are widely involved in the regulation of lineage commitment and differentiation of stem cells through multiple mechanisms. In this review, we will summarize the roles and molecular mechanism of lncRNAs including H19, MALAT1, MODR, HOTAIR, DANCR, MEG3, HoxA-AS3, and MIAT in osteogenesis ossification; lncRNA ZBED3-AS1 and CTA-941F9.9, DANCR, and HIT in chondrogenic differentiation; and lncRNA DANCR in osteoclast differentiation. These findings will facilitate the development and application of novel molecular drugs which regulate the balance of bone formation and absorption.

  15. Bioactivity evaluation of commercial calcium phosphate-based bioceramics for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Borrós, S.; Mas, A.

    2016-11-01

    Calcium phosphate-based bioceramics constitute a great promise for bone tissue engineering as they chemically resemble to mammalian bone and teeth. Their use is a viable alternative for bone regeneration as it avoids the use of autografts and allografts, which usually involves immunogenic reactions and patient’s discomfort. This work evolves around the study of the bioactivity potential of different commercially available bone substitutes based in calcium phosphate through the characterization of their ionic exchangeability when immersed in simulated body fluid (SBF). (Author)

  16. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid

    International Nuclear Information System (INIS)

    Ambrus, C.M.; Ambrus, J.L.

    1975-01-01

    Stumptail monkeys (Macaca speciosa) received lethal whole-body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colony-forming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls

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

    Science.gov (United States)

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

    2012-03-01

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

  18. Relevance of fiber integrated gelatin-nanohydroxyapatite composite scaffold for bone tissue regeneration

    Science.gov (United States)

    Halima Shamaz, Bibi; Anitha, A.; Vijayamohan, Manju; Kuttappan, Shruthy; Nair, Shantikumar; Nair, Manitha B.

    2015-10-01

    Porous nanohydroxyapatite (nanoHA) is a promising bone substitute, but it is brittle, which limits its utility for load bearing applications. To address this issue, herein, biodegradable electrospun microfibrous sheets of poly(L-lactic acid)-(PLLA)-polyvinyl alcohol (PVA) were incorporated into a gelatin-nanoHA matrix which was investigated for its mechanical properties, the physical integration of the fibers with the matrix, cell infiltration, osteogenic differentiation and bone regeneration. The inclusion of sacrificial fibers like PVA along with PLLA and leaching resulted in improved cellular infiltration towards the center of the scaffold. Furthermore, the treatment of PLLA fibers with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide enhanced their hydrophilicity, ensuring firm anchorage between the fibers and the gelatin-HA matrix. The incorporation of PLLA microfibers within the gelatin-nanoHA matrix reduced the brittleness of the scaffolds, the effect being proportional to the number of layers of fibrous sheets in the matrix. The proliferation and osteogenic differentiation of human adipose-derived mesenchymal stem cells was augmented on the fibrous scaffolds in comparison to those scaffolds devoid of fibers. Finally, the scaffold could promote cell infiltration, together with bone regeneration, upon implantation in a rabbit femoral cortical defect within 4 weeks. The bone regeneration potential was significantly higher when compared to commercially available HA (Surgiwear™). Thus, this biomimetic, porous, 3D composite scaffold could be offered as a promising candidate for bone regeneration in orthopedics.

  19. Periosteal Distraction Osteogenesis: An Effective Method for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Danyang Zhao

    2016-01-01

    Full Text Available The treatment of bone defects is challenging and controversial. As a new technology, periosteal distraction osteogenesis (PDO uses the osteogenicity of periosteum, which creates an artificial space between the bone surface and periosteum to generate new bone by gradually expanding the periosteum with no need for corticotomy. Using the newly formed bone of PDO to treat bone defects is effective, which can not only avoid the occurrence of immune-related complications, but also solve the problem of insufficient donor. This review elucidates the availability of PDO in the aspects of mechanisms, devices, strategies, and measures. Moreover, we also focus on the future prospects of PDO and hope that PDO will be applied to the clinical treatment of bone defects in the future.

  20. FEATURES OF THE REGENERATION PROCESS OF THE FILTER

    Directory of Open Access Journals (Sweden)

    S. Yu. Panov

    2015-01-01

    Full Text Available The regeneration system exercises significant influence on the efficiency and reliability of the filters. During operation of the filter it continuously increases the hydraulic resistance and the gas permeability of the filter material decreases as the deposition of the disperse phase capturable on the filter element, and to maintain the bandwidth of the filter in the filter element within the set must be periodically changed or regenerated. Thus, regeneration of a process of removing part of the dust layer with the purpose of full or partial reduction of the initial filter partitioning properties. On the basis of theoretical synthesis, physico-chemical effects of dust in layers, analysis of energy effects, developed methods of intensification of the process of regeneration of particulate filters. Pneumopulse regeneration of bag filter has been investigated, and based on it a regression equation for regeneration efficiency has been derived. It has been shown that pulse pressure exerts the dominant influence on the regeneration efficiency. The obtained model was used for assessment and prediction of the efficiency of the pneumopulse system of regeneration of bag filters at a number of structural materials producing enterprises in the Voronezh region.

  1. Hydrogels That Allow and Facilitate Bone Repair, Remodeling, and Regeneration.

    Science.gov (United States)

    Short, Aaron R; Koralla, Deepthi; Deshmukh, Ameya; Wissel, Benjamin; Stocker, Benjamin; Calhoun, Mark; Dean, David; Winter, Jessica O

    2015-10-28

    Bone defects can originate from a variety of causes, including trauma, cancer, congenital deformity, and surgical reconstruction. Success of the current "gold standard" treatment (i.e., autologous bone grafts) is greatly influenced by insufficient or inappropriate bone stock. There is thus a critical need for the development of new, engineered materials for bone repair. This review describes the use of natural and synthetic hydrogels as scaffolds for bone tissue engineering. We discuss many of the advantages that hydrogels offer as bone repair materials, including their potential for osteoconductivity, biodegradability, controlled growth factor release, and cell encapsulation. We also discuss the use of hydrogels in composite devices with metals, ceramics, or polymers. These composites are useful because of the low mechanical moduli of hydrogels. Finally, the potential for thermosetting and photo-cross-linked hydrogels as three-dimensionally (3D) printed, patient-specific devices is highlighted. Three-dimensional printing enables controlled spatial distribution of scaffold materials, cells, and growth factors. Hydrogels, especially natural hydrogels present in bone matrix, have great potential to augment existing bone tissue engineering devices for the treatment of critical size bone defects.

  2. Bone regeneration: Biomaterials as local delivery systems with improved osteoinductive properties.

    Science.gov (United States)

    Martin, Victor; Bettencourt, Ana

    2018-01-01

    Bone is a mineralized conjunctive tissue, with a unique trauma healing capability. However, the replacement or regeneration of lost bone is not always successful and becomes more difficult the wider the bone defect. A significant growth in the demand for orthopedic and maxillofacial surgical procedures as a result of population aging and increase in chronic diseases as diabetes is a fact and successful approaches for bone regeneration are still needed. Until today, autogenous bone graft continues to be the best solution even with important limitations, as quantity and the requirement of a donator area. Alternatively, local delivery systems combining an osteoconductive biomaterial with osteoinductive compounds as hormones, growth factors or drugs is a popular approach aiming to replace the need for autogenous bone grafts. Nevertheless, in spite of the intense research in the area, presently there is no system that can mimic all the biological functions of the autogenous bone grafts. In this context, the present work provides an overview of the most recent advances in the field of synthetic bone grafts. The opportunities and limitations are detailed along with the remaining gaps in the research that are still preventing the successful translation of more products into the market able to be a valuable option in comparison to the autogenous bone grafts. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. CHANGING OF THE BIOCHEMICAL INDICES ON REGENERATION OF EXPERIMENTAL DEFECT OF THE MANDIBLE BONE

    Directory of Open Access Journals (Sweden)

    A. Borysenko

    2012-09-01

    Full Text Available Summary. The results of an experimental biochemical investigation on the influence of the proposed drug composition for the experimental mandible bone defect regeneration in rats were presented. The high efficiency and osteoregenerative properties of this paste were shown. The experimental investigations showed that the proposed drug composition exerts a considerable normalization influence upon the biochemical indicators of bone mineral metabolism, comparable to Collapan influence.

  4. Bioactive polymeric–ceramic hybrid 3D scaffold for application in bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Torres, A.L.; Gaspar, V.M.; Serra, I.R.; Diogo, G.S.; Fradique, R. [CICS-UBI — Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã (Portugal); Silva, A.P. [CAST-UBI — Centre for Aerospace Science and Technologies, University of Beira Interior, Calçada Fonte do Lameiro, 6201-001 Covilhã (Portugal); Correia, I.J., E-mail: icorreia@ubi.pt [CICS-UBI — Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã (Portugal)

    2013-10-01

    The regeneration of large bone defects remains a challenging scenario from a therapeutic point of view. In fact, the currently available bone substitutes are often limited by poor tissue integration and severe host inflammatory responses, which eventually lead to surgical removal. In an attempt to address these issues, herein we evaluated the importance of alginate incorporation in the production of improved and tunable β-tricalcium phosphate (β-TCP) and hydroxyapatite (HA) three-dimensional (3D) porous scaffolds to be used as temporary templates for bone regeneration. Different bioceramic combinations were tested in order to investigate optimal scaffold architectures. Additionally, 3D β-TCP/HA vacuum-coated with alginate, presented improved compressive strength, fracture toughness and Young's modulus, to values similar to those of native bone. The hybrid 3D polymeric–bioceramic scaffolds also supported osteoblast adhesion, maturation and proliferation, as demonstrated by fluorescence microscopy. To the best of our knowledge this is the first time that a 3D scaffold produced with this combination of biomaterials is described. Altogether, our results emphasize that this hybrid scaffold presents promising characteristics for its future application in bone regeneration. - Graphical abstract: B-TCP:HA–alginate hybrid 3D porous scaffolds for application in bone regeneration. - Highlights: • The produced hybrid 3D scaffolds are prone to be applied in bone tissue engineering. • Alginate coated 3D scaffolds present high mechanical and biological properties. • In vitro assays for evaluation of human osteoblast cell attachment in the presence of the scaffolds • The hybrid 3D scaffolds present suitable mechanical and biological properties for use in bone regenerative medicine.

  5. Bioactive polymeric–ceramic hybrid 3D scaffold for application in bone tissue regeneration

    International Nuclear Information System (INIS)

    Torres, A.L.; Gaspar, V.M.; Serra, I.R.; Diogo, G.S.; Fradique, R.; Silva, A.P.; Correia, I.J.

    2013-01-01

    The regeneration of large bone defects remains a challenging scenario from a therapeutic point of view. In fact, the currently available bone substitutes are often limited by poor tissue integration and severe host inflammatory responses, which eventually lead to surgical removal. In an attempt to address these issues, herein we evaluated the importance of alginate incorporation in the production of improved and tunable β-tricalcium phosphate (β-TCP) and hydroxyapatite (HA) three-dimensional (3D) porous scaffolds to be used as temporary templates for bone regeneration. Different bioceramic combinations were tested in order to investigate optimal scaffold architectures. Additionally, 3D β-TCP/HA vacuum-coated with alginate, presented improved compressive strength, fracture toughness and Young's modulus, to values similar to those of native bone. The hybrid 3D polymeric–bioceramic scaffolds also supported osteoblast adhesion, maturation and proliferation, as demonstrated by fluorescence microscopy. To the best of our knowledge this is the first time that a 3D scaffold produced with this combination of biomaterials is described. Altogether, our results emphasize that this hybrid scaffold presents promising characteristics for its future application in bone regeneration. - Graphical abstract: B-TCP:HA–alginate hybrid 3D porous scaffolds for application in bone regeneration. - Highlights: • The produced hybrid 3D scaffolds are prone to be applied in bone tissue engineering. • Alginate coated 3D scaffolds present high mechanical and biological properties. • In vitro assays for evaluation of human osteoblast cell attachment in the presence of the scaffolds • The hybrid 3D scaffolds present suitable mechanical and biological properties for use in bone regenerative medicine

  6. Optimizing Segmental Bone Regeneration Using Functionally Graded Scaffolds

    Science.gov (United States)

    2012-10-01

    mechanical strength (130– 190 MPa).4 Cancellous bone accounts for the other 20% of the total bone mass and is highly porous (50%–90%), with *10% of the...bionanotechnology. Adv Mater 18, 1345, 2006. 96. Drury , J.L., and Mooney, D.J. Hydrogels for tissue engi- neering: scaffold design variables and applications. Bio

  7. Interplay of thymus and bone marrow regeneration in x-irradiated mice

    International Nuclear Information System (INIS)

    Hiesche, K.-D.

    1975-01-01

    aim of the prepresent investigation was to study the modifying effects of bone marrow cells on regeneration, after X-irradiation, of thymus and bone marrow cell populations. Data are presented which indicate that the cellular composition of the thymus and, in particular, the frequency of the stem cells in the organ at the time of radiation exposure determines thymic regeneration for about two weeks after irradiation. After this period, regeneration depends on new precursors from the bone marrow which have previously seeded the thymus. In contrast to the thymus, cellular restoration of the bone marrow is already initially dependent on the number of protected or transplanted marrow cells. Two phases in the recovery of thymic PHA-reactivity after irradiation were observed: one initial phase which is independent on the number of the available bone marrow cells, and a subsequent phase during which PHA-reactivity is slightly increased in mice irradiated with partly protected bone marrow in comparison to in total body irradiated animals. During the entire observation period, PHA-reactivity remains at a low level not exeeding 50 % of that in untreated mice. In contrast the thymus is fully repopulated with regard to the number of nonreactive cells. Alternative pathways of thymocyte development within the thymus are discussed. Bone marrow X cells were shown to be as sensitive to in vitro treatment with a specific H-2 antiserum as were lymphocytes from normal bone marrow. This finding was teken to indicate that the X cells represent a particular lymphoid cell type. A xenogeneic rabbit-anti-mouse embryo antiserum was more toxic to pre-irradiated bone marrow, with high proportion of X cells, than to bone marrow from untreated mice, using in vitro cytotoxicity test. A possible embryonic character of the X cells is discussed. (author)

  8. Interplay of thymus and bone marrow regeneration in x-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Hiesche, K D

    1975-01-01

    The aim of the present investigation was to study the modifying effects of bone marrow cells on regeneration, after X-irradiation, of thymus and bone marrow cell populations. Data are presented which indicate that the cellular composition of the thymus and, in particular, the frequency of the stem cells in the organ at the time of radiation exposure determines thymic regeneration for about two weeks after irradiation. After this period, regeneration depends on new precursors from the bone marrow which have previously seeded the thymus. In contrast to the thymus, cellular restoration of the bone marrow is already initially dependent on the number of protected or transplanted marrow cells. Two phases in the recovery of thymic PHA-reactivity after irradiation were observed: one initial phase which is independent on the number of the available bone marrow cells, and a subsequent phase during which PHA-reactivity is slightly increased in mice irradiated with partly protected bone marrow in comparison to in total body irradiated animals. During the entire observation period, PHA-reactivity remains at a low level not exeeding 50 % of that in untreated mice. In contrast the thymus is fully repopulated with regard to the number of nonreactive cells. Alternative pathways of thymocyte development within the thymus are discussed. Bone marrow X cells were shown to be as sensitive to in vitro treatment with a specific H-2 antiserum as were lymphocytes from normal bone marrow. This finding was teken to indicate that the X cells represent a particular lymphoid cell type. A xenogeneic rabbit-anti-mouse embryo antiserum was more toxic to pre-irradiated bone marrow, with high proportion of X cells, than to bone marrow from untreated mice, using in vitro cytotoxicity test. A possible embryonic character of the X cells is discussed.

  9. Graded porous polyurethane foam: A potential scaffold for oro-maxillary bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Giannitelli, S.M. [Department of Engineering, Tissue Engineering Unit, Università Campus Bio-Medico di Roma, Rome (Italy); Basoli, F. [Department of Chemical Science and Technology, University of Rome “Tor Vergata”, Rome (Italy); Mozetic, P. [Department of Engineering, Tissue Engineering Unit, Università Campus Bio-Medico di Roma, Rome (Italy); Piva, P.; Bartuli, F.N.; Luciani, F. [University of Rome “Tor Vergata”, Rome (Italy); Arcuri, C. [Department of Periodontics, University of Rome “Tor Vergata”, Rome (Italy); U.O.C.C. Odontostomatology, “S. Giovanni Calibita, Fatebenefratelli” Hospital, Rome (Italy); Trombetta, M. [Department of Engineering, Tissue Engineering Unit, Università Campus Bio-Medico di Roma, Rome (Italy); Rainer, A., E-mail: a.rainer@unicampus.it [Department of Engineering, Tissue Engineering Unit, Università Campus Bio-Medico di Roma, Rome (Italy); Licoccia, S. [Department of Chemical Science and Technology, University of Rome “Tor Vergata”, Rome (Italy)

    2015-06-01

    Bone tissue engineering applications demand for biomaterials offering a substrate for cell adhesion, migration, and proliferation, while inferring suitable mechanical properties to the construct. In the present study, polyurethane (PU) foams were synthesized to develop a graded porous material—characterized by a dense shell and a porous core—for the treatment of oro-maxillary bone defects. Foam was synthesized via a one-pot reaction starting from a polyisocyanate and a biocompatible polyester diol, using water as a foaming agent. Different foaming conditions were examined, with the aim of creating a dense/porous functional graded material that would perform at the same time as an osteoconductive scaffold for bone defect regeneration and as a membrane-barrier to gingival tissue ingrowth. The obtained PU was characterized in terms of morphological and mechanical properties. Biocompatibility assessment was performed in combination with bone-marrow-derived human mesenchymal stromal cells (hBMSCs). Our findings confirm that the material is potentially suitable for guided bone regeneration applications. - Highlights: • Graded porous polyurethane foams were synthesized via a one-pot foaming reaction. • The inner porous core might act as a scaffold for guided bone regeneration. • A dense outer shell was introduced to act as a barrier to gingival tissue ingrowth. • The synthesized foams were non-toxic and supportive of hBMSC adhesion.

  10. Graded porous polyurethane foam: A potential scaffold for oro-maxillary bone regeneration

    International Nuclear Information System (INIS)

    Giannitelli, S.M.; Basoli, F.; Mozetic, P.; Piva, P.; Bartuli, F.N.; Luciani, F.; Arcuri, C.; Trombetta, M.; Rainer, A.; Licoccia, S.

    2015-01-01

    Bone tissue engineering applications demand for biomaterials offering a substrate for cell adhesion, migration, and proliferation, while inferring suitable mechanical properties to the construct. In the present study, polyurethane (PU) foams were synthesized to develop a graded porous material—characterized by a dense shell and a porous core—for the treatment of oro-maxillary bone defects. Foam was synthesized via a one-pot reaction starting from a polyisocyanate and a biocompatible polyester diol, using water as a foaming agent. Different foaming conditions were examined, with the aim of creating a dense/porous functional graded material that would perform at the same time as an osteoconductive scaffold for bone defect regeneration and as a membrane-barrier to gingival tissue ingrowth. The obtained PU was characterized in terms of morphological and mechanical properties. Biocompatibility assessment was performed in combination with bone-marrow-derived human mesenchymal stromal cells (hBMSCs). Our findings confirm that the material is potentially suitable for guided bone regeneration applications. - Highlights: • Graded porous polyurethane foams were synthesized via a one-pot foaming reaction. • The inner porous core might act as a scaffold for guided bone regeneration. • A dense outer shell was introduced to act as a barrier to gingival tissue ingrowth. • The synthesized foams were non-toxic and supportive of hBMSC adhesion

  11. Structural and ultrastructural analyses of bone regeneration in rabbit cranial osteotomy: Piezosurgery versus traditional osteotomes.

    Science.gov (United States)

    Anesi, Alexandre; Ferretti, Marzia; Cavani, Francesco; Salvatori, Roberta; Bianchi, Michele; Russo, Alessandro; Chiarini, Luigi; Palumbo, Carla

    2018-01-01

    Clinical advantages of piezosurgery have been already proved. However, few investigations have focused on the dynamics of bone healing. The aim of this study was to evaluate, in adult rabbits, bone regeneration after cranial linear osteotomies with two piezoelectrical devices (Piezosurgery ® Medical - PM and Piezosurgery ® Plus - PP), comparing them with conventional rotary osteotomes (RO). PP was characterized by an output power three times higher than PM. Fifteen days after surgery, histomorphometric analyses showed that the osteotomy gap produced with PM and PP was about half the size of that produced by RO, and in a more advanced stage of recovery. Values of regenerated bone area with respect to the total osteotomy area were about double in PM and PP samples compared with RO ones, while the number of TRAP-positive (tartrate-resistant acid phosphatase positive) osteoclasts per linear surface showed a significant increase, suggesting greater bone remodelling. Under scanning electron microscopy, regenerated bone displayed higher cell density and less mineralized matrix compared with pre-existent bone for all devices used. Nanoindentation tests showed no changes in elastic modulus. In conclusion, PM/PP osteotomies can be considered equivalent to each other, and result in more rapid healing compared with those using RO. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  12. In Vitro and In Vivo Study of a Novel Porcine Collagen Membrane for Guided Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Eisner Salamanca

    2016-11-01

    Full Text Available For years, in order to improve bone regeneration and prevent the need of a second stage surgery to remove non-resorbable membranes, biological absorbable membranes have gradually been developed and applied in guided tissue regeneration (GTR. The present study’s main objective was to achieve space maintenance and bone regeneration using a new freeze-dried developed porcine collagen membrane, and compare it with an already commercial collagen membrane, when both were used with a bovine xenograft in prepared alveolar ridge bone defects. Prior to surgery, the membrane’s vitality analysis showed statistically significant higher cell proliferation in the test membrane over the commercial one. In six beagle dogs, commercial bone xenograft was packed in lateral ridge bone defects prepared in the left and right side and then covered with test porcine collagen membrane or commercial collagen membrane. Alveolar height changes were measured. Histomorphometric results, in vitro and in vivo properties indicated that the new porcine collagen membrane is biocompatible, enhances bone xenograft osteoconduction, and reduces the alveolar ridge height reabsorption rate.

  13. The role of allofibroblasts transplantation in cartilaginous tissue regeneration process

    OpenAIRE

    Khadjibaev Аbdukhakim Muminovich; Tilyakov Akbar Buriyevich; Magrupov Bokhodir Asadullaevich; Urazmetova Maisa Dmitriyevna; Ubaydullaev Bobur Sabirovich

    2017-01-01

    Aim of investigation. Ground of embryonal allofibroblasts in the process of cartilaginous tissue regeneration. Material and methods. Investigation is based on the study the results of stimulation cartilaginous tissue regeneration process in the conditions of embryonal allofibroblasts application in 24 experimental sexually mature rabbits in which the model of symphysis pubis rupture with its following recovery have been used. Pieces of cartilaginous tissue have been fixed in 10% neutral forma...

  14. Characteristic features of bone tissue regeneration in the vertebral bodies in the experiment with osteograft

    Science.gov (United States)

    Zaydman, A. M.; Predein, Yu. A.; Korel, A. V.; Shchelkunova, E. I.; Strokova, E. I.; Lastevskiy, A. D.; Rerikh, V. V.; Fomichev, N. G.; Falameeva, O. V.; Shevchenko, A. I.; Shevtcov, V. I.

    2017-09-01

    In the practice of orthopedic and trauma surgeons, there is a need to close bone tissue defects after removal of tumors or traumatic and dystrophic lesions. Currently, as cellular technologies are being developed, stem embryonic and pluripotent cells are widely introduced into practical medicine. The unpredictability of the spectrum of cell differentiations, up to oncogenesis, raised the question of creating biological structures committed toward osteogenic direction, capable of regenerating organo-specific graft at the optimal time. Such osteograft was created at the Novosibirsk Institute of Traumatology and Orthopaedics (patent RU 2574942). Its osteogenic orientation was confirmed by the morphological and immunohistochemical methods, and by the expression of bone genes. The regeneration potential of the osteograft was studied in the vertebral bodies of the mini piglet model. The study revealed that the regeneration of the vertebral body defect and the integration of the osteograft with the bed of the recipient proceeds according to the type of primary angiogenic osteogenesis within 30 days.

  15. Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

    NARCIS (Netherlands)

    Xu, Cui-Ping; Ji, Wen-Min; van den Brink, Gijs R.; Peppelenbosch, Maikel P.

    2006-01-01

    To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells. Fifty-four adult male Wistar rats were randomly

  16. Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

    NARCIS (Netherlands)

    Xu, Cui-Ping; Ji, Wen-Min; van den Brink, Gijs R.; Peppelenbosch, Maikel P.

    2006-01-01

    AIM: To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells. METHODS: Fifty-four adult male Wistar rats

  17. Bone marrow adipocytes promote the regeneration of stem cells and hematopoiesis by secreting SCF

    Science.gov (United States)

    Zhou, Bo O.; Yu, Hua; Yue, Rui; Zhao, Zhiyu; Rios, Jonathan J.; Naveiras, Olaia; Morrison, Sean J.

    2017-01-01

    Endothelial cells and Leptin Receptor+ (LepR+) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including Stem Cell Factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER+ progenitors, which represent ~5% of LepR+ cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited hematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR+ cells, but not endothelial, hematopoietic, or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 ‘fatless” mice exhibited delayed hematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes hematopoietic regeneration. PMID:28714970

  18. Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

    NARCIS (Netherlands)

    van Leeuwen, A. C.; Huddleston Slater, J. J. R.; Gielkens, P. F. M.; de Jong, J. R.; Grijpma, D. W.; Bos, R. R. M.

    The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague-Dawley rats, a

  19. Development of a PCL-silica nanoparticles composite membrane for Guided Bone Regeneration

    NARCIS (Netherlands)

    Castro, A.; Diba, M.; Kersten, M.; Jansen, J.A.; Beucken, J.J.J.P van den; Yang, F.

    2018-01-01

    The pivotal step in Guided Bone Regeneration (GBR) therapy is the insertion of a membrane for support and barrier functions. Here, we studied the effect of the addition of silica nanoparticles (Si-NPs) in electrospun poly(epsilon-caprolactone) (PCL) membranes to improve the mechanical and

  20. Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

    NARCIS (Netherlands)

    van Leeuwen, A.C.; Huddelston Slater, J.J.R.; Gielkens, P.F.M.; de Jong, J.R.; Grijpma, Dirk W.; Bos, R.R.M.

    2012-01-01

    The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague–Dawley rats, a

  1. Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF.

    Science.gov (United States)

    Zhou, Bo O; Yu, Hua; Yue, Rui; Zhao, Zhiyu; Rios, Jonathan J; Naveiras, Olaia; Morrison, Sean J

    2017-08-01

    Endothelial cells and leptin receptor + (LepR + ) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including stem cell factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER + progenitors, which represent ∼5% of LepR + cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited haematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR + cells, but not endothelial, haematopoietic or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 'fatless' mice exhibited delayed haematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes haematopoietic regeneration.

  2. Regeneration of calvarial defects by a composite of bioerodible polyorthoester and demineralized bone in rats

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Bang, G

    1992-01-01

    A study was performed to evaluate regeneration of defects in rat calvaria either unfilled or filled with a bioerodible polyorthoester only, demineralized bone only, or a composite of both. At 4 weeks, histological and radiographic studies showed that defects filled with a composite of bioerodible...... polyorthoester and demineralized bone or demineralized bone alone were bridged by bone. Unfilled defects or defects filled with polyorthoester only did not heal. The polyorthoester caused slight inflammation that subsided by 3 weeks, and only traces of the filler could be detected at 4 weeks. The polyorthoester...... provided local hemostasis when used either alone or in composites with demineralized bone. The composite implant was moldable, easily contoured, and technically easier to use than demineralized bone alone....

  3. Development of high strength hydroxyapatite for bone tissue regeneration using nanobioactive glass composites

    Science.gov (United States)

    Shrivastava, Pragya; Dalai, Sridhar; Sudera, Prerna; Sivam, Santosh Param; Vijayalakshmi, S.; Sharma, Pratibha

    2013-02-01

    With an increasing demand of biocompatible bone substitutes for the treatment of bone diseases and bone tissue regeneration, bioactive glass composites are being tested to improvise the osteoconductive as well as osteoinductive properties. Nanobioactive glass (nBG) composites, having composition of SiO2 70 mol%, CaO 26 mol % and P2O5 4 mol% were prepared by Freeze drying method using PEG-PPG-PEG co-polymer. Polymer addition improves the mechanical strength and porosity of the scaffold of nBG. Nano Bioactive glass composites upon implantation undergo specific reactions leading to the formation of crystalline hydroxyapatite (HA). This is tested in vitro using Simulated Body Fluid (SBF). This high strength hydroxyapatite (HA) layer acts as osteoconductive in cellular environment, by acting as mineral base of bones, onto which new bone cells proliferate leading to new bone formation. Strength of the nBG composites as well as HA is in the range of cortical and cancellous bone, thus proving significant for bone tissue regeneration substitutes.

  4. Development of high strength hydroxyapatite for bone tissue regeneration using nanobioactive glass composites

    International Nuclear Information System (INIS)

    Shrivastava, Pragya; Dalai, Sridhar; Vijayalakshmi, S.; Sudera, Prerna; Sivam, Santosh Param; Sharma, Pratibha

    2013-01-01

    With an increasing demand of biocompatible bone substitutes for the treatment of bone diseases and bone tissue regeneration, bioactive glass composites are being tested to improvise the osteoconductive as well as osteoinductive properties. Nanobioactive glass (nBG) composites, having composition of SiO 2 70 mol%, CaO 26 mol % and P 2 O 5 4 mol% were prepared by Freeze drying method using PEG-PPG-PEG co-polymer. Polymer addition improves the mechanical strength and porosity of the scaffold of nBG. Nano Bioactive glass composites upon implantation undergo specific reactions leading to the formation of crystalline hydroxyapatite (HA). This is tested in vitro using Simulated Body Fluid (SBF). This high strength hydroxyapatite (HA) layer acts as osteoconductive in cellular environment, by acting as mineral base of bones, onto which new bone cells proliferate leading to new bone formation. Strength of the nBG composites as well as HA is in the range of cortical and cancellous bone, thus proving significant for bone tissue regeneration substitutes.

  5. Particulate bioglass in the regeneration of alveolar bone in dogs: clinical, surgical and radiographic evaluations

    Directory of Open Access Journals (Sweden)

    Alexandre Couto Tsiomis

    2011-04-01

    Full Text Available Bone loss, either by trauma or other diseases, generates an increasing need for substitutes of this tissue. This study evaluated Bioglass as a bone substitute in the regeneration of the alveolar bone in mandibles of dogs by clinical, surgical and radiological analysis. Twenty-eight adult dogs were randomly separated into two equal groups. In each animal, a bone defect was created on the vestibular surface of the alveolar bone between the roots of the fourth right premolar tooth. In the treated group, the defect was immediately filled with bioglass, while in the control, it remained unfilled. Clinical evaluations were performed daily for a week, as well as x-rays immediately after surgery and at 8, 14, 21, 42, 60, 90 and 120 days post-operative. Most animals in both groups showed no signs of inflammation and wound healing was similar. Radiographic examination revealed a gradual increase of radiopacity in the region of the defect in the control group. In the treated group, initial radiopacity was higher than that of adjacent bone, decreasing until 21 days after surgery. Then it gradually increased until 120 days after surgery, when the defect became undetectable. The results showed that Bioglass integrates into bone tissue, is biocompatible and reduced the period for complete bone regeneration.

  6. Contemporary guided bone regeneration therapy for unaesthetic anterior peri-implantitis case

    Directory of Open Access Journals (Sweden)

    Benso Sulijaya

    2016-12-01

    Full Text Available Background: Dental implant is one of an alternative solutions reconstruction therapy for missing teeth. Complication of dental implant could occurs and leading to implant failure. In order to restore the complication, surgical treatment with guided bone regeneration (GBR is indicated. The potential use of bone substitutes is widely known to be able to regenerate the bone surrounding the implant and maintain bone volume. Purpose: The study aimed to demonstrate the effectiveness of implant-bone fully coverage by using sandwich technique of biphasic calcium phosphate (BCP and demineralized freeze-dried bone allografts (DFDBA bone substitutes combined with collagen resorbable membrane. Case: A 24-year-old male came with diagnosis of peri-implantitis on implant #11. Clinical finding indicated that implant thread was exposed on the labial aspect. Case management: After initial therapy including oral hygiene improvement performed, an operator did a contemporary GBR to correct the defect. Bone graft materials used were 40% β-tri calcium phosphate (β-TCP-60% hydroxyapatite (HA on the outer layer and DFDBA on the inner layer of the defect. Resorbable collagen membrane was used to cover the graft. Conclusion: GBR with sandwich technique could serve as one of the treatment choices for correcting an exposed anterior implant that would enhance the successful aesthetic outcome.

  7. Production and characterization of chitosan/gelatin/β-TCP scaffolds for improved bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Serra, I.R.; Fradique, R.; Vallejo, M.C.S.; Correia, T.R.; Miguel, S.P.; Correia, I.J., E-mail: icorreia@ubi.pt

    2015-10-01

    Recently, bone tissue engineering emerged as a viable therapeutic alternative, comprising bone implants and new personalized scaffolds to be used in bone replacement and regeneration. In this study, biocompatible scaffolds were produced by freeze-drying, using different formulations (chitosan, chitosan/gelatin, chitosan/β-TCP and chitosan/gelatin/β-TCP) to be used as temporary templates during bone tissue regeneration. Sample characterization was performed through attenuated total reflectance-Fourier transform infrared spectroscopy, X-ray diffraction and energy dispersive spectroscopy analysis. Mechanical characterization and porosity analysis were performed through uniaxial compression test and liquid displacement method, respectively. In vitro studies were also done to evaluate the biomineralization activity and the cytotoxic profile of the scaffolds. Scanning electron and confocal microscopy analysis were used to study cell adhesion and proliferation at the scaffold surface and within their structure. Moreover, the antibacterial activity of the scaffolds was also evaluated through the agar diffusion method. Overall, the results obtained revealed that the produced scaffolds are bioactive and biocompatible, allow cell internalization and show antimicrobial activity against Staphylococcus aureus. Such, make these 3D structures as potential candidates for being used on the bone tissue regeneration, since they promote cell adhesion and proliferation and also prevent biofilm development at their surfaces, which is usually the main cause of implant failure. - Highlights: • Production of 3D scaffolds composed by chitosan/gelatin/β-TCP by freeze-drying for bone regeneration • Physicochemical characterization of the bone substitutes by SEM, FTIR, XRD and EDS • Evaluation of the cytotoxic profile and antibacterial activity of the 3D structures through in vitro assays.

  8. Production and characterization of chitosan/gelatin/β-TCP scaffolds for improved bone tissue regeneration

    International Nuclear Information System (INIS)

    Serra, I.R.; Fradique, R.; Vallejo, M.C.S.; Correia, T.R.; Miguel, S.P.; Correia, I.J.

    2015-01-01

    Recently, bone tissue engineering emerged as a viable therapeutic alternative, comprising bone implants and new personalized scaffolds to be used in bone replacement and regeneration. In this study, biocompatible scaffolds were produced by freeze-drying, using different formulations (chitosan, chitosan/gelatin, chitosan/β-TCP and chitosan/gelatin/β-TCP) to be used as temporary templates during bone tissue regeneration. Sample characterization was performed through attenuated total reflectance-Fourier transform infrared spectroscopy, X-ray diffraction and energy dispersive spectroscopy analysis. Mechanical characterization and porosity analysis were performed through uniaxial compression test and liquid displacement method, respectively. In vitro studies were also done to evaluate the biomineralization activity and the cytotoxic profile of the scaffolds. Scanning electron and confocal microscopy analysis were used to study cell adhesion and proliferation at the scaffold surface and within their structure. Moreover, the antibacterial activity of the scaffolds was also evaluated through the agar diffusion method. Overall, the results obtained revealed that the produced scaffolds are bioactive and biocompatible, allow cell internalization and show antimicrobial activity against Staphylococcus aureus. Such, make these 3D structures as potential candidates for being used on the bone tissue regeneration, since they promote cell adhesion and proliferation and also prevent biofilm development at their surfaces, which is usually the main cause of implant failure. - Highlights: • Production of 3D scaffolds composed by chitosan/gelatin/β-TCP by freeze-drying for bone regeneration • Physicochemical characterization of the bone substitutes by SEM, FTIR, XRD and EDS • Evaluation of the cytotoxic profile and antibacterial activity of the 3D structures through in vitro assays

  9. The investigation of HTGR fuel regeneration process

    Energy Technology Data Exchange (ETDEWEB)

    Lazarev, L N; Bertina, L E; Popik, V P; Isakov, V P; Alkhimov, N B; Pokhitonov, Yu A

    1985-07-01

    The aim of this report is the investigation of HTGR fuel regeneration. The operation in the technologic scheme of uranium extraction from fuel depleted elements is separation of fuel from graphite. Available methods of graphite matrix destruction are: mechanical destruction, chemical destruction, and burning. Mechanical destruction is done in combination with leaching or chlorination. Methods of chemical destruction of graphite matrix are not sufficiently studied. Most of the investigations nowadays sre devoted to removal of graphite by burning.

  10. Study of the heavy water regeneration processes

    International Nuclear Information System (INIS)

    Cavcic, E.

    1965-11-01

    Experience derived from heavy water reactor operation showed degradation and dilution of heavy water to be inevitable and depends on the type of reactor. Dilution of heavy water during operation of the RA and the RB reactors is shown in this report. Principles and procedures of heavy water regeneration by electrolysis, fractional distillation, cleaning, prevention of tritium contamination are described as well as separation columns

  11. The investigation of HTGR fuel regeneration process

    International Nuclear Information System (INIS)

    Lazarev, L.N.; Bertina, L.E.; Popik, V.P.; Isakov, V.P.; Alkhimov, N.B.; Pokhitonov, Yu.A.

    1985-01-01

    The aim of this report is the investigation of HTGR fuel regeneration. The operation in the technologic scheme of uranium extraction from fuel depleted elements is separation of fuel from graphite. Available methods of graphite matrix destruction are: mechanical destruction, chemical destruction, and burning. Mechanical destruction is done in combination with leaching or chlorination. Methods of chemical destruction of graphite matrix are not sufficiently studied. Most of the investigations nowadays sre devoted to removal of graphite by burning

  12. Demineralized dentin matrix composite collagen material for bone tissue regeneration.

    Science.gov (United States)

    Li, Jianan; Yang, Juan; Zhong, Xiaozhong; He, Fengrong; Wu, Xiongwen; Shen, Guanxin

    2013-01-01

    Demineralized dentin matrix (DDM) had been successfully used in clinics as bone repair biomaterial for many years. However, particle morphology of DDM limited it further applications. In this study, DDM and collagen were prepared to DDM composite collagen material. The surface morphology of the material was studied by scanning electron microscope (SEM). MC3T3-E1 cells responses in vitro and tissue responses in vivo by implantation of DDM composite collagen material in bone defect of rabbits were also investigated. SEM analysis showed that DDM composite collagen material evenly distributed and formed a porous scaffold. Cell culture and animal models results indicated that DDM composite collagen material was biocompatible and could support cell proliferation and differentiation. Histological evaluation showed that DDM composite collagen material exhibited good biocompatibility, biodegradability and osteoconductivity with host bone in vivo. The results suggested that DDM composite collagen material might have a significant clinical advantage and potential to be applied in bone and orthopedic surgery.

  13. Post-irradiation thymocyte regeneration after bone marrow transplantation

    International Nuclear Information System (INIS)

    Boersma, W.J.A.

    1981-01-01

    Bone marrow cells were separated according to buoyant density, velocity sedimentation and cell surface charge. Fractionated (C3H x AKR)F 1 bone marrow cells were transplanted into lethally-irradiated C3H recipients. In all fractions, the CFUs content and the capacity to restore the thymus cell population were determined. For all the physical parameters tested, thymocyte progenitor cells show the same distribution as CFUs. The relationship between number of thymocyte progenitor cells and number of CFUs is dependent on density. Bone marrow progenitors of PHA responsive cells are of low buoyant density and show a distribution which resembles the distribution of the progenitors of Thy 1 positive cells. After transplantation of large numbers of bone marrow cells into irradiated mice, no significant change in the CFUs content of the thymus was observed. (author)

  14. 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.

  15. Novel Therapy for Bone Regeneration in Large Segmental Defects

    Science.gov (United States)

    2017-12-01

    variation . (B) After ComBat (Combing Batches) correction biological variables such as animal age and defect size accounted for largest variation in gene...growth plates), age accounted for more variation than defect size in PC1 (data not shown). This suggests, that age is a dominant factor in bone healing...correlates with histologic changes during fracture repair. J Bone Miner Res 1992; 7:1045-55. 103. Grimston SK, Goldberg DB, Watkins M, Brodt MD, Silva MJ

  16. 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.

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

    Science.gov (United States)

    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.

  18. The potential of mangosteen (Garcinia mangostana peel extract, combined with demineralized freeze-dried bovine bone xenograft, to reduce ridge resorption and alveolar bone regeneration in preserving the tooth extraction socket

    Directory of Open Access Journals (Sweden)

    Utari Kresnoadi

    2017-01-01

    Conclusion: The induction of MPEs and DFBBX is effective in reducing inflammation, lowering osteoclasts, decreasing alveolar bone resorption, and also increasing BMP2 expression and alveolar bone regeneration.

  19. Role of RHEB in Regulating Differentiation Fate of Mesenchymal Stem Cells for Cartilage and Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Sajjad Ashraf

    2017-04-01

    Full Text Available Advances in mesenchymal stem cells (MSCs and cell replacement therapies are promising approaches to treat cartilage and bone defects since substantial differentiation capacities of MSCs match the demands of tissue regeneration. Our understanding of the dynamic process requiring indispensable differentiation of MSCs remains limited. Herein, we describe the role of RHEB (Ras homolog enriched in brain regulating gene signature for differentiation of human adipose derived mesenchymal stem cells (ASCs into chondrogenic, osteogenic, and adipogenic lineages. RHEB-overexpression increases the proliferation of the ASCs. RHEB enhances the chondrogenic differentiation of ASCs in 3D culture via upregulation of SOX9 with concomitant increase in glycosaminoglycans (GAGs, and type II collagen (COL2. RHEB increases the osteogenesis via upregulation of runt related transcription factor 2 (RUNX2 with an increase in the calcium and phosphate contents. RHEB also increases the expression of osteogenic markers, osteonectin and osteopontin. RHEB knockdown ASCs were incapable of expressing sufficient SRY (Sex determining region Y-box 9 (SOX9 and RUNX2, and therefore had decreased chondrogenic and osteogenic differentiation. RHEB-overexpression impaired ASCs differentiation into adipogenic lineage, through downregulation of CCAAT/enhancer binding protein beta (C/EBPβ. Conversely, RHEB knockdown abolished the negative regulation of adipogenesis. We demonstrate that RHEB is a novel regulator, with a critical role in ASCs lineage determination, and RHEB-modulated ASCs may be useful as a cell therapy for cartilage and bone defect treatments.

  20. Hyperbaric Oxygen therapy effects on bone regeneration in Type 1 diabetes mellitus in rats.

    Science.gov (United States)

    Dias, Pâmella Coelho; Limirio, Pedro Henrique Justino Oliveira; Linhares, Camila Rodrigues Borges; Bergamini, Mariana Lobo; Rocha, Flaviana Soares; Morais, Richarlisson Borges de; Balbi, Ana Paula Coelho; Hiraki, Karen Renata Nakamura; Dechichi, Paula

    2018-01-29

    The aim of this study was evaluate the effect of HBO on diabetic rats. Twenty rats were distributed into four groups (n = 5): Control (C); Control + HBO (CH); Diabetes (D) and Diabetes + HBO (DH). Diabetes was induced by streptozotocin, and bone defects were created in both femurs in all animals. HBO therapy began immediately after surgery and was performed daily in the CH and DH groups. After 7 days, the animals were euthanized. The femurs were removed, demineralized, embedded in paraffin, and histologic images were analyzed. Qualitative histologic analyses showed more advanced stage bone regeneration in control groups (C and CH) compared with diabetic groups (D and DH). Histomorphometric analysis showed significantly increased bone neoformation in CH compared with the other groups (p  0.05). The mast cell population increased in CH compared with the other groups (C, D, and DH) (p < 0.05). The mast cell population did not differ between D and DH Groups. This study showed that HBO therapy improved early bone regeneration in diabetic rats and increased the mast cell population only in non-diabetic animals. HBO was shown to be important treatment for minimizing deleterious effects of diabetes on bone regeneration.

  1. Effects of 3D-Printed Polycaprolactone/β-Tricalcium Phosphate Membranes on Guided Bone Regeneration.

    Science.gov (United States)

    Shim, Jin-Hyung; Won, Joo-Yun; Park, Jung-Hyung; Bae, Ji-Hyeon; Ahn, Geunseon; Kim, Chang-Hwan; Lim, Dong-Hyuk; Cho, Dong-Woo; Yun, Won-Soo; Bae, Eun-Bin; Jeong, Chang-Mo; Huh, Jung-Bo

    2017-04-25

    This study was conducted to compare 3D-printed polycaprolactone (PCL) and polycaprolactone/β-tricalcium phosphate (PCL/β-TCP) membranes with a conventional commercial collagen membrane in terms of their abilities to facilitate guided bone regeneration (GBR). Fabricated membranes were tested for dry and wet mechanical properties. Fibroblasts and preosteoblasts were seeded into the membranes and rates and patterns of proliferation were analyzed using a kit-8 assay and by scanning electron microscopy. Osteogenic differentiation was verified by alizarin red S and alkaline phosphatase (ALP) staining. An in vivo experiment was performed using an alveolar bone defect beagle model, in which defects in three dogs were covered with different membranes. CT and histological analyses at eight weeks after surgery revealed that 3D-printed PCL/β-TCP membranes were more effective than 3D-printed PCL, and substantially better than conventional collagen membranes in terms of biocompatibility and bone regeneration and, thus, at facilitating GBR.

  2. Multifunctional nano-hydroxyapatite and alginate/gelatin based sticky gel composites for potential bone regeneration

    International Nuclear Information System (INIS)

    Cai, Yurong; Yu, Juhong; Kundu, Subhas C.; Yao, Juming

    2016-01-01

    To improve the fixations of the implant and implant-bone integration after joint arthroplasty from locally preventing inflammation and promoting the bone regeneration, we design a multifunctional biomaterial consisting of recombinant human bone morphogenetic protein 2 (rhBMP-2) and antibiotic loaded nano-hydroxyapatite with an alginate/gelatin sticky gel. We investigate its role for the prevention of the inflammation and possibility of inducing a new bone growth along with its adhesive ability. The stickiness exists in the composite, which may help to fix itself on the bone fracture surface. The composite sustains the antibacterial effect and promotes the proliferation and differentiation of MG63 cells in vitro. In vivo experimentation also shows that the composite gel has a role for the reduction of inflammation. It enhances the formation of new bone and blood vessels compared to both the sole rhBMP-2 and non-rhBMP-2/antibiotic loaded composite gels. The multifunctional composite provides a promising material for the prosthetic and bone tissue regeneration. - Highlights: • Multifunctional nanohydroxyapatite composite is fabricated. • The composite consists of nHAP, growth factor, antibiotic and alginate/gelatin gel. • The composite shows antibacterial effect and good cytocompatibility. • No adverse effect to the cells tested in vitro and in vivo.

  3. Multifunctional nano-hydroxyapatite and alginate/gelatin based sticky gel composites for potential bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Yurong; Yu, Juhong [The Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, National Engineering Lab of Textile Fiber Materials & Processing Technology, College of Materials and Textile, Zhejiang Sci-Tech University, Hangzhou 310018 (China); Kundu, Subhas C. [Department of Biotechnology, Indian Institute of Technology (IIT) Kharagpur, West Bengal 721302 (India); Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714 (Korea, Republic of); Yao, Juming, E-mail: yaoj@zstu.edu.cn [The Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, National Engineering Lab of Textile Fiber Materials & Processing Technology, College of Materials and Textile, Zhejiang Sci-Tech University, Hangzhou 310018 (China)

    2016-09-15

    To improve the fixations of the implant and implant-bone integration after joint arthroplasty from locally preventing inflammation and promoting the bone regeneration, we design a multifunctional biomaterial consisting of recombinant human bone morphogenetic protein 2 (rhBMP-2) and antibiotic loaded nano-hydroxyapatite with an alginate/gelatin sticky gel. We investigate its role for the prevention of the inflammation and possibility of inducing a new bone growth along with its adhesive ability. The stickiness exists in the composite, which may help to fix itself on the bone fracture surface. The composite sustains the antibacterial effect and promotes the proliferation and differentiation of MG63 cells in vitro. In vivo experimentation also shows that the composite gel has a role for the reduction of inflammation. It enhances the formation of new bone and blood vessels compared to both the sole rhBMP-2 and non-rhBMP-2/antibiotic loaded composite gels. The multifunctional composite provides a promising material for the prosthetic and bone tissue regeneration. - Highlights: • Multifunctional nanohydroxyapatite composite is fabricated. • The composite consists of nHAP, growth factor, antibiotic and alginate/gelatin gel. • The composite shows antibacterial effect and good cytocompatibility. • No adverse effect to the cells tested in vitro and in vivo.

  4. In silico Mechano-Chemical Model of Bone Healing for the Regeneration of Critical Defects: The Effect of BMP-2.

    Directory of Open Access Journals (Sweden)

    Frederico O Ribeiro

    Full Text Available The healing of bone defects is a challenge for both tissue engineering and modern orthopaedics. This problem has been addressed through the study of scaffold constructs combined with mechanoregulatory theories, disregarding the influence of chemical factors and their respective delivery devices. Of the chemical factors involved in the bone healing process, bone morphogenetic protein-2 (BMP-2 has been identified as one of the most powerful osteoinductive proteins. The aim of this work is to develop and validate a mechano-chemical regulatory model to study the effect of BMP-2 on the healing of large bone defects in silico. We first collected a range of quantitative experimental data from the literature concerning the effects of BMP-2 on cellular activity, specifically proliferation, migration, differentiation, maturation and extracellular matrix production. These data were then used to define a model governed by mechano-chemical stimuli to simulate the healing of large bone defects under the following conditions: natural healing, an empty hydrogel implanted in the defect and a hydrogel soaked with BMP-2 implanted in the defect. For the latter condition, successful defect healing was predicted, in agreement with previous in vivo experiments. Further in vivo comparisons showed the potential of the model, which accurately predicted bone tissue formation during healing, bone tissue distribution across the defect and the quantity of bone inside the defect. The proposed mechano-chemical model also estimated the effect of BMP-2 on cells and the evolution of healing in large bone defects. This novel in silico tool provides valuable insight for bone tissue regeneration strategies.

  5. Functionalized D-form self-assembling peptide hydrogels for bone regeneration

    Directory of Open Access Journals (Sweden)

    He B

    2016-04-01

    Full Text Available Bin He,1 Yunsheng Ou,1 Ao Zhou,1 Shuo Chen,1 Weikang Zhao,1 Jinqiu Zhao,2 Hong Li,3 Yong Zhu,1 Zenghui Zhao,1 Dianming Jiang1 1Department of Orthopedics, 2Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3School of Physical Science and Technology, Sichuan University, Chengdu, People’s Republic of China Abstract: Bone defects are very common in orthopedics, and there is great need to develop suitable bone grafts for transplantation in vivo. However, current bone grafts still encounter some limitations, including limited availability, immune rejection, poor osteoinduction and osteoconduction, poor biocompatibility and degradation properties, etc. Self-assembling peptide nanofiber scaffolds have emerged as an important substrate for cell culture and bone regeneration. We report on the structural features (eg, Congo red staining, circular dichroism spectroscopy, transmission electron microscopy, and rheometry assays and osteogenic ability of D-RADA16-RGD peptide hydrogels (with or without basic fibroblast growth factor due to the better stability of peptide bonds formed by these peptides compared with those formed by L-form peptides, and use them to fill the femoral condyle defect of Sprague Dawley rat model. The bone morphology change, two-dimensional reconstructions using microcomputed tomography, quantification of the microcomputed tomography analyses as well as histological analyses have demonstrated that RGD-modified D-form peptide scaffolds are able to enhance extensive bone regeneration. Keywords: bone defect, functionalized D-form self-assembling peptide, D-RADA16-RGD, peptide hydrogel, bone regeneration

  6. Use of platelet lysate for bone regeneration - are we ready for clinical translation?

    Science.gov (United States)

    Altaie, Ala; Owston, Heather; Jones, Elena

    2016-02-26

    Current techniques to improve bone regeneration following trauma or tumour resection involve the use of autograft bone or its substitutes supplemented with osteoinductive growth factors and/or osteogenic cells such as mesenchymal stem cells (MSCs). Although MSCs are most commonly grown in media containing fetal calf serum, human platelet lysate (PL) offers an effective alternative. Bone marrow - derived MSCs grown in PL-containing media display faster proliferation whilst maintaining good osteogenic differentiation capacity. Limited pre-clinical investigations using PL-expanded MSCs seeded onto osteoconductive scaffolds indicate good potential of such constructs to repair bone in vivo. In an alternative approach, nude PL-coated scaffolds without seeded MSCs have been proposed as novel regenerative medicine devices. Even though methods to coat scaffolds with PL vary, in vitro studies suggest that PL allows for MSC adhesion, migration and differentiation inside these scaffolds. Increased new bone formation and vascularisation in comparison to uncoated scaffolds have also been observed in vivo. This review outlines the state-of-the-art research in the field of PL for ex vivo MSC expansion and in vivo bone regeneration. To minimise inconsistency between the studies, further work is required towards standardisation of PL preparation in terms of the starting material, platelet concentration, leukocyte depletion, and the method of platelet lysis. PL quality control procedures and its "potency" assessment are urgently needed, which could include measurements of key growth and attachment factors important for MSC maintenance and differentiation. Furthermore, different PL formulations could be tailor-made for specific bone repair indications. Such measures would undoubtedly speed up clinical translation of PL-based treatments for bone regeneration.

  7. Composite biopolymers for bone regeneration enhancement in bony defects.

    Science.gov (United States)

    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.

  8. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute

    DEFF Research Database (Denmark)

    Stravinskas, M; Horstmann, P; Ferguson, J

    2016-01-01

    . Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. MATERIALS AND METHODS: We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery...... in patients treated surgically for chronic corticomedullary osteomyelitis. RESULTS: The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). CONCLUSIONS: This new biphasic bone...

  9. Guided bone regeneration with asymmetric collagen-chitosan membranes containing aspirin-loaded chitosan nanoparticles

    Directory of Open Access Journals (Sweden)

    Zhang J

    2017-12-01

    Full Text Available Jiayu Zhang,1 Shiqing Ma,1 Zihao Liu,1 Hongjuan Geng,1 Xin Lu,1 Xi Zhang,1 Hongjie Li,1 Chenyuan Gao,2 Xu Zhang,1 Ping Gao1 1School of Dentistry, Hospital of Stomatology, Tianjin Medical University, Tianjin, 2Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, People’s Republic of China Introduction: Membranes allowing the sustained release of drugs that can achieve cell adhesion are very promising for guided bone regeneration. Previous studies have suggested that aspirin has the potential to promote bone regeneration. The purpose of this study was to prepare a local drug delivery system with aspirin-loaded chitosan nanoparticles (ACS contained in an asymmetric collagen-chitosan membrane (CCM. Methods: In this study, the ACS were fabricated using different concentrations of aspirin (5 mg, 25 mg, 50 mg, and 75 mg. The drug release behavior of ACS was studied. Transmission electron microscopy (TEM and scanning electron microscopy (SEM were used to examine the micromorphology of ACS and aspirin-loaded chitosan nanoparticles contained in chitosan-collagen membranes (ACS-CCM. In vitro bone mesenchymal stem cells (BMSCs were cultured and critical-sized cranial defects on Sprague-Dawley rats were made to evaluate the effect of the ACS-CCM on bone regeneration.Results: Drug release behavior results of ACS showed that the nanoparticles fabricated in this study could successfully sustain the release of the drug. TEM showed the morphology of the nanoparticles. SEM images indicated that the asymmetric membrane comprised a loose collagen layer and a dense chitosan layer. In vitro studies showed that ACS-CCM could promote the proliferation of BMSCs, and that the degree of differentiated BMSCs seeded on CCMs containing 50 mg of ACS was higher than that of other membranes. Micro-computed tomography showed that 50 mg of ACS-CCM resulted in enhanced bone regeneration compared with the control group.Conclusion: This

  10. Development and characterization of a novel porous small intestine submucosa-hydroxyapatite scaffold for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Castilla Bolaños, Maria Alejandra, E-mail: ma.castilla964@uniandes.edu.co; Buttigieg, Josef; Briceño Triana, Juan Carlos

    2017-03-01

    The fabricated small intestine submucosa (SIS) – hydroxyapatite (HAp) sponges can act as biomimetic scaffolds to be utilized in tissue engineering and regeneration. Here we developed SIS-HAp sponges and investigated their mechanical, physical and chemical characteristics using scanning electron microscopy, Fourier transformed infrared spectroscopy, uniaxial compression, porosity, and swelling testing techniques. The results demonstrated mechanical properties superior to comparable bone substitutes fabricated with similar methods. SIS-HAp scaffolds possess an interconnected macroporosity, similar to that of trabecular bone, hence presenting a novel biomaterial that may serve as a superior bone substitute and tissue scaffold. - Highlights: • Small intestine submucosa (SIS) – hydroxyapatite (HAp) scaffolds were developed. • SIS-HAp scaffolds possess a trabecular bone-like structure. • FTIR indicated a molecular interaction between the organic groups of SIS and HAp. • SIS-HAp sponges presented a superior Young modulus to comparable bone substitutes.

  11. Development and characterization of a novel porous small intestine submucosa-hydroxyapatite scaffold for bone regeneration

    International Nuclear Information System (INIS)

    Castilla Bolaños, Maria Alejandra; Buttigieg, Josef; Briceño Triana, Juan Carlos

    2017-01-01

    The fabricated small intestine submucosa (SIS) – hydroxyapatite (HAp) sponges can act as biomimetic scaffolds to be utilized in tissue engineering and regeneration. Here we developed SIS-HAp sponges and investigated their mechanical, physical and chemical characteristics using scanning electron microscopy, Fourier transformed infrared spectroscopy, uniaxial compression, porosity, and swelling testing techniques. The results demonstrated mechanical properties superior to comparable bone substitutes fabricated with similar methods. SIS-HAp scaffolds possess an interconnected macroporosity, similar to that of trabecular bone, hence presenting a novel biomaterial that may serve as a superior bone substitute and tissue scaffold. - Highlights: • Small intestine submucosa (SIS) – hydroxyapatite (HAp) scaffolds were developed. • SIS-HAp scaffolds possess a trabecular bone-like structure. • FTIR indicated a molecular interaction between the organic groups of SIS and HAp. • SIS-HAp sponges presented a superior Young modulus to comparable bone substitutes.

  12. 3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications

    Science.gov (United States)

    Asa'ad, Farah; Giannì, Aldo Bruno; Giannobile, William V.; Rasperini, Giulio

    2016-01-01

    To ensure a successful dental implant therapy, the presence of adequate vertical and horizontal alveolar bone is fundamental. However, an insufficient amount of alveolar ridge in both dimensions is often encountered in dental practice due to the consequences of oral diseases and tooth loss. Although postextraction socket preservation has been adopted to lessen the need for such invasive approaches, it utilizes bone grafting materials, which have limitations that could negatively affect the quality of bone formation. To overcome the drawbacks of routinely employed grafting materials, bone graft substitutes such as 3D scaffolds have been recently investigated in the dental field. In this review, we highlight different biomaterials suitable for 3D scaffold fabrication, with a focus on “3D-printed” ones as bone graft substitutes that might be convenient for various applications related to implant therapy. We also briefly discuss their possible adoption for periodontal regeneration. PMID:27366149

  13. In vivo evaluation of a simvastatin-loaded nanostructured lipid carrier for bone tissue regeneration

    International Nuclear Information System (INIS)

    Yue, Xinxin; Niu, Mao; Zhang, Te; Wang, Cheng; Wu, Wangxi; Zhang, Qi; Lai, Chunhua; Zhou, Lei; Wang, Zhonglei

    2016-01-01

    Alveolar bone loss has long been a challenge in clinical dental implant therapy. Simvastatin (SV) has been demonstrated to exert excellent anabolic effects on bone. However, the successful use of SV to increase bone formation in vivo largely depends on the local concentration of SV at the site of action, and there have been continuing efforts to develop an appropriate delivery system. Specifically, nanostructured lipid carrier (NLC) systems have become a popular type of encapsulation carrier system. Therefore, SV-loaded NLCs (SNs) (179.4 nm in diameter) were fabricated in this study, and the osteogenic effect of the SNs was evaluated in a critical-sized rabbit calvarial defect. Our results revealed that the SNs significantly enhanced bone formation in vivo, as evaluated by hematoxylin and eosin (HE) staining, immunohistochemistry, and a fluorescence analysis. Thus, this novel nanostructured carrier system could be a potential encapsulation carrier system for SV in bone regeneration applications. (paper)

  14. 3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications

    Directory of Open Access Journals (Sweden)

    Farah Asa’ad

    2016-01-01

    Full Text Available To ensure a successful dental implant therapy, the presence of adequate vertical and horizontal alveolar bone is fundamental. However, an insufficient amount of alveolar ridge in both dimensions is often encountered in dental practice due to the consequences of oral diseases and tooth loss. Although postextraction socket preservation has been adopted to lessen the need for such invasive approaches, it utilizes bone grafting materials, which have limitations that could negatively affect the quality of bone formation. To overcome the drawbacks of routinely employed grafting materials, bone graft substitutes such as 3D scaffolds have been recently investigated in the dental field. In this review, we highlight different biomaterials suitable for 3D scaffold fabrication, with a focus on “3D-printed” ones as bone graft substitutes that might be convenient for various applications related to implant therapy. We also briefly discuss their possible adoption for periodontal regeneration.

  15. In vitro study of manganese-doped bioactive glasses for bone regeneration

    International Nuclear Information System (INIS)

    Miola, Marta; Brovarone, Chiara Vitale; Maina, Giovanni; Rossi, Federica; Bergandi, Loredana; Ghigo, Dario; Saracino, Silvia; Maggiora, Marina; Canuto, Rosa Angela; Muzio, Giuliana; Vernè, Enrica

    2014-01-01

    A glass belonging to the system SiO 2 –P 2 O 5 –CaO–MgO–Na 2 O–K 2 O was modified by introducing two different amounts of manganese oxide (MnO). Mn-doped glasses were prepared by melt and quenching technique and characterized by means of X-ray diffraction (XRD), scanning electron microscopy (SEM) observation and energy dispersion spectrometry (EDS) analysis. In vitro bioactivity test in simulated body fluid (SBF) showed a slight decrease in the reactivity kinetics of Mn-doped glasses compared to the glass used as control; however the glasses maintained a good degree of bioactivity. Mn-leaching test in SBF and minimum essential medium (MEM) revealed fluctuating trends probably due to a re-precipitation of Mn compounds during the bioactivity process. Cellular tests showed that all the Mn-doped glasses, up to a concentration of 50 μg/cm 2 (μg of glass powders/cm 2 of cell monolayer), did not produce cytotoxic effects on human MG-63 osteoblasts cultured for up to 5 days. Finally, biocompatibility tests demonstrated a good osteoblast proliferation and spreading on Mn-doped glasses and most of all that the Mn-doping can promote the expression of alkaline phosphatase (ALP) and some bone morphogenetic proteins (BMPs). - Highlights: • Novel bioactive glasses doped with manganese were prepared. • Mn-doped bioactive glasses were not cytotoxic towards human MG-63 osteoblasts. • The Mn introduction promotes the expression of ALP and bone morphogenetic proteins. • Mn-doped glass may be a promising material for bone regeneration procedures

  16. Consortium for Bone and Tissue Repair and Regeneration

    Science.gov (United States)

    2011-01-01

    develop the next generation of biomaterials and biosensors. • Developing joint programs to train the next generation of biomedical and biomaterials...nonunions. Clin Orthop Relat Res 205:299-308. Wolfe SA (1982). Autogenous bone grafts versus alloplastic material in maxillofacial surgery. Clin Plast

  17. A biocomposite of collagen nanofibers and nanohydroxyapatite for bone regeneration

    NARCIS (Netherlands)

    Ribeiro, N.; Sousa, S.R.; van Blitterswijk, Clemens; Moroni, Lorenzo; Monteiro, F.J.

    2014-01-01

    This work aims to design a synthetic construct that mimics the natural bone extracellular matrix through innovative approaches based on simultaneous type I collagen electrospinning and nanophased hydroxyapatite (nanoHA) electrospraying using non-denaturating conditions and non-toxic reagents. The

  18. Novel Therapy for Bone Regeneration in Large Segmental Defects

    Science.gov (United States)

    2016-10-01

    final letter will be forth coming. Task 2. Perform surgeries on minipigs and evaluate bone healing with x-ray. Task 2a. Fabricate Scaffolds...2008;29(32):4300–5. 90. Raschke M, Kolbeck S, Bail H, Schmidmaier G, Flyvbjerg A, Lindner T, et al. Homologous growth hormone accelerates healing of

  19. Alveolar bone regeneration pattern following surgical and non ...

    African Journals Online (AJOL)

    One hundred and fifty six interproximal sites, with periodontal pockets deeper than 5mm and showing loss of bone on standard dental periapical radiographs, were treated by subgingival instrumentation and open periodontal flap debridement in 12 patients properly motivated and given thorough oral hygiene instructions.

  20. Calcium-containing scaffolds induce bone regeneration by regulating mesenchymal stem cell differentiation and migration.

    Science.gov (United States)

    Aquino-Martínez, Rubén; Angelo, Alcira P; Pujol, Francesc Ventura

    2017-11-16

    Osteoinduction and subsequent bone formation rely on efficient mesenchymal stem cell (MSC) recruitment. It is also known that migration is induced by gradients of growth factors and cytokines. Degradation of Ca 2+ -containing biomaterials mimics the bone remodeling compartment producing a localized calcium-rich osteoinductive microenvironment. The aim of our study was to determine the effect of calcium sulfate (CaSO 4 ) on MSC migration. In addition, to evaluate the influence of CaSO 4 on MSC differentiation and the potential molecular mechanisms involved. A circular calvarial bone defect (5 mm diameter) was created in the parietal bone of 35 Balb-C mice. We prepared and implanted a cell-free agarose/gelatin scaffold alone or in combination with different CaSO 4 concentrations into the bone defects. After 7 weeks, we determined the new bone regenerated by micro-CT and histological analysis. In vitro, we evaluated the CaSO 4 effects on MSC migration by both wound healing and agarose spot assays. Osteoblastic gene expression after BMP-2 and CaSO 4 treatment was also evaluated by qPCR. CaSO 4 increased MSC migration and bone formation in a concentration-dependent manner. Micro-CT analysis showed that the addition of CaSO 4 significantly enhanced bone regeneration compared to the scaffold alone. The histological evaluation confirmed an increased number of endogenous cells recruited into the cell-free CaSO 4 -containing scaffolds. Furthermore, MSC migration in vitro and active AKT levels were attenuated when CaSO 4 and BMP-2 were in combination. Addition of LY294002 and Wortmannin abrogated the CaSO 4 effects on MSC migration. Specific CaSO 4 concentrations induce bone regeneration of calvarial defects in part by acting on the host's undifferentiated MSCs and promoting their migration. Progenitor cell recruitment is followed by a gradual increment in osteoblast gene expression. Moreover, CaSO 4 regulates BMP-2-induced MSC migration by differentially activating the PI3

  1. Calcium-containing scaffolds induce bone regeneration by regulating mesenchymal stem cell differentiation and migration

    Directory of Open Access Journals (Sweden)

    Rubén Aquino-Martínez

    2017-11-01

    Full Text Available Abstract Background Osteoinduction and subsequent bone formation rely on efficient mesenchymal stem cell (MSC recruitment. It is also known that migration is induced by gradients of growth factors and cytokines. Degradation of Ca2+-containing biomaterials mimics the bone remodeling compartment producing a localized calcium-rich osteoinductive microenvironment. The aim of our study was to determine the effect of calcium sulfate (CaSO4 on MSC migration. In addition, to evaluate the influence of CaSO4 on MSC differentiation and the potential molecular mechanisms involved. Methods A circular calvarial bone defect (5 mm diameter was created in the parietal bone of 35 Balb-C mice. We prepared and implanted a cell-free agarose/gelatin scaffold alone or in combination with different CaSO4 concentrations into the bone defects. After 7 weeks, we determined the new bone regenerated by micro-CT and histological analysis. In vitro, we evaluated the CaSO4 effects on MSC migration by both wound healing and agarose spot assays. Osteoblastic gene expression after BMP-2 and CaSO4 treatment was also evaluated by qPCR. Results CaSO4 increased MSC migration and bone formation in a concentration-dependent manner. Micro-CT analysis showed that the addition of CaSO4 significantly enhanced bone regeneration compared to the scaffold alone. The histological evaluation confirmed an increased number of endogenous cells recruited into the cell-free CaSO4-containing scaffolds. Furthermore, MSC migration in vitro and active AKT levels were attenuated when CaSO4 and BMP-2 were in combination. Addition of LY294002 and Wortmannin abrogated the CaSO4 effects on MSC migration. Conclusions Specific CaSO4 concentrations induce bone regeneration of calvarial defects in part by acting on the host’s undifferentiated MSCs and promoting their migration. Progenitor cell recruitment is followed by a gradual increment in osteoblast gene expression. Moreover, CaSO4 regulates BMP-2-induced

  2. Converted marine coral hydroxyapatite implants with growth factors: In vivo bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Nandi, Samit K., E-mail: samitnandi1967@gmail.com [Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences, Kolkata (India); Kundu, Biswanath, E-mail: biswa_kundu@rediffmail.com [Bioceramics and Coating Division, CSIR-Central Glass and Ceramic Research Institute, Kolkata (India); Mukherjee, Jayanta [Institute of Animal Health and Veterinary Biologicals, Kolkata (India); Mahato, Arnab; Datta, Someswar; Balla, Vamsi Krishna [Bioceramics and Coating Division, CSIR-Central Glass and Ceramic Research Institute, Kolkata (India)

    2015-04-01

    Herein we report rabbit model in vivo bone regeneration of hydrothermally converted coralline hydroxyapatite (HCCHAp) scaffolds without (group I) and with growth factors namely insulin like growth factor-1 (IGF-1) (group II) and bone morphogenetic protein-2 (BMP-2) (group III). All HCCHAp scaffolds have been characterized for phase purity and morphology before implantation. Calcined marine coral was hydrothermally converted using a mineralizer/catalyst to phase pure HAp retaining original pore structure and geometry. After sintering at 1250 °C, the HCCHAp found to have ~ 87% crystallinity, 70–75% porosity and 2 ± 0.5 MPa compressive strength. In vitro growth factor release study at day 28 revealed 77 and 98% release for IGF-1 and BMP-2, respectively. The IGF-1 release was more sustained than BMP-2. In vivo bone healing of different groups was compared using chronological radiology, histological evaluations, scanning electron microscopy and fluorochrome labeling up to 90 days of implantation. In vivo studies showed substantial reduction in radiolucent zone and decreased radiodensity of implants in group II followed by group III and group I. These observations clearly suggest in-growth of osseous tissue, initiation of bone healing and complete union between implants and natural bone in group II implants. A statistical score sheet based on histological observations showed an excellent osseous tissue formation in group II and group III scaffolds and moderate bone regeneration in group I scaffolds. - Highlights: • In vivo bone regeneration of hydrothermally converted coralline hydroxyapatite • Scaffolds with and without growth factors (IGF-1 and BMP-2) • In vitro drug release was more sustained for IGF-1 than BMP-2. • Growth factor significantly improved osseous tissue formation of implanted scaffold. • Established through detailed statistical score sheet from histological observations.

  3. Converted marine coral hydroxyapatite implants with growth factors: In vivo bone regeneration

    International Nuclear Information System (INIS)

    Nandi, Samit K.; Kundu, Biswanath; Mukherjee, Jayanta; Mahato, Arnab; Datta, Someswar; Balla, Vamsi Krishna

    2015-01-01

    Herein we report rabbit model in vivo bone regeneration of hydrothermally converted coralline hydroxyapatite (HCCHAp) scaffolds without (group I) and with growth factors namely insulin like growth factor-1 (IGF-1) (group II) and bone morphogenetic protein-2 (BMP-2) (group III). All HCCHAp scaffolds have been characterized for phase purity and morphology before implantation. Calcined marine coral was hydrothermally converted using a mineralizer/catalyst to phase pure HAp retaining original pore structure and geometry. After sintering at 1250 °C, the HCCHAp found to have ~ 87% crystallinity, 70–75% porosity and 2 ± 0.5 MPa compressive strength. In vitro growth factor release study at day 28 revealed 77 and 98% release for IGF-1 and BMP-2, respectively. The IGF-1 release was more sustained than BMP-2. In vivo bone healing of different groups was compared using chronological radiology, histological evaluations, scanning electron microscopy and fluorochrome labeling up to 90 days of implantation. In vivo studies showed substantial reduction in radiolucent zone and decreased radiodensity of implants in group II followed by group III and group I. These observations clearly suggest in-growth of osseous tissue, initiation of bone healing and complete union between implants and natural bone in group II implants. A statistical score sheet based on histological observations showed an excellent osseous tissue formation in group II and group III scaffolds and moderate bone regeneration in group I scaffolds. - Highlights: • In vivo bone regeneration of hydrothermally converted coralline hydroxyapatite • Scaffolds with and without growth factors (IGF-1 and BMP-2) • In vitro drug release was more sustained for IGF-1 than BMP-2. • Growth factor significantly improved osseous tissue formation of implanted scaffold. • Established through detailed statistical score sheet from histological observations

  4. The Incorporation of Strontium to Improve Bone-Regeneration Ability of Mesoporous Bioactive Glasses

    Directory of Open Access Journals (Sweden)

    Sonia Fiorilli

    2018-04-01

    Full Text Available Over the recent years, mesoporous bioactive glasses (MBGs gained interest as bone regeneration systems, due to their excellent bioactivity and ability to release therapeutic molecules. In order to improve the bone regeneration ability of MBGs, the incorporation of Sr2+ ions, due to its recognized pro-osteogenenic potential, represents a very promising strategy. In this study, MBGs based on the SiO2–CaO system and containing different percentages (2 and 4 mol % of strontium were prepared by two synthesis methods, in the form of microspheres and nanoparticles. Sr-containing MBGs were characterized by FE-SEM, XRD and N2 adsorption/desorption analysis. The in vitro bioactivity in SBF resulted excellent. The assessment of fibroblast cell (line L929 viability showed that Sr-containing MBGs were biocompatible both in form of micro- and nanoparticles. The osteogenic response of osteoblast-like SAOS-2 cells was investigated by analysing the expression of GAPDH, COL1a1, RANKL, SPARC, OPG and ALPL genes, as cell differentiation markers. The results indicate that the incorporation of Sr into MBG is beneficial for bone regeneration as promotes a pro-osteogenic effect, paving the way to the design of advanced devices enabled by these nanocarriers also in combination with drug release, for the treatment of bone pathologies, particularly in patients with osteoporosis.

  5. Process for the regeneration of metallic catalysts

    Science.gov (United States)

    Katzer, James R.; Windawi, Hassan

    1981-01-01

    A method for the regeneration of metallic hydrogenation catalysts from the class consisting of Ni, Rh, Pd, Ir, Pt and Ru poisoned with sulfur, with or without accompanying carbon deposition, comprising subjecting the catalyst to exposure to oxygen gas in a concentration of about 1-10 ppm. intermixed with an inert gas of the group consisting of He, A, Xe, Kr, N.sub.2 and air substantially free of oxygen to an extent such that the total oxygen molecule throughout is in the range of about 10 to 20 times that of the hydrogen sulfide molecular exposure producing the catalyst poisoning while maintaining the temperature in the range of about 300.degree. to 500.degree. C.

  6. Regeneration

    Science.gov (United States)

    George A. Schier; Wayne D. Shepperd; John R. Jones

    1985-01-01

    There are basically two approaches to regenerating aspen stands-sexual reproduction using seed, or vegetative regeneration by root suckering. In the West, root suckering is the most practical method. The advantage of having an existing, well established root system capable of producing numerous root suckers easily outweighs natural or artificial reforestation in the...

  7. BoneCeramic graft regenerates alveolar defects but slows orthodontic tooth movement with less root resorption.

    Science.gov (United States)

    Ru, Nan; Liu, Sean Shih-Yao; Bai, Yuxing; Li, Song; Liu, Yunfeng; Wei, Xiaoxia

    2016-04-01

    BoneCeramic (Straumann, Basel, Switzerland) can regenerate bone in alveolar defects after tooth extraction, but it is unknown whether it is feasible to move a tooth through BoneCeramic grafting sites. The objective of this study was to investigate 3-dimensional real-time root resorption and bone responses in grafted sites during orthodontic tooth movement. Sixty 5-week-old rats were randomly assigned to 3 groups to receive BoneCeramic, natural bovine cancellous bone particles (Bio-Oss; Geistlich Pharma, Wolhusen, Switzerland), or no graft, after the extraction of the maxillary left first molar. After 4 weeks, the maxillary left second molar was moved into the extraction site for 28 days. Dynamic bone microstructures and root resorption were evaluated using in-vivo microcomputed tomography. Stress distribution and corresponding tissue responses were examined by the finite element method and histology. Mixed model analysis of variance was performed to compare the differences among time points with Bonferroni post-hoc tests at the significance level of P root resorption volumes and craters, and the highest bone volume fraction, trabecular number, and mean trabecular thickness, followed by the Bio-Oss and the control groups. The highest stress accumulated in the cervical region of the mesial roots. BoneCeramic has better osteoconductive potential and induces less root resorption compared with Bio-Oss grafting and naturally recovered extraction sites. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  8. Novel Therapy for Bone Regeneration in Large Segmental Defects

    Science.gov (United States)

    2014-10-01

    detailed bone analysis (and the majority of blood biochemistries will be completed together at the end of the study), the bulk of our findings will be...resume care for the first 48 hours as preferred by our large animal veterinarian. This brings us to 4p Friday afternoon at which time Dr. Cheng, our...postdoctoral fellow, and the combination of medical students split coverage from 4p Friday evening until 8a Monday morning for the post-operative

  9. Pilot study on orthodontic space closure after guided bone regeneration.

    Science.gov (United States)

    Reichert, Christoph; Wenghöfer, Matthias; Götz, Werner; Jäger, Andreas

    2011-03-01

    In the present study, the benefit of moving teeth into extraction sockets preserved by a bone substitute was evaluated. This was performed to determine whether this was advantageous for orthodontic space closure. Socket preservation employing the bony alveolus in patients presenting the orthodontic indication for premolar extraction therapy was performed. Analogue premolars were extracted in a split-mouth design. One extraction alveolus was filled with a silica matrix-embedded, nanocrystalline hydroxyapatite bone substitute, with the other acting as a control. The orthodontic space was then closed using NiTi closed coil springs (200 g). Photographs and X-rays were acquired for documentation. Space closure succeeded without complications, e.g., root resorptions or inflammations. Gingival invaginations occurred in two of the control sites. A difference in the velocity of extraction space closure in one patient was also observed. Orthodontic tooth movement using this bone replacement material is possible according to these study results. This technique, thus, warrants further investigation in future clinical trials focusing on preventive means to reduce the development of gingival invaginations.

  10. Bone Regeneration Is Promoted by Orally Administered Bovine Lactoferrin in a Rabbit Tibial Distraction Osteogenesis Model.

    Science.gov (United States)

    Li, Wenyang; Zhu, Songsong; Hu, Jing

    2015-07-01

    Lactoferrin, an iron-binding glycoprotein which belongs to the transferrin family, has been shown to promote bone growth. However, reports regarding effects of lactoferrin on bone regeneration during distraction osteogenesis are limited. Our study was designed to investigate the effect of bovine lactoferrin treatment on bone formation of the distracted callus. We asked whether bovine lactoferrin enhances bone formation of the distraction callus as determined by (1) radiographic and histologic appearances; (2) dual-energy x-ray absorptiometry (DXA) analysis of bone mineral composition and bone mineral density; (3) micro-CT measures of trabecular architecture; and (4) biomechanical strength of the healing bone. Additionally, serology, reverse transcription (RT)-PCR, and immunohistochemistry were used to explore the possible mechanisms of bovine lactoferrin use on bone formation during distraction osteogenesis. Unilateral tibial osteodistraction was performed on 80 New Zealand White rabbits with a distraction rate of 1 mm per day for 10 days. Animals then were divided randomly into two groups: (1) vehicle and (2) bovine lactoferrin. At 4 and 8 weeks after completion of distraction, the animals were sacrificed. Lengthened tibias and serum samples were obtained and subjected to radiologic, DXA, micro-CT, histologic, and biomechanical examinations, and serum, RT-PCR and immunohistochemical analyses. Radiologic, DXA, micro-CT, histologic, and biomechanical examinations indicated that bovine lactoferrin treatment not only accelerated bone formation at early stages of distraction osteogenesis but also promoted bone consolidation at late stages. The ultimate force of the distracted calluses was increased by 37% (118.8 ± 6.65 N in the lactoferrin group and 86.5 ± 5.47 N in the vehicle group; p bovine lactoferrin treatment significantly increased serum levels of bone alkaline phosphatase and decreased serum levels of tartrate resistant acid phosphatase 5b. In addition, RT

  11. [Factors affecting bone regeneration in Ilizarov callus distraction].

    Science.gov (United States)

    Fink, B; Krieger, M; Schneider, T; Menkhaus, S; Fischer, J; Rüther, W

    1995-12-01

    We evaluated the X-rays of 36 patients who underwent 50 callus distractions. With the aid of a computerized digitalisation system for analogue films, the relative X-ray density of the distraction area was calculated for each X-ray. These relative X-ray densities were figured graphically for the duration of treatment for each patient. In the consolidation phase, the graph of each patient had a logarithmic relationship. The gradients of the logarithmic density curves were considered an indicator of the quantity of new bone formation. These gradients were correlated to the following clinical parameters: age of the patient, beginning of distraction after corticotomy, average speed of distraction, average weight bearing during the distraction and consolidation phase, location of corticotomy (distal femur versus proximal tibia) and diclofenac medication. Except for the location of the corticotomy and diclofenac, all parameters had an influence on osteoneogenesis by callus distraction. The parameters affecting new bone formation the most were the age of the patient and weight bearing. Patients aged under 18 years (p = 0.005), beginning of distraction later than 8 days (p = 0.109), an average distraction speed below 1 mm/day (p = 0.079), and average weight bearing of more than 30 kg (p = 0.068 for the distraction phase and p = 0.089 for the consolidation phase) showed a quantitatively higher rate of new bone formation by callus distraction than the patients in the other groups. Patients with a shorter leg due to poliomyelitis and one patient with an amniotic leg tie showed a slower increase in X-ray density graphs than the other patients.

  12. A Comparative Study of Bio artificial Bone Tissue Poly-L-lactic Acid/Polycaprolactone and PLLA Scaffolds Applied in Bone Regeneration

    International Nuclear Information System (INIS)

    Weng, W.; Song, Sh.; Cao, L.; Chen, X.; Cai, Y.; Li, H.; Zhou, Q.; Zhang, J.; Su, J.

    2014-01-01

    Bio artificial bone tissue engineering is an increasingly popular technique to repair bone defect caused by injury or disease. This study aimed to investigate the feasibility of PLLA/PCL (poly-L-lactic acid/polycaprolactone) by a comparison study of PLLA/PCL and PLLA scaffolds applied in bone regeneration. Thirty healthy mature New Zealand rabbits on which 15 mm distal ulna defect model had been established were selected and then were divided into three groups randomly: group A (repaired with PLLA scaffold), group B (repaired with PLLA/PCL scaffold), and group C (no scaffold) to evaluate the bone-remodeling ability of the implants. Micro-CT examination revealed the prime bone regeneration ability of group B in three groups. Bone mineral density of surgical site in group B was higher than group A but lower than group C. Meanwhile, the bone regeneration in both groups A and B proceeded with signs of inflammation for the initial fast degradation of scaffolds. As a whole, PLLA/PCL scaffolds in vivo initially degrade fast and were better suited to repair bone defect than PLLA in New Zealand rabbits. Furthermore, for the low mineral density of new bone and rapid degradation of the scaffolds, more researches were necessary to optimize the composite for bone regeneration.

  13. Molecular Mechanisms of Soft Tissue Regeneration and Bone Formation in Mice: Implications in Fracture Repair and Wound Healing in Humans

    National Research Council Canada - National Science Library

    Baylink, David

    2003-01-01

    The primary goal of the project funded by the U.S. Army is to identify genes which play an anabolic role in bone tissue and soft tissue function, particularly during regeneration, and to clarify the function of these genes...

  14. Sustained delivery of biomolecules from gelatin carriers for applications in bone regeneration.

    Science.gov (United States)

    Song, Jiankang; Leeuwenburgh, Sander Cg

    2014-08-01

    Local delivery of therapeutic biomolecules to stimulate bone regeneration has matured considerably during the past decades, but control over the release of these biomolecules still remains a major challenge. To this end, suitable carriers that allow for tunable spatial and temporal delivery of biomolecules need to be developed. Gelatin is one of the most widely used natural polymers for the controlled and sustained delivery of biomolecules because of its biodegradability, biocompatibility, biosafety and cost-effectiveness. The current study reviews the applications of gelatin as carriers in form of bulk hydrogels, microspheres, nanospheres, colloidal gels and composites for the programmed delivery of commonly used biomolecules for applications in bone regeneration with a specific focus on the relationship between carrier properties and delivery characteristics.

  15. Bilayered construct for simultaneous regeneration of alveolar bone and periodontal ligament.

    Science.gov (United States)

    Nivedhitha Sundaram, M; Sowmya, S; Deepthi, S; Bumgardener, Joel D; Jayakumar, R

    2016-05-01

    Periodontitis is an inflammatory disease that causes destruction of tooth-supporting tissues and if left untreated leads to tooth loss. Current treatments have shown limited potential for simultaneous regeneration of the tooth-supporting tissues. To recreate the complex architecture of the periodontium, we developed a bilayered construct consisting of poly(caprolactone) (PCL) multiscale electrospun membrane (to mimic and regenerate periodontal ligament, PDL) and a chitosan/2wt % CaSO4 scaffold (to mimic and regenerate alveolar bone). Scanning electron microscopy results showed the porous nature of the scaffold and formation of beadless electrospun multiscale fibers. The fiber diameter of microfiber and nanofibers was in the range of 10 ± 3 µm and 377 ± 3 nm, respectively. The bilayered construct showed better protein adsorption compared to the control. Osteoblastic differentiation of human dental follicle stem cells (hDFCs) on chitosan/2wt % CaSO4 scaffold showed maximum alkaline phosphatase at seventh day followed by a decline thereafter when compared to chitosan control scaffold. Fibroblastic differentiation of hDFCs was confirmed by the expression of PLAP-1 and COL-1 proteins which were more prominent on PCL multiscale membrane in comparison to control membranes. Overall these results show that the developed bilayered construct might serve as a good candidate for the simultaneous regeneration of the alveolar bone and PDL. © 2015 Wiley Periodicals, Inc.

  16. The temporal course of mucoperiosteal flap revascularization at guided bone regeneration treated implant sites: a pilot study

    NARCIS (Netherlands)

    Milstein, D.M.J.; Mathura, K.R.; Lindeboom, J.A.H.; Ramsoekh, D.; Lindeboom, R.; Ince, C.

    2009-01-01

    Aims: To investigate post-operative capillary density regeneration in healing mucoperiosteal flaps at guided bone regeneration-treated implant sites. Material and Methods: A non-invasive post-operative investigation was performed in 10 patients using orthogonal polarization spectral (OPS) imaging

  17. The temporal course of mucoperiosteal flap revascularization at guided bone regeneration-treated implant sites: a pilot study

    NARCIS (Netherlands)

    Milstein, Dan M. J.; Mathura, Keshen R.; Lindeboom, Jerôme A. H.; Ramsoekh, Dewkoemar; Lindeboom, Robert; Ince, Can

    2009-01-01

    P>Aims To investigate post-operative capillary density regeneration in healing mucoperiosteal flaps at guided bone regeneration-treated implant sites. Material and Methods A non-invasive post-operative investigation was performed in 10 patients using orthogonal polarization spectral (OPS) imaging

  18. Influence of bone marrow-derived mesenchymal stem cells pre-implantation differentiation approach on periodontal regeneration in vivo.

    Science.gov (United States)

    Cai, Xinjie; Yang, Fang; Yan, Xiangzhen; Yang, Wanxun; Yu, Na; Oortgiesen, Daniel A W; Wang, Yining; Jansen, John A; Walboomers, X Frank

    2015-04-01

    The implantation of bone marrow-derived mesenchymal stem cells (MSCs) has previously been shown successful to achieve periodontal regeneration. However, the preferred pre-implantation differentiation strategy (e.g. maintenance of stemness, osteogenic or chondrogenic induction) to obtain optimal periodontal regeneration is still unknown. This in vivo study explored which differentiation approach is most suitable for periodontal regeneration. Mesenchymal stem cells were obtained from Fischer rats and seeded onto poly(lactic-co-glycolic acid)/poly(ɛ-caprolactone) electrospun scaffolds, and then pre-cultured under different in vitro conditions: (i) retention of multilineage differentiation potential; (ii) osteogenic differentiation approach; and (iii) chondrogenic differentiation approach. Subsequently, the cell-scaffold constructs were implanted into experimental periodontal defects of Fischer rats, with empty scaffolds as controls. After 6 weeks of implantation, histomorphometrical analyses were applied to evaluate the regenerated periodontal tissues. The chondrogenic differentiation approach showed regeneration of alveolar bone and ligament tissues. The retention of multilineage differentiation potential supported only ligament regeneration, while the osteogenic differentiation approach boosted alveolar bone regeneration. Chondrogenic differentiation of MSCs before implantation is a useful strategy for regeneration of alveolar bone and periodontal ligament, in the currently used rat model. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Bone regeneration of calvarial defect using marine calcareous-derived beta-tricalcium phosphate macrospheres

    Directory of Open Access Journals (Sweden)

    Joshua Chou

    2014-02-01

    Full Text Available The aim of this study was to examine the bone regeneration properties of beta-tricalcium phosphate hydrothermally converted from foraminifera carbonate exoskeleton in the repair of rat calvarial defect. These natural materials possess unique interconnected porous network with uniform pore size distribution, which can be potentially advantageous. In total, 20 adult male Wistar rats received full-thickness calvarial defect with a diameter of 5 mm. The rate of newly formed bone was measured radiologically by X-ray and micro-computed tomography and by histologic examination. After 2 weeks, the beta-tricalcium phosphate group exhibited full closure of the defect site, while control group remained unrestored at the end of the 6-week experimentation. It was observed that the newly regenerated bone thickened over the course of the experiment in the beta-tricalcium phosphate group. No soft tissue reaction was observed around the beta-tricalcium phosphate implant and the rats remained healthy. These results showed that repair of the calvarial defect can be achieved by biomimetic beta-tricalcium phosphate macrospheres, which hold potential for application as bone grafts for bone augmentation surgeries.

  20. In vitro and in vivo investigations on bone regeneration potential of laminated hydroxyapatite/gelatin nanocomposite scaffold along with DBM

    Energy Technology Data Exchange (ETDEWEB)

    Tavakol, Shima [School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Department of Medical Nanotechnology (Iran, Islamic Republic of); Ragerdi Kashani, Iraj [School of Medicine, Tehran University of Medical Sciences, Department of Anatomy (Iran, Islamic Republic of); Azami, Mahmood [School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Department of Tissue Engineering (Iran, Islamic Republic of); Khoshzaban, Ahad [Tehran University of Medical Sciences, Iranian Tissue Bank Research and Preparation Center (Iran, Islamic Republic of); Tavakol, Behnaz [Kashan University of Medical Sciences, Department of Medicine (Iran, Islamic Republic of); Kharrazi, Sharmin [School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Department of Medical Nanotechnology (Iran, Islamic Republic of); Ebrahimi, Somayeh [University of Tarbiat Moallem, Department of Biology, Faculty of Sciences (Iran, Islamic Republic of); Rezayat Sorkhabadi, Seyed Mahdi, E-mail: sh_tavakol@razi.tums.ac.ir [School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Department of Medical Nanotechnology (Iran, Islamic Republic of)

    2012-12-15

    Bone regeneration ability of a scaffold strongly depends on its structure and the size of its components. In this study, a nanostructured scaffold was designed for bone repair using nano hydroxyapatite (nHA) (8-16 nm Multiplication-Sign 50-80 nm) and gelatin (GEL) as main components. In vitro investigations of calcium matrix deposition and gene expression of the seeded cells for this scaffold, demineralized bone matrix (DBM), scaffold plus DBM, and the control group were carried out. Bone regeneration in rat calvarium with critical defect size after 1, 4, and 8 weeks post implantation was investigated. The calcium matrix depositions by the osteoblast and RUNX2, ALP, osteonectin, and osteocalcin gene expression in scaffold were more significant than in other groups. Histomorphometry analysis confirmed in vitro results. In vitro and in vivo bone regeneration were least in scaffold plus DBM group. Enhanced effects in scaffold could be attributed to the shape and size of nHA particles and good architecture of the scaffold. Reduction of bone regeneration might be due to tight bonding of BMPs and nHA particles in the third group. Results obtained from this study confirmed that nano-scale size of the main components and the scaffold architecture (pore diameter, interconnectivity pores, etc.) have significant effects on bone regeneration ability of the scaffold and are important parameters in designing a temporary bone substitute.

  1. In vitro and in vivo investigations on bone regeneration potential of laminated hydroxyapatite/gelatin nanocomposite scaffold along with DBM

    International Nuclear Information System (INIS)

    Tavakol, Shima; Ragerdi Kashani, Iraj; Azami, Mahmood; Khoshzaban, Ahad; Tavakol, Behnaz; Kharrazi, Sharmin; Ebrahimi, Somayeh; Rezayat Sorkhabadi, Seyed Mahdi

    2012-01-01

    Bone regeneration ability of a scaffold strongly depends on its structure and the size of its components. In this study, a nanostructured scaffold was designed for bone repair using nano hydroxyapatite (nHA) (8–16 nm × 50–80 nm) and gelatin (GEL) as main components. In vitro investigations of calcium matrix deposition and gene expression of the seeded cells for this scaffold, demineralized bone matrix (DBM), scaffold plus DBM, and the control group were carried out. Bone regeneration in rat calvarium with critical defect size after 1, 4, and 8 weeks post implantation was investigated. The calcium matrix depositions by the osteoblast and RUNX2, ALP, osteonectin, and osteocalcin gene expression in scaffold were more significant than in other groups. Histomorphometry analysis confirmed in vitro results. In vitro and in vivo bone regeneration were least in scaffold plus DBM group. Enhanced effects in scaffold could be attributed to the shape and size of nHA particles and good architecture of the scaffold. Reduction of bone regeneration might be due to tight bonding of BMPs and nHA particles in the third group. Results obtained from this study confirmed that nano-scale size of the main components and the scaffold architecture (pore diameter, interconnectivity pores, etc.) have significant effects on bone regeneration ability of the scaffold and are important parameters in designing a temporary bone substitute.

  2. Effects of 3D-Printed Polycaprolactone/?-Tricalcium Phosphate Membranes on Guided Bone Regeneration

    OpenAIRE

    Shim, Jin-Hyung; Won, Joo-Yun; Park, Jung-Hyung; Bae, Ji-Hyeon; Ahn, Geunseon; Kim, Chang-Hwan; Lim, Dong-Hyuk; Cho, Dong-Woo; Yun, Won-Soo; Bae, Eun-Bin; Jeong, Chang-Mo; Huh, Jung-Bo

    2017-01-01

    This study was conducted to compare 3D-printed polycaprolactone (PCL) and polycaprolactone/β-tricalcium phosphate (PCL/β-TCP) membranes with a conventional commercial collagen membrane in terms of their abilities to facilitate guided bone regeneration (GBR). Fabricated membranes were tested for dry and wet mechanical properties. Fibroblasts and preosteoblasts were seeded into the membranes and rates and patterns of proliferation were analyzed using a kit-8 assay and by scanning electron micro...

  3. Effect of local administration of platelet-rich plasma and guided tissue regeneration on the level of bone resorption in early dental implant insertion

    Directory of Open Access Journals (Sweden)

    Duka Miloš

    2008-01-01

    Full Text Available Background/Aim. Osseointegration is a result of cellular migration, differentiation, bone formation, and bone remodeling on the surface of an implant. Each of these processes depends on platelets and blood coagulum. Platelet-rich plasma (PRP is used to improve osseointegration and stability of implants. The aim of the research was to test the influence that PRP and guided tissue regeneration in bone defects have on bone defect filling and the level of bone resorption in early implant insertion. Methods. This experimental study included 10 dogs. A total of 40 BCT implants were inserted, 4 in each dog (two on the left side and two on the right side, with guided tissue regeneration. Radiologic analyses were done immediately after the insertion and 10 weeks after the insertion. Bone defect filling was measured by a graduated probe 10 weeks after the implant insertion. The following protocols were tested: I - PRP in combination with bovine deproteinized bone (BDB and resorptive membrane of bovine origin (RBDM, II - BDB + RBDM, III - PRP + RBDM and IV - RBDM. Results. The applied protocols affected differently the bone defect filling and the level of bone resorption. Significantly better results (the lowest bone resorption were achieved with protocol I (PRP + BDB + RBDM in comparison with protocols III (PRP + RBDM and IV (RBDM, but not with protocol II (BDB + RBDM. On the other hand, no significant difference was found among protocols II (BDB + RBDM, III (PRP + RBDM and IV (RBDM in the level of bone tissue resorption. Conslusion. The bone defect filling was largest and the level of bone resorption was lowest in the protocol with PRP applied in combination with BDB and RBDM.

  4. Guided bone regeneration with a synthetic biodegradable membrane: a comparative study in dogs.

    Science.gov (United States)

    Jung, Ronald E; Kokovic, Vladimir; Jurisic, Milan; Yaman, Duygu; Subramani, Karthikeyan; Weber, Franz E

    2011-08-01

    The aim of the present study was to compare a newly developed biodegradable polylactide/polyglycolide/N-methyl-2-pyrrolidone (PLGA/NMP) membrane with a standard resorbable collagen membrane (RCM) in combination with and without the use of a bone substitute material (deproteinized bovine bone mineral [DBBM]) looking at the proposed tenting effect and bone regeneration. In five adult German sheepdogs, the mandibular premolars P2, P3, P4, and the molar M1 were bilaterally extracted creating two bony defects on each site. A total of 20 dental implants were inserted and allocated to four different treatment modalities within each dog: PLGA/NMP membrane only (Test 1), PLGA/NMP membrane with DBBM (Test 2), RCM only (negative control), and RCM with DBBM (positive control). A histomorphometric analysis was performed 12 weeks after implantation. For statistical analysis, a Friedman test and subsequently a Wilcoxon signed ranks test were applied. In four out of five PLGA/NMP membrane-treated defects, the membranes had broken into pieces without the support of DBBM. This led to a worse outcome than in the RCM group. In combination with DBBM, both membranes revealed similar amounts of area of bone regeneration and bone-to-implant contact without significant differences. On the level of the third implant thread, the PLGA/NMP membrane induced more horizontal bone formation beyond the graft than the RCM. The newly developed PLGA/NMP membrane performs equally well as the RCM when applied in combination with DBBM. Without bone substitute material, the PLGA/NMP membrane performed worse than the RCM in challenging defects, and therefore, a combination with a bone substitute material is recommended. © 2010 John Wiley & Sons A/S.

  5. Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy

    Directory of Open Access Journals (Sweden)

    Isaac A. Rodriguez

    2014-01-01

    Full Text Available Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP. PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in both in vitro and in vivo scenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use.

  6. Virus immobilization on biomaterial scaffolds through biotin-avidin interaction for improving bone regeneration.

    Science.gov (United States)

    Hu, Wei-Wen; Wang, Zhuo; Krebsbach, Paul H

    2016-02-01

    To spatially control therapeutic gene delivery for potential tissue engineering applications, a biotin-avidin interaction strategy was applied to immobilize viral vectors on biomaterial scaffolds. Both adenoviral vectors and gelatin sponges were biotinylated and avidin was applied to link them in a virus-biotin-avidin-biotin-material (VBABM) arrangement. The tethered viral particles were stably maintained within scaffolds and SEM images illustrated that viral particles were evenly distributed in three-dimensional (3D) gelatin sponges. An in vivo study demonstrated that transgene expression was restricted to the implant sites only and transduction efficiency was improved using this conjugation method. For an orthotopic bone regeneration model, adenovirus encoding BMP-2 (AdBMP2) was immobilized to gelatin sponges before implanting into critical-sized bone defects in rat calvaria. Compared to gelatin sponges with AdBMP2 loaded in a freely suspended form, the VBABM method enhanced gene transfer and bone regeneration was significantly improved. These results suggest that biotin-avidin immobilization of viral vectors to biomaterial scaffolds may be an effective strategy to facilitate tissue regeneration. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Examining the feasibility of clinical grade CD271+ enrichment of mesenchymal stromal cells for bone regeneration.

    Directory of Open Access Journals (Sweden)

    Richard J Cuthbert

    Full Text Available Current clinical trials utilize mesenchymal stromal cells (MSCs expanded in culture, however these interventions carry considerable costs and concerns pertaining to culture-induced losses of potency. This study assessed the feasibility of new clinical-grade technology to obtain uncultured MSC isolates from three human intra-osseous tissue sources based on immunomagnetic selection for CD271-positive cells.MSCs were isolated from bone marrow (BM aspirates or surgical waste materials; enzymatically digested femoral heads (FHs and reamer irrigator aspirator (RIA waste fluids. Flow cytometry for the CD45-/lowCD73+CD271+ phenotype was used to evaluate uncultured MSCs before and after selection, and to measure MSC enrichment in parallel to colony forming-unit fibroblast assay. Trilineage differentiation assays and quantitative polymerase chain-reaction for key transcripts involved in bone regeneration was used to assess the functional utility of isolated cells for bone repair.Uncultured CD45-/lowCD271+ MSCs uniformly expressed CD73, CD90 and CD105 but showed variable expression of MSCA-1 and SUSD2 (BM>RIA>FH. MSCs were enriched over 150-fold from BM aspirates and RIA fluids, whereas the highest MSC purities were obtained from FH digests. Enriched fractions expressed increased levels of BMP-2, COL1A2, VEGFC, SPARC and CXCL12 transcripts (BM>RIA>FH, with the highest up-regulation detected for CXCL12 in BM (>1300-fold. Following culture expansion, CD271-selected MSCS were tri-potential and phenotypically identical to plastic adherence-selected MSCs.A CD271-based GMP-compliant immunomagnetic selection resulted in a substantial increase in MSC purity and elevated expression of transcripts involved in bone formation, vascularisation and chemo-attraction. Although this technology, particularly from RIA fluids, can be immediately applied by orthopaedic surgeons as autologous therapy, further improvements in MSC purities and pre-clinical testing of product

  8. Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

    Directory of Open Access Journals (Sweden)

    Zhang X

    2018-01-01

    Full Text Available Xiaochen Zhang,1,* Quan Yu,2,* Yan-an Wang,1 Jun Zhao2 1Department of Oral and Maxillofacial-Head and Neck Oncology, 2Department of Orthodontics, College of Stomatology, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China *These authors contributed equally to this work Introduction: To induce sufficient new bone formation, high doses of bone morphogenetic protein-2 (BMP-2 are applied in regenerative medicine that often induce serious side effects. Therefore, improved treatment strategies are required. Here, we investigate whether the delivery of BMP-2 lyophilized in the presence of trehalose reduced the dose of BMP-2 required for bone regeneration. Materials and methods: A new growth factor delivery system was fabricated using BMP-2-loaded TiO2 nanotubes by lyophilization with trehalose (TiO2-Lyo-Tre-BMP-2. We measured BMP-2 release characteristics, bioactivity, and stability, and determined the effects on the osteogenic differentiation of bone marrow stromal cells in vitro. Additionally, we evaluated the ability of this formulation to regenerate new bone around implants in rat femur defects by micro-computed tomography (micro-CT, sequential fluorescent labelling, and histological analysis. Results: Compared with absorbed BMP-2-loaded TiO2 nanotubes (TiO2-BMP-2, TiO2-Lyo-Tre-BMP-2 exhibited sustained release, consistent bioactivity, and higher stability of BMP-2, and resulted in greater osteogenic differentiation of BMSCs. Eight weeks post-operation, TiO2-Lyo-Tre-BMP-2 nanotubes, with various dosages of BMP-2, regenerated larger amounts of new bone than TiO2-BMP-2 nanotubes. Conclusion: Our findings indicate that delivery of BMP-2 lyophilized with trehalose may be a promising method to reduce the dose of BMP-2 and avoid the associated side effects. Keywords: bone morphogenetic protein-2, dose reduction, delivery system, trehalose, lyophilization, TiO2 nanotubes, BMP-2, regenerative medicine, surface

  9. Bioactive Nano-fibrous Scaffold for Vascularized Craniofacial Bone Regeneration

    DEFF Research Database (Denmark)

    Prabha, Rahul Damodaran; Kraft, David Christian Evar; Harkness, Linda

    2018-01-01

    the limitation of cell penetration of electrospun scaffolds and improve on its osteoconductive nature, in this study, we fabricated a novel electrospun composite scaffold of polyvinyl alcohol (PVA) - poly (ε) caprolactone (PCL) - Bioceramic (HAB), namely, PVA-PCL-HAB. The scaffold prepared by dual...... electrospinning of PVA and PCL with HAB overcomes reduced cell attachment associated with hydrophobic poly (ε) caprolactone (PCL) by combination with a hydrophilic polyvinyl alcohol (PVA) and the bioceramic (HAB) can contribute to enhance osteo-conductivity. We characterized the physicochemical...... and biocompatibility properties of the new scaffold material. Our results indicate PVA-PCL-HAB scaffolds support attachment and growth of stromal stem cells; (human bone marrow skeletal (mesenchymal) stem cells (hMSC) and dental pulp stem cells (DPSC)). In addition, the scaffold supported in vitro osteogenic...

  10. Natural regeneration processes in big sagebrush (Artemisia tridentata)

    Science.gov (United States)

    Schlaepfer, Daniel R.; Lauenroth, William K.; Bradford, John B.

    2014-01-01

    Big sagebrush, Artemisia tridentata Nuttall (Asteraceae), is the dominant plant species of large portions of semiarid western North America. However, much of historical big sagebrush vegetation has been removed or modified. Thus, regeneration is recognized as an important component for land management. Limited knowledge about key regeneration processes, however, represents an obstacle to identifying successful management practices and to gaining greater insight into the consequences of increasing disturbance frequency and global change. Therefore, our objective is to synthesize knowledge about natural big sagebrush regeneration. We identified and characterized the controls of big sagebrush seed production, germination, and establishment. The largest knowledge gaps and associated research needs include quiescence and dormancy of embryos and seedlings; variation in seed production and germination percentages; wet-thermal time model of germination; responses to frost events (including freezing/thawing of soils), CO2 concentration, and nutrients in combination with water availability; suitability of microsite vs. site conditions; competitive ability as well as seedling growth responses; and differences among subspecies and ecoregions. Potential impacts of climate change on big sagebrush regeneration could include that temperature increases may not have a large direct influence on regeneration due to the broad temperature optimum for regeneration, whereas indirect effects could include selection for populations with less stringent seed dormancy. Drier conditions will have direct negative effects on germination and seedling survival and could also lead to lighter seeds, which lowers germination success further. The short seed dispersal distance of big sagebrush may limit its tracking of suitable climate; whereas, the low competitive ability of big sagebrush seedlings may limit successful competition with species that track climate. An improved understanding of the

  11. Development of Magnesium and Siloxane-containing Vaterite and its Composite Materials for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Shinya eYamada

    2015-12-01

    Full Text Available Development of novel biomaterials with Mg2+, Ca2+ and silicate ions releasability for bone regeneration is now in progress. Several inorganic ions have been reported to stimulate bone-forming cells. We featured Ca2+, silicate and especially Mg2+ ions as growth factors for osteoblasts. Various biomaterials, such as ceramic powders and organic-inorganic composites, releasing the ions have been developed and investigated in their cytocompatibilities in our previous work. Through the investigation, providing the three ions was found to be effective to activate osteogenic cells. Mg and siloxane-containing vaterite (MgSiV was prepared by a carbonation process as an inorganic particles, which can provide simultaneously releasing ability of Ca2+, silicate and Mg2+ ions to biodegradable polymers. Poly(L-lactic acid (PLLA- and bioactive PLLA-based composites containing vaterite coatings were discussed on their degradability and cytocompatibility using a metallic Mg substrate as Mg2+ ion source. PLLA/SiV composite film, which has a releasability of silicate ions besides Ca2+ ion, was coated on a pure Mg substrate to be compared with the PLLA/V coating. The degradability and releasability of inorganic ions were morphologically and quantitatively monitored in a cell culture medium. The bonding strength between the coatings and Mg substrates was one of the key factors to control Mg2+ ion release from the substrates. The cell culture tests were conducted using mouse osteoblast-like cells (MC3T3-E1 cells; cellular morphology, proliferation and differentiation on the materials were evaluated. The PLLA/V and PLLA/SiV coatings on Mg substrates were found to enhance the proliferation; especially the PLLA/SiV coating possessed a higher ability of inducing the osteogenic differentiation of the cells.

  12. Magnetic biodegradable Fe3O4/CS/PVA nanofibrous membranes for bone regeneration

    International Nuclear Information System (INIS)

    Wei Yan; Zhang Xuehui; Hu Xiaoyang; Deng Xuliang; Song Yu; Lin Yuanhua; Han Bing; Wang Xinzhi

    2011-01-01

    In recent years, interest in magnetic biomimetic scaffolds for tissue engineering has increased considerably. The aim of this study is to develop magnetic biodegradable fibrous materials with potential use in bone regeneration. Magnetic biodegradable Fe 3 O 4 /chitosan (CS)/poly vinyl alcohol (PVA) nanofibrous membranes were achieved by electrospinning with average fiber diameters ranging from 230 to 380 nm and porosity of 83.9-85.1%. The influences of polymer concentration, applied voltage and Fe 3 O 4 nanoparticles loading on the fabrication of nanofibers were investigated. The polymer concentration of 4.5 wt%, applied voltage of 20 kV and Fe 3 O 4 nanoparticles loading of lower than 5 wt% could produce homogeneous, smooth and continuous Fe 3 O 4 /CS/PVA nanofibrous membranes. X-ray diffraction (XRD) data confirmed that the crystalline structure of the Fe 3 O 4 , CS and PVA were maintained during electrospinning process. Fourier transform infrared spectroscopy (FT-IR) demonstrated that the Fe 3 O 4 loading up to 5 wt% did not change the functional groups of CS/PVA greatly. Transmission electron microscopy (TEM) showed islets of Fe 3 O 4 nanoparticles evenly distributed in the fibers. Weak ferrimagnetic behaviors of membranes were revealed by vibrating sample magnetometer (VSM) test. Tensile test exhibited Young's modulus of membranes that were gradually enhanced with the increase of Fe 3 O 4 nanoparticles loading, while ultimate tensile stress and ultimate strain were slightly reduced by Fe 3 O 4 nanoparticles loading of 5%. Additionally, MG63 human osteoblast-like cells were seeded on the magnetic nanofibrous membranes to evaluate their bone biocompatibility. Cell growth dynamics according to MTT assay and scanning electron microscopy (SEM) observation exhibited good cell adhesion and proliferation, suggesting that this magnetic biodegradable Fe 3 O 4 /CS/PVA nanofibrous membranes can be one of promising biomaterials for facilitation of osteogenesis.

  13. Ionic Colloidal Molding as a Biomimetic Scaffolding Strategy for Uniform Bone Tissue Regeneration.

    Science.gov (United States)

    Zhang, Jian; Jia, Jinpeng; Kim, Jimin P; Shen, Hong; Yang, Fei; Zhang, Qiang; Xu, Meng; Bi, Wenzhi; Wang, Xing; Yang, Jian; Wu, Decheng

    2017-05-01

    Inspired by the highly ordered nanostructure of bone, nanodopant composite biomaterials are gaining special attention for their ability to guide bone tissue regeneration through structural and biological cues. However, bone malformation in orthopedic surgery is a lingering issue, partly due to the high surface energy of traditional nanoparticles contributing to aggregation and inhomogeneity. Recently, carboxyl-functionalized synthetic polymers have been shown to mimic the carboxyl-rich surface motifs of non-collagenous proteins in stabilizing hydroxyapatite and directing intrafibrillar mineralization in-vitro. Based on this biomimetic approach, it is herein demonstrated that carboxyl functionalization of poly(lactic-co-glycolic acid) can achieve great material homogeneity in nanocomposites. This ionic colloidal molding method stabilizes hydroxyapatite precursors to confer even nanodopant packing, improving therapeutic outcomes in bone repair by remarkably improving mechanical properties of nanocomposites and optimizing controlled drug release, resulting in better cell in-growth and osteogenic differentiation. Lastly, better controlled biomaterial degradation significantly improved osteointegration, translating to highly regular bone formation with minimal fibrous tissue and increased bone density in rabbit radial defect models. Ionic colloidal molding is a simple yet effective approach of achieving materials homogeneity and modulating crystal nucleation, serving as an excellent biomimetic scaffolding strategy to rebuild natural bone integrity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Concise review: bridging the gap: bone regeneration using skeletal stem cell-based strategies-where are we now?

    DEFF Research Database (Denmark)

    Dawson, Jonathan I; Kanczler, Janos; Kassem, Moustapha

    2014-01-01

    Skeletal stem cells confer to bone its innate capacity for regeneration and repair. Bone regeneration strategies seek to harness and enhance this regenerative capacity for the replacement of tissue damaged or lost through congenital defects, trauma, functional/esthetic problems, and a broad range...... for musculoskeletal regeneration. Stem Cells 2014;32:35-44...... of diseases associated with an increasingly aged population. This review describes the state of the field and current steps to translate and apply skeletal stem cell biology in the clinic and the problems therein. Challenges are described along with key strategies including the isolation and ex vivo expansion...

  15. The Kinetics of Ampicillin Release from Hydroxyapatite for Bones Regeneration

    Directory of Open Access Journals (Sweden)

    Giovanilton Ferreira da Silva

    2009-01-01

    Full Text Available Semisynthetic beta-lactam antibiotics are among the most used pharmaceuticals. Their use in veterinary and human medicine is in continuous expansion. There is a growing need for developing bioactive implants. Advantages of implantable drug delivery tools can include high release efficiency, precise dose control, low toxicity, and allow to overcome disadvantages connected with conventional methods. In this respect, hydroxyapatite (HA is an elective material. It enables to produce architectures similar to those of real bones. Here we studied a kinetic model to describe ampicillin release from HA. In the course of adsorption experiment, ampicillin was dissolved, maintained at 30∘C and shaken at 60 strokes/minute. Samples were withdrawn periodically for analysis and then returned to the mixture. Adsorbed amounts were measured by the difference of the concentration of the antibiotics before and after adsorption using UV adsorption at 225 nm. The aim of this work was to evaluate its application as ampicillin delivery carrier.

  16. Ovalbumin-BasedPorous Scaffolds for Bone Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Gabrielle Farrar

    2010-01-01

    Full Text Available Cell differentiation on glutaraldehyde cross-linked ovalbumin scaffolds was the main focus of this research. Salt leaching and freeze drying were used to create a three-dimensional porous structure. Average pore size was 147.84±40.36 μm and 111.79±30.71 μm for surface and cross sectional area, respectively. Wet compressive strength and elastic modulus were 6.8±3.6 kPa. Average glass transition temperature was 320.1±1.4°C. Scaffolds were sterilized with ethylene oxide prior to seeding MC3T3-E1 cells. Cells were stained with DAPI and Texas red to determine morphology and proliferation. Average cell numbers increased between 4-hour- and 96-hour-cultured scaffolds. Alkaline phosphatase and osteocalcin levels were measured at 3, 7, 14, and 21 days. Differentiation studies showed an increase in osteocalcin at 21 days and alkaline phosphatase levels at 14 days, both indicating differentiation occurred. This work demonstrated the use of ovalbumin scaffolds for a bone tissue engineering application.

  17. Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies

    NARCIS (Netherlands)

    Pot, M.W.; Kuppevelt, T.H. van; Gonzales, V.K.; Buma, P.; Hout, J. in't; Vries, R.B.M. de; Daamen, W.F.

    2017-01-01

    Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline

  18. Results of bone regenerate study after osteosynthesis with bioinert and calcium phosphate-coated bioactive implants in experimental femoral neck fractures (experimental study

    Directory of Open Access Journals (Sweden)

    K. S. Kazanin

    2015-01-01

    Full Text Available Objective - to analyze the results of X-ray, cytomorphometric and immunohistochemistry experimental studies of bone regenerates after osteosynthesis with bioinert and calcium phosphate-coated bioactive implants. Material and methods. The study was conducted on experimental femoral neck fractures in rabbit males. Reparative osteogenesis processes were studied in groups of bioinert titanium implant osteosynthesis and calcium phosphate-coated bioactive titanium implant osteosynthesis. The animals were clinically followed-up during the postoperative period. X-ray, cytomorphometric and immunohistochemistry studies of samples extracted from femoral bones were conducted over time on days 1, 7, 14, 30 and 60. The animal experiments were kept and treated according to recommendations of international standards, Helsinki Declaration on animal welfare and approved by the local ethics committee. All surgeries were performed under anesthesia, and all efforts were made to minimize the suffering of the animals. Results. In the animal group without femoral neck fracture osteosynthesis, femoral neck pseudoarthrosis was observed at the end of the experiment. The results of cytomorphometric and immunohistochemistry studies conducted on day 60 of the experiment confirmed that the cellular composition of the bone regenerate in the group of calcium phosphate-coated bioactive titanium implants corresponded to a more mature bone tissue than in the group of bioinert titanium implants. Conclusion. The results of the statistical analysis of cytomorphometric and immunohistochemistry data show that the use of calcium phosphate-coated bioactive titanium implants allows to achieve significantly earlier bone tissue regeneration.

  19. Reduced graphene oxide aerogel networks with soft interfacial template for applications in bone tissue regeneration

    Science.gov (United States)

    Asha, S.; Ananth, A. Nimrodh; Jose, Sujin P.; Rajan, M. A. Jothi

    2018-05-01

    Reduced Graphene Oxide aerogels (A-RGO), functionalized with chitosan, were found to induce and/or accelerate the mineralization of hydroxyapatite. The functionalized chitosan acts as a soft interfacial template on the surface of A-RGO assisting the growth of hydroxyapatite particles. The mineralization on these soft aerogel networks was performed by soaking the aerogels in simulated body fluid, relative to time. Polymer-induced mineralization exhibited an ordered arrangement of hydroxyapatite particles on reduced graphene oxide aerogel networks with a higher crystalline index (IC) of 1.7, which mimics the natural bone formation indicating the importance of the polymeric interfacial template. These mineralized aerogels which mimic the structure and composition of natural bone exhibit relatively higher rate of cell proliferation, osteogenic differentiation and osteoid matrix formation proving it to be a potential scaffold for bone tissue regeneration.

  20. Incorporation of stromal cell-derived factor-1 alpha in PCL/gelatin electrospun membranes for guided bone regeneration

    NARCIS (Netherlands)

    Ji, W.; Yang, F.; Ma, J.L.; Bouma, M.J.; Boerman, O.C.; Chen, Z.; Beucken, J.J.J.P van den; Jansen, J.A.

    2013-01-01

    The goal of this work was to evaluate the effect of membrane functionalization with a chemotactic factor on cell recruitment and bone formation in order to develop a bioactive membrane for guided bone regeneration (GBR) applications. To this end. GBR membranes were prepared by electrospinning using

  1. Oily calcium hydroxide suspension (Osteoinductal) used as an adjunct to guided bone regeneration: an experimental study in rats.

    NARCIS (Netherlands)

    Stavropoulos, A.; Geenen, C.; Nyengaard, J.R.; Karring, T.; Sculean, A.

    2007-01-01

    OBJECTIVES: To evaluate whether an oily calcium hydroxide suspension (OCHS) promotes bone healing when used as an adjunct to guided bone regeneration (GBR). MATERIAL AND METHODS: Rigid, hemispherical, teflon capsules were placed with their open part facing the lateral surface of the ramus on both

  2. Histological Evaluation of Degradable Guided Bone Regeneration Membranes Prepared from Poly(trimethylene carbonate) and Biphasic Calcium Phosphate Composites

    NARCIS (Netherlands)

    Zeng, Ni; van Leeuwen, Anne; Bos, Ruud R.M.; Grijpma, Dirk W.; Kuijer, Roel

    2013-01-01

    In oral and maxillofacial surgery, guided bone regeneration using barrier membranes is an important strategy to treat bone defects. The currently used barrier membranes have important disadvantages. Barrier membranes prepared from resorbable poly(trimethylene carbonate) (PTMC) performed as well as

  3. Histological evaluation of degradable guided bone regeneration membranes prepared from poly(trimethylene carbonate) and biphasic calcium phosphate composites

    NARCIS (Netherlands)

    Zeng, Ni; van Leeuwen, Anne; Bos, Ruud R.M.; Grijpma, Dirk W.; Kuijer, Roel

    2013-01-01

    In oral and maxillofacial surgery, guided bone regeneration using barrier membranes is an important strategy to treat bone defects. The currently used barrier membranes have important disadvantages. Barrier membranes prepared from resorbable poly(trimethylene carbonate) (PTMC) performed as well as

  4. In vitro and in vivo bioactivity assessment of a polylactic acid/hydroxyapatite composite for bone regeneration

    NARCIS (Netherlands)

    Danoux, Charlene; Barbieri, D.; Yuan, Huipin; de Bruijn, Joost Dick; van Blitterswijk, Clemens; Habibovic, Pamela

    2014-01-01

    Synthetic bone graft substitutes based on composites consisting of a polymer and a calcium-phosphate (CaP) ceramic are developed with the aim to satisfy both mechanical and bioactivity requirements for successful bone regeneration. In the present study, we have employed extrusion to produce a

  5. 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.

  6. Selective laser melting-produced porous titanium scaffolds regenerate bone in critical size cortical bone defects

    NARCIS (Netherlands)

    J. van der Stok (Johan); O.P. van der Jagt (Olav); S. Amin Yavari (Saber); M.F.P. de Haas (Mirthe); J.H. Waarsing (Jan); H. Jahr (Holger); E.M.M. van Lieshout (Esther); P. Patka (Peter); J.A.N. Verhaar (Jan); A.A. Zadpoor (Amir Abbas); H.H. Weinans (Harrie)

    2013-01-01

    textabstractPorous titanium scaffolds have good mechanical properties that make them an interesting bone substitute material for large bone defects. These scaffolds can be produced with selective laser melting, which has the advantage of tailoring the structure's architecture. Reducing the strut

  7. 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

  8. Epithelial architectural destruction is necessary for bone marrow derived cell contribution to regenerating prostate epithelium.

    Science.gov (United States)

    Palapattu, Ganesh S; Meeker, Alan; Harris, Timothy; Collector, Michael I; Sharkis, Saul J; DeMarzo, Angelo M; Warlick, Christopher; Drake, Charles G; Nelson, William G

    2006-08-01

    Using various nonphysiological tissue injury/repair models numerous studies have demonstrated the capacity of bone marrow derived cells to contribute to the repopulation of epithelial tissues following damage. To investigate whether this phenomenon might also occur during periods of physiological tissue degeneration/regeneration we compared the ability of bone marrow derived cells to rejuvenate the prostate gland in mice that were castrated and then later treated with dihydrotestosterone vs mice with prostate epithelium that had been damaged by lytic virus infection. Using allogenic bone marrow grafts from female donor transgenic mice expressing green fluorescent protein transplanted into lethally irradiated males we were able to assess the contributions of bone marrow derived cells to recovery of the prostatic epithelium in 2 distinct systems, including 1) surgical castration followed 1 week later by dihydrotestosterone replacement and 2) intraprostatic viral injection. Eight to 10-week-old male C57/Bl6 mice were distributed among bone marrow donor-->recipient/prostate injury groups, including 5 with C57/Bl6-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/vehicle injection, 4 with green fluorescent protein-->C57/Bl6/virus injection and 3 each with green fluorescent protein-->C57/Bl6/castration without and with dihydrotestosterone, respectively. Prostate tissues were harvested 3 weeks after dihydrotestosterone replacement or 14 days following intraprostatic viral injection. Prostate tissue immunofluorescence was performed with antibodies against the epithelial marker cytokeratin 5/8, the hematopoietic marker CD45 and green fluorescent protein. Mice that sustained prostate injury from vaccinia virus infection with concomitant severe inflammation and glandular disruption showed evidence of bone marrow derived cell reconstitution of prostate epithelium, that is approximately 4% of all green

  9. Bone regeneration by gelatin hydro-gel seat containing BMP-2 and its application to canine orbital floor fracture Model

    International Nuclear Information System (INIS)

    Mochizuki, Yuichi

    2007-01-01

    Reported are preparation of the gel seat in the title (GHG) for sustained release of BMP-2 (bone morphogenetic protein-2) and its application to the fracture model of orbital floor of the dog. The chemically linked GHG was prepared from gelatin and glutaraldehyde and lyophilized. BMP-2 solution was dropped on the GHG seat to be contained there. To see the biobehavior of BMP-2 and GHG, they were labeled with 125 I and were given subcutaneously in the back of nude mice, of which remaining radioactivity was periodically measured by Aloka ARC-310B gamma counter. This experiment revealed the sustained release of BMP-2 along with degradation of the GHG. Then a complex of the GHG and bio-degradable polymer (L-lactide-ε-caprolactone) was prepared and implanted to the artificially fractured region (10 x 10 mm) of dog orbit floor, of which recovering process was evaluated by analysis of bone structure with soft X-ray (SOFRON, TRS-1005) roentgenography, histology, and micro-CT imaging (Comscantecno's Scan Xmate-A090S) for trabecular bone volume, thickness, number and separation. This experiment revealed that new bone was effectively induced to regenerate on the complex, of which structure was found similar to the normal trabecula. Thus in future, the complex can be useful for ideal treatment of the orbit floor fracture without necessity of donor. (R.T.)

  10. Effect of concentrated growth factor combined with guided bone regeneration on cell proliferation and bone resorption in patients with severe periodontitis

    Directory of Open Access Journals (Sweden)

    Qiang Gao

    2017-10-01

    Full Text Available Objective: To study the effect of concentrated growth factor (CGF combined with guided bone regeneration on cell proliferation and bone resorption in patients with severe periodontitis. Methods: Patients with severe periodontitis who were treated in Stomatology Department of Shenmu Hospital between May 2014 and February 2017 were selected as the research subjects and randomly divided into two groups, surgery + CGF group received concentrated growth factor combined with guided bone regeneration, and pure surgery group received guided bone regeneration. The contents of inflammatory response, cell proliferation and bone resorption markers in gingival crevicular fluid were determined 1 week after treatment. Results: 1 week after treatment, HMGB1, ICAM1, E-selectin, Smac, FasL, Caspase-8, Caspase-9, Caspase-3, RANKL and NTX contents in gingival crevicular fluid of surgery + CGF group were significantly lower than those of pure surgery group while PD-L1, hBD-3, Wnt3a, BGP and OPG contents were significantly higher than those of pure surgery group. Conclusion: Concentrated growth factor combined with guided bone regeneration for severe periodontitis can inhibit inflammatory response, apoptosis and bone resorption, which is beneficial to the reconstruction of periodontal tissue.

  11. Treatment of Severely Resorbed Maxilla Due to Peri-Implantitis by Guided Bone Regeneration Using a Customized Allogenic Bone Block: A Case Report

    Directory of Open Access Journals (Sweden)

    Oliver Blume

    2017-10-01

    Full Text Available The objective of this case report is to introduce a customized CAD/CAM freeze-dried bone allograft (FDBA block for its use in Guided Bone Regeneration (GBR procedures for severely deficient maxillary bones. Additionally, a special newly developed remote incision technique is presented to avoid wound dehiscence. The results show optimal integration behavior of the FDBA block after six months and the formation of new vital bone. Thus, the results of the present case report confirm the use of the customized CAD/CAM bone block for augmentation of complex defects in the maxillary aesthetic zone as a successful treatment concept.

  12. Scaffold of chitosan-sodium alginate and hydroxyapatite with application potential for bone regeneration

    International Nuclear Information System (INIS)

    Rebelo, Marcia de A.; Alves, Thais F.R.; Lopes, Francielly C.C.N; Oliveira Junior, Jose Martins de; Pontes, Katiusca S.; Fogaca, Bruna A.C.; Chaud, Marco V.

    2015-01-01

    Scaffold for organic tissue regeneration are architectural, three-dimensional, porous, biocompatible and biodegradable devices. The first challenges to be met in the development of these devices to mimic the biomechanical properties of the target tissue. The aim of this study was to develop and to characterize scaffolds composed of chitosan (Ch), sodium alginate (SA), hydroxyapatite (HA). The scaffolds were obtained by lyophilization. HA has been incorporated into the polymer dispersion in Ch-AS concentration of 20 and 60%. The mechanical properties of the scaffold were determined by tensile and compression tests. Swelling capacity was assessed in the presence of simulated saliva, purified water, HCl 0.01M, NaOH 0.01M. The calcium content was quantified using fluorescence X-rays. Analysis of the results indicates that the Qt-AS-HA-60% scaffold obtained by lyophilization meets promising properties for bone tissue regeneration. (author)

  13. Bone Regeneration of Rat Tibial Defect by Zinc-Tricalcium Phosphate (Zn-TCP Synthesized from Porous Foraminifera Carbonate Macrospheres

    Directory of Open Access Journals (Sweden)

    Joshua Chou

    2013-12-01

    Full Text Available Foraminifera carbonate exoskeleton was hydrothermally converted to biocompatible and biodegradable zinc-tricalcium phosphate (Zn-TCP as an alternative biomimetic material for bone fracture repair. Zn-TCP samples implanted in a rat tibial defect model for eight weeks were compared with unfilled defect and beta-tricalcium phosphate showing accelerated bone regeneration compared with the control groups, with statistically significant bone mineral density and bone mineral content growth. CT images of the defect showed restoration of cancellous bone in Zn-TCP and only minimal growth in control group. Histological slices reveal bone in-growth within the pores and porous chamber of the material detailing good bone-material integration with the presence of blood vessels. These results exhibit the future potential of biomimetic Zn-TCP as bone grafts for bone fracture repair.

  14. BONE REGENERATION AFTER DEMINERALIZED BONE MATRIX AND CASTOR OIL (RICINUS COMMUNIS) POLYURETHANE IMPLANTATION

    Science.gov (United States)

    Leite, Fábio Renato Manzolli; Ramalho, Lizeti Toledo de Oliveira

    2008-01-01

    Innocuous biocompatible materials have been searched to repair or reconstruct bone defects. Their goal is to restore the function of live or dead tissues. This study compared connective tissue and bone reaction when exposed to demineralized bovine bone matrix and a polyurethane resin derived from castor bean (Ricinus communis). Forty-five rats were assigned to 3 groups of 15 animals (control, bovine bone and polyurethane). A cylindrical defect was created on mandible base and filled with bovine bone matrix and the polyurethane. Control group received no treatment. Analyses were performed after 15, 45 and 60 days (5 animals each). Histological analysis revealed connective tissue tolerance to bovine bone with local inflammatory response similar to that of the control group. After 15 days, all groups demonstrated similar outcomes, with mild inflammatory reaction, probably due to the surgical procedure rather than to the material. In the polymer group, after 60 days, scarce multinucleated cells could still be observed. In general, all groups showed good stability and osteogenic connective tissue with blood vessels into the surgical area. The results suggest biocompatibility of both materials, seen by their integration into rat mandible. Moreover, the polyurethane seems to be an alternative in bone reconstruction and it is an inexhaustible source of biomaterial. PMID:19089203

  15. Comparison of Bone Resorption Rates after Intraoral Block Bone and Guided Bone Regeneration Augmentation for the Reconstruction of Horizontally Deficient Maxillary Alveolar Ridges

    Directory of Open Access Journals (Sweden)

    B. Alper Gultekin

    2016-01-01

    Full Text Available Purpose. Bone atrophy after tooth loss may leave insufficient bone for implant placement. We compared volumetric changes after autogenous ramus block bone grafting (RBG or guided bone regeneration (GBR in horizontally deficient maxilla before implant placement. Materials and Methods. In this retrospective study, volumetric changes at RBG or GBR graft sites were evaluated using cone-beam computed tomography. The primary outcome variable was the volumetric resorption rate. Secondary outcomes were bone gain, graft success, and implant insertion torque. Results. Twenty-four patients (28 grafted sites were included (GBR, 15; RBG, 13. One patient (RBG suffered mucosal dehiscence at the recipient site 6 weeks after surgery, which healed spontaneously. Mean volume reduction in the GBR and RBG groups was 12.48 ± 2.67% and 7.20 ± 1.40%, respectively. GBR resulted in significantly more bone resorption than RBG (P0.05. Conclusions. Both RBG and GBR hard-tissue augmentation techniques provide adequate bone graft volume and stability for implant insertion. However, GBR causes greater resorption at maxillary augmented sites than RBG, which clinicians should consider during treatment planning.

  16. Effects of laser photherapy on bone defects grafted with mineral trioxide aggregate, bone morphogenetic proteins, and guided bone regeneration: a Raman spectroscopic study.

    Science.gov (United States)

    Pinheiro, Antonio L B; Aciole, Gilberth T S; Cangussú, Maria Cristina T; Pacheco, Marcos T T; Silveira, Landulfo

    2010-12-15

    We have used Raman analysis to assess bone healing on different models. Benefits on the isolated or combined use of mineral trioxide aggregate, bone morphogenetic proteins, guided bone regeneration and laser on bone repair have been reported, but not their combination. We studied peaks of hydroxyapatite and CH groups on defects grafted with MTA, treated or not with laser, BMPs, and GBR. Ninety rats were divided in 10 groups each, subdivided into three subgroups. Laser (λ850 nm) was applied at every other day for 2 weeks. Raman readings were taken at the surface of the defect. Statistical analysis (CHA) showed significant differences between all groups (p = 0.001) and between Group II and all other (p hydroxyapatite (CHA) that is indicative of greater calcification and resistance of the bone. We conclude that the association of the MTA with laser phototherapy (LPT) and/or not with GBR resulted in a better bone repair. The use of the MTA associated to IR LPT resulted in a more advanced and quality bone repair. Copyright © 2010 Wiley Periodicals, Inc.

  17. Hydroxyapatite fiber reinforced poly(alpha-hydroxy ester) foams for bone regeneration

    Science.gov (United States)

    Thomson, R. C.; Yaszemski, M. J.; Powers, J. M.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    1998-01-01

    A process has been developed to manufacture biodegradable composite foams of poly(DL-lactic-co-glycolic acid) (PLGA) and hydroxyapatite short fibers for use in bone regeneration. The processing technique allows the manufacture of three-dimensional foam scaffolds and involves the formation of a composite material consisting of a porogen material (either gelatin microspheres or salt particles) and hydroxyapatite short fibers embedded in a PLGA matrix. After the porogen is leached out, an open-cell composite foam remains which has a pore size and morphology defined by the porogen. By changing the weight fraction of the leachable component it was possible to produce composite foams with controlled porosities ranging from 0.47 +/- 0.02 to 0.85 +/- 0.01 (n = 3). Up to a polymer:fiber ratio of 7:6, short hydroxyapatite fibers served to reinforce low-porosity PLGA foams manufactured using gelatin microspheres as a porogen. Foams with a compressive yield strength up to 2.82 +/- 0.63 MPa (n = 3) and a porosity of 0.47 +/- 0.02 (n = 3) were manufactured using a polymer:fiber weight ratio of 7:6. In contrast, high-porosity composite foams (up to 0.81 +/- 0.02, n = 3) suitable for cell seeding were not reinforced by the introduction of increasing quantities of hydroxyapatite short fibers. We were therefore able to manufacture high-porosity foams which may be seeded with cells but which have minimal compressive yield strength, or low porosity foams with enhanced osteoconductivity and compressive yield strength.

  18. In Vitro Mimetic Models for the Bone-Cartilage Interface Regeneration.

    Science.gov (United States)

    Bicho, Diana; Pina, Sandra; Oliveira, J Miguel; Reis, Rui L

    2018-01-01

    In embryonic development, pure cartilage structures are in the basis of bone-cartilage interfaces. Despite this fact, the mature bone and cartilage structures can vary greatly in composition and function. Nevertheless, they collaborate in the osteochondral region to create a smooth transition zone that supports the movements and forces resulting from the daily activities. In this sense, all the hierarchical organization is involved in the maintenance and reestablishment of the equilibrium in case of damage. Therefore, this interface has attracted a great deal of interest in order to understand the mechanisms of regeneration or disease progression in osteoarthritis. With that purpose, in vitro tissue models (either static or dynamic) have been studied. Static in vitro tissue models include monocultures, co-cultures, 3D cultures, and ex vivo cultures, mostly cultivated in flat surfaces, while dynamic models involve the use of bioreactors and microfluidic systems. The latter have emerged as alternatives to study the cellular interactions in a more authentic manner over some disadvantages of the static models. The current alternatives of in vitro mimetic models for bone-cartilage interface regeneration are overviewed and discussed herein.

  19. MicroRNA-467g inhibits new bone regeneration by targeting Ihh/Runx-2 signaling.

    Science.gov (United States)

    Kureel, Jyoti; John, Aijaz A; Dixit, Manisha; Singh, Divya

    2017-04-01

    MicroRNAs are important post transcriptional regulators of gene expression and play critical role in osteoblast differentiation. In this study we report miR-467g, an uncharacterized novel miRNA, in regulation of osteoblast functions. Over-expression of miR-467g inhibited osteoblast differentiation. Target prediction analysis tools and experimental validation by luciferase 3' UTR reporter assay identified Runx-2 as a direct target of miR-467g. Over expression of miR-467g in osteoblasts down regulated Runx-2 and Ihh signaling components. Furthermore, silencing of miR-467g was done to see its role in Ihh and Runx-2 mediated bone healing and regeneration in a drill hole injury model in BALB/c mice. Silencing of miR-467g led to significant increase in new bone regeneration and Ihh and Runx-2 localization at injury site in a day dependent manner. In conclusion, miR-467g negatively regulates osteogenesis by targeting Ihh/Runx-2 signaling. We, thus, propose that therapeutic approaches targeting miR-467g could be useful in enhancing the new bone formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Effects of 3D-Printed Polycaprolactone/β-Tricalcium Phosphate Membranes on Guided Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Jin-Hyung Shim

    2017-04-01

    Full Text Available This study was conducted to compare 3D-printed polycaprolactone (PCL and polycaprolactone/β-tricalcium phosphate (PCL/β-TCP membranes with a conventional commercial collagen membrane in terms of their abilities to facilitate guided bone regeneration (GBR. Fabricated membranes were tested for dry and wet mechanical properties. Fibroblasts and preosteoblasts were seeded into the membranes and rates and patterns of proliferation were analyzed using a kit-8 assay and by scanning electron microscopy. Osteogenic differentiation was verified by alizarin red S and alkaline phosphatase (ALP staining. An in vivo experiment was performed using an alveolar bone defect beagle model, in which defects in three dogs were covered with different membranes. CT and histological analyses at eight weeks after surgery revealed that 3D-printed PCL/β-TCP membranes were more effective than 3D-printed PCL, and substantially better than conventional collagen membranes in terms of biocompatibility and bone regeneration and, thus, at facilitating GBR.

  1. Bio-functionalized MWCNT/hyperbranched polyurethane bionanocomposite for bone regeneration

    International Nuclear Information System (INIS)

    Das, Beauty; Karak, Niranjan; Chattopadhyay, Pronobesh; Upadhyay, Aadesh; Maji, Somnath; Maity, Tapas Kumar; Purkayastha, Manashi Das; Mohanta, Charu lata

    2015-01-01

    The proper fabrication of biomaterials, particularly for purposes like bone regeneration, is of the utmost importance for the clinical success of materials that fulfill the design criteria at bio-interfacial milieu. Building on this aspect, a polyurethane nanocomposite (PNC) was fabricated by the combination of rapeseed protein functionalized multi-walled carbon nanotubes (MWCNTs) and vegetable-oil-based hyperbranched polyurethane. Biofunctionalized MWCNTs showed incredible biocompatibility compared to pristine MWCNTs as ascertained via in vitro and in vivo studies. PNC showed enhanced MG63 cell differentiation ability compared to the control and carboxyl functionalized MWCNT-based nanocomposite, as postulated by alkaline phosphatase activity together with better cellular adhesion, spreading and proliferation. Consequently, a critical-sized fracture gap (6 mm) bridged by the sticky PNC scaffold illustrated rapid bone neoformation within 30–45 d, with 90–93% of the defect area filling up. Histopathological studies demonstrated the reorganization of the normal tibial architecture and biodegradation of the implant. The subsequent toxicological study through cytokine expression, biochemical analysis and hematological studies suggested non-immunogenic and non-toxic effects of PNCs and their degraded/leached products. Their excellent bio-physiological features with high load-bearing ability (49–55.5 Mpa), ductility (675–790%) and biodegradability promote them as the best alternative biomaterials for bone regeneration in a comprehensive manner. (paper)

  2. Lyophilized platelet-rich fibrin (PRF) promotes craniofacial bone regeneration through Runx2.

    Science.gov (United States)

    Li, Qi; Reed, David A; Min, Liu; Gopinathan, Gokul; Li, Steve; Dangaria, Smit J; Li, Leo; Geng, Yajun; Galang, Maria-Therese; Gajendrareddy, Praveen; Zhou, Yanmin; Luan, Xianghong; Diekwisch, Thomas G H

    2014-05-14

    Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF) as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF). LPRF caused a 4.8-fold±0.4-fold elevation in Runt-related transcription factor 2 (Runx2) expression in alveolar bone cells, compared to a 3.6-fold±0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (pfibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering.

  3. Lyophilized Platelet-Rich Fibrin (PRF Promotes Craniofacial Bone Regeneration through Runx2

    Directory of Open Access Journals (Sweden)

    Qi Li

    2014-05-01

    Full Text Available Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF. LPRF caused a 4.8-fold ± 0.4-fold elevation in Runt-related transcription factor 2 (Runx2 expression in alveolar bone cells, compared to a 3.6-fold ± 0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (p < 0.001 when compared to fresh PRF. When applied in a rat craniofacial defect model for six weeks, LPRF resulted in 97% bony coverage of the defect, compared to 84% for fresh PRF, 64% for fibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering.

  4. Bone regeneration based on nano-hydroxyapatite and hydroxyapatite/chitosan nanocomposites: an in vitro and in vivo comparative study

    International Nuclear Information System (INIS)

    Tavakol, S.; Nikpour, M. R.; Amani, A.; Soltani, M.; Rabiee, S. M.; Rezayat, S. M.; Chen, P.; Jahanshahi, M.

    2013-01-01

    Surface morphology, surface wettability, and size distribution of biomaterials affect their in vitro and in vivo bone regeneration potential. Since nano-hydroxyapatite has a great chemical and structural similarity to natural bone and dental tissues, incorporated biomaterial of such products could improve bioactivity and bone bonding ability. In this research, nano-hydroxyapatite (23 ± 0.09 nm) and its composites with variety of chitosan content [2, 4, and 6 g (45 ± 0.19, 32 ± 0.12, and 28 ± 0.12 nm, respectively)] were prepared via an in situ hybridization route. Size distribution of the particles, protein adsorption, and calcium deposition of powders by the osteoblast cells, gene expression and percentage of new bone formation area were investigated. The highest degree of bone regeneration potential was observed in nano-hydroxyapatite powder, while the bone regeneration was lowest in nano-hydroxyapatite with 6 g of chitosan. Regarding these data, suitable size distribution next to size distribution of hydroxyapatite in bone, smaller size, higher wettability, lower surface roughness of the nano-hydroxyapatite particles and homogeneity in surface resulted in higher protein adsorption, cell differentiation and percentage of bone formation area. Results obtained from in vivo and in vitro tests confirmed the role of surface morphology, surface wettability, mean size and size distribution of biomaterial besides surface chemistry as a temporary bone substitute.

  5. The combined use of rhBMP-2/ACS, autogenous bone graft, a bovine bone mineral biomaterial, platelet-rich plasma, and guided bone regeneration at nonsubmerged implant placement for supracrestal bone augmentation. A case report.

    Science.gov (United States)

    Sclar, Anthony G; Best, Steven P

    2013-01-01

    This case report presents the clinical application and outcomes of the use of a combined approach to treat a patient with a severe alveolar defect. Recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier, along with autogenous bone graft, bovine bone mineral, platelet-rich plasma, and guided bone regeneration, were used simultaneous with nonsubmerged implant placement. At 1 year postsurgery, healthy peri-implant soft tissues and radiographically stable peri-implant crestal bone levels were observed along with locally increased radiographic bone density. In addition, a cone beam computed tomography (CBCT) scan demonstrated apparent supracrestal peri-implant bone augmentation with the appearance of normal alveolar ridge contours, including the facial bone wall.

  6. Selective laser melting-produced porous titanium scaffolds regenerate bone in critical size cortical bone defects.

    Science.gov (United States)

    Van der Stok, Johan; Van der Jagt, Olav P; Amin Yavari, Saber; De Haas, Mirthe F P; Waarsing, Jan H; Jahr, Holger; Van Lieshout, Esther M M; Patka, Peter; Verhaar, Jan A N; Zadpoor, Amir A; Weinans, Harrie

    2013-05-01

    Porous titanium scaffolds have good mechanical properties that make them an interesting bone substitute material for large bone defects. These scaffolds can be produced with selective laser melting, which has the advantage of tailoring the structure's architecture. Reducing the strut size reduces the stiffness of the structure and may have a positive effect on bone formation. Two scaffolds with struts of 120-µm (titanium-120) or 230-µm (titanium-230) were studied in a load-bearing critical femoral bone defect in rats. The defect was stabilized with an internal plate and treated with titanium-120, titanium-230, or left empty. In vivo micro-CT scans at 4, 8, and 12 weeks showed more bone in the defects treated with scaffolds. Finally, 18.4 ± 7.1 mm(3) (titanium-120, p = 0.015) and 18.7 ± 8.0 mm(3) (titanium-230, p = 0.012) of bone was formed in those defects, significantly more than in the empty defects (5.8 ± 5.1 mm(3) ). Bending tests on the excised femurs after 12 weeks showed that the fusion strength reached 62% (titanium-120) and 45% (titanium-230) of the intact contralateral femurs, but there was no significant difference between the two scaffolds. This study showed that in addition to adequate mechanical support, porous titanium scaffolds facilitate bone formation, which results in high mechanical integrity of the treated large bone defects. Copyright © 2012 Orthopaedic Research Society.

  7. In vitro characterization of 3D printed scaffolds aimed at bone tissue regeneration.

    Science.gov (United States)

    Boga, João C; Miguel, Sónia P; de Melo-Diogo, Duarte; Mendonça, António G; Louro, Ricardo O; Correia, Ilídio J

    2018-05-01

    The incidence of fractures and bone-related diseases like osteoporosis has been increasing due to aging of the world's population. Up to now, grafts and titanium implants have been the principal therapeutic approaches used for bone repair/regeneration. However, these types of treatment have several shortcomings, like limited availability, risk of donor-to-recipient infection and tissue morbidity. To overcome these handicaps, new 3D templates, capable of replicating the features of the native tissue, are currently being developed by researchers from the area of tissue engineering. These 3D constructs are able to provide a temporary matrix on which host cells can adhere, proliferate and differentiate. Herein, 3D cylindrical scaffolds were designed to mimic the natural architecture of hollow bones, and to allow nutrient exchange and bone neovascularization. 3D scaffolds were produced with tricalcium phosphate (TCP)/alginic acid (AA) using a Fab@home 3D printer. Furthermore, graphene oxide (GO) was incorporated into the structure of some scaffolds to further enhance their mechanical properties. The results revealed that the scaffolds incorporating GO displayed greater porosity, without impairing their mechanical properties. These scaffolds also presented a controlled swelling profile, enhanced biomineralization capacity and were able to increase the Alkaline Phosphatase (ALP) activity. Such characteristics make TCP/AA scaffolds functionalized with GO promising 3D constructs for bone tissue engineering applications. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Evaluation of the Effect of Plasma Rich in Growth Factors (PRGF on Bone Regeneration

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    M. Paknejad

    2012-01-01

    Full Text Available Objective: Reconstruction methods are an essential prerequisite for functional rehabilitation of the stomatognathic system. Plasma rich in growth factors (PRGF offers a new and potentially useful adjunct to bone substitute materials in bone reconstructive surgery. This study was carried out to investigate the influ-ence of PRGF and fibrin membrane on regeneration of bony defects with and without deproteinized bovine bone mineral (DBBM on rabbit calvaria. Materials and Methods: Twelve New Zealand white rabbits were included in this randomized, blinded, prospective study. Four equal 3.3×6.6 mm cranial bone defects were created and immediately grafted with DBBM, PRGF+DBBM, PRGF+fibrin membrane and no treatment as control. The defects were evaluated with histologic and histomorphometric analysis performed 4 and 8 weeks later. Results: Adding PRGF to DBBM led to increased bone formation as compared with the control group in 4- and 8-week intervals. In DBBM and PRGF+fibrin membrane samples, no significant increase was seen compared to the control group. There was also a significant increase in the rate of biodegradation of DBBM particles with the addition of PRGF in the 8-week interval. Neither noti-ceable foreign body reaction nor any severe inflammation was seen in each of the specimens evaluated. Conclusion: Under the limitation of this study, adding PRGF to DBBM enhanced osteogenesis in rabbit calvarias. Applying autologous fibrin membrane in the de-fects was not helpful.

  9. Evaluation of the Effect of Plasma Rich in Growth Factors (PRGF) on Bone Regeneration.

    Science.gov (United States)

    Paknejad, M; Shayesteh, Y Soleymani; Yaghobee, S; Shariat, S; Dehghan, M; Motahari, P

    2012-01-01

    Reconstruction methods are an essential prerequisite for functional rehabilitation of the stomatognathic system. Plasma rich in growth factors (PRGF) offers a new and potentially useful adjunct to bone substitute materials in bone reconstructive surgery. This study was carried out to investigate the influence of PRGF and fibrin membrane on regeneration of bony defects with and without deproteinized bovine bone mineral (DBBM) on rabbit calvaria. Twelve New Zealand white rabbits were included in this randomized, blinded, prospective study. Four equal 3.3×6.6 mm cranial bone defects were created and immediately grafted with DBBM, PRGF+DBBM, PRGF+fibrin membrane and no treatment as control. The defects were evaluated with histologic and histomorphometric analysis performed 4 and 8 weeks later. Adding PRGF to DBBM led to increased bone formation as compared with the control group in 4- and 8-week intervals. In DBBM and PRGF+fibrin membrane samples, no significant increase was seen compared to the control group. There was also a significant increase in the rate of biodegradation of DBBM particles with the addition of PRGF in the 8-week interval. Neither noticeable foreign body reaction nor any severe inflammation was seen in each of the specimens evaluated. Under the limitation of this study, adding PRGF to DBBM enhanced osteogenesis in rabbit calvarias. Applying autologous fibrin membrane in the defects was not helpful.

  10. Setd7 and its contribution to boron-induced bone regeneration in B-MBG scaffolds.

    Science.gov (United States)

    Yin, Chengcheng; Jia, Xiaoshi; Miron, Richard J; Long, Qiaoyun; Xu, Hudi; Wei, Yan; Wu, Min; Zhang, Yufeng; Li, Zubing

    2018-04-20

    Boron (B), a trace element found in the human body, plays an important role for health of bone by promoting the proliferation and differentiation of osteoblasts. Our research group previously fabricated B-mesoporous bioactive glass (MBG) scaffolds, which successfully promoted osteogenic differentiation of osteoblasts when compared to pure MBG scaffolds without boron. However, the mechanisms of the positive effect of B-MBG scaffolds on osteogenesis remains unknown. Therefore, we performed in-vivo experiments in an OVX rat models with pure MBG scaffolds and compared them to B-MBG scaffold. As a result, we found that B-MBG scaffold induced more new bone regeneration compared to pure MBG scaffold and examined genes related to bone regeneration induced by B-MBG scaffold through RNA-seq to obtain target genes and epigenetic mechanisms. The results demonstrated an increased expression and affiliation of Setd7 in the B-MBG group when compared to the MBG group. Immunofluorescent staining from our in vivo samples further demonstrated a higher localization of Setd7 and H3K4me3 in Runx2-positive cells in defects treated with B-MBG scaffolds. KEGG results suggested that specifically Wnt/β-catenin signaling pathway was highly activated in new bone area associated with B-MBG scaffolds. Thereafter, in vitro studies with human bone marrow stem cells (hBMSCs) stimulated by extracted liquid of B-MBG was associated with significantly elevated levels of Setd7, as well as H3K4me3 when compared to MBG alone. To verify the role of Setd7 in new bone formation in the presence of Boron, Setd7 was knocked down in hBMSCs with stimulation of the extracted liquids of B-MBG or MBG scaffolds. The result showed that osteoblast differentiation of hBMSCs was inhibited when Setd7 was knocked down, which could not be rescued by the extract liquids of B-MBG scaffolds confirming its role in osteoblast differentiation and bone regeneration. As a histone methylase, Setd7 may be expected to be a potential

  11. The Axolotl Fibula as a Model for the Induction of Regeneration across Large Segment Defects in Long Bones of the Extremities

    Science.gov (United States)

    Chen, Xiaoping; Song, Fengyu; Jhamb, Deepali; Li, Jiliang; Bottino, Marco C.; Palakal, Mathew J.; Stocum, David L.

    2015-01-01

    We tested the ability of the axolotl (Ambystoma mexicanum) fibula to regenerate across segment defects of different size in the absence of intervention or after implant of a unique 8-braid pig small intestine submucosa (SIS) scaffold, with or without incorporated growth factor combinations or tissue protein extract. Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone. By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases. These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process. PMID:26098852

  12. The Axolotl Fibula as a Model for the Induction of Regeneration across Large Segment Defects in Long Bones of the Extremities.

    Directory of Open Access Journals (Sweden)

    Xiaoping Chen

    Full Text Available We tested the ability of the axolotl (Ambystoma mexicanum fibula to regenerate across segment defects of different size in the absence of intervention or after implant of a unique 8-braid pig small intestine submucosa (SIS scaffold, with or without incorporated growth factor combinations or tissue protein extract. Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone. By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases. These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process.

  13. Polycaprolactone nanofiber interspersed collagen type-I scaffold for bone regeneration: a unique injectable osteogenic scaffold

    International Nuclear Information System (INIS)

    Baylan, Nuray; Ditto, Maggie; Lawrence, Joseph G; Yildirim-Ayan, Eda; Bhat, Samerna; Lecka-Czernik, Beata

    2013-01-01

    promoting osteoblast phenotype progression for bone regeneration. (paper)

  14. Comparative effectiveness of using resorbable membranes of polylactic acid and collagen in regeneration of bone defects in patients with periimplantitis

    Directory of Open Access Journals (Sweden)

    Gudaryan A.A.

    2014-03-01

    Full Text Available The article presents the results of comparative study of effectiveness of usage of separation membranes from polylactic acid (PLA and collagen in carrying out targeted regeneration of bone tissue in 22 patients with periimplantitis. Purpose: To conduct a comparative clinico-radiological efficiency of PLA membrane and collagen membranes in removing bone defects of the alveolar bone in patients with periimplantitis in clinic. It was found that depending on the type of membrane, bone tissue growth occurs not in the same way. Surgery in treatment of periimplantitis using osteo-inducing agent «Bio-Oss» and PLA membranes allows to reach full recovery of bone in bone defects in 90.9 % of patients versus 63.63 % of cases with collagen membranes. Thus, reconstitution of bone in bone defects in periimplantitis is more of full value in using PLA membranes than with membranes from collagen.

  15. Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function.

    Science.gov (United States)

    Hamann, Christine; Goettsch, Claudia; Mettelsiefen, Jan; Henkenjohann, Veit; Rauner, Martina; Hempel, Ute; Bernhardt, Ricardo; Fratzl-Zelman, Nadja; Roschger, Paul; Rammelt, Stefan; Günther, Klaus-Peter; Hofbauer, Lorenz C

    2011-12-01

    Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (-20%) and mineralized matrix formation (-55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40-80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.

  16. A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

    Directory of Open Access Journals (Sweden)

    Eap S

    2015-02-01

    Full Text Available Sandy Eap,1,2,* Laetitia Keller,1–3,* Jessica Schiavi,1,2 Olivier Huck,1,2 Leandro Jacomine,4 Florence Fioretti,1,2 Christian Gauthier,4 Victor Sebastian,1,3,5 Pascale Schwinté,1,2 Nadia Benkirane-Jessel1,21INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France; 2Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France; 3Department of Chemical Engineering, Aragon Nanoscience Institute, University of Zaragoza, Zaragoza, Spain; 4CNRS (National Center for Scientific Research, ICS (Charles Sadron Institute, Strasbourg, France; 5Networking Research Center of Bioengineering, Biomaterials and Nanomedicine, Zaragoza, Spain*These authors contributed equally to this workAbstract: New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone nanofibrous implant (from 700 µm to 1 cm thick was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII, 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days’ implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7

  17. Preparation of Emulsifying Wax/GMO Nanoparticles and Evaluation as a Delivery System for Repurposing Simvastatin in Bone Regeneration.

    Science.gov (United States)

    Eskinazi-Budge, Aaron; Manickavasagam, Dharani; Czech, Tori; Novak, Kimberly; Kunzler, James; Oyewumi, Moses O

    2018-05-30

    Simvastatin (Sim) is a widely known drug in the treatment of hyperlipidemia that has attracted so much attention in bone regeneration based on its potential osteoanabolic effect. However, repurposing of Sim in bone regeneration will require suitable delivery systems that can negate undesirable off-target/side effects. In this study, we have investigated a new lipid nanoparticle (NP) platform that was fabricated using a binary blend of emulsifying wax (Ewax) and glyceryl monooleate (GMO). Using the binary matrix materials, NPs loaded with Sim (0-500 µg/mL) were prepared and showed an average particle size of about 150 nm. NP size stability was dependent on Sim concentration loaded in NPs. The suitability of NPs prepared with the binary matrix materials in Sim delivery for potential application in bone regeneration was supported by biocompatibility in pre-osteoclastic and pre-osteoblastic cells. Additional data demonstrated that biofunctional Sim was released from NPs that facilitated differentiation of osteoblasts (cells that form bones) while inhibiting differentiation of osteoclasts (cells that resorb bones). The overall work demonstrated the preparation of NPs from Ewax/GMO blends and characterization to ascertain potential suitability in Sim delivery for bone regeneration. Additional studies on osteoblast and osteoclast functions are warranted to fully evaluate the efficacy simvastatin-loaded Ewax/GMO NPs using in-vitro and in-vivo approaches.

  18. Biocompatibility of single-walled carbon nanotube composites for bone regeneration.

    Science.gov (United States)

    Gupta, A; Liberati, T A; Verhulst, S J; Main, B J; Roberts, M H; Potty, A G R; Pylawka, T K; El-Amin Iii, S F

    2015-05-01

    The purpose of this study was to evaluate in vivo biocompatibility of novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic acid) (PLAGA) composites for applications in bone and tissue regeneration. A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight and 12 weeks post-implantation were compared with control (Sham) and PLAGA (five rats per group/point in time). Rats were observed for signs of morbidity, overt toxicity, weight gain and food consumption, while haematology, urinalysis and histopathology were completed when the animals were killed. No mortality and clinical signs were observed. All groups showed consistent weight gain, and the rate of gain for each group was similar. All groups exhibited a similar pattern for food consumption. No difference in urinalysis, haematology, and absolute and relative organ weight was observed. A mild to moderate increase in the summary toxicity (sumtox) score was observed for PLAGA and SWCNT/PLAGA implanted animals, whereas the control animals did not show any response. Both PLAGA and SWCNT/PLAGA showed a significantly higher sumtox score compared with the control group at all time intervals. However, there was no significant difference between PLAGA and SWCNT/PLAGA groups. Our results demonstrate that SWCNT/PLAGA composites exhibited in vivo biocompatibility similar to the Food and Drug Administration approved biocompatible polymer, PLAGA, over a period of 12 weeks. These results showed potential of SWCNT/PLAGA composites for bone regeneration as the low percentage of SWCNT did not elicit a localised or general overt toxicity. Following the 12-week exposure, the material was considered to have an acceptable biocompatibility to warrant further long-term and more invasive in vivo studies. Cite this article: Bone Joint Res 2015;4:70-7. ©2015 The British Editorial

  19. Role of HTRA1 in bone formation and regeneration: In vitro and in vivo evaluation.

    Directory of Open Access Journals (Sweden)

    Gladys Filliat

    Full Text Available The role of mammalian high temperature requirement protease A1 (HTRA1 in somatic stem cell differentiation and mineralized matrix formation remains controversial, having been demonstrated to impart either anti- or pro-osteogenic effects, depending on the in vitro cell model used. The aim of this study was therefore to further evaluate the role of HTRA1 in regulating the differentiation potential and lineage commitment of murine mesenchymal stem cells in vitro, and to assess its influence on bone structure and regeneration in vivo. Our results demonstrated that short hairpin RNA-mediated ablation of Htra1 in the murine mesenchymal cell line C3H10T1/2 increased the expression of several osteogenic gene markers, and significantly enhanced matrix mineralization in response to BMP-2 stimulation. These effects were concomitant with decreases in the expression of chondrogenic gene markers, and increases in adipogenic gene expression and lipid accrual. Despite the profound effects of loss-of-function of HTRA1 on this in vitro osteochondral model, these were not reproduced in vivo, where bone microarchitecture and regeneration in 16-week-old Htra1-knockout mice remained unaltered as compared to wild-type controls. By comparison, analysis of femurs from 52-week-old mice revealed that bone structure was better preserved in Htra1-knockout mice than age-matched wild-type controls. These findings therefore provide additional insights into the role played by HTRA1 in regulating mesenchymal stem cell differentiation, and offer opportunities for improving our understanding of how this multifunctional protease may act to influence bone quality.

  20. Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering

    Science.gov (United States)

    Lienemann, Philipp S.; Metzger, Stéphanie; Kiveliö, Anna-Sofia; Blanc, Alain; Papageorgiou, Panagiota; Astolfo, Alberto; Pinzer, Bernd R.; Cinelli, Paolo; Weber, Franz E.; Schibli, Roger; Béhé, Martin; Ehrbar, Martin

    2015-05-01

    Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue. However, micro-CT fails to provide spatiotemporal information on biological processes ongoing during bone regeneration. Conversely, due to the versatile applicability and cost-effectiveness, single photon emission computed tomography (SPECT) would be an ideal technique for assessing such biological processes with high sensitivity and for nuclear imaging comparably high resolution (designed poly(ethylene glycol)-based hydrogels that release bone morphogenetic protein to guide the healing of critical sized calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and micro-CT evaluations we determine the spatiotemporal course of bone formation and remodeling within this synthetic hydrogel implant. End point evaluations by high resolution micro-CT and histological evaluation confirm the value of this approach to follow and optimize bone-inducing biomaterials.

  1. Stable subcutaneous cartilage regeneration of bone marrow stromal cells directed by chondrocyte sheet.

    Science.gov (United States)

    Li, Dan; Zhu, Lian; Liu, Yu; Yin, Zongqi; Liu, Yi; Liu, Fangjun; He, Aijuan; Feng, Shaoqing; Zhang, Yixin; Zhang, Zhiyong; Zhang, Wenjie; Liu, Wei; Cao, Yilin; Zhou, Guangdong

    2017-05-01

    In vivo niche plays an important role in regulating differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. This study explored the feasibility that chondrocyte sheet created chondrogenic niche retained chondrogenic phenotype of BMSC engineered cartilage (BEC) in subcutaneous environments. Porcine BMSCs were seeded into biodegradable scaffolds followed by 4weeks of chondrogenic induction in vitro to form BEC, which were wrapped with chondrocyte sheets (Sheet group), acellular small intestinal submucosa (SIS, SIS group), or nothing (Blank group) respectively and then implanted subcutaneously into nude mice to trace the maintenance of chondrogenic phenotype. The results showed that all the constructs in Sheet group displayed typical cartilaginous features with abundant lacunae and cartilage specific matrices deposition. These samples became more mature with prolonged in vivo implantation, and few signs of ossification were observed at all time points except for one sample that had not been wrapped completely. Cell labeling results in Sheet group further revealed that the implanted BEC directly participated in cartilage formation. Samples in both SIS and Blank groups mainly showed ossified tissue at all time points with partial fibrogenesis in a few samples. These results suggested that chondrocyte sheet could create a chondrogenic niche for retaining chondrogenic phenotype of BEC in subcutaneous environment and thus provide a novel research model for stable ectopic cartilage regeneration based on stem cells. In vivo niche plays an important role in directing differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. The current study demonstrated that chondrocyte sheet generated by

  2. Mesenchymal Stem Cells in Bone Tissue Regeneration and Application to Bone Healing

    Czech Academy of Sciences Publication Activity Database

    Crha, M.; Nečas, A.; Srnec, R.; Janovec, J.; Raušer, P.; Urbanová, L.; Plánka, L.; Jančář, J.; Amler, Evžen

    2009-01-01

    Roč. 78, č. 4 (2009), s. 635-642 ISSN 0001-7213 R&D Projects: GA MŠk 2B06130; GA AV ČR IAA500390702 Institutional research plan: CEZ:AV0Z50390703 Keywords : tissue engineering * biomaterials * segmental bone lesion Subject RIV: BO - Biophysics Impact factor: 0.403, year: 2009

  3. 45S5 bioglass: modifications in the structural arrangement to meet specific needs in bone regeneration

    International Nuclear Information System (INIS)

    Silva, A.C.; Braga, J.F.C.; Aparecida, A.H.

    2011-01-01

    After surgical implantation the osteoinductivity property, observed in bioactive materials, is mainly due to the formation of calcium phosphate on these materials surface when in body fluids contact. The dissolution and diffusion phenomena in bioglass are result of it's structural arrangement and govern the osteoinductivity property. In structural arrangement of bioglass, silica segments are linked by phosphate groups, defining the distance between the vitreous network segments and thereby influence of cations diffusion rate through the network and the dissolution rate. Thus, the induced changes in arrangement of phosphate groups can control the intensity of material osteoinductivity in order to fit bone regeneration requirements. In this study, P_2O_5 nanoclusters formation were induced in bioglass 45S5 network structure. The bioactive glasses were prepared by melting at 1500°C in platinum crucibles and annealed between 2 and 24 h at 500°C. The characterization was performed using the following techniques, X-ray diffraction (XRD), Infrared spectroscopy (FT-IR) and hydrolytic resistance. In bioglasses 24 hours heat-treated, there was evidence of nanocrystals formation, dissolution rate, significant increase and consequently the property of osteoinductive. The obtained results indicated the potential of development of biomaterials for specific applications in bone regeneration. (author)

  4. Highly porous polymer-derived wollastonite-hydroxycarbonate apatite ceramics for bone regeneration.

    Science.gov (United States)

    Fiocco, L; Li, S; Bernardo, E; Stevens, M M; Jones, J R

    2016-04-12

    A novel strategy was employed to synthesize highly porous wollastonite-hydroxycarbonate apatite ceramic scaffolds for bone regeneration. A commercial liquid preceramic polymer filled with micro-CaCO3 powders was foamed at low temperature (at 350 °C), using the decomposition of a hydrazine additive, and then converted into ceramic by a treatment at 700 °C. Hydroxycarbonate apatite was later developed by a phosphatization treatment of ceramized foams, in a P-rich solution, while wollastonite was obtained by a second firing, at 900 °C. The effectiveness of the method was proven by x-ray diffraction analysis, showing the presence of the two expected crystalline phases. Porosity, interconnect size distribution and mechanical strength were in the range that is thought to be suitable for bone regeneration in non-load bearing sites (compressive strength ≈ 3 MPa, porosity ≈ 90%, modal interconnect diameter ≈ 130-160 μm). In addition, bioactivity and ion release rate were assessed in simulated body fluid (SBF). MC3T3 osteoblast precursor cells were able to colonize the material in vitro through the pore architecture and expressed osteogenic markers.

  5. A short review: Recent advances in electrospinning for bone tissue regeneration

    Directory of Open Access Journals (Sweden)

    Song-Hee Shin

    2012-12-01

    Full Text Available Nanofibrous structures developed by electrospinning technology provide attractive extracellular matrix conditions for the anchorage, migration, and differentiation of tissue cells, including those responsible for the regeneration of hard tissues. Together with the ease of set up and cost-effectiveness, the possibility to produce nanofibers with a wide range of compositions and morphologies is the merit of electrospinning. Significant efforts have exploited the development of bone regenerative nanofibers, which includes tailoring of composite/hybrid compositions that are bone mimicking and the surface functionalization such as mineralization. Moreover, by utilizing bioactive molecules such as adhesive proteins, growth factors, and chemical drugs, in concert with the nanofibrous matrices, it is possible to provide artificial materials with improved cellular responses and therapeutic efficacy. These studies have mainly focused on the regulation of stem cell behaviors for use in regenerative medicine and tissue engineering. While there are some challenges in achieving controllable delivery of bioactive molecules and complex-shaped three-dimensional scaffolds for tissue engineering, the electrospun nanofibrous matrices can still have a beneficial impact in the area of hard-tissue regeneration.

  6. Bone Marrow–Derived Cells Home to and Regenerate Retinal Pigment Epithelium after Injury

    Science.gov (United States)

    Harris, Jeffrey R.; Brown, Gary A. J.; Jorgensen, Marda; Kaushal, Shalesh; Ellis, E. Ann; Grant, Maria B.; Scott, Edward W.

    2013-01-01

    Purpose To determine whether hematopoietic stem and progenitor cells (HSCs/HPCs) can home to and regenerate the retinal pigment epithelium (RPE) after induced injury. Methods Enriched HSCs/HPCs from green fluorescent protein (gfp) transgenic mice were transplanted into irradiated recipient mice to track bone marrow–derived cells. Physical damage was induced by breaching Bruch’s membrane and inducing vascular endothelial growth factor A (VEGFa) expression to promote neovascularization. RPE damage was also induced by sodium iodate injection (40 mg/kg) into wild-type or albino C57Bl/6 mice. Cell morphology, gfp expression, the presence of the Y chromosome, and the presence of melanosomes were used to determine whether the injured RPE was being repaired by the donor bone marrow. Results Injury to the RPE recruits HSC/HPC–derived cells to incorporate into the RPE layer and differentiate into an RPE phenotype. A portion of the HSCs/HPCs adopt RPE morphology, express melanosomes, and integrate into the RPE without cell fusion. Conclusions HSCs/HPCs can migrate to the RPE layer after physical or chemical injury and regenerate a portion of the damaged cell layer. PMID:16639022

  7. Post-irradiation regeneration of early B-lymphocyte precursor cells in mouse bone marrow

    International Nuclear Information System (INIS)

    Park, Y.-H.; Osmond, D.G.

    1989-01-01

    To examine the sequential development of early B-cell precursors in mouse bone marrow, B-lineage cells have been examined during a wave of post-irradiation regeneration. Cell phenotypes have been defined for (i) terminal deoxynucleotidyl transferase (TdT); (ii) B220 glycoprotein, (iii) μ heavy chains in the cytoplasm (cμ) and at the cell surface (sμ). Three populations of μ - cells (TdT + 14.8 - ; TdT + 14.8 + ; TdT - 14.8 + ) have been proposed to be early B-cell precursors which would give rise to cμ + sμ - pre-B cells and to sμ + B lymphocytes. The timing, cell-size shifts and progressive amplification of the waves of regeneration accord with a dynamic model in which the TdT + 14.8 - , TdT + 14.8 + and TdT - 14.8 + cells form three successive stages in B-cell differentiation before the expression of μ chains, presumptively including the stage of μ chain gene rearrangement. In addition, the results provide an experimental system for the enrichment of early B-cell precursors in mouse bone marrow. (author)

  8. Three-Dimensional Printing of Hollow-Struts-Packed Bioceramic Scaffolds for Bone Regeneration.

    Science.gov (United States)

    Luo, Yongxiang; Zhai, Dong; Huan, Zhiguang; Zhu, Haibo; Xia, Lunguo; Chang, Jiang; Wu, Chengtie

    2015-11-04

    Three-dimensional printing technologies have shown distinct advantages to create porous scaffolds with designed macropores for application in bone tissue engineering. However, until now, 3D-printed bioceramic scaffolds only possessing a single type of macropore have been reported. Generally, those scaffolds with a single type of macropore have relatively low porosity and pore surfaces, limited delivery of oxygen and nutrition to surviving cells, and new bone tissue formation in the center of the scaffolds. Therefore, in this work, we present a useful and facile method for preparing hollow-struts-packed (HSP) bioceramic scaffolds with designed macropores and multioriented hollow channels via a modified coaxial 3D printing strategy. The prepared HSP scaffolds combined high porosity and surface area with impressive mechanical strength. The unique hollow-struts structures of bioceramic scaffolds significantly improved cell attachment and proliferation and further promoted formation of new bone tissue in the center of the scaffolds, indicating that HSP ceramic scaffolds can be used for regeneration of large bone defects. In addition, the strategy can be used to prepare other HSP ceramic scaffolds, indicating a universal application for tissue engineering, mechanical engineering, catalysis, and environmental materials.

  9. Synergistic intrafibrillar/extrafibrillar mineralization of collagen scaffolds based on a biomimetic strategy to promote the regeneration of bone defects

    Directory of Open Access Journals (Sweden)

    Wang Y

    2016-05-01

    Full Text Available Yao Wang,1 Ngo Van Manh,1,2 Haorong Wang,1 Xue Zhong,1 Xu Zhang,1 Changyi Li1 1School of Dentistry, Hospital of Stomatology, Tianjin Medical University, Tianjin, People’s Republic of China; 2Thaibinh University of Medicine and Pharmacy, Thaibinh, Vietnam Abstract: The mineralization of collagen scaffolds can improve their mechanical properties and biocompatibility, thereby providing an appropriate microenvironment for bone regeneration. The primary purpose of the present study is to fabricate a synergistically intra- and extrafibrillar mineralized collagen scaffold, which has many advantages in terms of biocompatibility, biomechanical properties, and further osteogenic potential. In this study, mineralized collagen scaffolds were fabricated using a traditional mineralization method (ie, immersed in simulated body fluid as a control group and using a biomimetic method based on the polymer-induced liquid precursor process as an experimental group. In the polymer-induced liquid precursor process, a negatively charged polymer, carboxymethyl chitosan (CMC, was used to stabilize amorphous calcium phosphate (ACP to form nanocomplexes of CMC/ACP. Collagen scaffolds mineralized based on the polymer-induced liquid precursor process were in gel form such that nanocomplexes of CMC/ACP can easily be drawn into the interstices of the collagen fibrils. Scanning electron microscopy and transmission electron microscopy were used to examine the porous micromorphology and synergistic mineralization pattern of the collagen scaffolds. Compared with simulated body fluid, nanocomplexes of CMC/ACP significantly increased the modulus of the collagen scaffolds. The results of in vitro experiments showed that the cell count and differentiated degrees in the experimental group were higher than those in the control group. Histological staining and micro-computed tomography showed that the amount of new bone regenerated in the experimental group was larger than that in the

  10. Human Urine Derived Stem Cells in Combination with β-TCP Can Be Applied for Bone Regeneration.

    Directory of Open Access Journals (Sweden)

    Junjie Guan

    Full Text Available Bone tissue engineering requires highly proliferative stem cells that are easy to isolate. Human urine stem cells (USCs are abundant and can be easily harvested without using an invasive procedure. In addition, in our previous studies, USCs have been proved to be able to differentiate into osteoblasts, chondrocytes, and adipocytes. Therefore, USCs may have great potential and advantages to be applied as a cell source for tissue engineering. However, there are no published studies that describe the interactions between USCs and biomaterials and applications of USCs for bone tissue engineering. Therefore, the objective of the present study was to evaluate the interactions between USCs with a typical bone tissue engineering scaffold, beta-Tricalcium Phosphate (β-TCP, and to determine whether the USCs seeded onto β-TCP scaffold can promote bone regeneration in a segmental femoral defect of rats. Primary USCs were isolated from urine and seeded on β-TCP scaffolds. Results showed that USCs remained viable and proliferated within β-TCP. The osteogenic differentiation of USCs within the scaffolds was demonstrated by increased alkaline phosphatase activity and calcium content. Furthermore, β-TCP with adherent USCs (USCs/β-TCP were implanted in a 6-mm critical size femoral defect of rats for 12 weeks. Bone regeneration was determined using X-ray, micro-CT, and histologic analyses. Results further demonstrated that USCs in the scaffolds could enhance new bone formation, which spanned bone defects in 5 out of 11 rats while β-TCP scaffold alone induced modest bone formation. The current study indicated that the USCs can be used as a cell source for bone tissue engineering as they are compatible with bone tissue engineering scaffolds and can stimulate the regeneration of bone in a critical size bone defect.

  11. A bioactive metallurgical grade porous silicon-polytetrafluoroethylene sheet for guided bone regeneration applications.

    Science.gov (United States)

    Chadwick, E G; Clarkin, O M; Raghavendra, R; Tanner, D A

    2014-01-01

    The properties of porous silicon make it a promising material for a host of applications including drug delivery, molecular and cell-based biosensing, and tissue engineering. Porous silicon has previously shown its potential for the controlled release of pharmacological agents and in assisting bone healing. Hydroxyapatite, the principle constituent of bone, allows osteointegration in vivo, due to its chemical and physical similarities to bone. Synthetic hydroxyapatite is currently applied as a surface coating to medical devices and prosthetics, encouraging bone in-growth at their surface and improving osseointegration. This paper examines the potential for the use of an economically produced porous silicon particulate-polytetrafluoroethylene sheet for use as a guided bone regeneration device in periodontal and orthopaedic applications. The particulate sheet is comprised of a series of microparticles in a polytetrafluoroethylene matrix and is shown to produce a stable hydroxyapatite on its surface under simulated physiological conditions. The microstructure of the material is examined both before and after simulated body fluid experiments for a period of 1, 7, 14 and 30 days using Scanning Electron Microscopy. The composition is examined using a combination of Energy Dispersive X-ray Spectroscopy, Thin film X-ray diffraction, Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy and the uptake/release of constituents at the fluid-solid interface is explored using Inductively Coupled Plasma-Optical Emission Spectroscopy. Microstructural and compositional analysis reveals progressive growth of crystalline, 'bone-like' apatite on the surface of the material, indicating the likelihood of close bony apposition in vivo.

  12. Effects of a chitosan membrane coated with polylactic and polyglycolic acid on bone regeneration in a rat calvarial defect

    International Nuclear Information System (INIS)

    Jung, Ui-Won; Song, Kun-Young; Kim, Chang-Sung; Lee, Yong-Keun; Cho, Kyoo-Sung; Kim, Chong-Kwan; Choi, Seong-Ho

    2007-01-01

    The purpose of this study was to evaluate the effects of a chitosan membrane coated with polylactic and polyglycolic acid (PLGA) on bone regeneration in a rat calvarial defect. Surgical implantation of chitosan membranes resulted in enhanced local bone formation at both 2 and 8 weeks. In conclusion, the chitosan membrane coated with PLGA had a significant potential to induce bone formation in the rat calvarial defect model. Within the selected PLGA dose range and observation intervals, there appeared to be no meaningful differences in bone formation

  13. Siliceous mesostructured cellular foams/ poly(3-hydroxybutyrate-co-3-hydroxyhexanoate composite biomaterials for bone regeneration

    Directory of Open Access Journals (Sweden)

    Yang S

    2014-10-01

    Full Text Available Shengbing Yang,1,* Shuogui Xu,2,* Panyu Zhou,2,* Jing Wang,3 Honglue Tan,4 Yang Liu,5 TingTing Tang,4 ChangSheng Liu1,3,5 1The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Changhai Hospital, Department of Orthopedics, the Second Military Medical University, Shanghai, People’s Republic of China; 3Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China; 4Shanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine China, Shanghai, People’s Republic of China; 5Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China *These authors contributed equally to this workAbstract: Osteoinductive and biodegradable composite biomaterials for bone regeneration were prepared by combining poly(3-hydroxybutyrate-co-3-hydroxyhexanoate (PHBHHx with siliceous mesostructured cellular foams (SMC, using the porogen leaching method. Surface hydrophilicity, morphology, and recombinant human bone morphogenetic protein 2 adsorption/release behavior of the SMC/PHBHHx scaffolds were analyzed. Results of scanning electron microscopy indicated that the SMC was uniformly dispersed in the PHBHHx scaffolds, and SMC modification scaffolds have an interconnected porous architecture with pore sizes ranging from 200 to 400 µm. The measurements of the water contact angles suggested that the incorporation of SMC into PHBHHx improves the hydrophilicity of the composite. In vitro studies with simulated body fluid show great improvements to bioactivity and biodegradability versus pure PHBHHx scaffolds. Cell adhesion and cell proliferation on the scaffolds was also evaluated, and the new

  14. Tyrosine-derived polycarbonate scaffolds for bone regeneration in a rabbit radius critical-size defect model

    International Nuclear Information System (INIS)

    Kim, Jinku; McBride, Sean; Donovan, Amy; Hollinger, Jeffrey O; Darr, Aniq; Magno, Maria Hanshella R

    2015-01-01

    The aim of the study was to determine bone regeneration in a rabbit radius critical-size defect (CSD) model using a specific polymer composition (E1001(1k)) from a library of tyrosine-derived polycarbonate scaffolds coated with a calcium phosphate (CP) formulation (E1001(1k) + CP) supplemented with recombinant human bone morphogenetic protein-2 (rhBMP-2). Specific doses of rhBMP-2 (0, 17, and 35 μg/scaffold) were used. E1001(1k) + CP scaffolds were implanted in unilateral segmental defects (15 mm length) in the radial diaphyses of New Zealand White rabbits. At 4 and 8 weeks post-implantation, bone regeneration was determined using micro-computed tomography (µCT), histology, and histomorphometry. The quantitative outcome data suggest that E1001(1k) + CP scaffolds with rhBMP-2 were biocompatible and promoted bone regeneration in segmental bone defects. Histological examination of the implant sites showed that scaffolds made of E1001(1k) + CP did not elicit adverse cellular or tissue responses throughout test periods up to 8 weeks. Noteworthy is that the incorporation of a very small amount of rhBMP-2 into the scaffolds (as low as 17 μg/defect site) promoted significant bone regeneration compared to scaffolds consisting of E1001(1k) + CP alone. This finding indicates that E1001(1k) + CP may be an effective platform for bone regeneration in a critical size rabbit radius segmental defect model, requiring only a minimal dose of rhBMP-2. (paper)

  15. 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.

  16. 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.

  17. Utilization of d-PTFE Barriers for Post-Extraction Bone Regeneration in Preparation for Dental Implants.

    Science.gov (United States)

    Greenstein, Gary; Carpentieri, Joseph R

    2015-01-01

    Guided bone regeneration (GBR) can be used to restore a defective alveolar ridge after extractions before or in combination with implant placement. It may also be employed after extractions to reduce crestal bone resorption and maximize bone fill of sockets. Resorbable or nonresorbable barriers (eg, expanded polytetrafluoroethylene [e-PTFE]) can be used when performing GBR procedures, but they need to be completely submerged to attain optimal results. Dense polytetrafluoroethylene (d-PTFE) is a type of nonresorbable barrier that circumvents the necessity to attain primary closure after placement of bone grafts, thereby reducing patient morbidity. This article addresses topics pertaining to d-PTFE utilization, including characteristics and advantages of d-PTFE barriers, time needed for osteoid tissue to become impervious to penetration by flap connective tissue, relevant clinical studies, and limitations of available data. Clinical photographs and radiographs of successfully treated cases are presented to illustrate the efficacy of d-PTFE barriers in regenerating defective bony plates after extractions.

  18. Synthesis of bioactive poly(ethylene glycol)/SiO2-CaO-P2O5 hybrids for bone regeneration

    International Nuclear Information System (INIS)

    Liu Wei; Wu Xiaohong; Zhan Hongbing; Yan Fuhua

    2012-01-01

    Poly(ethylene glycol) (PEG)/SiO 2 -CaO-P 2 O 5 hybrid xerogels were prepared using a room temperature sol-gel process. The advantage of this hybrid material over conventional composites is the molecular scale interactions between the bioactive inorganic components and the biodegradable organic components. Since PEG was added into the sol when the hydrolysis of tetraethoxysilane occurred, the molecular chain of PEG was penetrated into the SiO 2 networks to form a semi-IPN structure. Due to the excellent biocompatibility and aqueous solubility of PEG molecules, as well as the bioactivity of the inorganic components, the biological and mechanical properties of this hybrid xerogel exhibit great potential for bone regeneration applications. The formation of hydroxyapatite was observed when the xerogel was immersed into simulated body fluid, demonstrating good bioactivity of the hybrid. The cell toxicity test also demonstrated that the hybrid material is suitable for the proliferation of MC3T3-E1 cells. Thus, the PEG/SiO 2 -CaO-P 2 O 5 hybrid xerogel has great potential to meet the demands of bone regeneration materials. - Highlights: ► PEG was penetrated into the SiO 2 networks to form a semi-IPN structure. ► This hybrid xerogel exhibit great potential for bone regeneration applications. ► SEM micrographs confirm the bioactivity of the samples.

  19. 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.

  20. The effectiveness of the use of xenogeneic bone blocks mixed with autologous Concentrated Growth Factors (CGF in bone regeneration techniques: a case series

    Directory of Open Access Journals (Sweden)

    E. Gheno

    2014-06-01

    Full Text Available Aim: Different types of biomaterials and surgical techniques are currently used for the augmentation of atrophic ridges in view of implant supported restorations. The aim of this study was to clinically and histologically evaluate the combination of Concentrated Growth Factors (CGF and xenogeneic bone in vertical and/or horizontal ridge augmentation. Materials and methods: Seven patients (3 males and 4 females, who required oral implant and ridge augmentation surgery, were selected: 3 implants were placed during the surgery and 4 implants were inserted 4 months later, in order to allow complete graft integration. All implants were loaded after a 4-month healing time. The following parameters were assessed: a the capability of CGF to permeate the bone scaffold; b the degree of bone regeneration; c the clinical success rate. Results: The results obtained showed that: a with the used medical device porous bone scaffolds can be effectively permeated by the CGF; b the permeated grafting material resulted in effective bone regeneration, as confirmed by histomorphometric analysis; c all implants were successfully in function at the 12 months follow-up. Conclusion: This technique can be safely performed in the dental office under local anesthesia, so it can be considered a viable option in bone regeneration surgery.

  1. Evaluation of the effect of a gamma irradiated DBM-pluronic F127 composite on bone regeneration in Wistar rat.

    Directory of Open Access Journals (Sweden)

    Tamer Al Kayal

    Full Text Available Demineralized bone matrix (DBM is widely used for bone regeneration. Since DBM is prepared in powder form its handling properties are not optimal and limit the clinical use of this material. Various synthetic and biological carriers have been used to enhance the DBM handling. In this study we evaluated the effect of gamma irradiation on the physical-chemical properties of Pluronic and on bone morphogenetic proteins (BMPs amount in DBM samples. In vivo studies were carried out to investigate the effect on bone regeneration of a gamma irradiated DBM-Pluronic F127 (DBM-PF127 composite implanted in the femur of rats. Gamma irradiation effects (25 kGy on physical-chemical properties of Pluronic F127 were investigated by rheological and infrared analysis. The BMP-2/BMP-7 amount after DBM irradiation was evaluated by ELISA. Bone regeneration capacity of DBM-PF127 containing 40% (w/w of DBM was investigated in transcortical holes created in the femoral diaphysis of Wistar rat. Bone porosity, repaired bone volume and tissue organization were evaluated at 15, 30 and 90 days by Micro-CT and histological analysis. The results showed that gamma irradiation did not induce significant modification on physical-chemical properties of Pluronic, while a decrease in BMP-2/BMP-7 amount was evidenced in sterilized DBM. Micro-CT and histological evaluation at day 15 post-implantation revealed an interconnected trabeculae network in medullar cavity and cellular infiltration and vascularization of DBM-PF127 residue. In contrast a large rate of not connected trabeculae was observed in Pluronic filled and unfilled defects. At 30 and 90 days the DBM-PF127 samples shown comparable results in term of density and thickness of the new formed tissue respect to unfilled defect. In conclusion a gamma irradiated DBM-PF127 composite, although it may have undergone a significant decrease in the concentration of BMPs, was able to maintains bone regeneration capability.

  2. Evaluation of the effects of platelet-rich fibrin on bone regeneration in diabetic rabbits.

    Science.gov (United States)

    Durmuşlar, M Cenk; Ballı, Umut; Öngöz Dede, Figen; Bozkurt Doğan, Şeyma; Mısır, A Ferhat; Barış, Emre; Yılmaz, Zehra; Çelik, H Hamdi; Vatansever, Alper

    2016-02-01

    This study aimed to investigate the effect of platelet-rich fibrin on bone regeneration in critical size defects in the calvaria of diabetic rabbits. In total, 40 male New Zealand rabbits, were divided into two groups a non-diabetic control group (Group A) and a diabetic experimental group (Group B). Two bicortical circular defects 15 mm in diameter were created in the parietal bone of each animal. Each group was further divided into four groups: subgroup E, the defect was left empty; subgroup PRF, the defects were filled only with PRF; subgroup AB, the defects were filled with autogenous bone; subgroup AB + PRF, the defects were filled with autogenous bone combined with PRF. The animals sacrificed at 4 weeks and 8 weeks. Bone formation was assessed by micro-computed tomography (micro-CT) scanning, histological and histomorphometric analysis. The total percent of new bone was the lowest in group A-E (6.77 ± 0.21 at 4 weeks, 11.01 ± 0.37 at 8 weeks) and highest in group A-AB + PRF (21.66 ± 0.91 at 4 weeks, 37.46 ± 1.25 at 8 weeks; p < 0.05). The mean percent of new bone was greatest in group B-AB + PRF at 4 and 8 weeks (16.87 ± 0.92, 29.59 ± 1.09, respectively) and lowest in group B-E (5.83 ± 0.09 at 4 weeks, 7.36 ± 1.02 at 8 weeks). This study, despite its limitations, showed that PRF can be used safely and that PRF induced bone healing in diabetic rabbits. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. All rights reserved.

  3. Influence of quercetin and nanohydroxyapatite modifications of decellularized goat-lung scaffold for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Sweta K. [Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, 247667 (India); Kumar, Ritesh [Center for Computational Biology, University of Kansas, Kansas 66045 (United States); Mishra, Narayan C., E-mail: mishrawise@gmail.com [Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, 247667 (India)

    2017-02-01

    In the present study, goat-lung scaffold was fabricated by decellularization of lung tissue and verified for complete cell removal by DNA quantification, DAPI and H&E staining. The scaffold was then modified by crosslinking with quercetin and nanohydroxyapatite (nHAp), and characterized to evaluate the suitability of quercetin-crosslinked nHAp-modified scaffold for regeneration of bone tissue. The crosslinking chemistry between quercetin and decellularized scaffold was established theoretically by AutoDock Vina program (in silico docking study), which predicted multiple intermolecular hydrogen bonding interactions between quercetin and decellularized scaffold, and FTIR spectroscopy analysis also proved the same. From MTT assay and SEM studies, it was found that the quercetin-crosslinked nHAp-modified decellularized scaffold encouraged better growth and proliferation of bone-marrow derived mesenchymal stem cells (BMMSCs) in comparison to unmodified decellularized scaffold, quercetin-crosslinked decellularized scaffold and nHAp-modified decellularized scaffold. Alkaline Phosphatase (ALP) assay results showed highest expression of ALP over quercetin-crosslinked nHAp-modified scaffold among all the tested scaffolds (unmodified decellularized scaffold, quercetin-crosslinked decellularized scaffold and nHAp-modified decellularized scaffold) − indicating that quercetin and nHAp is very much efficient in stimulating the differentiation of BMMSCs into osteoblast cells. Alizarin red test quantified in vitro mineralization (calcium deposits), and increased expression of alizarin red over quercetin-crosslinked nHAp-modified scaffold indicating better stimulation of osteogenesis in BMMSCs. The above findings suggest that quercetin-crosslinked nHAp-modified decellularized goat-lung scaffold provides biomimetic bone-like microenvironment for BMMSCs to differentiate into osteoblast and could be applied as a potential promising biomaterial for bone regeneration. - Highlights:

  4. Diatomite reinforced chitosan composite membrane as potential scaffold for guided bone regeneration.

    Science.gov (United States)

    Tamburaci, Sedef; Tihminlioglu, Funda

    2017-11-01

    In this study, natural silica source, diatomite, incorporated novel chitosan based composite membranes were fabricated and characterized for bone tissue engineering applications as possible bone regeneration membrane. The effect of diatomite loading on the mechanical, morphological, chemical, thermal and surface properties, wettability and in vitro cytotoxicity and cell proliferation on of composite membranes were investigated and observed by tensile test, atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), protein adsorption assay, air/water contact angle analysis and WST-1 respectively. Swelling studies were also performed by water absorption capacity determination. Results showed that incorporation of diatomite to the chitosan matrix increased the surface roughness, swelling capacity and tensile modulus of membranes. An increase of about 52% in Young's modulus was achieved for 10wt% diatomite composite membranes compared with chitosan membranes. High cell viability results were obtained with indirect extraction method. Besides, in vitro cell proliferation and ALP activity results showed that diatom incorporation significantly increased the ALP activity of Saos-2 cells cultured on chitosan membranes. The novel composite membranes prepared in the present study with tunable properties can be considered as a potential candidate as a scaffold in view of its enhanced physical & chemical properties as well as biological activities for bone tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Chitosan(PEO)/silica hybrid nanofibers as a potential biomaterial for bone regeneration.

    Science.gov (United States)

    Toskas, Georgios; Cherif, Chokri; Hund, Rolf-Dieter; Laourine, Ezzeddine; Mahltig, Boris; Fahmi, Amir; Heinemann, Christiane; Hanke, Thomas

    2013-05-15

    New hybrid nanofibers prepared with chitosan (CTS), containing a total amount of polyethylene oxide (PEO) down to 3.6wt.%, and silica precursors were produced by electrospinning. The solution of modified sol-gel particles contained tetraethoxysilane (TEOS) and the organosilane 3-glycidyloxypropyltriethoxysilane (GPTEOS). This is rending stable solution toward gelation and contributing in covalent bonding with chitosan. The fibers encompass advantages of biocompatible polymer template silicate components to form self-assembled core-shell structure of the polymer CTS/PEO encapsulated by the silica. Potential applicability of this hybrid material to bone tissue engineering was studied examining its cellular compatibility and bioactivity. The nanofiber matrices were proved cytocompatible when seeded with bone-forming 7F2-cells, promoting attachment and proliferation over 7 days. These found to enhance a fast apatite formation by incorporation of Ca(2+) ions and subsequent immersion in modified simulated body fluid (m-SBF). The tunable properties of these hybrid nanofibers can find applications as active biomaterials in bone repair and regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Biomineralization of Fucoidan-Peptide Blends and Their Potential Applications in Bone Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Harrison T. Pajovich

    2017-09-01

    Full Text Available Fucoidan (Fuc, a natural polysaccharide derived from brown seaweed algae, and gelatin (Gel were conjugated to form a template for preparation of biomimetic scaffolds for potential applications in bone tissue regeneration. To the Fuc–Gel we then incorporated the peptide sequence MTNYDEAAMAIASLN (MTN derived from the E-F hand domain, known for its calcium binding properties. To mimic the components of the extracellular matrix of bone tissue, the Fuc–Gel–MTN assemblies were incubated in simulated body fluid (SBF to induce biomineralization, resulting in the formation of β-tricalcium phosphate, and hydroxyapatite (HAp. The formed Fuc–Gel–MTN–beta–TCP/HAP scaffolds were found to display an average Young’s Modulus value of 0.32 GPa (n = 5 with an average surface roughness of 91 nm. Rheological studies show that the biomineralized scaffold exhibited higher storage and loss modulus compared to the composites formed before biomineralization. Thermal phase changes were studied through DSC and TGA analysis. XRD and EDS analyses indicated a biphasic mixture of β-tricalcium phosphate and hydroxyapatite and the composition of the scaffold. The scaffold promoted cell proliferation, differentiation and displayed actin stress fibers indicating the formation of cell-scaffold matrices in the presence of MT3C3-E1 mouse preosteoblasts. Osteogenesis and mineralization were found to increase with Fuc–Gel–MTN–beta–TCP/HAP scaffolds. Thus, we have developed a novel scaffold for possible applications in bone tissue engineering.

  7. Stem cell property of postmigratory cranial neural crest cells and their utility in alveolar bone regeneration and tooth development.

    Science.gov (United States)

    Chung, Il-Hyuk; Yamaza, Takayoshi; Zhao, Hu; Choung, Pill-Hoon; Shi, Songtao; Chai, Yang

    2009-04-01

    The vertebrate neural crest is a multipotent cell population that gives rise to a variety of different cell types. We have discovered that postmigratory cranial neural crest cells (CNCCs) maintain mesenchymal stem cell characteristics and show potential utility for the regeneration of craniofacial structures. We are able to induce the osteogenic differentiation of postmigratory CNCCs, and this differentiation is regulated by bone morphogenetic protein (BMP) and transforming growth factor-beta signaling pathways. After transplantation into a host animal, postmigratory CNCCs form bone matrix. CNCC-formed bones are distinct from bones regenerated by bone marrow mesenchymal stem cells. In addition, CNCCs support tooth germ survival via BMP signaling in our CNCC-tooth germ cotransplantation system. Thus, we conclude that postmigratory CNCCs preserve stem cell features, contribute to craniofacial bone formation, and play a fundamental role in supporting tooth organ development. These findings reveal a novel function for postmigratory CNCCs in organ development, and demonstrate the utility of these CNCCs in regenerating craniofacial structures.

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

    Science.gov (United States)

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

    2009-10-01

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

  9. Production of Composite Scaffold Containing Silk Fibroin, Chitosan, and Gelatin for 3D Cell Culture and Bone Tissue Regeneration.

    Science.gov (United States)

    Li, Jianqing; Wang, Qiuke; Gu, Yebo; Zhu, Yu; Chen, Liang; Chen, Yunfeng

    2017-11-08

    BACKGROUND Bone tissue engineering, a powerful tool to treat bone defects, is highly dependent on use of scaffolds. Both silk fibroin (SF) and chitosan (Cs) are biocompatible and actively studied for reconstruction of tissue engineering. Gelatin (Gel) is also widely applied in the biomedical field due to its low antigenicity and physicochemical stability. MATERIAL AND METHODS In this study, 4 different types of scaffolds were constructed - SF, SF/Cs, SF/Gel, and SF/Cs/Gel - and we compared their physical and chemical properties as well as biological characterization of these scaffolds to determine the most suitable scaffold for use in bone regeneration. First, these scaffolds were produced via chemical cross-linking method and freeze-drying technique. Next, the characterization of internal structure was studied using scanning electron microscopy and the porosity was evaluated by liquid displacement method. Then, we compared physicochemical properties such as water absorption rate and degradation property. Finally, MC3T3-E1 cells were inoculated on the scaffolds to study the biocompatibility and osteogenesis of the three-dimensional (3D) scaffolds in vitro. RESULTS The composite scaffold formed by all 3 components was the best for use in bone regeneration. CONCLUSIONS We conclude that the best scaffold among the 4 studied for MC3T3-E1 cells is our SF/Cs/Gel scaffold, suggesting a new choice for bone regeneration that can be used to treat bone defects or fractures in clinical practice.

  10. The process of urban regeneration in context of information society

    Directory of Open Access Journals (Sweden)

    Bazik Dragana

    2006-01-01

    Full Text Available This paper deals with the concept of innovation of the urban regeneration process in context of transformations which are generated by information-communication technologies. From one aspect, Serbia has an exceptional human potential presented in number of 13,000 graduates each year, or in share of 42% of population who speaks English, which is the largest among all Eastern and Central European countries. This forms a basis for formulation of strategies of information society development in Serbia as well as for economic adjustments based upon knowledge, and for tracing the way to future knowledge society, i.e. eEurope 2020. On the other hand, we are witnessing an intensive development of huge complexes of mega and hypermarkets as a present dominant way for our city spaces' regeneration. At the same time, experiences from some other locations point to the deterioration of cities' urban identity as a consequence of the global capital infiltration and of development within an urban tissue of a huge complex of multi-national companies. Aiming to overcome the mistakes portrayed by international experience, as well as potential oversights that may occur because of routine and mismatch between certain phases of the sustainable development process, this paper makes an emphasis on the importance of an integral evaluation of the information society development trends and the spatial aspects of urban regeneration. It is essential to adjust devastated urban spaces as artifacts of one technological era to the actual information era with indication of future digital knowledge era, i.e. to plan, design and develop *according to new technological requirements and possibilities for new working places and new quality of living.

  11. Influence of titanium implant surface characteristics on bone regeneration in dehiscence-type defects: an experimental study in dogs.

    Science.gov (United States)

    Schwarz, Frank; Sager, Martin; Kadelka, Ines; Ferrari, Daniel; Becker, Jürgen

    2010-05-01

    The aim of the present study was to compare bone regeneration in dehiscence-type defects at titanium implants with chemically modified sandblasted/acid-etched (modSLA) or dual acid-etched surfaces with a calcium phosphate nanometre particle modification (DCD/CaP). Buccal dehiscence-type defects were surgically created following implant site preparation in both the upper and the lower jaws of 12 fox hounds. Both types of implants were randomly allocated in a split-mouth design and left to heal in a submerged position for 2 and 8 weeks. Dissected blocks were processed for histomorphometrical analysis [e.g. new bone height (NBH), percentage of bone-to-implant contact (BIC), area of new bone fill (BF), and area of mineralized tissue (MT) within BF]. At 2 and 8 weeks, both groups revealed comparable mean BF (2.3+/-0.6 to 2.5+/-0.6 mm(2)versus 2.0+/-0.6 to 1.4+/-0.5 mm(2)) and MT (31.1+/-14.3-83.2+/-8.2%versus 38.9+/-15.9-84.4+/-6.3%) values. However, modSLA implants revealed significantly higher mean NBH (2.4+/-0.8 to 3.6+/-0.3 mm versus 0.9+/-0.8 to 1.8+/-1.4 mm) and BIC (53.3+/-11.3-79.5+/-6.6%versus 19.3+/-16.4-47.2+/-30.7%) values than DCD/CaP implants. ModSLA implants may have a higher potential to support osseointegration in dehiscence-type defects than DCD/CaP implants.

  12. 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.

  13. 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.

  14. Direct metal laser sintering (DMLS) of a customized titanium mesh for prosthetically guided bone regeneration of atrophic maxillary arches.

    Science.gov (United States)

    Ciocca, L; Fantini, M; De Crescenzio, F; Corinaldesi, G; Scotti, R

    2011-11-01

    This study describes a protocol for the direct manufacturing of a customized titanium mesh using CAD-CAM procedures and rapid prototyping to augment maxillary bone and minimize surgery when severe atrophy or post-oncological deformities are present. Titanium mesh and particulate autogenous plus bovine demineralised bone were planned for patient rehabilitation. Bone augmentation planning was performed using the pre-op CT data set in relation to the prosthetic demands, minimizing the bone volume to augment at the minimum necessary for implants. The containment mesh design was used to prototype the 0.6 mm thickness customized titanium mesh, by direct metal laser sintering. The levels of regenerated bone were calculated using the post-op CT data set, through comparison with the pre-op CT data set. The mean vertical height difference of the crestal bone was 2.57 mm, while the mean buccal-palatal dimension of thickness difference was 3.41 mm. All planned implants were positioned after an 8 month healing period using two-step implant surgery, and finally restored with a partial fixed prosthesis. We present a viable and reproducible method to determine the correct bone augmentation prior to implant placement and CAD-CAM to produce a customized direct laser-sintered titanium mesh that can be used for bone regeneration.

  15. Secretomes from bone marrow-derived mesenchymal stromal cells enhance periodontal tissue regeneration.

    Science.gov (United States)

    Kawai, Takamasa; Katagiri, Wataru; Osugi, Masashi; Sugimura, Yukiko; Hibi, Hideharu; Ueda, Minoru

    2015-04-01

    Periodontal tissue regeneration with the use of mesenchymal stromal cells (MSCs) has been regarded as a future cell-based therapy. However, low survival rates and the potential tumorigenicity of implanted MSCs could undermine the efficacy of cell-based therapy. The use of conditioned media from MSCs (MSC-CM) may be a feasible approach to overcome these limitations. The aim of this study was to confirm the effect of MSC-CM on periodontal regeneration. MSC-CM were collected during their cultivation. The concentrations of the growth factors in MSC-CM were measured with the use of enzyme-linked immunoassay. Rat MSCs (rMSCs) and human umbilical vein endothelial cells cultured in MSC-CM were assessed on wound-healing and angiogenesis. The expressions of osteogenetic- and angiogenic-related genes of rMSCs cultured in MSC-CM were quantified by means of real-time reverse transcriptase-polymerase chain reaction analysis. In vivo, periodontal defects were prepared in the rat models and the collagen sponges with MSC-CM were implanted. MSC-CM includes insulin-like growth factor-1, vascular endothelial growth factor, transforming growth factor-β1 and hepatocyte growth factor. In vitro, wound-healing and angiogenesis increased significantly in MSC-CM. The levels of expression of osteogenetic- and angiogenic-related genes were significantly upregulated in rMSCs cultured with MSC-CM. In vivo, in the MSC-CM group, 2 weeks after implantation, immunohistochemical analysis showed several CD31-, CD105-or FLK-1-positive cells occurring frequently. At 4 weeks after implantation, regenerated periodontal tissue was observed in MSC-CM groups. The use of MSC-CM may be an alternative therapy for periodontal tissue regeneration because several cytokines included in MSC-CM will contribute to many processes of complicated periodontal tissue regeneration. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  16. Bone regeneration in experimental animals using calcium phosphate cement combined with platelet growth factors and human growth hormone.

    Science.gov (United States)

    Emilov-Velev, K; Clemente-de-Arriba, C; Alobera-García, M Á; Moreno-Sansalvador, E M; Campo-Loarte, J

    2015-01-01

    Many substances (growth factors and hormones) have osteoinduction properties and when added to some osteoconduction biomaterial they accelerate bone neoformation properties. The materials included 15 New Zealand rabbits, calcium phosphate cement (Calcibon(®)), human growth hormone (GH), and plasma rich in platelets (PRP). Each animal was operated on in both proximal tibias and a critical size bone defect of 6mm of diameter was made. The animals were separated into the following study groups: Control (regeneration only by Calcibon®), PRP (regeneration by Calcibon® and PRP), GH (regeneration by Calcibon® and GH). All the animals were sacrificed at 28 days. An evaluation was made of the appearance of the proximal extreme of rabbit tibiae in all the animals, and to check the filling of the critical size defect. A histological assessment was made of the tissue response, the presence of new bone formation, and the appearance of the biomaterial. Morphometry was performed using the MIP 45 image analyser. ANOVA statistical analysis was performed using the Statgraphics software application. The macroscopic appearance of the critical defect was better in the PRP and the GH group than in the control group. Histologically greater new bone formation was found in the PRP and GH groups. No statistically significant differences were detected in the morphometric study between bone formation observed in the PRP group and the control group. Significant differences in increased bone formation were found in the GH group (p=0.03) compared to the other two groups. GH facilitates bone regeneration in critical defects filled with calcium phosphate cement in the time period studied in New Zealand rabbits. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  17. Sequentially-crosslinked biomimetic bioactive glass/gelatin methacryloyl composites hydrogels for bone regeneration.

    Science.gov (United States)

    Zheng, Jiafu; Zhao, Fujian; Zhang, Wen; Mo, Yunfei; Zeng, Lei; Li, Xian; Chen, Xiaofeng

    2018-08-01

    In recent years, gelatin-based composites hydrogels have been intensively investigated because of their inherent bioactivity, biocompatibility and biodegradability. Herein, we fabricated photocrosslinkable biomimetic composites hydrogels from bioactive glass (BG) and gelatin methacryloyl (GelMA) by a sequential physical and chemical crosslinking (gelation + UV) approach. The results showed that the compressive modulus of composites hydrogels increased significantly through the sequential crosslinking approach. The addition of BG resulted in a significant increase in physiological stability and apatite-forming ability. In vitro data indicated that BG/GelMA composites hydrogels promoted cell attachment, proliferation and differentiation. Overall, the BG/GelMA composites hydrogels combined the advantages of good biocompatibility and bioactivity, and had potential applications in bone regeneration. Copyright © 2018. Published by Elsevier B.V.

  18. A conceptually new type of bio-hybrid scaffold for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Tampieri, A; Landi, E; Valentini, F; Sandri, M; D' Alessandro, T [ISTEC-CNR, Institute of Science and Technology for Ceramics-National Research Council, via Granarolo, 64-48018 Faenza (RA) (Italy); Dediu, V [ISMN-CNR, Institute of Nanostructured Materials-National Research Council, via P Gobetti, 101-40135 Bologna (Italy); Marcacci, M, E-mail: elena.landi@istec.cnr.it [Istituti Ortopedici Rizzoli, Laboratorio di Biomeccanica, Via di Barbiano, 1/10-40136 Bologna (Italy)

    2011-01-07

    Magnetic bio-hybrid porous scaffolds have been synthesized, nucleating nano-apatite in situ on self-assembling collagen, in the presence of magnetite nano-particles. The magnetic phase acted as a sort of cross-linking agent for the collagen, inducing a chemico-physical-mechanical stabilization of the material and allowing us to control the porosity network of the scaffold. Gradients of bio-mineralization and magnetization were also developed for osteochondral application. The good potentiality of the material as a biomedical device, able to offer assistance to bone regeneration through scaffold reloading with specific factors guided by an external magnetic field, has been preliminarily investigated. Up to now the proof of this concept has been realized through in vitro assessments.

  19. Trans-differentiation via Epigenetics: A New Paradigm in the Bone Regeneration.

    Science.gov (United States)

    Cho, Young-Dan; Ryoo, Hyun-Mo

    2018-02-01

    In regenerative medicine, growing cells or tissues in the laboratory is necessary when damaged cells can not heal by themselves. Acquisition of the required cells from the patient's own cells or tissues is an ideal option without additive side effects. In this context, cell reprogramming methods, including the use of induced pluripotent stem cells (iPSCs) and trans-differentiation, have been widely studied in regenerative research. Both approaches have advantages and disadvantages, and the possibility of de-differentiation because of the epigenetic memory of iPSCs has strengthened the need for controlling the epigenetic background for successful cell reprogramming. Therefore, interest in epigenetics has increased in the field of regenerative medicine. Herein, we outline in detail the cell trans-differentiation method using epigenetic modification for bone regeneration in comparison to the use of iPSCs.

  20. Fabrication and characterization of two-layered nanofibrous membrane for guided bone and tissue regeneration application.

    Science.gov (United States)

    Masoudi Rad, Maryam; Nouri Khorasani, Saied; Ghasemi-Mobarakeh, Laleh; Prabhakaran, Molamma P; Foroughi, Mohammad Reza; Kharaziha, Mahshid; Saadatkish, Niloufar; Ramakrishna, Seeram

    2017-11-01

    Membranes used in dentistry act as a barrier to prevent invasion of intruder cells to defected area and obtains spaces that are to be subsequently filled with new bone and provide required bone volume for implant therapy when there is insufficient volume of healthy bone at implant site. In this study a two-layered bioactive membrane were fabricated by electrospinning whereas one layer provides guided bone regeneration (GBR) and fabricated using poly glycerol sebacate (PGS)/polycaprolactone (PCL) and Beta tri-calcium phosphate (β-TCP) (5, 10 and 15%) and another one containing PCL/PGS and chitosan acts as guided tissue regeneration (GTR). The morphology, chemical, physical and mechanical characterizations of the membranes were studied using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), tensile testing, then biodegradability and bioactivity properties were evaluated. In vitro cell culture study was also carried out to investigate proliferation and mineralization of cells on different membranes. Transmission electron microscope (TEM) and SEM results indicated agglomeration of β-TCP nanoparticles in the structure of nanofibers containing 15% β-TCP. Moreover by addition of β-TCP from 5% to 15%, contact angle decreased due to hydrophilicity of nanoparticles and bioactivity was found to increase. Mechanical properties of the membrane increased by incorporation of 5% and 10% of β-TCP in the structure of nanofibers, while addition of 15% of β-TCP was found to deteriorate mechanical properties of nanofibers. Although the presence of 5% and 10% of nanoparticles in the nanofibers increased proliferation of cells on GBR layer, cell proliferation was observed to decrease by addition of 15% β-TCP in the structure of nanofibers which is likely due to agglomeration of nanoparticles in the nanofiber structure. Our overall results revealed PCL/PGS containing 10% β-TCP could be selected as the optimum GBR membrane

  1. MAPLE deposition of polypyrrole-based composite layers for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Paun, Irina Alexandra, E-mail: irina.paun@physics.pub.ro [Faculty of Applied Sciences, University Politehnica of Bucharest, RO-060042 (Romania); National Institute for Laser, Plasma and Radiation Physics, Magurele, Bucharest RO-077125 (Romania); Acasandrei, Adriana Maria [Horia Hulubei National Institute for Physics and Nuclear Engineering IFIN-HH, Magurele, Bucharest RO-077125 (Romania); Luculescu, Catalin Romeo, E-mail: catalin.luculescu@inflpr.ro [National Institute for Laser, Plasma and Radiation Physics, Magurele, Bucharest RO-077125 (Romania); Mustaciosu, Cosmin Catalin [Horia Hulubei National Institute for Physics and Nuclear Engineering IFIN-HH, Magurele, Bucharest RO-077125 (Romania); Ion, Valentin [National Institute for Laser, Plasma and Radiation Physics, Magurele, Bucharest RO-077125 (Romania); Mihailescu, Mona; Vasile, Eugenia [Faculty of Applied Sciences, University Politehnica of Bucharest, RO-060042 (Romania); Dinescu, Maria, E-mail: dinescum@nipne.ro [National Institute for Laser, Plasma and Radiation Physics, Magurele, Bucharest RO-077125 (Romania)

    2015-12-01

    Highlights: • PPy-based composite layers for bone regeneration were produced by MAPLE. • Conductive PPy nanograins were embedded in insulating PLGA and PU matrices. • PLGA was chosen for providing biodegradability and PU for toughness and elasticity. • The layers conductivities reached 10{sup −2} S/cm for PPy loadings of 1:10 weight ratios. • The layers promoted osteoblast viability, proliferation and mineralization. - Abstract: We report on biocompatible, electrically conductive layers of polypyrrole (PPy)-based composites obtained by Matrix Assisted Pulsed Laser Evaporation (MAPLE) for envisioned bone regeneration. In order to preserve the conductivity of the PPy while overcoming its lack of biodegradability and low mechanical resilience, conductive PPy nanograins were embedded in two biocompatible, insulating polymeric matrices, i.e. poly(lactic-co-glycolic)acid (PLGA) and polyurethane (PU). PLGA offers the advantage of full biodegradability into non-toxic products, while PU provides toughness and elasticity. The PPy nanograins formed micro-domains and networks within the PLGA and PU matrices, in a compact spatial arrangement favorable for electrical percolation. The proposed approach allowed us to obtain PPy-based composite layers with biologically meaningful conductivities up to 10{sup −2} S/cm for PPy loadings as low as 1:10 weight ratios. Fluorescent staining and viability assays showed that the MG63 osteoblast-like cells cultured on the PPy-based layers deposited by MAPLE were viable and retained their capacity to proliferate. The performance of the proposed method was demonstrated by quantitative evaluation of the calcium phosphate deposits from the cultured cells, as indicative for cell mineralization. Electrical stimulation using 200 μA currents passing through the PPy-based layers, during a time interval of 4 h, enhanced the osteogenesis in the cultured cells. Despite their lowest conductivity, the PPy/PU layers showed the best

  2. Antibody-Mediated Osseous Regeneration for Bone Tissue Engineering in Canine Segmental Defects

    Directory of Open Access Journals (Sweden)

    A. Khojasteh

    2018-01-01

    Full Text Available Among many applications of therapeutic monoclonal antibodies (mAbs, a unique approach for regenerative medicine has entailed antibody-mediated osseous regeneration (AMOR. In an effort to identify a clinically relevant model of craniofacial defect, the present study investigated the efficacy of mAb specific for bone morphogenetic protein- (BMP- 2 to repair canine segmental mandibular continuity defect model. Accordingly, a 15 mm unilateral segmental defect was created in mandible and fixated with a titanium plate. Anorganic bovine bone mineral with 10% collagen (ABBM-C was functionalized with 25 μg/mL of either chimeric anti-BMP-2 mAb or isotype-matched mAb (negative control. Recombinant human (rh BMP-2 served as positive control. Morphometric analyses were performed on computed tomography (CT and histologic images. Bone densities within healed defect sites at 12 weeks after surgery were 1360.81 ± 10.52 Hounsfield Unit (HU, 1044.27 ± 141.16 HU, and 839.45 ± 179.41 HU, in sites with implanted anti-BMP-2 mAb, rhBMP-2, and isotype mAb groups, respectively. Osteoid bone formation in anti-BMP-2 mAb (42.99% ± 8.67 and rhBMP-2 (48.97% ± 2.96 groups was not significantly different but was higher (p<0.05 than in sites with isotype control mAb (26.8% ± 5.35. In view of the long-term objective of translational application of AMOR in humans, the results of the present study demonstrated the feasibility of AMOR in a large clinically relevant animal model.

  3. 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.

  4. Bone regeneration in osteoporosis by delivery BMP-2 and PRGF from tetronic-alginate composite thermogel.

    Science.gov (United States)

    Segredo-Morales, Elisabet; García-García, Patricia; Reyes, Ricardo; Pérez-Herrero, Edgar; Delgado, Araceli; Évora, Carmen

    2018-05-30

    As the life expectancy of the world population increases, osteoporotic (OP) fracture risk increase. Therefore in the present study a novel injectable thermo-responsive hydrogel loaded with microspheres of 17β-estradiol, microspheres of bone morphogenetic protein-2 (BMP-2) and plasma rich in growth factors (PRGF) was applied locally to regenerate a calvaria critical bone defect in OP female rats. Three systems were characterized: Tetronic® 1307 (T-1307) reinforced with alginate (T-A), T-A with PRGF and T-A-PRGF with microspheres. The addition of the microspheres increased the viscosity but the temperature for the maximum viscosity did not change (22-24 °C). The drugs were released during 6 weeks in one fast phase (three days) followed by a long slow phase. In vivo evaluation was made in non-OP and OP rats treated with T-A, T-A with microspheres of 17β-estradiol (T-A-βE), T-A-βE prepared with PRGF (T-A-PRGF-βE), T-A-βE with microspheres of BMP-2 (T-A-βE-BMP-2) and the combination of the three (T-A-PRGF-βE-BMP). After 12 weeks, histological and histomorphometric analyzes showed a synergic effect due to the addition of BMP-2 to the T-A-βE formulation. The PRGF did not increased the bone repair. The new bone filling the OP defect was less mineralized than in the non-OP groups. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. [Ultrasound scanning of the distraction regenerate in case of multilocus elongation of the fragments in patients with defects of long bones].

    Science.gov (United States)

    Menshikova, T I; Borzunov, D Iu; Dolganova, T I

    2014-01-01

    It was done ultrasound examination of distraction regenerates in patients with defect of bone tissue. The first group included 4 patients who had the size of congenital bone tissue defect 15.8±8.1 cm; the second group (3 patients) included posttraumatic defects with defect size 11.75±3.6 cm; the third group (4 patients) included posttraumatic defects with defect size 11±5.3 cm. It was discovered the particularities of distraction regenerate structural condition in case of low level of reparative osteogenesis. In the first group "ischemic" regenerate was characterized by slow formation of bone trabecules. In the second group "ischemic" regenerate had one or two hypo-echogenic cystic-like formations in the intermediate regenerate area. All patients of the third group had organotypic remodeling of the regenerate according to terms of distraction and fixation.

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

    Science.gov (United States)

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

    2014-02-01

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

  7. Materials and scaffolds in medical 3D printing and bioprinting in the context of bone regeneration.

    Science.gov (United States)

    Heller, Martin; Bauer, Heide-Katharina; Goetze, Elisabeth; Gielisch, Matthias; Ozbolat, Ibrahim T; Moncal, Kazim K; Rizk, Elias; Seitz, Hermann; Gelinsky, Michael; Schröder, Heinz C; Wang, Xiaohong H; Müller, Werner E G; Al-Nawas, Bilal

    The structural and functional repair of lost bone is still one of the biggest challenges in regenerative medicine. In many cases, autologous bone is used for the reconstruction of bone tissue; however, the availability of autologous material is limited, which always means additional stress to the patient. Due to this, more and more frequently various biocompatible materials are being used instead for bone augmentation. In this context, in order to ensure the structural function of the bone, scaffolds are implanted and fixed into the bone defect, depending on the medical indication. Nevertheless, for the surgeon, every individual clinical condition in which standardized scaffolds have to be aligned is challenging, and in many cases the alignment is not possible without limitations. Therefore, in the last decades, 3D printing (3DP) or additive manufacturing (AM) of scaffolds has become one of the most innovative approaches in surgery to individualize and improve the treatment of patients. Numerous biocompatible materials are available for 3DP, and various printing techniques can be applied, depending on the process conditions of these materials. Besides these conventional printing techniques, another promising approach in the context of medical AM is 3D bioprinting, a technique which makes it possible to print human cells embedded in special carrier substances to generate functional tissues. Even the direct printing into bone defects or lesions becomes possible. 3DP is already improving the treatment of patients, and has the potential to revolutionize regenerative medicine in future.

  8. Angiogenesis and bone regeneration of porous nano-hydroxyapatite/coralline blocks coated with rhVEGF165 in critical-size alveolar bone defects in vivo

    Directory of Open Access Journals (Sweden)

    Du B

    2015-03-01

    Full Text Available Bing Du,1,2 Weizhen Liu,1 Yue Deng,1,3 Shaobing Li,1 Xiangning Liu,4 Yan Gao,1 Lei Zhou1 1Department of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Center of Stomatology, The First People’s Hospital of Foshan, Foshan, Guangdong, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, Qingdao Stomatological Hospital, Qingdao, People’s Republic of China; 4Department of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China Abstract: To improve the regenerative performance of nano-hydroxyapatite/coralline (nHA/coral block grafting in a canine mandibular critical-size defect model, nHA/coral blocks were coated with recombinant human vascular endothelial growth factor165 (rhVEGF via physical adsorption (3 µg rhVEGF165 per nHA/coral block. After the nHA/coral blocks and VEGF/nHA/coral blocks were randomly implanted into the mandibular box-shaped defects in a split-mouth design, the healing process was evaluated by histological observation and histomorphometric and immunohistological analyses. The histological evaluations revealed the ingrowth of newly formed blood vessels and bone at the periphery and cores of the blocks in both groups at both 3 and 8 weeks postsurgery, respectively. In the histomorphometric analysis, the VEGF/nHA/coral group exhibited a larger quantity of new bone formation at 3 and 8 weeks postsurgery. The percentages of newly formed bone within the entire blocks in the VEGF/nHA/coral group were 27.3%±8.1% and 39.3%±12.8% at 3 weeks and 8 weeks, respectively, and these values were slightly greater than those of the nHA/coral group (21.7%±3.0% and 32.6%±10.3%, respectively, but the differences were not significant (P>0.05. The immunohistological evaluations revealed that the neovascular density in the VEGF/nHA/coral group (146±32.9 vessel/mm2 was much greater than

  9. Comparative study of hydroxyapatite from eggshells and synthetic hydroxyapatite for bone regeneration.

    Science.gov (United States)

    Lee, Sang-Woon; Kim, Seong-Gon; Balázsi, Csaba; Chae, Weon-Sik; Lee, Hee-Ok

    2012-03-01

    The objective of this study was to evaluate the physical properties of synthetic hydroxyapatite (sHA) and hydroxyapatite from eggshells (eHA) by Fourier-transform infrared (FT-IR) and x-ray diffraction (XRD) and to compare the regenerative ability of the bone using sHA and eHA in a rabbit calvarial defect model. FT-IR and XRD were used to compare the physical properties of sHA and eHA. sHA was purchased from Sigma, and eHA was kindly donated from the Hungarian academy of science. Sixteen New Zealand white rabbits were used for the animal study. After the formation of a bilateral parietal bony defect (diameter 8.0 mm), either sHA or eHA was grafted into the defect. The defect in the control was left unfilled. Bone regeneration was evaluated by histomorphometry at 4 and 8 weeks after the operation. The peak broadening of the XRD experiments were in agreement with scanning electron microscope observation; the sHA had a smaller granule size than the eHA. The eHA had impurities phases of CaO (International Center for Diffraction Data (ICDD) 075-0264) and Ca(OH)(2) (ICDD 072-0156). Total new bone was 17.11 ± 10.24% in the control group, 28.81 ± 12.63% in sHA group, and 25.68 ± 10.89% in eHA group at 4 weeks after the operation. The difference was not statistically significant (P > .05). Total new bone at 8 weeks after the operation was 27.50 ± 10.89% in the control group, 38.62 ± 17.42% in sHA group, and 41.99 ± 8.44% in the eHA group. When comparing the sHA group to the control group, the difference was not statistically significant (P > .05). However, the eHA group was significantly different from the control group (P = .038). When comparing the eHA group to the sHA group, the difference was not statistically significant (P > .05). Both types of HA showed higher bone formation than the unfilled control. However, eHA had significantly higher bone formation than the unfilled control at 8 weeks after operation. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Three dimensional printing of calcium sulfate and mesoporous bioactive glass scaffolds for improving bone regeneration in vitro and in vivo

    Science.gov (United States)

    Qi, Xin; Pei, Peng; Zhu, Min; Du, Xiaoyu; Xin, Chen; Zhao, Shichang; Li, Xiaolin; Zhu, Yufang

    2017-02-01

    In the clinic, bone defects resulting from infections, trauma, surgical resection and genetic malformations remain a significant challenge. In the field of bone tissue engineering, three-dimensional (3D) scaffolds are promising for the treatment of bone defects. In this study, calcium sulfate hydrate (CSH)/mesoporous bioactive glass (MBG) scaffolds were successfully fabricated using a 3D printing technique, which had a regular and uniform square macroporous structure, high porosity and excellent apatite mineralization ability. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured on scaffolds to evaluate hBMSC attachment, proliferation and osteogenesis-related gene expression. Critical-sized rat calvarial defects were applied to investigate the effect of CSH/MBG scaffolds on bone regeneration in vivo. The in vitro results showed that CSH/MBG scaffolds stimulated the adhesion, proliferation, alkaline phosphatase (ALP) activity and osteogenesis-related gene expression of hBMSCs. In vivo results showed that CSH/MBG scaffolds could significantly enhance new bone formation in calvarial defects compared to CSH scaffolds. Thus 3D printed CSH/MBG scaffolds would be promising candidates for promoting bone regeneration.

  11. Pigs are useful for the molecular study of bone inflammation and regeneration in humans

    DEFF Research Database (Denmark)

    Lüthje, Freja Lea; Skovgaard, Kerstin; Jensen, Henrik Elvang

    2018-01-01

    Pigs are used with increased frequency to model different kinds of orthopedic surgical conditions. In order to show the full potential of porcine models in orthopedic research, it is therefore required to examine the expression of bone regulatory genes in pigs affected by orthopedic surgery...... euthanized five days after drilling of the bone. The molecular response of 73 different genes was analyzed using a high-throughput quantitative polymerase chain reaction platform and compared to histopathology. Histologically, it was found that bone remodeling was initiated on day 5 after surgery...... and was associated with upregulation of several genes involved in bone degradation and formation ( CTSK, ACP5, IBSP, RANK, RANKL and COL1A1). Interleukin-6 and several acute-phase proteins (C3, SAA and ITIH4) were significantly upregulated, indicating their importance in the initial process of healing...

  12. Effects of LED phototherapy on bone defects grafted with MTA, bone morphogenetic proteins and guided bone regeneration: a Raman spectroscopic study.

    Science.gov (United States)

    Pinheiro, Antonio L B; Soares, Luiz G P; Cangussú, Maria Cristina T; Santos, Nicole R S; Barbosa, Artur Felipe S; Silveira Júnior, Landulfo

    2012-09-01

    We studied peaks of calcium hydroxyapatite (CHA) and protein and lipid CH groups in defects grafted with mineral trioxide aggregate (MTA) treated or not with LED irradiation, bone morphogenetic proteins and guided bone regeneration. A total of 90 rats were divided into ten groups each of which was subdivided into three subgroups (evaluated at 15, 21 and 30 days after surgery). Defects were irradiated with LED light (wavelength 850 ± 10 nm) at 48-h intervals for 15 days. Raman readings were taken at the surface of the defects. There were no statistically significant differences in the CHA peaks among the nonirradiated defects at any of the experimental time-points. On the other hand, there were significant differences between the defects filled with blood clot and the irradiated defects at all time-points (p Raman spectral analysis indicate that infrared LED light irradiation improves the deposition of CHA in healing bone grafted or not with MTA.

  13. Nanocomposites of Polyacrylic Acid Nanogels and Biodegradable Polyhydroxybutyrate for Bone Regeneration and Drug Delivery

    Directory of Open Access Journals (Sweden)

    Mikael Larsson

    2014-01-01

    Full Text Available Biodegradable cell scaffolds and local drug delivery to stimulate cell response are currently receiving much scientific attention. Here we present a nanocomposite that combines biodegradation with controlled release of lithium, which is known to enhance bone growth. Nanogels of lithium neutralized polyacrylic acid were synthesized by microemulsion-templated polymerization and were incorporated into a biodegradable polyhydroxybutyrate (PHB matrix. Nanogel size was characterized using dynamic light scattering, and the nanocomposites were characterized with regard to structure using scanning electron microscopy, mechanical properties using tensile testing, permeability using tritiated water, and lithium release in PBS using a lithium specific electrode. The nanogels were well dispersed in the composites and the mechanical properties were good, with a decrease in elastic modulus being compensated by increased tolerance to strain in the wet state. Approximately half of the lithium was released over about three hours, with the remaining fraction being trapped in the PHB for subsequent slow release during biodegradation. The prepared nanocomposites seem promising for use as dual functional scaffolds for bone regeneration. Here lithium ions were chosen as model drug, but the nanogels could potentially act as carriers for larger and more complex drugs, possibly while still carrying lithium.

  14. Rhombicuboctahedron unit cell based scaffolds for bone regeneration: geometry optimization with a mechanobiology - driven algorithm.

    Science.gov (United States)

    Boccaccio, Antonio; Fiorentino, Michele; Uva, Antonio E; Laghetti, Luca N; Monno, Giuseppe

    2018-02-01

    In a context more and more oriented towards customized medical solutions, we propose a mechanobiology-driven algorithm to determine the optimal geometry of scaffolds for bone regeneration that is the most suited to specific boundary and loading conditions. In spite of the huge number of articles investigating different unit cells for porous biomaterials, no studies are reported in the literature that optimize the geometric parameters of such unit cells based on mechanobiological criteria. Parametric finite element models of scaffolds with rhombicuboctahedron unit cell were developed and incorporated into an optimization algorithm that combines them with a computational mechanobiological model. The algorithm perturbs iteratively the geometry of the unit cell until the best scaffold geometry is identified, i.e. the geometry that allows to maximize the formation of bone. Performances of scaffolds with rhombicuboctahedron unit cell were compared with those of other scaffolds with hexahedron unit cells. We found that scaffolds with rhombicuboctahedron unit cell are particularly suited for supporting medium-low loads, while, for higher loads, scaffolds with hexahedron unit cells are preferable. The proposed algorithm can guide the orthopaedic/surgeon in the choice of the best scaffold to be implanted in a patient-specific anatomic region. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Controlling Adult Stem Cell Behavior Using Nanodiamond-Reinforced Hydrogel: Implication in Bone Regeneration Therapy.

    Science.gov (United States)

    Pacelli, Settimio; Maloney, Ryan; Chakravarti, Aparna R; Whitlow, Jonathan; Basu, Sayantani; Modaresi, Saman; Gehrke, Stevin; Paul, Arghya

    2017-07-26

    Nanodiamonds (NDs) have attracted considerable attention as drug delivery nanocarriers due to their low cytotoxicity and facile surface functionalization. Given these features, NDs have been recently investigated for the fabrication of nanocomposite hydrogels for tissue engineering. Here we report the synthesis of a hydrogel using photocrosslinkable gelatin methacrylamide (GelMA) and NDs as a three-dimensional scaffold for drug delivery and stem cell-guided bone regeneration. We investigated the effect of different concentration of NDs on the physical and mechanical properties of the GelMA hydrogel network. The inclusion of NDs increased the network stiffness, which in turn augmented the traction forces generated by human adipose stem cells (hASCs). We also tested the ability of NDs to adsorb and modulate the release of a model drug dexamethasone (Dex) to promote the osteogenic differentiation of hASCs. The ND-Dex complexes modulated gene expression, cell area, and focal adhesion number in hASCs. Moreover, the integration of the ND-Dex complex within GelMA hydrogels allowed a higher retention of Dex over time, resulting in significantly increased alkaline phosphatase activity and calcium deposition of encapsulated hASCs. These results suggest that conventional GelMA hydrogels can be coupled with conjugated NDs to develop a novel platform for bone tissue engineering.

  16. Fabrication of large-pore mesoporous Ca-Si-based bioceramics for bone regeneration

    Directory of Open Access Journals (Sweden)

    Zeng D

    2017-11-01

    Full Text Available Deliang Zeng,1,2 Xingdi Zhang,3 Xiao Wang,1,2 Lingyan Cao,1 Ao Zheng,1,2 Jiahui Du,1,2 Yongsheng Li,3 Qingfeng Huang,1 Xinquan Jiang1,2 1Department of Prosthodontics, School of Medicine, Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Oral Bioengineering Laboratory, Shanghai Research Institute of Stomatology, School of Medicine, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Laboratory of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China Abstract: Our previous study revealed that mesoporous Ca-Si-based materials exhibited excellent osteoconduction because dissolved ions could form a layer of hydroxycarbonate apatite on the surface of the materials. However, the biological mechanisms underlying bone regeneration were largely unknown. The main aim of this study was to evaluate the osteogenic ability of large-pore mesoporous Ca-Si-based bioceramics (LPMSCs by alkaline phosphatase assay, real-time PCR analysis, von Kossa, and alizarin red assay. Compared with large-pore mesoporous silica (LPMS, LPMSCs had a better effect on the osteogenic differentiation of dental pulp cells. LPMSC-2 and LPMSC-3 with higher calcium possessed better osteogenic abilities than LPMSC-1, which may be related to the calcium-sensing receptor pathway. Furthermore, the loading capacity for recombinant human platelet-derived growth factor-BB was satisfactory in LPMSCs. In vivo, the areas of new bone formation in the calvarial defect repair were increased in the LPMSC-2 and LPMSC-3 groups compared with the LPMSC-1 and LPMS groups. We concluded that LPMSC-2 and LPMSC-3 possessed both excellent osteogenic abilities and satisfactory loading capacities, which may be

  17. Amorphous hydroxyapatite-sintered polymeric scaffolds for bone tissue regeneration: physical characterization studies.

    Science.gov (United States)

    Cushnie, Emily K; Khan, Yusuf M; Laurencin, Cato T

    2008-01-01

    Given the inherent shortcomings of autografts and allografts, donor-site morbidity and risk of disease transmission, respectively, alternatives to traditional bone grafting options are warranted. To this end, poly(lactide-co-glycolide) (PLAGA) and in situ-synthesized amorphous hydroxyapatite (HA) were used to construct three-dimensional microsphere-based composite scaffolds of varying HA content for bone regeneration. In the current study, the effect of adding amorphous HA to the PLAGA scaffolds on their physical characteristics and in vitro degradation mechanism was investigated. Porosimetry and uniaxial compression testing were used to analyze the internal structure and elastic modulus of the scaffolds, respectively. Additionally, gel permeation chromatography (GPC) was performed to assess the polymer molecular weight over the course of an 8-week degradation study. HA content (17% or 27%) of the composite scaffolds was found to increase scaffold pore volume from 33.86% for pure polymer scaffolds, to 40.49% or 46.29%, depending on the amount of incorporated HA. This increased pore volume provided the composite scaffolds with a greater surface area and a corresponding decrease in elastic modulus. Scaffold degradation studies conducted over 8 weeks showed PLAGA to degrade in a first-order mechanism, with the rate of polymer degradation for the 27% HA composite scaffold being significantly slower than that of the pure PLAGA scaffold (degradation constants of 0.0324 and 0.0232 week(-1), respectively). These results suggest that the addition of amorphous HA to PLAGA microspheres resulted in porous, bioactive scaffolds that offer potential as alternative bone grafting materials for the field of regenerative medicine. (c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.

  18. Hydroxyapatite/polylactide biphasic combination scaffold loaded with dexamethasone for bone regeneration.

    Science.gov (United States)

    Son, Jun-Sik; Kim, Su-Gwan; Oh, Ji-Su; Appleford, Mark; Oh, Sunho; Ong, Joo L; Lee, Kyu-Bok

    2011-12-15

    This study presents a novel design of a ceramic/polymer biphasic combination scaffold that mimics natural bone structures and is used as a bone graft substitute. To mimic the natural bone structures, the outside cortical-like shells were composed of porous hydroxyapatite (HA) with a hollow interior using a polymeric template-coating technique; the inner trabecular-like core consisted of porous poly(D,L-lactic acid) (PLA) that was loaded with dexamethasone (DEX) and was directly produced using a particle leaching/gas forming technique to create the inner diameter of the HA scaffold. It was observed that the HA and PLA parts of the fabricated HA/PLA biphasic scaffold contained open and interconnected pore structures, and the boundary between both parts was tightly connected without any gaps. It was found that the structure of the combination scaffold was analogous to that of natural bone based on micro-computed tomography analysis. Additionally, the dense, uniform apatite layer was formed on the surface of the HA/PLA biphasic scaffold through a biomimetic process, and DEX was successfully released from the PLA of the biphasic scaffold over a 1-month period. This release caused human embryonic palatal mesenchyme cells to proliferate, differentiate, produce ECM, and form tissue in vitro. Therefore, it was concluded that this functionally graded scaffold is similar to natural bone and represents a potential bone-substitute material. Copyright © 2011 Wiley Periodicals, Inc.

  19. The influence of platelet-rich fibrin on angiogenesis in guided bone regeneration using xenogenic bone substitutes: a study of rabbit cranial defects.

    Science.gov (United States)

    Yoon, Jong-Suk; Lee, Sang-Hwa; Yoon, Hyun-Joong

    2014-10-01

    The purpose of this study was to investigate the influence of platelet-rich fibrin (PRF) on angiogenesis and osteogenesis in guided bone regeneration (GBR) using xenogenic bone in rabbit cranial defects. In each rabbit, 2 circular bone defects, one on either side of the midline, were prepared using a reamer drill. Each of the experimental sites received bovine bone with PRF, and each of the control sites received bovine bone alone. The animals were sacrificed at 1 week (n = 4), 2 weeks (n = 3) and 4 weeks (n = 3). Biopsy samples were examined histomorphometrically by light microscopy, and expression of vascular endothelial growth factor (VEGF) was determined by immunohistochemical staining. At all experimental time points, immunostaining intensity for VEGF was consistently higher in the experimental group than in the control group. However, the differences between the control group and the experimental group were not statistically significant in the histomorphometrical and immunohistochemical examinations. The results of this study suggest that PRF may increase the number of marrow cells. However, PRF along with xenogenic bone substitutes does not show a significant effect on bony regeneration. Further large-scale studies are needed to confirm our results. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  20. Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo.

    Science.gov (United States)

    Wei, Xiaowei; Zhao, Dewei; Wang, Benjie; Wang, Wei; Kang, Kai; Xie, Hui; Liu, Baoyi; Zhang, Xiuzhi; Zhang, Jinsong; Yang, Zhenming

    2016-03-01

    Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum-host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing. © 2016 by the Society for Experimental Biology and Medicine.

  1. Preparation and Characterization of Resorbable Bacterial Cellulose Membranes Treated by Electron Beam Irradiation for Guided Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Sung-Jun An

    2017-10-01

    Full Text Available Bacterial cellulose (BC is an excellent biomaterial with many medical applications. In this study, resorbable BC membranes were prepared for guided bone regeneration (GBR using an irradiation technique for applications in the dental field. Electron beam irradiation (EI increases biodegradation by severing the glucose bonds of BC. BC membranes irradiated at 100 kGy or 300 kGy were used to determine optimal electron beam doses. Electron beam irradiated BC membranes (EI-BCMs were evaluated by scanning electron microscopy (SEM, attenuated total reflectance-Fourier transform infrared (ATR-FTIR spectroscopy, thermal gravimetric analysis (TGA, and using wet tensile strength measurements. In addition, in vitro cell studies were conducted in order to confirm the cytocompatibility of EI-BCMs. Cell viabilities of NIH3T3 cells on 100k and 300k EI-BCMs (100 kGy and 300 kGy irradiated BC membranes were significantly greater than on NI-BCMs after 3 and 7 days (p < 0.05. Bone regeneration by EI-BCMs and their biodegradabilities were also evaluated using in vivo rat calvarial defect models for 4 and 8 weeks. Histometric results showed 100k EI-BCMs exhibited significantly larger new bone area (NBA; % than 300k EI-BCMs at 8 weeks after implantation (p < 0.05. Mechanical, chemical, and biological analyses showed EI-BCMs effectively interacted with cells and promoted bone regeneration.

  2. Chitosan-Graphene Oxide 3D scaffolds as Promising Tools for Bone Regeneration in Critical-Size Mouse Calvarial Defects.

    Science.gov (United States)

    Hermenean, Anca; Codreanu, Ada; Herman, Hildegard; Balta, Cornel; Rosu, Marcel; Mihali, Ciprian Valentin; Ivan, Alexandra; Dinescu, Sorina; Ionita, Mariana; Costache, Marieta

    2017-11-30

    Limited self-regenerating capacity of human skeleton makes the reconstruction of critical size bone defect a significant challenge for clinical practice. Aimed for regenerating bone tissues, this study was designed to investigate osteogenic differentiation, along with bone repair capacity of 3D chitosan (CHT) scaffolds enriched with graphene oxide (GO) in critical-sized mouse calvarial defect. Histopathological/histomorphometry and scanning electron microscopy(SEM) analysis of the implants revealed larger amount of new bone in the CHT/GO-filled defects compared with CHT alone (p < 0.001). When combined with GO, CHT scaffolds synergistically promoted the increase of alkaline phosphatase activity both in vitro and in vivo experiments. This enhanced osteogenesis was corroborated with increased expression of bone morphogenetic protein (BMP) and Runx-2 up to week 4 post-implantation, which showed that GO facilitates the differentiation of osteoprogenitor cells. Meanwhile, osteogenesis was promoted by GO at the late stage as well, as indicated by the up-regulation of osteopontin and osteocalcin at week 8 and overexpressed at week 18, for both markers. Our data suggest that CHT/GO biomaterial could represent a promising tool for the reconstruction of large bone defects, without using exogenous living cells or growth factors.

  3. Acemannan sponges stimulate alveolar bone, cementum and periodontal ligament regeneration in a canine class II furcation defect model.

    Science.gov (United States)

    Chantarawaratit, P; Sangvanich, P; Banlunara, W; Soontornvipart, K; Thunyakitpisal, P

    2014-04-01

    Periodontal disease is a common infectious disease, found worldwide, causing the destruction of the periodontium. The periodontium is a complex structure composed of both soft and hard tissues, thus an agent applied to regenerate the periodontium must be able to stimulate periodontal ligament, cementum and alveolar bone regeneration. Recent studies demonstrated that acemannan, a polysaccharide extracted from Aloe vera gel, stimulated both soft and hard tissue healing. This study investigated effect of acemannan as a bioactive molecule and scaffold for periodontal tissue regeneration. Primary human periodontal ligament cells were treated with acemannan in vitro. New DNA synthesis, expression of growth/differentiation factor 5 and runt-related transcription factor 2, expression of vascular endothelial growth factor, bone morphogenetic protein-2 and type I collagen, alkaline phosphatase activity, and mineralized nodule formation were determined using [(3)H]-thymidine incorporation, reverse transcription-polymerase chain reaction, enzyme-linked immunoabsorbent assay, biochemical assay and alizarin red staining, respectively. In our in vivo study, premolar class II furcation defects were made in four mongrel dogs. Acemannan sponges were applied into the defects. Untreated defects were used as a negative control group. The amount of new bone, cementum and periodontal ligament formation were evaluated 30 and 60 d after the operation. Acemannan significantly increased periodontal ligament cell proliferation, upregulation of growth/differentiation factor 5, runt-related transcription factor 2, vascular endothelial growth factor, bone morphogenetic protein 2, type I collagen and alkaline phosphatase activity, and mineral deposition as compared with the untreated control group in vitro. Moreover, acemannan significantly accelerated new alveolar bone, cementum and periodontal ligament formation in class II furcation defects. Our data suggest that acemannan could be a candidate

  4. Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

    Directory of Open Access Journals (Sweden)

    Ribeiro-Resende Victor

    2012-07-01

    Full Text Available Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC, satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2 is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS. Results Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL region of the lumbar spinal cord (LSC in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly. Conclusion We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.

  5. Influence of the association between platelet-rich fibrin and bovine bone on bone regeneration. A histomorphometric study in the calvaria of rats.

    Science.gov (United States)

    Oliveira, M R; deC Silva, A; Ferreira, S; Avelino, C C; Garcia, I R; Mariano, R C

    2015-05-01

    This study aimed to investigate the effects of platelet-rich fibrin (PRF) associated or not with Bio-Oss on bone defects in the calvaria of rats. A critical-size defect of 5-mm diameter was performed in the calvaria of 48 rats. These animals were divided into six groups of eight animals each, according to the treatment received: homogeneous clot, autogenous clot, autogenous PRF, homogeneous PRF, Bio-Oss, or Bio-Oss associated with PRF. The animals were euthanized after 30 or 60 days. Bone regeneration was evaluated by histomorphometric analysis. The highest mean percentages of new bone formation at 30 days (54.05% ± 5.78) and 60 days (63.58% ± 5.78) were observed in the Bio-Oss associated with PRF group; in particular, the percentage of new bone at 30 days was significantly higher than that of all of the other groups (P<0.01). At 60 days, the Bio-Oss associated with PRF (63.58% ± 5.78) and Bio-Oss (57.34% ± 5.78) groups had similar results, and both showed a statistical difference compared to the other groups. PRF had a positive effect on bone regeneration only when associated with Bio-Oss. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  6. Biomimetic three-dimensional nanocrystalline hydroxyapatite and magnetically synthesized single-walled carbon nanotube chitosan nanocomposite for bone regeneration

    Directory of Open Access Journals (Sweden)

    Im O

    2012-04-01

    Full Text Available Owen Im1, Jian Li2, Mian Wang2, Lijie Grace Zhang2,3, Michael Keidar2,31Department of Biomedical Engineering, Duke University, Durham, NC; 2Department of Mechanical and Aerospace Engineering, 3Institute for Biomedical Engineering and Institute for Nanotechnology, The George Washington University, Washington, DC, USABackground: Many shortcomings exist in the traditional methods of treating bone defects, such as donor tissue shortages for autografts and disease transmission for allografts. The objective of this study was to design a novel three-dimensional nanostructured bone substitute based on magnetically synthesized single-walled carbon nanotubes (SWCNT, biomimetic hydrothermally treated nanocrystalline hydroxyapatite, and a biocompatible hydrogel (chitosan. Both nanocrystalline hydroxyapatite and SWCNT have a biomimetic nanostructure, excellent osteoconductivity, and high potential to improve the load-bearing capacity of hydrogels.Methods: Specifically, three-dimensional porous chitosan scaffolds with different concentrations of nanocrystalline hydroxyapatite and SWCNT were created to support the growth of human osteoblasts (bone-forming cells using a lyophilization procedure. Two types of SWCNT were synthesized in an arc discharge with a magnetic field (B-SWCNT and without a magnetic field (N-SWCNT for improving bone regeneration.Results: Nanocomposites containing magnetically synthesized B-SWCNT had superior cytocompatibility properties when compared with nonmagnetically synthesized N-SWCNT. B-SWCNT have much smaller diameters and are twice as long as their nonmagnetically prepared counterparts, indicating that the dimensions of carbon nanotubes can have a substantial effect on osteoblast attachment.Conclusion: This study demonstrated that a chitosan nanocomposite with both B-SWCNT and 20% nanocrystalline hydroxyapatite could achieve a higher osteoblast density when compared with the other experimental groups, thus making this nanocomposite

  7. Hyaline cartilage regeneration by combined therapy of microfracture and long-term bone morphogenetic protein-2 delivery.

    Science.gov (United States)

    Yang, Hee Seok; La, Wan-Geun; Bhang, Suk Ho; Kim, Hak-Jun; Im, Gun-Il; Lee, Haeshin; Park, Jung-Ho; Kim, Byung-Soo

    2011-07-01

    Microfracture of cartilage induces migration of bone-marrow-derived mesenchymal stem cells. However, this treatment often results in fibrocartilage regeneration. Growth factors such as bone morphogenetic protein (BMP)-2 induce the differentiation of bone-marrow-derived mesenchymal stem cells into chondrocytes, which can be used for hyaline cartilage regeneration. Here, we tested the hypothesis that long-term delivery of BMP-2 to cartilage defects subjected to microfracture results in regeneration of high-quality hyaline-like cartilage, as opposed to short-term delivery of BMP-2 or no BMP-2 delivery. Heparin-conjugated fibrin (HCF) and normal fibrin were used as carriers for the long- and short-term delivery of BMP-2, respectively. Rabbit articular cartilage defects were treated with microfracture combined with one of the following: no treatment, fibrin, short-term delivery of BMP-2, HCF, or long-term delivery of BMP-2. Eight weeks after treatment, histological analysis revealed that the long-term delivery of BMP-2 group (microfracture + HCF + BMP-2) showed the most staining with alcian blue. A biochemical assay, real-time polymerase chain reaction assay and Western blot analysis all revealed that the long-term delivery of BMP-2 group had the highest glucosaminoglycan content as well as the highest expression level of collagen type II. Taken together, the long-term delivery of BMP-2 to cartilage defects subjected to microfracture resulted in regeneration of hyaline-like cartilage, as opposed to short-term delivery or no BMP-2 delivery. Therefore, this method could be more convenient for hyaline cartilage regeneration than autologous chondrocyte implantation due to its less invasive nature and lack of cell implantation.

  8. Poly (glycerol sebacate) elastomer supports bone regeneration by its mechanical properties being closer to osteoid tissue rather than to mature bone.

    Science.gov (United States)

    Zaky, S H; Lee, K W; Gao, J; Jensen, A; Verdelis, K; Wang, Y; Almarza, A J; Sfeir, C

    2017-05-01

    Mechanical load influences bone structure and mass. Arguing the importance of load-transduction, we investigated the mechanisms inducing bone formation using an elastomeric substrate. We characterized Poly (glycerol sebacate) (PGS) in vitro for its mechanical properties, compatibility with osteoprogenitor cells regarding adhesion, proliferation, differentiation under compression versus static cultures and in vivo for the regeneration of a rabbit ulna critical size defect. The load-transducing properties of PGS were compared in vitro to a stiffer poly lactic-co-glycolic-acid (PLA/PGA) scaffold of similar porosity and interconnectivity. Under cyclic compression for 7days, we report focal adhesion kinase overexpression on the less stiff PGS and upregulation of the transcription factor Runx2 and late osteogenic markers osteocalcin and bone sialoprotein (1.7, 4.0 and 10.0 folds increase respectively). Upon implanting PGS in the rabbit ulna defect, histology and micro-computed tomography analysis showed complete gap bridging with new bone by the PGS elastomer by 8weeks while minimal bone formation was seen in empty controls. Immunohistochemical analysis demonstrated the new bone to be primarily regenerated by recruited osteoprogenitors cells expressing periostin protein during early phase of maturation similar to physiological endochondral bone development. This study confirms PGS to be osteoconductive contributing to bone regeneration by recruiting host progenitor/stem cell populations and as a load-transducing substrate, transmits mechanical signals to the populated cells promoting differentiation and matrix maturation toward proper bone remodeling. We hence conclude that the material properties of PGS being closer to osteoid tissue rather than to mineralized bone, allows bone maturation on a substrate mechanically closer to where osteoprogenitor/stem cells differentiate to develop mature load-bearing bone. The development of effective therapies for bone and

  9. A high concentration of recombinant human bone morphogenetic protein-2 induces low-efficacy bone regeneration in sinus augmentation: a histomorphometric analysis in rabbits.

    Science.gov (United States)

    Hong, Ji-Youn; Kim, Min-Soo; Lim, Hyun-Chang; Lee, Jung-Seok; Choi, Seong-Ho; Jung, Ui-Won

    2016-12-01

    The aim of the study was to elucidate the efficacy of bone regeneration at the early stage of healing in rabbit sinuses grafted with a biphasic calcium phosphate (BCP) carrier soaked in a high concentration of recombinant human bone morphogenetic protein-2 (rhBMP-2). Both maxillary sinuses of eight male rabbits were used. The sinus on one side (assigned randomly) was grafted with BCP loaded with rhBMP-2 (1.5 mg/ml; test group) using a soaking method, while the other was grafted with saline-soaked BCP (control group). After a 2-week healing period, the sinuses were analyzed by micro-computed tomography and histomorphometry. The total augmented area and soft tissue space were significantly larger in the test group than in the control group, whereas the opposite was true for the area of residual material and newly formed bone. Most of the new bone in the test group was localized to the Schneiderian membrane (SM), while very little bone formation was observed in the window and center regions of the sinus. New bone was distributed evenly in the control group sinuses. Within the limitations of this study, it appeared that application of a high concentration of rhBMP-2 soaked onto a BCP carrier inhibited bone regeneration from the pristine bone and increased soft tissue swelling and inflammatory response at the early healing stage of sinus augmentation, although osteoinductive potential was found along the SM. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Covalent binding of bone morphogenetic protein-2 and transforming growth factor-β3 to 3D plotted scaffolds for osteochondral tissue regeneration

    NARCIS (Netherlands)

    Di Luca, Andrea; Klein Gunnewiek, Michel; Vancso, Julius; van Blitterswijk, Clemens; Benetti, Edmondo Maria; Moroni, Lorenzo

    2017-01-01

    Engineering the osteochondral tissue presents some challenges mainly relying in its function of transition from the subchondral bone to articular cartilage and the gradual variation in several biological, mechanical, and structural features. A possible solution for osteochondral regeneration might

  11. External fixation of femoral defects in athymic rats: Applications for human stem cell implantation and bone regeneration

    Directory of Open Access Journals (Sweden)

    Terasa Foo

    2013-01-01

    Full Text Available An appropriate animal model is critical for the research of stem/progenitor cell therapy and tissue engineering for bone regeneration in vivo. This study reports the design of an external fixator and its application to critical-sized femoral defects in athymic rats. The external fixator consists of clamps and screws that are readily available from hardware stores as well as Kirschner wires. A total of 35 rats underwent application of the external fixator with creation of a 6-mm bone defect in one femur of each animal. This model had been used in several separate studies, including implantation of collagen gel, umbilical cord blood mesenchymal stem cells, endothelial progenitor cells, or bone morphogenetic protein-2. One rat developed fracture at the proximal pin site and two rats developed deep tissue infection. Pin loosening was found in nine rats, but it only led to the failure of external fixation in two animals. In 8 to 10 weeks, various degrees of bone growth in the femoral defects were observed in different study groups, from full repair of the bone defect with bone morphogenetic protein-2 implantation to fibrous nonunion with collagen gel implantation. The external fixator used in these studies provided sufficient mechanical stability to the bone defects and had a comparable complication rate in athymic rats as in immunocompetent rats. The external fixator does not interfere with the natural environment of a bone defect. This model is particularly valuable for investigation of osteogenesis of human stem/progenitor cells in vivo.

  12. Biomimetic three-dimensional nanocrystalline hydroxyapatite and magnetically synthesized single-walled carbon nanotube chitosan nanocomposite for bone regeneration

    Science.gov (United States)

    Im, Owen; Li, Jian; Wang, Mian; Zhang, Lijie Grace; Keidar, Michael

    2012-01-01

    Background Many shortcomings exist in the traditional methods of treating bone defects, such as donor tissue shortages for autografts and disease transmission for allografts. The objective of this study was to design a novel three-dimensional nanostructured bone substitute based on magnetically synthesized single-walled carbon nanotubes (SWCNT), biomimetic hydrothermally treated nanocrystalline hydroxyapatite, and a biocompatible hydrogel (chitosan). Both nanocrystalline hydroxyapatite and SWCNT have a biomimetic nanostructure, excellent osteoconductivity, and high potential to improve the load-bearing capacity of hydrogels. Methods Specifically, three-dimensional porous chitosan scaffolds with different concentrations of nanocrystalline hydroxyapatite and SWCNT were created to support the growth of human osteoblasts (bone-forming cells) using a lyophilization procedure. Two types of SWCNT were synthesized in an arc discharge with a magnetic field (B-SWCNT) and without a magnetic field (N-SWCNT) for improving bone regeneration. Results Nanocomposites containing magnetically synthesized B-SWCNT had superior cytocompatibility properties when compared with nonmagnetically synthesized N-SWCNT. B-SWCNT have much smaller diameters and are twice as long as their nonmagnetically prepared counterparts, indicating that the dimensions of carbon nanotubes can have a substantial effect on osteoblast attachment. Conclusion This study demonstrated that a chitosan nanocomposite with both B-SWCNT and 20% nanocrystalline hydroxyapatite could achieve a higher osteoblast density when compared with the other experimental groups, thus making this nanocomposite promising for further exploration for bone regeneration. PMID:22619545

  13. Efficacy of platelet rich plasma and hydroxyapatite crystals in bone regeneration after surgical removal of mandibular third molars.

    Science.gov (United States)

    Kaur, Preeti; Maria, Anisha

    2013-03-01

    This study evaluates the efficacy of platelet rich plasma (PRP) & porous hydroxyapatite crystals in bone regeneration after surgical removal of mandibular third molar with the help of radiographs and its comparison with control side. A total of 40 patients; both male and female aged between 18 and 35 years, who had impacted mandibular third molars were randomly selected for this study. Twenty patients were taken for control group and 20 patients for study group. The extraction socket of the study group was packed with PRP and hydroxyapatite granules and that of control group was sutured without PRP and hydroxyapatite. The bone density of both extraction sockets were evaluated radiographically using gray level histogram and compared periodically on immediate postoperative day, 1st and 3rd month postoperatively and postoperative sequelae of both the control group and study group in terms of oedema & pain or any other adverse reactions were also assessed. Data suggested evidence of early bone formation and maturation radiographically in study group as compared to control group. The percentage of facial swelling was numerically greater on the control side as compared to the study side, Pain was also assessed with VAS and it was found that the severity of pain was equal in both study and control groups and the results were not significant. This study clearly indicated a definitive improvement in the wound healing, increase in bone density, which signifies and highlights the use of PRP and hydroxyapatite granules, certainly as a valid method in inducing and accelerating bone regeneration.

  14. Evaluation of Spontaneous Bone Regeneration after Enucleation of Large Cysts of the Jaws using Radiographic Computed Software.

    Science.gov (United States)

    Wagdargi, Shivaraj S; Rai, Kirthi Kumar; Arunkumar, K V; Katkol, Basavraj; Arakeri, Gururaj

    2016-06-01

    Spontaneous regeneration of bone is commonly seen in the small surgical defects caused by enucleation of cysts. However, in case of large surgical defects caused by the enucleation, spontaneous regeneration of bone is a rare phenomenon and it depends on factors, such as age of the patient, intact periosteum, and proper stabilization. The study included 16 patients, who reported to the department of oral and maxillofacial surgery with the complaint of pain and swelling in the jaws diagnosed as cyst. The sample included equal numbers of male and female subjects aged between 15 and 40 years. Panoramic radiographs were taken pre- and postoperatively on day 2 of the enucleation. The dimensions of the cyst were evaluated on the radiograph according to the proforma. Subsequent radiographs were taken at regular intervals of 1.5, 3, and 6 months using standard parameters and were analyzed using MCID™ analysis software of imaging research. Mean reduction was seen in up to 39 and 60% in the cystic cavity size and increase in the mean density up to 59 and 90.2% at 3 and 6 months intervals respectively. Spontaneous bone regeneration was seen even after primary closure of the large cystic defect without the need for placement of foreign substances or grafts and it also eliminated the complications resulting from placement of foreign substance. Further studies are required in a larger sample with longer follow-up durations to confirm the outcome of the present work for the benefit of patients. The present study depicted that spontaneous bone regeneration can occur with accepted results after simple enucleation of jaw cyst without the aid of any graft material. Hence, simple enucleation may be considered as a first line of treatment modality for cystic lesion of the jaws. This simplifies the surgical procedure, decreases the economic and biologic costs, and reduces the risk of postoperative complications. Follow-up is necessary along with patient's compliance for the success of

  15. [Development of a novel absorbable nanofiber chitosan-collagen membrane by electrospinning and the preliminary study on guided bone regeneration].

    Science.gov (United States)

    Gao, B; Li, X J; Lin, M; Li, Y Y; Dong, Y

    2018-02-09

    Objective: To evaluate the application effect of nanofiber chitosan-collagen membrane (NCM) on guided bone regeneration (GBR). Methods: The mixture of collagen, chitosan, polyethylene oxide was used to make up the NCM by electrospinning, then the NCM was crosslinked by glutaraldehyde vapor. The physical property of the NCM was measured by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). MC3T3-E1 osteoblasts were cultured on NCM to characterize the biocompatibility. The effectiveness of four groups [contrast group, Bio-gide membrane (BGM), compressed chitosan-collagen menbrane (CCM), NCM/CCM] on bone regeneration were evaluated in critical-sized defects (diameter = 5 mm) in SD rats. Results: When the mixed solution consists of 4.0% collagen, 1.0% chitosan and 3.5% polyethylene oxide, the NCM could be validly fabricated by electrospinning. After cross-linking by glutaraldehyde vapor, the tensile strength and the stability of NCM in damp was enhanced. No cytotoxicity of the NCM was detected on MC3T3-E1 osteoblasts. In vivo study showed that the new bone regeneration ratio of NCM/CCM group was [(43.10±1.49)%], and this was similar to that of the group of BGM [(41.36±2.60)%] ( P> 0.05), but higher than that of the CCM group [(33.10±1.41)%] and the contrast group [(7.22±2.46)%] ( P< 0.05). Conclusions: The NCM can promote new bone regeneration effectively in GBR procedure.

  16. Cellular reactions of osteoblast-like cells to a novel nanocomposite membrane for guided bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Meng Yao [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Department of Orthodontics, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Liu Man [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Stomatology Health Care Center, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518048 (China); Wang Shaoan [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Mo Anchun [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China)], E-mail: moanchun@163.com; Huang, Cui [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Zuo Yi; Li Jidong [Research Center for Nano-biomaterials, Sichuan University, Chengdu 610041 (China)

    2008-11-15

    This study investigated the bioactivity and biocompatibility of hydroxyapatite nanoparticles (n-HA)/Polyamide-66 (PA66) nanocomposite membrane and expanded-polytetrafluoroethylene (e-PTFE) membrane (as control) to MG63 osteoblast-like cells. The attachment and proliferation of the cells on the porous surface of nHA/PA66 membrane and the surface of e-PTFE membrane were evaluated by scanning electron microscope (SEM) observation and the MTT assay. The bioactivity of the cells on the surface of the two membranes was evaluated by testing cell viability and alkaline phosphatase (ALP) activities. The results suggested that the bioresponse of MG63 osteoblast-like cells on the porous surface of nHA/PA66 membrane was better than the bioresponse on the opposite surface of e-PTFE membrane. Because of a better cell attachment manner, there is a potential utilization of the guided bone regeneration (GBR) membrane to substitute nHA/PA66 membrane for e-PTFE membra0008.

  17. Properties and in vitro biological evaluation of nano-hydroxyapatite/chitosan membranes for bone guided regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Cheng Xianmiao [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, 610064 Chengdu (China); Department of Chemistry, Sichuan University, 610064 Chengdu (China); Li Yubao [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, 610064 Chengdu (China)], E-mail: nic7504@scu.edu.cn; Zuo Yi; Zhang Li [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, 610064 Chengdu (China); Li Jidong [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, 610064 Chengdu (China); Department of Chemistry, Sichuan University, 610064 Chengdu (China); Wang Huanan [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, 610064 Chengdu (China)

    2009-01-01

    Nano-hydroxyapatite(n-HA)/chitosan(CS) composite membranes were prepared by solvent casting and evaporation methods for the function of guided bone regeneration (GBR). The effect of n-HA content and solvent evaporation temperature on the properties of the composite membranes was studied. The n-HA/CS membranes were analyzed by scanning electron microscopy, Fourier transformed infrared spectroscopy, X-ray diffraction, swelling measurement, mechanical test, cell culture and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenylte-2H-tetrazolium bromide) assay. The results show that the surface roughness and micropores of the composite membranes increase with the rise of n-HA content, suitable for adhesion, crawl and growth of cells. The hydroxyapatite holds nano size and distributes uniformly in the composite membranes. Chemical bond interaction exists between Ca ions and -OH groups of n-HA and -NH{sub 2} or -OH groups of CS. The n-HA content and solvent evaporation temperature have obvious influence on the swelling ratio, tensile strength and elongation rate of the composite membranes. Cell culture and MTT assays show that n-HA and its content can affect the proliferation of cells. The n-HA/CS composite membranes have no negative effect on the cell morphology, viability and proliferation and possess good biocompatibility. This study makes the n-HA/CS composite membrane be a prospective biodegradable GBR membrane for future applications.

  18. Properties and in vitro biological evaluation of nano-hydroxyapatite/chitosan membranes for bone guided regeneration

    International Nuclear Information System (INIS)

    Cheng Xianmiao; Li Yubao; Zuo Yi; Zhang Li; Li Jidong; Wang Huanan

    2009-01-01

    Nano-hydroxyapatite(n-HA)/chitosan(CS) composite membranes were prepared by solvent casting and evaporation methods for the function of guided bone regeneration (GBR). The effect of n-HA content and solvent evaporation temperature on the properties of the composite membranes was studied. The n-HA/CS membranes were analyzed by scanning electron microscopy, Fourier transformed infrared spectroscopy, X-ray diffraction, swelling measurement, mechanical test, cell culture and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenylte-2H-tetrazolium bromide) assay. The results show that the surface roughness and micropores of the composite membranes increase with the rise of n-HA content, suitable for adhesion, crawl and growth of cells. The hydroxyapatite holds nano size and distributes uniformly in the composite membranes. Chemical bond interaction exists between Ca ions and -OH groups of n-HA and -NH 2 or -OH groups of CS. The n-HA content and solvent evaporation temperature have obvious influence on the swelling ratio, tensile strength and elongation rate of the composite membranes. Cell culture and MTT assays show that n-HA and its content can affect the proliferation of cells. The n-HA/CS composite membranes have no negative effect on the cell morphology, viability and proliferation and possess good biocompatibility. This study makes the n-HA/CS composite membrane be a prospective biodegradable GBR membrane for future applications

  19. Injectable TEMPO-oxidized nanofibrillated cellulose/biphasic calcium phosphate hydrogel for bone regeneration.

    Science.gov (United States)

    Safwat, Engie; Hassan, Mohammad L; Saniour, Sayed; Zaki, Dalia Yehia; Eldeftar, Mervat; Saba, Dalia; Zazou, Mohamed

    2018-05-01

    Nanofibrillated cellulose, obtained from rice straw agricultural wastes was used as a substrate for the preparation of a new injectable and mineralized hydrogel for bone regeneration. Tetramethyl pyridine oxyl (TEMPO) oxidized nanofibrillated cellulose, was mineralized through the incorporation of a prepared and characterized biphasic calcium phosphate at a fixed ratio of 50 wt%. The TEMPO-oxidized rice straw nanofibrillated cellulose was characterized using transmission electron microscopy, Fourier transform infrared, and carboxylic content determination. The injectability and viscosity of the prepared hydrogel were evaluated using universal testing machine and rheometer testing, respectively. Cytotoxicity and alkaline phosphatase level tests on osteoblast like-cells for in vitro assessment of the biocompatibility were investigated. Results revealed that the isolated rice straw nanofibrillated cellulose is a nanocomposite of the cellulose nanofibers and silica nanoparticles. Rheological properties of the tested materials are suitable for use as injectable material and of nontoxic effect on osteoblast-like cells, as revealed by the positive alkaline phosphate assay. However, nanofibrillated cellulose/ biphasic calcium phosphate hydrogel showed higher cytotoxicity and lower bioactivity test results when compared to that of nanofibrillated cellulose.

  20. Immediate implant placement and provisionalization with simultaneous guided bone regeneration in the esthetic zone

    Directory of Open Access Journals (Sweden)

    Chih-Long Chen

    2011-03-01

    Full Text Available The procedure for immediate implant placement and provisionalization is time-saving, possibly with only one surgical intervention required, although allowing maximal preservation of peri-implant tissues. In this case, we extracted a fractured maxillary right central incisor of a 46-year-old woman with high esthetic expectations, and a transmucosal implant was immediately installed. Simultaneous guided bone regeneration was performed to correct the defects at the facial side of the socket and augment the alveolar ridge horizontally. Primary stability of the implant body and wound closure without tension were confirmed. Connection of a 15° angled abutment and fabrication of a provisional acrylic resin crown without occlusal contact were also completed in the same appointment. After intensive follow-up and soft-tissue molding for 6 months, the customized zirconia abutment and all-ceramic crown were definitively fabricated. During the 18-month follow-up period, the patient was satisfied with the esthetic and functional results.

  1. Influence of surface features of hydroxyapatite on the adsorption of proteins relevant to bone regeneration.

    Science.gov (United States)

    Fernández-Montes Moraleda, Belén; San Román, Julio; Rodríguez-Lorenzo, Luís M

    2013-08-01

    Protein-surface interaction may determine the success or failure of an implanted device. Not much attention have been paid to the specific surface parametes of hydroxyapatite (OHAp) that modulates and determines the formation and potential activity of the layer of proteins that is first formed when the material get in contact with the host tissue. the influence of specific surface area (SSA), crystallite size (CS) and particle size (PS) of OHAp on the adsorption of proteins relevant for bone regeneration is evaluated in this article. OHAp have been prepared by a wet chemical reaction of Ca(OH)2 with H3PO4. One set of reactions included poly acrylic acid in the reactant solution to modify the properties of the powder. Fibrinogen (Fg) Fraction I, type I: from Human plasma, (67% Protein), and Fibronectin (Fn) from Human plasma were selected to perform the adsorption experiments. The analysis of protein adsorption was carried out by UV/Vis spectrometry. A lower SSA and a different aspect ratio are obtained when the acrylic acid is included in the reaction badge. The deconvolution of the amide I band on the Raman spectra of free and adsorbed proteins reveals that the interaction apatite-protein happens through the carboxylate groups of the proteins. The combined analysis of CS, SSA and PS should be considered on the design of OHAp materials intended to interact with proteins. Copyright © 2013 Wiley Periodicals, Inc.

  2. Cellular reactions of osteoblast-like cells to a novel nanocomposite membrane for guided bone regeneration

    International Nuclear Information System (INIS)

    Meng Yao; Liu Man; Wang Shaoan; Mo Anchun; Huang, Cui; Zuo Yi; Li Jidong

    2008-01-01

    This study investigated the bioactivity and biocompatibility of hydroxyapatite nanoparticles (n-HA)/Polyamide-66 (PA66) nanocomposite membrane and expanded-polytetrafluoroethylene (e-PTFE) membrane (as control) to MG63 osteoblast-like cells. The attachment and proliferation of the cells on the porous surface of nHA/PA66 membrane and the surface of e-PTFE membrane were evaluated by scanning electron microscope (SEM) observation and the MTT assay. The bioactivity of the cells on the surface of the two membranes was evaluated by testing cell viability and alkaline phosphatase (ALP) activities. The results suggested that the bioresponse of MG63 osteoblast-like cells on the porous surface of nHA/PA66 membrane was better than the bioresponse on the opposite surface of e-PTFE membrane. Because of a better cell attachment manner, there is a potential utilization of the guided bone regeneration (GBR) membrane to substitute nHA/PA66 membrane for e-PTFE membrane

  3. Attachment and growth of human bone marrow derived mesenchymal stem cells on regenerated antheraea pernyi silk fibroin films

    Energy Technology Data Exchange (ETDEWEB)

    Luan Xiying [Institute of Medical Biotechnology, Jiangsu Province Key Laboratory of Stem Cell, Suzhou University, Suzhou 215007 (China); Wang Yong [Institute of Medical Biotechnology, Jiangsu Province Key Laboratory of Stem Cell, Suzhou University, Suzhou 215007 (China); Duan Xiang [Institute of Medical Biotechnology, Jiangsu Province Key Laboratory of Stem Cell, Suzhou University, Suzhou 215007 (China); Duan Qiaoyan [Institute of Medical Biotechnology, Jiangsu Province Key Laboratory of Stem Cell, Suzhou University, Suzhou 215007 (China); Li Mingzhong [School of Materials Engineering, Suzhou University, Suzhou 215006 (China); Lu Shenzhou [School of Materials Engineering, Suzhou University, Suzhou 215006 (China); Zhang Huanxiang [Institute of Medical Biotechnology, Jiangsu Province Key Laboratory of Stem Cell, Suzhou University, Suzhou 215007 (China); Zhang Xueguang [Institute of Medical Biotechnology, Jiangsu Province Key Laboratory of Stem Cell, Suzhou University, Suzhou 215007 (China)

    2006-12-15

    Silk fibroin of the silkworm Bombyx mori has been studied extensively, while the research on Antheraea pernyi silk fibroin (A. pernyi SF) in biomaterials is only at an early stage. In this study, the attachment, morphology, growth and phenotype of human bone marrow derived mesenchymal stem cells (hBMSCs) cultured on the regenerated A. pernyi SF films were studied in vitro. The results indicated that the attachment of hBMSCs on the regenerated A. pernyi SF films was almost the same as that on the collagen films. MTT and cell counting analyses demonstrated that the growth of hBMSCs on the regenerated A. pernyi SF films was better than that on controls. Moreover, electron scanning microscopy and fluorescence-activated cell sorting assays showed that the regenerated A. pernyi SF supported hBMSCs growth and functional maintenance compared with the controls. These data suggest that the regenerated A. pernyi SF, like Bombyx mori silk fibroin (B. mori SF) and collagen, can support hBMSCs attachment, growth and phenotypic maintenance, and has better biocompatibilities for hBMSCs in vitro culture.

  4. Attachment and growth of human bone marrow derived mesenchymal stem cells on regenerated antheraea pernyi silk fibroin films

    International Nuclear Information System (INIS)

    Luan Xiying; Wang Yong; Duan Xiang; Duan Qiaoyan; Li Mingzhong; Lu Shenzhou; Zhang Huanxiang; Zhang Xueguang

    2006-01-01

    Silk fibroin of the silkworm Bombyx mori has been studied extensively, while the research on Antheraea pernyi silk fibroin (A. pernyi SF) in biomaterials is only at an early stage. In this study, the attachment, morphology, growth and phenotype of human bone marrow derived mesenchymal stem cells (hBMSCs) cultured on the regenerated A. pernyi SF films were studied in vitro. The results indicated that the attachment of hBMSCs on the regenerated A. pernyi SF films was almost the same as that on the collagen films. MTT and cell counting analyses demonstrated that the growth of hBMSCs on the regenerated A. pernyi SF films was better than that on controls. Moreover, electron scanning microscopy and fluorescence-activated cell sorting assays showed that the regenerated A. pernyi SF supported hBMSCs growth and functional maintenance compared with the controls. These data suggest that the regenerated A. pernyi SF, like Bombyx mori silk fibroin (B. mori SF) and collagen, can support hBMSCs attachment, growth and phenotypic maintenance, and has better biocompatibilities for hBMSCs in vitro culture

  5. New Insights into Osteogenic and Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells and Their Potential Clinical Applications for Bone Regeneration in Pediatric Orthopaedics

    Directory of Open Access Journals (Sweden)

    Nicola Giuliani

    2013-01-01

    Full Text Available Human mesenchymal stem cells (hMSCs are pluripotent adult stem cells capable of being differentiated into osteoblasts, adipocytes, and chondrocytes. The osteogenic differentiation of hMSCs is regulated either by systemic hormones or by local growth factors able to induce specific intracellular signal pathways that modify the expression and activity of several transcription factors. Runt-related transcription factor 2 (Runx2 and Wnt signaling-related molecules are the major factors critically involved in the osteogenic differentiation process by hMSCs, and SRY-related high-mobility-group (HMG box transcription factor 9 (SOX9 is involved in the chondrogenic one. hMSCs have generated a great interest in the field of regenerative medicine, particularly in bone regeneration. In this paper, we focused our attention on the molecular mechanisms involved in osteogenic and chondrogenic differentiation of hMSC, and the potential clinical use of hMSCs in osteoarticular pediatric disease characterized by fracture nonunion and pseudarthrosis.

  6. Novel biocompatible polymeric blends for bone regeneration: Material and matrix design and development

    Science.gov (United States)

    Deng, Meng

    characterized for miscibility, mechanical properties, degradation kinetics, and in vitro osteocompatibility. Primary rat osteoblasts (PRO) isolated from rat calvaria were used to evaluate their in vitro osteocompatibility. The blends were also characterized for in vivo biodegradability and biocompatibility using a rat subcutaneous implantation model. Successful in vivo scaffold-based tissue regeneration greatly depends on the scaffold material biocompatibility, mechanical stability, and scaffold architecture to promote tissue in-growth. The other part of the work in the dissertation is focused on the development of mechanically competent bioresorbable nano-structured three-dimensional (3D) hiomimetic scaffolds for bone tissue engineering applications. Scaffold material selection was based on achieving improved mechanical stability, in vitro osteoblast performance, and in vivo biocompatibility. A miscible PNGEGPhPh-PLAGA blend system developed and characterized in the first part of the thesis work was chosen to fabricate a nanofiber-based mechanically competent biomimetic scaffold via electrospinning. Due to its versatility, controllability and reproducibility, the technique of electrospinning was adopted to produce blend nanofibers. The polymer solution concentration and electrospinning parameters were optimized to produce blend fibers in the range of 50-500 nm to mimic dimensions of collagen fibrils present in the natural extracellular matrix of native bone. These blend nanofiber matrices supported PRO adhesion, proliferation and showed an elevated phenotype expression compared to PLAGA nanofibers. Orienting electrospun nanofibers in a concentric manner with an open central cavity created a mechanically competent 3D scaffold mimicking the bone marrow cavity, as well as, the lamellar structure of bone. The 3D biomimetic scaffold exhibited a similar characteristic mechanical behavior to that of native bone. Compressive modulus of the scaffold was found to be within the range of

  7. Wollastonite nanofiber–doped self-setting calcium phosphate bioactive cement for bone tissue regeneration

    Directory of Open Access Journals (Sweden)

    Guo H

    2012-07-01

    incorporation of WNFs into CPC improved the biological properties for wnf-CPC. Following the implantation of wnf-CPC into bone defects of rabbits, histological evaluation showed that wnf-CPC enhanced the efficiency of new bone formation in comparison with CPC, indicating excellent biocompatibility and osteogenesis of wnf-CPC. In conclusion, wnf-CPC exhibited promising prospects in bone regeneration.Keywords: calcium phosphate cement, degradability, cell and tissue responses, biocompatibility

  8. Bone Regeneration Using a Mixture of Silicon-Substituted Coral HA and β-TCP in a Rat Calvarial Bone Defect Model

    Directory of Open Access Journals (Sweden)

    Jiyeon Roh

    2016-02-01

    Full Text Available The demand of bone graft materials has been increasing. Among various origins of bone graft materials, natural coral composed of up to 99% calcium carbonate was chosen and converted into hydroxyapatite (HA; silicon was then substituted into the HA. Then, the Si-HA was mixed with β-tricalcium phosphate (TCP in the ratios 100:0 (S100T0, 70:30 (S70T30, 60:40 (S60T40, and 50:50 (S50T50. The materials were implanted for four and eight weeks in a rat calvarial bone defect model (8 mm. The MBCPTM (HA:β-TCP = 60:40, Biomatalante, Vigneux de Bretagne, France was used as a control. After euthanasia, the bone tissue was analyzed by making histological slides. From the results, S60T40 showed the fastest bone regeneration in four weeks (p < 0.05. In addition, S60T40, S50T50, and MBCPTM showed significant new bone formation in eight weeks (p < 0.05. In conclusion, Si-HA/TCP showed potential as a bone graft material.

  9. Transplantation of bone-marrow-derived cells into a nerve guide resulted in transdifferentiation into Schwann cells and effective regeneration of transected mouse sciatic nerve.

    Science.gov (United States)

    Pereira Lopes, Fátima Rosalina; Frattini, Flávia; Marques, Suelen Adriani; Almeida, Fernanda Martins de; de Moura Campos, Lenira Camargo; Langone, Francesco; Lora, Silvano; Borojevic, Radovan; Martinez, Ana Maria Blanco

    2010-10-01

    Peripheral nerves possess the capacity of self-regeneration after traumatic injury. Nevertheless, the functional outcome after peripheral-nerve regeneration is often poor, especially if the nerve injuries occur far from their targets. Aiming to optimize axon regeneration, we grafted bone-marrow-derived cells (BMDCs) into a collagen-tube nerve guide after transection of the mouse sciatic nerve. The control group received only the culture medium. Motor function was tested at 2, 4, and 6 weeks after surgery, using the sciatic functional index (SFI), and showed that functional recovery was significantly improved in animals that received the cell grafts. After 6 weeks, the mice were anesthetized, perfused transcardially, and the sciatic nerves were dissected and processed for transmission electron microscopy and light microscopy. The proximal and distal segments of the nerves were compared, to address the question of improvement in growth rate; the results revealed a maintenance and increase of nerve regeneration for both myelinated and non-myelinated fibers in distal segments of the experimental group. Also, quantitative analysis of the distal region of the regenerating nerves showed that the numbers of myelinated fibers, Schwann cells (SCs) and g-ratio were significantly increased in the experimental group compared to the control group. The transdifferentiation of BMDCs into Schwann cells was confirmed by double labeling with S100/and Hoechst staining. Our data suggest that BMDCs transplanted into a nerve guide can differentiate into SCs, and improve the growth rate of nerve fibers and motor function in a transected sciatic-nerve model.

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

    Directory of Open Access Journals (Sweden)

    Ze Tang

    Full Text Available Tantalum, as a potential metallic implant biomaterial, is attracting more and more attention because of its excellent anticorrosion and biocompatibility. However, its significantly high elastic modulus and large mechanical incompatibility with bone tissue make it unsuitable for load-bearing implants. In this study, porous tantalum coatings were first successfully fabricated on titanium substrates by vacuum plasma spraying (VPS, which would exert the excellent biocompatibility of tantalum and alleviate the elastic modulus of tantalum for bone tissue. We evaluated cytocompatibility and osteogenesis activity of the porous tantalum coatings using human bone marrow stromal cells (hBMSCs and its ability to repair rabbit femur bone defects. The morphology and actin cytoskeletons of hBMSCs were observed via electron microscopy and confocal, and the cell viability, proliferation and osteogenic differentiation potential of hBMSCs were examined quantitatively by PrestoBlue assay, Ki67 immunofluorescence assay, real-time PCR technology and ALP staining. For in vivo detection, the repaired femur were evaluated by histomorphology and double fluorescence labeling 3 months postoperation. Porous tantalum coating surfaces promoted hBMSCs adhesion, proliferation, osteogenesis activity and had better osseointegration and faster new bone formation rate than titanium coating control. Our observation suggested that the porous tantalum coatings had good biocompatibility and could enhance osseoinductivity in vitro and promote new bone formation in vivo. The porous tantalum coatings prepared by VPS is a promising strategy for bone regeneration.

  11. Histologic and histomorphometric evaluation of bone regeneration using nanocrystalline hydroxyapatite and human freeze-dried bone graft : An experimental study in rabbit.

    Science.gov (United States)

    Sadeghi, Rokhsareh; Najafi, Mohammad; Semyari, Hassan; Mashhadiabbas, Fatemeh

    2017-03-01

    Bone regeneration is an important concern in periodontal treatment and implant dentistry. Different biomaterials and surgical techniques have been used for this purpose. The aim of the present study was to compare the effect of nanocrystalline hydroxyapatite and human freeze-dried bone graft (FDBG) in regeneration of rabbit calvarium bony defects by histologic and histomorphometric evaluation. In this experimental study, three similar defects, measuring 8 mm in diameter, were created in the calvaria of 16 white New Zealand rabbits. Two defects were filled with FDBG and nanocrystalline hydroxyapatite silica gel, while the other one remained unfilled to be considered as control. All the defects were covered with collagen membranes. During the healing period, two animals perished; so 14 rabbits were divided into two groups: half of them were euthanized after 6 weeks of healing and the other half after 12 weeks. The specimens were subjected to histologic and histomorphometric examinations for assessment of the following variables: percentage of bone formation and residual graft material, inflammation scores, patterns of bone formation and type of newly formed bone. The percentages of new bone formation after 6 weeks were 14.22 ± 7.85, 21.57 ± 6.91, and 20.54 ± 10.07% in FDBG, NanoBone, and control defects. These values were 27.54 ± 20.19, 23.86 ± 6.27, and 26.48 ± 14.18% in 12-week specimens, respectively. No significant differences were found in the amount of bone formation between the groups. With regard to inflammation, the control and NanoBone groups showed significantly less inflammation compared to FDBG at the 6-week healing phase (P = 0.04); this difference was not significant in the 12-week specimens. Based on the results of this experimental study, both NanoBone and FDBG exhibited a similar effect on bone formation.

  12. Evaluating the Bone Tissue Regeneration Capability of the Chinese Herbal Decoction Danggui Buxue Tang from a Molecular Biology Perspective

    Directory of Open Access Journals (Sweden)

    Wen-Ling Wang

    2014-01-01

    Full Text Available Large bone defects are a considerable challenge to reconstructive surgeons. Numerous traditional Chinese herbal medicines have been used to repair and regenerate bone tissue. This study investigated the bone regeneration potential of Danggui Buxue Tang (DBT, a Chinese herbal decoction prepared from Radix Astragali (RA and Radix Angelicae Sinensis (RAS, from a molecular biology perspective. The optimal ratio of RA and RAS used in DBT for osteoblast culture was obtained by colorimetric and alkaline phosphatase (ALP activity assays. Moreover, the optimal concentration of DBT for bone cell culture was also determined by colorimetric, ALP activity, nodule formation, Western blotting, wound-healing, and tartrate-resistant acid phosphatase activity assays. Consequently, the most appropriate weight ratio of RA to RAS for the proliferation and differentiation of osteoblasts was 5 : 1. Moreover, the most effective concentration of DBT was 1,000 μg/mL, which significantly increased the number of osteoblasts, intracellular ALP levels, and nodule numbers, while inhibiting osteoclast activity. Additionally, 1,000 μg/mL of DBT was able to stimulate p-ERK and p-JNK signal pathway. Therefore, DBT is highly promising for use in accelerating fracture healing in the middle or late healing periods.

  13. 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.

  14. 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

  15. Contribution of different bone marrow-derived cell types in endometrial regeneration using an irradiated murine model.

    Science.gov (United States)

    Gil-Sanchis, Claudia; Cervelló, Irene; Khurana, Satish; Faus, Amparo; Verfaillie, Catherine; Simón, Carlos

    2015-06-01

    To study the involvement of seven types of bone marrow-derived cells (BMDCs) in the endometrial regeneration in mice after total body irradiation. Prospective experimental animal study. University research laboratories. β-Actin-green fluorescent protein (GFP) transgenic C57BL/6-Tg (CAG-EGFP) and C57BL/6J female mice. The BMDCs were isolated from CAG-EGFP mice: unfractionated bone marrow cells, hematopoietic progenitor cells, endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs). In addition three murine GFP(+) cell lines were used: mouse Oct4 negative BMDC multipotent adult progenitor cells (mOct4(-)BM-MAPCs), BMDC hypoblast-like stem cells (mOct4(+) BM-HypoSCs), and MSCs. All cell types were injected through the tail vein of 9 Gy-irradiated C57BL/6J female mice. Flow cytometry, cell culture, bone marrow transplantation assays, histologic evaluation, immunohistochemistry, proliferation, apoptosis, and statistical analysis. After 12 weeks, histologic analysis revealed that uteri of mice with mOct4(-)BM-MAPCs and MSC line were significantly smaller than uteri of mice with uncultured BMDCs or mOct4(+) BM-HypoSCs. The percentage of engrafted GFP(+) cells ranged from 0.13%-4.78%. Expression of Ki-67 was lower in all uteri from BMDCs treated mice than in the control, whereas TUNEL(+) cells were increased in the EPCs and mOct4(+)BM-HypoSCs groups. Low number of some BMDCs can be found in regenerating endometrium, including stromal, endotelial, and epithelial compartments. Freshly isolated MSCs and EPCs together with mOct4(+) BM-HypoSCs induced the greatest degree of regeneration, whereas culture isolated MSCs and mOct4(-)BM-MAPCs transplantation may have an inhibitory effect on endometrial regeneration. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Effect of low-intensity pulsed ultrasound on bone regeneration: biochemical and radiologic analyses.

    Science.gov (United States)

    Pomini, Karina T; Andreo, Jesus C; Rodrigues, Antonio de C; de O Gonçalves, Jéssica B; Daré, Letícia R; German, Iris J S; Rosa, Geraldo M; Buchaim, Rogerio L

    2014-04-01

    The purpose of this study was to evaluate the effects of low-intensity pulsed ultrasound at 1.0 MHz on the healing process of fractures with bone loss in the rat fibula by alkaline phosphate level measurement and radiologic analyses. Thirty 70-day-old male Wistar rats underwent a bone resection of 2.5 to 3.0 mm between the proximal and middle third of the right fibular diaphysis. The animals were randomly divided into 3 experimental groups: reference (uninjured), control (injured only), and treated (injured and treated with 5 applications of ultrasound, interspersed by 2 days of rest, beginning 24 hours after the osteotomy). Euthanasia was performed at experimental periods of 7 and 14 days. The right hind limb was removed for radiologic analysis. The blood was collected via cardiac puncture to determine the serum alkaline phosphatase activity. The bone fractures had not been completely consolidated in the treated and control group when analysis of the bone took place. At day 7, the serum alkaline phosphatase activity was higher in the treated group (mean ± SD, 72.17 ± 7.02 U/L) compared to the control (65.26 ± 8.41 U/L) and reference (67.21 ± 7.86 U/L) groups. At day 14, higher alkaline phosphatase activity was seen in the control group (68.96 ± 8.12 U/L) compared to the treated (66.09 ± 8.46 U/L) and reference (67.14 ± 7.96 U/L) groups. The biochemical and radiologic results suggest that low-intensity pulsed ultrasound can be used as an auxiliary method to consolidate fractures and probably reduces the bone healing time, offering clinical benefits.

  17. Osseointegration of subperiosteal implants using bovine bone substitute and various membranes

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  18. Regeneration of FBGs during the HFCVD diamond-fiber coating process

    Science.gov (United States)

    Alberto, Nélia J.; Kalinowski, Hypolito J.; Neto, Victor F.; Nogueira, Rogério N.

    2014-08-01

    In this work, the regeneration of saturated fiber Bragg gratings during the diamond coating of the fiber is presented. Due to the high temperatures characteristic of the hot filament chemical vapor deposition (HFCVD) process (around 800 ºC), uniform fiber Bragg gratings (FBGs) are not appropriate to be coated. Nevertheless, regenerated Bragg gratings are a suitable solution for this drawback. Its production process involves the inscription of a saturated FBG followed by a time consuming heat treatment. Here it is proposed to take advantage of the high temperatures characteristic of the HFCVD process to simultaneous regenerate the grating and coat the fiber with diamond.

  19. Synthesis of calcium-phosphate and chitosan bioceramics for bone regeneration

    Directory of Open Access Journals (Sweden)

    MELLATIE R. FINISIE

    2001-12-01

    Full Text Available Bioceramic composites were obtained from chitosan and hydroxyapatite pastes synthesized at physiological temperature according to two different syntheses approaches. Usual analytical techniques (X-ray diffraction analysis, Fourier transformed infrared spectroscopy, Thermo gravimetric analysis, Scanning electron microscopy, X-ray dispersive energy analysis and Porosimetry were employed to characterize the resulting material. The aim of this investigation was to study the bioceramic properties of the pastes with non-decaying behavior from chitosan-hydroxyapatite composites. Chitosan, which also forms a water-insoluble gel in the presence of calcium ions, and has been reported to have pharmacologically beneficial effects on osteoconductivity, was added to the solid phase of the hydroxyapatite powder. The properties exhibited by the chitosan-hydroxyapatite composites were characteristic of bioceramics applied as bone substitutes. Hydroxyapatite contents ranging from 85 to 98% (w/w resulted in suitable bioceramic composites for bone regeneration, since they showed a non-decaying behavior, good mechanical properties and suitable pore sizes.Compósitos biocerâmicos foram obtidos a partir de pastas de quitosana e hidroxiapatita, preparadas a temperatura fisiológica seguindo dois métodos diferentes de síntese. As técnicas analíticas usuais (Análise de difração de raios-X, Espectroscopia de absorção no infravermelho com transformada de Fourier, Análise termogravimétrica, Microscopia eletrônica de varredura, Análise por energia dispersiva de raios-X, e Porosimetria foram empregadas para caracterizar o material resultante. O objetivo deste trabalho foi estudar as propriedades biocerâmicas das pastas relativas ao comportamento de não-desintegração dos compósitos de quitosana-hidroxiapatita. A quitosana, que também forma um gel insolúvel em água na presença de íons cálcio, e tem mostrado possuir efeitos farmacologicamente ben

  20. Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen matrix

    Energy Technology Data Exchange (ETDEWEB)

    Cholas, Rahmatullah, E-mail: rahmat.cholas@gmail.com; Kunjalukkal Padmanabhan, Sanosh, E-mail: sanosh2001@gmail.com; Gervaso, Francesca; Udayan, Gayatri; Monaco, Graziana; Sannino, Alessandro; Licciulli, Antonio

    2016-06-01

    Biomimetic scaffolds with a structural and chemical composition similar to native bone tissue may be promising for bone tissue regeneration. In the present work hydroxyapatite mesoporous microspheres (mHA) were incorporated into collagen scaffolds containing an ordered interconnected macroporosity. The mHA were obtained by spray drying of a nano hydroxyapatite slurry prepared by the precipitation technique. X-ray diffraction (XRD) analysis revealed that the microspheres were composed only of hydroxyapatite (HA) phase, and energy-dispersive x-ray spectroscopy (EDS) analysis revealed the Ca/P ratio to be 1.69 which is near the value for pure HA. The obtained microspheres had an average diameter of 6 μm, a specific surface area of 40 m{sup 2}/g as measured by Brunauer-Emmett-Teller (BET) analysis, and Barrett-Joyner-Halenda (BJH) analysis showed a mesoporous structure with an average pore diameter of 16 nm. Collagen/HA-microsphere (Col/mHA) composite scaffolds were prepared by freeze-drying followed by dehydrothermal crosslinking. SEM observations of Col/mHA scaffolds revealed HA microspheres embedded within a porous collagen matrix with a pore size ranging from a few microns up to 200 μm, which was also confirmed by histological staining of sections of paraffin embedded scaffolds. The compressive modulus of the composite scaffold at low and high strain values was 1.7 and 2.8 times, respectively, that of pure collagen scaffolds. Cell proliferation measured by the MTT assay showed more than a 3-fold increase in cell number within the scaffolds after 15 days of culture for both pure collagen scaffolds and Col/mHA composite scaffolds. Attractive properties of this composite scaffold include the potential to load the microspheres for drug delivery and the controllability of the pore structure at various length scales. - Highlights: • Mesoporous hydroxyapatite microsphere(mHA) synthesized by spray drying method • Porous collagen/mHA composite scaffold made by freeze

  1. Mechanical and cytotoxicity evaluation of nanostructured hydroxyapatite-bredigite scaffolds for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Eilbagi, Marjan; Emadi, Rahmatollah; Raeissi, Keyvan [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Kharaziha, Mahshid, E-mail: ma.kharaziha@gmail.com [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Valiani, Ali [Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73441 (Iran, Islamic Republic of)

    2016-11-01

    Despite the attractive characteristics of three-dimensional pure hydroxyapatite (HA) scaffolds, due to their weak mechanical properties, researches have focused on the development of composite scaffolds via introducing suitable secondary components. The aim of this study was to develop, for the first time, three-dimensional HA-bredigite (Ca{sub 7}MgSi{sub 4}O{sub 16}) scaffolds containing various amounts of bredigite nanopowder (0, 5, 10 and 15 wt.%) using space holder technique. Transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy and X-ray diffraction spectroscopy were applied in order to study the morphology, fracture surface and phase compositions of nanopowders and scaffolds. Furthermore, the effects of scaffold composition on the mechanical properties, bioactivity, biodegradability, and cytotoxicity were also evaluated. Results showed that the composite scaffolds with average pore size in the range of 220–310 μm, appearance porosity of 63.1–75.9% and appearance density of 1.1 ± 0.04 g/cm{sup 3} were successfully developed, depending on bredigite content. Indeed, the micropore size of the scaffolds reduced with increasing bredigite content confirming that the sinterability of the scaffolds was improved. Furthermore, the compression strength and modulus of the scaffolds significantly enhanced via incorporation of bredigite content from 0 to 15 wt.%. The composite scaffolds revealed superior bioactivity and biodegradability with increasing bredigite content. Moreover, MTT assay confirmed that HA-15 wt.% bredigite scaffold significantly promoted cell proliferation compared to tissue culture plate (control) and HA scaffold. Based on these results, three-dimensional HA-bredigite scaffolds could be promising replacements for HA scaffolds in bone regeneration. - Highlights: • Nanostructured hydroxyapatite-bredigite composite scaffolds were developed using space holder technique. • Presence of bredigite

  2. Functionalized PCL/HA nanocomposites as microporous membranes for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Basile, Maria Assunta; Gomez d' Ayala, Giovanna; Malinconico, Mario [Institute for Polymers, Composites and Biomaterials, CNR, Via Campi Flegrei 34, Pozzuoli (Naples) (Italy); Laurienzo, Paola, E-mail: paola.laurienzo@ipcb.cnr.it [Institute for Polymers, Composites and Biomaterials, CNR, Via Campi Flegrei 34, Pozzuoli (Naples) (Italy); Coudane, Jean; Nottelet, Benjamin [Institut des Biomolécules Max Mousseron (IBMM), Artificial Biopolymers Group, CNRS UMR 5247, University of Montpellier 1, Faculty of Pharmacy, 15 Av. C. Flahault, Montpellier 34093 (France); Ragione, Fulvio Della [Department of Biochemistry and Biophysics, Second University of Naples, Via L. De Crecchio 7, Naples (Italy); Oliva, Adriana, E-mail: adriana.oliva@unina2.it [Department of Biochemistry and Biophysics, Second University of Naples, Via L. De Crecchio 7, Naples (Italy)

    2015-03-01

    In the present work, microporous membranes based on poly(ε-caprolactone) (PCL) and PCL functionalized with amine (PCL-DMAEA) or anhydride groups (PCL-MAGMA) were realized by solvent–non solvent phase inversion and proposed for use in Guided Tissue Regeneration (GTR). Nanowhiskers of hydroxyapatite (HA) were also incorporated in the polymer matrix to realize nanocomposite membranes. Scanning Electron Microscopy (SEM) showed improved interfacial adhesion with HA for functionalized polymers, and highlighted substantial differences in the porosity. A relationship between the developed porous structure of the membrane and the chemical nature of grafted groups was proposed. Compared to virgin PCL, hydrophilicity increases for functionalized PCL, while the addition of HA influences significantly the hydrophilic characteristics only in the case of virgin polymer. A significant increase of in vitro degradation rate was found for PCL-MAGMA based membranes, and at lower extent of PCL-DMAEA membranes. The novel materials were investigated regarding their potential as support for cell growth in bone repair using multipotent mesenchymal stromal cells (MSC) as a model. MSC plated onto the various membranes were analyzed in terms of adhesion, proliferation and osteogenic capacity that resulted to be related to chemical as well as porous structure. In particular, PCL-DMAEA and the relative nanocomposite membranes are the most promising in terms of cell-biomaterial interactions. - Graphical abstract: Functionalized PCL is used to realize nanocomposites with hydroxyapatite (HA) in the form of microporous membranes. The influence of different grafted groups on mechanical properties, in vitro degradation, porous membrane structure and interaction with mesenchymal stromal cells (MSC) is discussed. - Highlights: • Functionalized PCL shows faster in vitro degradation rate. • Functionalized PCL shows superior cell adhesion, proliferation and differentiation. • Nanocomposites based

  3. Functionalized PCL/HA nanocomposites as microporous membranes for bone regeneration

    International Nuclear Information System (INIS)

    Basile, Maria Assunta; Gomez d'Ayala, Giovanna; Malinconico, Mario; Laurienzo, Paola; Coudane, Jean; Nottelet, Benjamin; Ragione, Fulvio Della; Oliva, Adriana

    2015-01-01

    In the present work, microporous membranes based on poly(ε-caprolactone) (PCL) and PCL functionalized with amine (PCL-DMAEA) or anhydride groups (PCL-MAGMA) were realized by solvent–non solvent phase inversion and proposed for use in Guided Tissue Regeneration (GTR). Nanowhiskers of hydroxyapatite (HA) were also incorporated in the polymer matrix to realize nanocomposite membranes. Scanning Electron Microscopy (SEM) showed improved interfacial adhesion with HA for functionalized polymers, and highlighted substantial differences in the porosity. A relationship between the developed porous structure of the membrane and the chemical nature of grafted groups was proposed. Compared to virgin PCL, hydrophilicity increases for functionalized PCL, while the addition of HA influences significantly the hydrophilic characteristics only in the case of virgin polymer. A significant increase of in vitro degradation rate was found for PCL-MAGMA based membranes, and at lower extent of PCL-DMAEA membranes. The novel materials were investigated regarding their potential as support for cell growth in bone repair using multipotent mesenchymal stromal cells (MSC) as a model. MSC plated onto the various membranes were analyzed in terms of adhesion, proliferation and osteogenic capacity that resulted to be related to chemical as well as porous structure. In particular, PCL-DMAEA and the relative nanocomposite membranes are the most promising in terms of cell-biomaterial interactions. - Graphical abstract: Functionalized PCL is used to realize nanocomposites with hydroxyapatite (HA) in the form of microporous membranes. The influence of different grafted groups on mechanical properties, in vitro degradation, porous membrane structure and interaction with mesenchymal stromal cells (MSC) is discussed. - Highlights: • Functionalized PCL shows faster in vitro degradation rate. • Functionalized PCL shows superior cell adhesion, proliferation and differentiation. • Nanocomposites based

  4. Mesenchymal stem cells-seeded bio-ceramic construct for bone regeneration in large critical-size bone defect in rabbit

    Directory of Open Access Journals (Sweden)

    Maiti SK

    2016-11-01

    Full Text Available Bone marrow derived mesenchymal stem cells (BMSC represent an attractive cell population for tissue engineering purpose. The objective of this study was to determine whether the addition of recombinant human bone morphogenetic protein (rhBMP-2 and insulin-like growth factor (IGF-1 to a silica-coated calcium hydroxyapatite (HASi - rabbit bone marrow derived mesenchymal stem cell (rBMSC construct promoted bone healing in a large segmental bone defect beyond standard critical -size radial defects (15mm in rabbits. An extensively large 30mm long radial ostectomy was performed unilaterally in thirty rabbits divided equally in five groups. Defects were filled with a HASi scaffold only (group B; HASi scaffold seeded with rBMSC (group C; HASi scaffold seeded with rBMSC along with rhBMP-2 and IGF-1 in groups D and E respectively. The same number of rBMSC (five million cells and concentration of growth factors rhBMP-2 (50µg and IGF-1 (50µg was again injected at the site of bone defect after 15 days of surgery in their respective groups. An empty defect served as the control group (group A. Radiographically, bone healing was evaluated at 7, 15, 30, 45, 60 and 90 days post implantation. Histological qualitative analysis with microCT (µ-CT, haematoxylin and eosin (H & E and Masson’s trichrome staining were performed 90 days after implantation. All rhBMP-2-added constructs induced the formation of well-differentiated mineralized woven bone surrounding the HASi scaffolds and bridging bone/implant interfaces as early as eight weeks after surgery. Bone regeneration appeared to develop earlier with the rhBMP-2 constructs than with the IGF-1 added construct. Constructs without any rhBMP-2 or IGF-1 showed osteoconductive properties limited to the bone junctions without bone ingrowths within the implantation site. In conclusion, the addition of rhBMP-2 to a HASi scaffold could promote bone generation in a large critical-size-defect.

  5. Ribose mediated crosslinking of collagen-hydroxyapatite hybrid scaffolds for bone tissue regeneration using biomimetic strategies.

    Science.gov (United States)

    Krishnakumar, Gopal Shankar; Gostynska, Natalia; Campodoni, Elisabetta; Dapporto, Massimiliano; Montesi, Monica; Panseri, Silvia; Tampieri, Anna; Kon, Elizaveta; Marcacci, Maurilio; Sprio, Simone; Sandri, Monica

    2017-08-01

    This study explores for the first time the application of ribose as a highly biocompatible agent for the crosslinking of hybrid mineralized constructs, obtained by bio-inspired mineralization of self-assembling Type I collagen matrix with magnesium-doped-hydroxyapatite nanophase, towards a biomimetic mineralized 3D scaffolds (MgHA/Coll) with excellent compositional and structural mimicry of bone tissue. To this aim, two different crosslinking mechanisms in terms of pre-ribose glycation (before freeze drying) and post-ribose glycation (after freeze drying) were investigated. The obtained results explicate that with controlled freeze-drying, highly anisotropic porous structures with opportune macro-micro porosity are obtained. The physical-chemical features of the scaffolds characterized by XRD, FTIR, ICP and TGA demonstrated structural mimicry analogous to the native bone. The influence of ribose greatly assisted in decreasing solubility and increased enzymatic resistivity of the scaffolds. In addition, enhanced mechanical behaviour in response to compressive forces was achieved. Preliminary cell culture experiments reported good cytocompatibility with extensive cell adhesion, proliferation and colonization. Overall, scaffolds developed by pre-ribose glycation process are preferred, as the related crosslinking technique is more facile and robust to obtain functional scaffolds. As a proof of concept, we have demonstrated that ribose crosslinking is cost-effective, safe and functionally effective. This study also offers new insights and opportunities in developing promising scaffolds for bone tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Preparation of in situ hardening composite microcarriers: Calcium phosphate cement combined with alginate for bone regeneration

    Science.gov (United States)

    Park, Jung-Hui; Lee, Eun-Jung; Knowles, Jonathan C

    2014-01-01

    Novel microcarriers consisting of calcium phosphate cement and alginate were prepared for use as three-dimensional scaffolds for the culture and expansion of cells that are effective for bone tissue engineering. The calcium phosphate cement-alginate composite microcarriers were produced by an emulsification of the composite aqueous solutions mixed at varying ratios (calcium phosphate cement powder/alginate solution = 0.8–1.2) in an oil bath and the subsequent in situ hardening of the compositions during spherodization. Moreover, a porous structure could be easily created in the solid microcarriers by soaking the produced microcarriers in water and a subsequent freeze-drying process. Bone mineral-like apatite nanocrystallites were shown to rapidly develop on the calcium phosphate cement–alginate microcarriers under moist conditions due to the conversion of the α-tricalcium phosphate phase in the calcium phosphate cement into a carbonate–hydroxyapatite. Osteoblastic cells cultured on the microspherical scaffolds were proven to be viable, with an active proliferative potential during 14 days of culture, and their osteogenic differentiation was confirmed by the determination of alkaline phosphatase activity. The in situ hardening calcium phosphate cement–alginate microcarriers developed herein may be used as potential three-dimensional scaffolds for cell delivery and tissue engineering of bone. PMID:23836845

  7. 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.

  8. Mussel-inspired graphene oxide nanosheet-enwrapped Ti scaffolds with drug-encapsulated gelatin microspheres for bone regeneration.

    Science.gov (United States)

    Han, Lu; Sun, Honglong; Tang, Pengfei; Li, Pengfei; Xie, Chaoming; Wang, Menghao; Wang, Kefeng; Weng, Jie; Tan, Hui; Ren, Fuzeng; Lu, Xiong

    2018-02-27

    Graphene oxide (GO) attracts considerable attention for biomedical applications owing to its unique nanostructure and remarkable physicochemical characteristics. However, it is challenging to uniformly deposit GO on chemically inert Ti scaffolds, which have good biocompatibility and wide applications in bone engineering. In this study, a GO-functionalized Ti porous scaffold (GO/Ti scaffold) was prepared by depositing GO onto polydopamine (PDA) modified Ti scaffolds. The mussel-inspired PDA modification facilitated the interaction between GO and Ti surfaces, leading to a uniform coverage of GO on Ti scaffolds. BMP2 and vancomycin (Van) were separately encapsulated into gelatin microspheres (GelMS). Then, drug-containing GelMS were assembled on GO/Ti scaffolds and anchored by the functional groups of GO. The modified scaffold independently delivered multiple biomolecules with different physiochemical properties, without interfering with each other. Thus, the GO/Ti scaffold has the dual functions of inducing bone regeneration and preventing bacterial infection. In summary, this mussel-inspired GO/Ti hybrid scaffold combined the good mechanical properties of Ti scaffolds and the advantages of GO nanosheets. GO nanosheets with their unique nanostructure and functional groups, together with GelMS on Ti scaffolds, are suitable carriers for drug delivery and provide adhesive sites for cell adhesion and create nanostructured environments for bone regeneration.

  9. Development of an Injectable Calcium Phosphate/Hyaluronic Acid Microparticles System for Platelet Lysate Sustained Delivery Aiming Bone Regeneration.

    Science.gov (United States)

    Babo, Pedro S; Santo, Vítor E; Gomes, Manuela E; Reis, Rui L

    2016-11-01

    Despite the biocompatibility and osteoinductive properties of calcium phosphate (CaP) cements their low biodegradability hampers full bone regeneration. Herein the incorporation of CaP cement with hyaluronic acid (HAc) microparticles loaded with platelet lysate (PL) to improve the degradability and biological performance of the cements is proposed. Cement formulations incorporating increasing weight ratios of either empty HAc microparticles or microparticles loaded with PL (10 and 20 wt%) are developed as well as cements directly incorporating PL. The direct incorporation of PL improves the mechanical properties of the plain cement, reaching values similar to native bone. Morphological analysis shows homogeneous particle distribution and high interconnectivity between the HAc microparticles. The cements incorporating PL (with or without the HAc microparticles) present a sustained release of PL proteins for up to 8 d. The sustained release of PL modulates the expression of osteogenic markers in seeded human adipose tissue derived stem cells, thus suggesting the stimulatory role of this hybrid system toward osteogenic commitment and bone regeneration applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Comparative Efficacies of a 3D-Printed PCL/PLGA/β-TCP Membrane and a Titanium Membrane for Guided Bone Regeneration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jin-Hyung Shim

    2015-10-01

    Full Text Available This study was conducted to evaluate the effects of a 3D-printed resorbable polycaprolactone/poly(lactic-co-glycolic acid/β-tricalcium phosphate (PCL/PLGA/β-TCP membrane on bone regeneration and osseointegration in areas surrounding implants and to compare results with those of a non-resorbable titanium mesh membrane. After preparation of PCL/PLGA/β-TCP membranes using extrusion-based 3D printing technology; mechanical tensile testing and in vitro cell proliferation testing were performed. Implant surgery and guided bone regeneration were performed randomly in three groups (a no membrane group, a titanium membrane group, and a PCL/PLGA/β-TCP membrane group (n = 8 per group. Histological and histometric analyses were conducted to evaluate effects on bone regeneration and osseointegration. Using the results of mechanical testing; a PCL/PLGA/β-TCP ratio of 2:6:2 was selected. The new bone areas (% in buccal defects around implants were highest in the PCL/PLGA/β-TCP group and significantly higher than in the control group (p < 0.05. Bone-to-implant contact ratios (% were also significantly higher in the PCL/PLGA/β-TCP and titanium groups than in the control group (p < 0.05. When the guided bone regeneration procedure was performed using the PCL/PLGA/β-TCP membrane; new bone formation around the implant and osseointegration were not inferior to those of the non-resorbable pre-formed titanium mesh membrane.

  11. Kaolinite adsorption-regeneration system for dyestuff treatment by Fenton based processes.

    Science.gov (United States)

    Rosales, Emilio; Anasie, Delia; Pazos, Marta; Lazar, Iuliana; Sanromán, M Angeles

    2018-05-01

    The regeneration and reuse of adsorbents is a subject of interest nowadays in order to reduce the pollution and the wastes generated in the adsorption wastewater treatment. In this work, the regeneration of the spent kaolinite by different advanced oxidation processes (Fenton, electro-Fenton and electrokinetic-Fenton) was evaluated. Initially, it was confirmed the ability of a low cost clayey material, kaolinite, for the adsorption of model dye such as Rhodamine B showing Freundlich isotherm fitting. Then, the regeneration and consequent degradation of the pollutant in the adsorbent by Fenton based processes was carried out. The role of different parameters affecting the regeneration process (H 2 O 2 :Fe 2+ ratio, liquid:solid ratio) were evaluated. Working at 100:1 H 2 O 2 :Fe 2+ ratio and 30min near complete dye removal (around 97%) from kaolinite was obtained by Fenton treatment. After that, a two-stage treatment for adsorption-regeneration was evaluated during five treatment cycles demonstrating its viability for regeneration of the adsorbent through dye degradation. Based on the successful application of Fenton technique, the improvement of the treatment by electro-Fenton and electrokinetic-Fenton were studied for different solid:liquid ratios achieving satisfactory regeneration values. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The impact of zoledronic acid on regenerate and native bone after consolidation and removal of the external fixator: an animal model study.

    Science.gov (United States)

    Saghieh, Said; Khoury, Nabil J; Tawil, Ayman; Masrouha, Karim Z; Musallam, Khaled M; Khalaf, Kinda; Dosh, Laura; Jaouhari, Rosemarie Reich; Birjawi, Ghina; El-Hajj-Fuleihan, Ghada

    2010-02-01

    We investigated the role of zoledronic acid on the regenerate and native bone after consolidation and removal of the external fixator in a rabbit model of distraction osteogenesis using 28 New Zealand white rabbits. The rabbits were randomly distributed into two groups. The first group received three doses of zoledronic acid (ZA) 0.1 mg/kg subcutaneously at weekly intervals while the second group received injections of sterile saline. Distraction started on day 7 at a rate of 0.8 mm/day for 12 days. At week 3 the average lengthening, regenerate density, and regenerate continuity were comparable between the two groups. At week 11 the regenerate in the treated group had a significant increase in Bone Mineral Density (BMD) and Bone Mineral Content (BMC) compared to the placebo group. On axial compression, the regenerate showed an increase in the peak load and a higher modulus of elasticity in the treated group. At 6 months, radiographs demonstrated signs of osteopenia of the proximal metaphysis in the control group, and failure of new bone formation around the pin sites in the treated group. BMC and BMD value differences between the two groups were not statistically significant. Histologically, there was persistence of more bone trabeculae in the medullary canal of the regenerate with the persistence of the pin-holes in the treated group. Mechanically, the regenerates in the treated group remain stronger in resisting the axial compression. The proximal fragment in the treated group exhibited a statistically significant decrease in the peak load, toughness and efail %. In conclusion, bisphosphonate-treated rabbits have a stronger regenerate during distraction, and directly after removal of the fixator. They do not develop disuse osteopenia in their lengthened tibia. This treatment may shorten the time in the external fixator and prevent fragility fractures in the treated extremity. However, its long-term safety has not yet been established. (c) 2009 Elsevier Inc. All

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

    Science.gov (United States)

    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

  14. Bone Adaptation as an Evolutionary Process

    DEFF Research Database (Denmark)

    Bagge, Mette

    1998-01-01

    . The memory of past loadings is included in themodel to account for the delay in the bone response from the loadchanges. The remodeling rate equation is derived from the structuraloptimization task of maximizing the stiffness in each time step. Additional informationscan be extracted from the optimization...... process; the remodelingequilibrium parameter where no apposition or resorption takes place is defined asthe element optimality conditions and the optimal design is used as aninitial design for the onset ofthe remodeling simulation. Some examples of boneadaptation resulting from load changes is given....

  15. Efficacy of Platelet-Rich-Plasma (PRP and Highly Purified Bovine Xenograft (Laddec® Combination in Bone Regeneration after Cyst Enucleation: Radiological and Histological Evaluation

    Directory of Open Access Journals (Sweden)

    Sabrina Pappalardo

    2013-10-01

    Full Text Available Objectives: The purpose of the present study was to evaluate the efficacy of adding platelet-rich plasma (PRP to a new highly purified bovine allograft (Laddec® in the bone regeneration of cystic bony defects augmented following cystectomy.Material and Methods: Study sample included 20 patients undergoing cystectomy in which the bone defect was filled with PRP and Laddec®. All patients were examined with periapical radiographs before operation and at follow-up. After 3 months, at re-entry surgery for implant placement, bone core was taken for histological and histomorphometric analysis.Results: The postoperative successive radiographs showed a good regeneration of bone in the height of bony defects with application of PRP to bone graft. By the first postoperative month, about 48% of the defect was filled, which gradually increased in each month and showed about 90% of defect-fill by 6 months. Histological and histomorphometric analysis, showed a significant presence of bone tissue and vessels, with newly formed bone in contact with anorganic bone particles. The mean volume of vital bone was 68 ± 1.6% and the mean percentage of vital bone was 48 ± 2.4%. The mean percentage of inorganic particles in tissues was 20 ± 1.2% of the total volume. All the samples analyzed did not evidence the presence of inflammatory cells.Conclusions: The results of this study showed how the use of Laddec® in association with platelet-rich plasma allows bone regeneration and has a potential for routine clinical use for regeneration of cystic bony defects.

  16. Developmental and adult-specific processes contribute to de novo neuromuscular regeneration in the lizard tail.

    Science.gov (United States)

    Tokuyama, Minami A; Xu, Cindy; Fisher, Rebecca E; Wilson-Rawls, Jeanne; Kusumi, Kenro; Newbern, Jason M

    2018-01-15

    Peripheral nerves exhibit robust regenerative capabilities in response to selective injury among amniotes, but the regeneration of entire muscle groups following volumetric muscle loss is limited in birds and mammals. In contrast, lizards possess the remarkable ability to regenerate extensive de novo muscle after tail loss. However, the mechanisms underlying reformation of the entire neuromuscular system in the regenerating lizard tail are not completely understood. We have tested whether the regeneration of the peripheral nerve and neuromuscular junctions (NMJs) recapitulate processes observed during normal neuromuscular development in the green anole, Anolis carolinensis. Our data confirm robust axonal outgrowth during early stages of tail regeneration and subsequent NMJ formation within weeks of autotomy. Interestingly, NMJs are overproduced as evidenced by a persistent increase in NMJ density 120 and 250 days post autotomy (DPA). Substantial Myelin Basic Protein (MBP) expression could also be detected along regenerating nerves indicating that the ability of Schwann cells to myelinate newly formed axons remained intact. Overall, our data suggest that the mechanism of de novo nerve and NMJ reformation parallel, in part, those observed during neuromuscular development. However, the prolonged increase in NMJ number and aberrant muscle differentiation hint at processes specific to the adult response. An examination of the coordinated exchange between peripheral nerves, Schwann cells, and newly synthesized muscle of the regenerating neuromuscular system may assist in the identification of candidate molecules that promote neuromuscular recovery in organisms incapable of a robust regenerative response. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Synthesis and characterization of strontium-substituted hydroxyapatite nanoparticles for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Frasnelli, Matteo, E-mail: matteo.frasnelli@unitn.it [Department of Industrial Engineering, University of Trento, Via Sommarive 9, 38123 Trento (Italy); INSTM Research Unit, Via G. Giusti 9, 50123 Firenze (Italy); Cristofaro, Francesco [Department of Molecular Medicine, Center for Health Technologies (CHT), University of Pavia, Viale Taramelli 3/b, 27100 Pavia (Italy); Sglavo, Vincenzo M. [Department of Industrial Engineering, University of Trento, Via Sommarive 9, 38123 Trento (Italy); INSTM Research Unit, Via G. Giusti 9, 50123 Firenze (Italy); Dirè, Sandra; Callone, Emanuela [Department of Industrial Engineering, University of Trento, Via Sommarive 9, 38123 Trento (Italy); “Klaus Müller” NMR Laboratory, Department of Industrial Engineering, University of Trento, Via Sommarive 9, 38123 Trento (Italy); Ceccato, Riccardo [Department of Industrial Engineering, University of Trento, Via Sommarive 9, 38123 Trento (Italy); Bruni, Giovanna [Department of Chemistry, Physical-Chemistry Section, University of Pavia, Viale Taramelli 16, 27100 Pavia (PV) (Italy); Cornaglia, Antonia Icaro [Department of Experimental Medicine, Faculty of Medicine, University of Pavia (Italy); Visai, Livia [Department of Molecular Medicine, Center for Health Technologies (CHT), University of Pavia, Viale Taramelli 3/b, 27100 Pavia (Italy); Department of Occupational Medicine, Toxicology and Environmental Risks, S. Maugeri Foundation, IRCCS, Via S. Boezio, 28, 27100 Pavia (PV) (Italy)

    2017-02-01

    The production of stable suspensions of strontium-substituted hydroxyapatite (Sr-HA) nanopowders, as Sr ions vector for bone tissue regeneration, was carried out in the present work. Sr-HA nanopowders were synthesized via aqueous precipitation methods using Sr{sup 2+} amount from 0 to 100 mol% and were characterized by several complementary techniques such as solid-state Nuclear Magnetic Resonance spectroscopy, X-ray diffraction, Infrared spectroscopy, N{sub 2} physisorption and Transmission Electron Microscopy. The substitution of Ca{sup 2+} with Sr{sup 2+} in HA is always isomorphic with gradual evolution between the two limit compositions (containing 100% Ca and 100% Sr), this pointing out the homogeneity of the synthesized nanopowders and the complete solubility of strontium in HA lattice. Strontium addition is responsible for an increasing c/a ratio in the triclinic unit cell. A significant variation of the nanopowders shape and dimension is also observed, a preferential growth along the c-axis direction being evident at higher strontium loads. Modifications in the local chemical environment of phosphate and hydroxyl groups in the apatite lattice are also observed. Stable suspensions were produced by dispersing the synthesized nanopowders in bovine serum albumin. Characterization by Dynamic Light Scattering and ζ-potential determination allowed to show that Ca{sup 2+} → Sr{sup 2+} substitution influences the hydrodynamic diameter, which is always twice the particles size determined by TEM, the nanoparticles being always negatively charged as a result from the albumin rearrangement upon the interaction with nanoparticles surface. The biocompatibility of the suspensions was studied in terms of cell viability, apoptosis, proliferation and morphology, using osteosarcoma cell line SAOS-2. The data pointed out an increased cell proliferation for HA nanoparticles containing larger Sr{sup 2+} load, the cells morphology remaining essentially unaffected. - Highlights

  18. Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model.

    Science.gov (United States)

    Saito, Akiko; Ooki, Akio; Nakamura, Takashi; Onodera, Shoko; Hayashi, Kamichika; Hasegawa, Daigo; Okudaira, Takahito; Watanabe, Katsuhito; Kato, Hiroshi; Onda, Takeshi; Watanabe, Akira; Kosaki, Kenjiro; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Sakamoto, Teruo; Yamaguchi, Akira; Sueishi, Kenji; Azuma, Toshifumi

    2018-01-22

    Runt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy is performed in addition to drug therapy. However, MSC-based therapy for osteoporosis in CCD patients is difficult due to a reduction in the ability of MSCs to differentiate into osteoblasts resulting from impaired RUNX2 function. Here, we investigated whether induced pluripotent stem cells (iPSCs) properly differentiate into osteoblasts after repairing the RUNX2 mutation in iPSCs derived from CCD patients to establish normal iPSCs, and whether engraftment of osteoblasts derived from properly reverted iPSCs results in better regeneration in immunodeficient rat calvarial bone defect models. Two cases of CCD patient-derived induced pluripotent stem cells (CCD-iPSCs) were generated using retroviral vectors (OCT3/4, SOX2, KLF4, and c-MYC) or a Sendai virus SeVdp vector (KOSM302L). Reverted iPSCs were established using programmable nucleases, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-derived RNA-guided endonucleases, to correct mutations in CCD-iPSCs. The mRNA expressions of osteoblast-specific markers were analyzed using quantitative reverse-transcriptase polymerase chain reaction. iPSCs-derived osteoblasts were transplanted into rat calvarial bone defects, and bone regeneration was evaluated using microcomputed tomography analysis and histological analysis. Mutation analysis showed that both contained nonsense mutations: one at the very beginning of exon 1 and the other at the initial position of the nuclear matrix-targeting signal. The osteoblasts derived from CCD-iPSCs (CCD-OBs) expressed low levels of several osteoblast differentiation markers, and transplantation of these osteoblasts into calvarial bone defects created in rats with

  19. Process based analysis of manually controlled drilling processes for bone

    Science.gov (United States)

    Teicher, Uwe; Achour, Anas Ben; Nestler, Andreas; Brosius, Alexander; Lauer, Günter

    2018-05-01

    The machining operation drilling is part of the standard repertoire for medical applications. This machining cycle, which is usually a multi-stage process, generates the geometric element for the subsequent integration of implants, which are screwed into the bone in subsequent processes. In addition to the form, shape and position of the generated drill hole, it is also necessary to use a technology that ensures an operation with minimal damage. A surface damaged by excessive mechanical and thermal energy input shows a deterioration in the healing capacity of implants and represents a structure with complications for inflammatory reactions. The resulting loads are influenced by the material properties of the bone, the used technology and the tool properties. An important aspect of the process analysis is the fact that machining of bone is in most of the cases a manual process that depends mainly on the skills of the operator. This includes, among other things, the machining time for the production of a drill hole, since manual drilling is a force-controlled process. Experimental work was carried out on the bone of a porcine mandible in order to investigate the interrelation of the applied load during drilling. It can be shown that the load application can be subdivided according to the working feed direction. The entire drilling process thus consists of several time domains, which can be divided into the geometry-generating feed motion and a retraction movement of the tool. It has been shown that the removal of the tool from the drill hole has a significant influence on the mechanical load input. This fact is proven in detail by a new evaluation methodology. The causes of this characteristic can also be identified, as well as possible ways of reducing the load input.

  20. The ultrastructure and processing properties of Straumann Bone Ceramic and NanoBone.

    Science.gov (United States)

    Dietze, S; Bayerlein, T; Proff, P; Hoffmann, A; Gedrange, T

    2006-02-01

    The ultrastructure, fundamental chemistry, and processing modes of fully synthetic bone grafting materials are relevant to the reconstruction of osseous defects. Rapid progress in the profitable market of biomaterials has led to the development of various bone substitutes. Despite all these efforts, an ideal and full substitute of autologous bone is not yet in sight. With regard to anorganic calcium phosphate ceramics, Straumann Bone Ceramic and NanoBone are compared. These have a similar composition and are osteoconductive, which indispensably requires contact with well-vascularised bone.

  1. Magnetic biodegradable Fe{sub 3}O{sub 4}/CS/PVA nanofibrous membranes for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Wei Yan; Zhang Xuehui; Hu Xiaoyang; Deng Xuliang [Department of Geriatric Dentistry, School and Hospital of Stomatology, Peking University, Beijing, 100081 (China); Song Yu; Lin Yuanhua [State Key Laboratory of New Ceramics and Fine Processing, Department of Materials Science and Engineering, Tsinghua University, Beijing, 100084 (China); Han Bing [Department of Orthodontics, School and Hospital of Stomatology, Peking University, Beijing, 100081 (China); Wang Xinzhi, E-mail: kqdengxuliang@bjmu.edu.cn [Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, 100081 (China)

    2011-10-15

    In recent years, interest in magnetic biomimetic scaffolds for tissue engineering has increased considerably. The aim of this study is to develop magnetic biodegradable fibrous materials with potential use in bone regeneration. Magnetic biodegradable Fe{sub 3}O{sub 4}/chitosan (CS)/poly vinyl alcohol (PVA) nanofibrous membranes were achieved by electrospinning with average fiber diameters ranging from 230 to 380 nm and porosity of 83.9-85.1%. The influences of polymer concentration, applied voltage and Fe{sub 3}O{sub 4} nanoparticles loading on the fabrication of nanofibers were investigated. The polymer concentration of 4.5 wt%, applied voltage of 20 kV and Fe{sub 3}O{sub 4} nanoparticles loading of lower than 5 wt% could produce homogeneous, smooth and continuous Fe{sub 3}O{sub 4}/CS/PVA nanofibrous membranes. X-ray diffraction (XRD) data confirmed that the crystalline structure of the Fe{sub 3}O{sub 4}, CS and PVA were maintained during electrospinning process. Fourier transform infrared spectroscopy (FT-IR) demonstrated that the Fe{sub 3}O{sub 4} loading up to 5 wt% did not change the functional groups of CS/PVA greatly. Transmission electron microscopy (TEM) showed islets of Fe{sub 3}O{sub 4} nanoparticles evenly distributed in the fibers. Weak ferrimagnetic behaviors of membranes were revealed by vibrating sample magnetometer (VSM) test. Tensile test exhibited Young's modulus of membranes that were gradually enhanced with the increase of Fe{sub 3}O{sub 4} nanoparticles loading, while ultimate tensile stress and ultimate strain were slightly reduced by Fe{sub 3}O{sub 4} nanoparticles loading of 5%. Additionally, MG63 human osteoblast-like cells were seeded on the magnetic nanofibrous membranes to evaluate their bone biocompatibility. Cell growth dynamics according to MTT assay and scanning electron microscopy (SEM) observation exhibited good cell adhesion and proliferation, suggesting that this magnetic biodegradable Fe{sub 3}O{sub 4}/CS/PVA nanofibrous

  2. Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration

    Science.gov (United States)

    2013-01-01

    Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

  3. Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration.

    Science.gov (United States)

    Albanese, Antonino; Licata, Maria E; Polizzi, Bianca; Campisi, Giuseppina

    2013-06-13

    Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

  4. Calcium phosphate coated Keratin-PCL scaffolds for potential bone tissue regeneration.

    Science.gov (United States)

    Zhao, Xinxin; Lui, Yuan Siang; Choo, Caleb Kai Chuen; Sow, Wan Ting; Huang, Charlotte Liwen; Ng, Kee Woei; Tan, Lay Poh; Loo, Joachim Say Chye

    2015-04-01

    The incorporation of hydroxyapatite (HA) nanoparticles within or on the surface of electrospun polymeric scaffolds is a popular approach for bone tissue engineering. However, the fabrication of osteoconductive composite scaffolds via benign processing conditions still remains a major challenge to date. In this work, a new method was developed to achieve a uniform coating of calcium phosphate (CaP) onto electrospun keratin-polycaprolactone composites (Keratin-PCL). Keratin within PCL was crosslinked to decrease its solubility, before coating of CaP. A homogeneous coating was achieved within a short time frame (~10min) by immersing the scaffolds into Ca(2+) and (PO4)(3-) solutions separately. Results showed that the incorporation of keratin into PCL scaffolds not only provided nucleation sites for Ca(2+) adsorption and subsequent homogeneous CaP surface deposition, but also facilitated cell-matrix interactions. An improvement in the mechanical strength of the resultant composite scaffold, as compared to other conventional coating methods, was also observed. This approach of developing a biocompatible bone tissue engineering scaffold would be adopted for further in vitro osteogenic differentiation studies in the future. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Acceleration of bone development and regeneration through the Wnt/β-catenin signaling pathway in mice heterozygously deficient for GSK-3β

    International Nuclear Information System (INIS)

    Arioka, Masaki; Takahashi-Yanaga, Fumi; Sasaki, Masanori; Yoshihara, Tatsuya; Morimoto, Sachio; Takashima, Akihiko; Mori, Yoshihide; Sasaguri, Toshiyuki

    2013-01-01

    Highlights: •The Wnt/β-catenin signaling pathway was activated in GSK-3β +/− mice. •The cortical and trabecular bone volumes were increased in GSK-3β +/− mice. •Regeneration of a partial bone defect was accelerated in GSK-3β +/− mice. -- Abstract: Glycogen synthase kinase (GSK)-3β plays an important role in osteoblastogenesis by regulating the Wnt/β-catenin signaling pathway. Therefore, we investigated whether GSK-3β deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3β (GSK-3β +/− ). The amounts of β-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3β +/− mice were significantly increased compared with those of wild-type mice, indicating that Wnt/β-catenin signals were enhanced in GSK-3β +/− mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3β +/− mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3β deficiency on bone regeneration, we established a partial bone defect in the femur and observed new bone at 14 days after surgery. The volume and mineral density of the new bone were significantly higher in GSK-3β +/− mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3β, probably through activation of the Wnt/β-catenin signaling pathway

  6. Acceleration of bone development and regeneration through the Wnt/β-catenin signaling pathway in mice heterozygously deficient for GSK-3β

    Energy Technology Data Exchange (ETDEWEB)

    Arioka, Masaki [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Takahashi-Yanaga, Fumi, E-mail: yanaga@clipharm.med.kyushu-u.ac.jp [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Global Medical Science Education Unit, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Sasaki, Masanori [Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Yoshihara, Tatsuya; Morimoto, Sachio [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Takashima, Akihiko [Department of Aging Neurobiology, National Center for Geriatrics and Gerontology, Oobu (Japan); Mori, Yoshihide [Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Sasaguri, Toshiyuki [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan)

    2013-11-01

    Highlights: •The Wnt/β-catenin signaling pathway was activated in GSK-3β{sup +/−} mice. •The cortical and trabecular bone volumes were increased in GSK-3β{sup +/−} mice. •Regeneration of a partial bone defect was accelerated in GSK-3β{sup +/−} mice. -- Abstract: Glycogen synthase kinase (GSK)-3β plays an important role in osteoblastogenesis by regulating the Wnt/β-catenin signaling pathway. Therefore, we investigated whether GSK-3β deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3β (GSK-3β{sup +/−}). The amounts of β-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3β{sup +/−} mice were significantly increased compared with those of wild-type mice, indicating that Wnt/β-catenin signals were enhanced in GSK-3β{sup +/−} mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3β{sup +/−} mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3β deficiency on bone regeneration, we established a partial bone defect in the femur and observed new bone at 14 days after surgery. The volume and mineral density of the new bone were significantly higher in GSK-3β{sup +/−} mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3β, probably through activation of the Wnt/β-catenin signaling pathway.

  7. Hydrostatic pressure in combination with topographical cues affects the fate of bone marrow‐derived human mesenchymal stem cells for bone tissue regeneration

    Science.gov (United States)

    El Haj, Alicia J.

    2017-01-01

    Abstract Topographical and mechanical cues are vital for cell fate, tissue development in vivo, and to mimic the native cell growth environment in vitro. To date, the combinatory effect of mechanical and topographical cues as not been thoroughly investigated. This study investigates the effect of PCL nanofiber alignment and hydrostatic pressure on stem cell differentiation for bone tissue regeneration. Bone marrow‐derived human mesenchymal stem cells were seeded onto standard tissue culture plastic and electrospun random and aligned nanofibers. These substrates were either cultured statically or subjected to intermittent hydrostatic pressure at 270 kPa, 1 Hz for 60 min daily over 21 days in osteogenic medium. Data revealed higher cell metabolic activities for all mechanically stimulated cell culture formats compared with non‐stimulated controls; and random fibers compared with aligned fibers. Fiber orientation influenced cell morphology and patterns of calcium deposition. Significant up‐regulation of Collagen‐I, ALP, and Runx‐2 were observed for random and aligned fibers following mechanical stimulation; highest levels of osteogenic markers were expressed when hydrostatic pressure was applied to random fibers. These results indicate that fiber alignment and hydrostatic pressure direct stem cell fate and are important stimulus for tissue regeneration. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: A: 629–640, 2018. PMID:28984025

  8. Hydrostatic pressure in combination with topographical cues affects the fate of bone marrow-derived human mesenchymal stem cells for bone tissue regeneration.

    Science.gov (United States)

    Reinwald, Yvonne; El Haj, Alicia J

    2018-03-01

    Topographical and mechanical cues are vital for cell fate, tissue development in vivo, and to mimic the native cell growth environment in vitro. To date, the combinatory effect of mechanical and topographical cues as not been thoroughly investigated. This study investigates the effect of PCL nanofiber alignment and hydrostatic pressure on stem cell differentiation for bone tissue regeneration. Bone marrow-derived human mesenchymal stem cells were seeded onto standard tissue culture plastic and electrospun random and aligned nanofibers. These substrates were either cultured statically or subjected to intermittent hydrostatic pressure at 270 kPa, 1 Hz for 60 min daily over 21 days in osteogenic medium. Data revealed higher cell metabolic activities for all mechanically stimulated cell culture formats compared with non-stimulated controls; and random fibers compared with aligned fibers. Fiber orientation influenced cell morphology and patterns of calcium deposition. Significant up-regulation of Collagen-I, ALP, and Runx-2 were observed for random and aligned fibers following mechanical stimulation; highest levels of osteogenic markers were expressed when hydrostatic pressure was applied to random fibers. These results indicate that fiber alignment and hydrostatic pressure direct stem cell fate and are important stimulus for tissue regeneration. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: A: 629-640, 2018. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc.

  9. A tissue engineering solution for segmental defect regeneration in load-bearing long bones.

    Science.gov (United States)

    Reichert, Johannes C; Cipitria, Amaia; Epari, Devakara R; Saifzadeh, Siamak; Krishnakanth, Pushpanjali; Berner, Arne; Woodruff, Maria A; Schell, Hanna; Mehta, Manav; Schuetz, Michael A; Duda, Georg N; Hutmacher, Dietmar W

    2012-07-04

    The reconstruction of large defects (>10 mm) in humans usually relies on bone graft transplantation. Limiting factors include availability of graft material, comorbidity, and insufficient integration into the damaged bone. We compare the gold standard autograft with biodegradable composite scaffolds consisting of medical-grade polycaprolactone and tricalcium phosphate combined with autologous bone marrow-derived mesenchymal stem cells (MSCs) or recombinant human bone morphogenetic protein 7 (rhBMP-7). Critical-sized defects in sheep--a model closely resembling human bone formation and structure--were treated with autograft, rhBMP-7, or MSCs. Bridging was observed within 3 months for both the autograft and the rhBMP-7 treatment. After 12 months, biomechanical analysis and microcomputed tomography imaging showed significantly greater bone formation and superior strength for the biomaterial scaffolds loaded with rhBMP-7 compared to the autograft. Axial bone distribution was greater at the interfaces. With rhBMP-7, at 3 months, the radial bone distribution within the scaffolds was homogeneous. At 12 months, however, significantly more bone was found in the scaffold architecture, indicating bone remodeling. Scaffolds alone or with MSC inclusion did not induce levels of bone formation comparable to those of the autograft and rhBMP-7 groups. Applied clinically, this approach using rhBMP-7 could overcome autograft-associated limitations.

  10. Immunohistochemical localization of host and donor-derived cells in the regenerating thymus of radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    Ceredig, R.; Schreyer, M.

    1984-01-01

    The anatomical distribution of CBA (Thy-1.2) host and AKR (Thy-1.1) donor-derived cells in the regenerating thymus of AKR → CBA radiation bone marrow chimeras was investigated. Cryostat sections of chimeric thymuses were incubated with biotin-conjugated monoclonal anti-Thy-1 antibodies specific for host and donor-derived cells and the distribution of the corresponding Thy-1 antigen revealed by the immunoperoxidase staining technique. The thymus was initially repopulated by Thy-1.2 + host-derived cells, but by 28 days following bone marrow reconstitution the few remaining host cells were found mostly in the thymus medulla. However, occasional Thy-1.2 + cells were still present in extramedullary, primarily cortical, sites. Donor-derived (Thy-1.1 + ) cells were first seen in the 11-day chimeric thymus as single cells frequently closely associated with blood vessels in medullary areas. By 17 days, the cortex contained many Thy-1.1 + cells, although occasional single positive cells were still present in the medulla. Changes in the anatomical distribution of host and donor-derived cells in the regenerating chimeric thymus appeared to correlate with changes in their Thy-1 fluorescence profile as determined by flow microfluorometry. (Auth.)

  11. 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

  12. iPS cell technologies and their prospect for bone regeneration and disease modeling: A mini review

    Directory of Open Access Journals (Sweden)

    Maria Csobonyeiova

    2017-07-01

    Full Text Available Bone disorders are a group of varied acute and chronic traumatic, degenerative, malignant or congenital conditions affecting the musculoskeletal system. They are prevalent in society and, with an ageing population, the incidence and impact on the population’s health is growing. Severe persisting pain and limited mobility are the major symptoms of the disorder that impair the quality of life in affected patients. Current therapies only partially treat the disorders, offering management of symptoms, or temporary replacement with inert materials. However, during the last few years, the options for the treatment of bone disorders have greatly expanded, thanks to the advent of regenerative medicine. Skeletal cell-based regeneration medicine offers promising reparative therapies for patients. Mesenchymal stem (stromal cells from different tissues have been gradually translated into clinical practice; however, there are a number of limitations. The introduction of reprogramming methods and the subsequent production of induced pluripotent stem cells provides a possibility to create human-specific models of bone disorders. Furthermore, human-induced pluripotent stem cell-based autologous transplantation is considered to be future breakthrough in the field of regenerative medicine. The main goal of the present paper is to review recent applications of induced pluripotent stem cells in bone disease modeling and to discuss possible future therapy options. The present article contributes to the dissemination of scientific and pre-clinical results between physicians, mainly orthopedist and thus supports the translation to clinical practice.

  13. A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration

    Directory of Open Access Journals (Sweden)

    Dyondi D

    2012-12-01

    Full Text Available Deepti Dyondi,1 Thomas J Webster,2 Rinti Banerjee11Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India; 2Nanomedicine Laboratories, Division of Engineering and Department of Orthopedics, Brown University, Providence, RI, USAAbstract: Gellan xanthan gels have been shown to be excellent carriers for growth factors and as matrices for several tissue engineering applications. Gellan xanthan gels along with chitosan nanoparticles of 297 ± 61 nm diameter, basic fibroblast growth factor (bFGF, and bone morphogenetic protein 7 (BMP7 were employed in a dual growth factor delivery system to promote the differentiation of human fetal osteoblasts. An injectable system with ionic and temperature gelation was optimized and characterized. The nanoparticle loaded gels showed significantly improved cell proliferation and differentiation due to the sustained release of growth factors. A differentiation marker study was conducted, analyzed, and compared to understand the effect of single vs dual growth factors and free vs encapsulated growth factors. Dual growth factor loaded gels showed a higher alkaline phosphatase and calcium deposition compared to single growth factor loaded gels. The results suggest that encapsulation and stabilization of growth factors within nanoparticles and gels are promising for bone regeneration. Gellan xanthan gels also showed antibacterial effects against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, the common pathogens in implant failure.Keywords: bone tissue engineering, bone morphogenetic protein 7 (BMP7, basic fibroblast growth factor (bFGF, hydrogel, nanoparticles, osteoblasts

  14. Bone regeneration: in vitro evaluation of the behaviour of osteoblast-like MG63 cells placed in contact with polylactic-co-glycolic acid, deproteinized bovine bone and demineralized freeze-dried bone allograft.

    Science.gov (United States)

    Pappalardo, S; Mastrangelo, F; Reale Marroccia, D; Cappello, V; Ciampoli, C; Carlino, V; Tanteri, L; Costanzo, M; Sinatra, F; Tetè, S

    2008-01-01

    Insufficient bone density of the alveolar crests, caused by loss of the dental elements, sometimes impedes the primary stability of an integrated bone implant. The techniques of bone regeneration allow to obtain a sufficient quantity of alveolar bone to permit the implant rehabilitation of the edentulous crests. Today several grafting materials are available and they have different characteristics, according to their structure, which influence the different behaviour of the grafting materials to the bone and the implant surface. The aim of this study is to evaluate the interaction between a human osteosarcoma MG63 cell line and three different biomaterials: polylactic-co-glycolic acid (PLAGA), deproteinized bovine bone and demineralised freeze-dried bone allograft (DFDBA). From this study a different behaviour emerges of the osteoblast-like MG63 cells in relation to the sublayer on which these cells were placed in culture. The results of the study, in fact, demonstrate that the most osteoconductive material of the three analysed is the DFDBA, followed by DPBB. On the contrary, the PLGA, because of its roughness, does not seem to represent a valid support for cell growth, and does not encourage any morphologic modification in tumor cells. Furthermore, deproteinized bovine bone shows a differentiating effect which could lead to hypothesise an osteoconductive capacity of this biomaterial. Further studies should be carried out with the aim of explaining the results obtained.

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

    Science.gov (United States)

    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

  16. Optimization of Deacetylation Process for Regenerated Cellulose Hollow Fiber Membranes

    Directory of Open Access Journals (Sweden)

    Xuezhong He

    2017-01-01

    Full Text Available Cellulose acetate (CA hollow fibers were spun from a CA+ Polyvinylpyrrolidone (PVP/N-methyl-2-pyrrolidone (NMP/H2O dope solution and regenerated by deacetylation. The complete deacetylation time of 0.5 h was found at a high concentration (0.2 M NaOH ethanol (96% solution. The reaction rate of deacetylation with 0.5 M NaOH was faster in a 50% ethanol compared to a 96 vol.% ethanol. The hydrogen bond between CA and tertiary amide group of PVP was confirmed. The deacetylation parameters of NaOH concentration, reaction time, swelling time, and solution were investigated by orthogonal experimental design (OED method. The degree of cross-linking, the residual acetyl content, and the PVP content in the deacetylated membranes were determined by FTIR analysis. The conjoint analysis in the Statistical Product and Service Solutions (SPSS software was used to analyze the OED results, and the importance of the deacetylation parameters was sorted as Solution > Swelling time > Reaction time > Concentration. The optimal deacetylation condition of 96 vol.% ethanol solution, swelling time 24 h, the concentration of NaOH (0.075 M, and the reaction time (2 h were identified. The regenerated cellulose hollow fibers under the optimal deacetylation condition can be further used as precursors for preparation of hollow fiber carbon membranes.

  17. Comprehensive Review of Adipose Stem Cells and Their Implication in Distraction Osteogenesis and Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Mina W. Morcos

    2015-01-01

    Full Text Available Bone is one of the most dynamic tissues in the human body that can heal following injury without leaving a scar. However, in instances of extensive bone loss, this intrinsic capacity of bone to heal may not be sufficient and external intervention becomes necessary. Several techniques are available to address this problem, including autogenous bone grafts and allografts. However, all these techniques have their own limitations. An alternative method is the technique of distraction osteogenesis, where gradual and controlled distraction of two bony segments after osteotomy leads to induction of new bone formation. Although distraction osteogenesis usually gives satisfactory results, its major limitation is the prolonged duration of time required before the external fixator is removed, which may lead to numerous complications. Numerous methods to accelerate bone formation in the context of distraction osteogenesis have been reported. A viable alternative to autogenous bone grafts for a source of osteogenic cells is mesenchymal stem cells from bone marrow. However, there are certain problems with bone marrow aspirate. Hence, scientists have investigated other sources for mesenchymal stem cells, specifically adipose tissue, which has been shown to be an excellent source of mesenchymal stem cells. In this paper, the potential use of adipose stem cells to stimulate bone formation is discussed.

  18. Mesoporous bioactive glass surface modified poly(lactic-co-glycolic acid electrospun fibrous scaffold for bone regeneration

    Directory of Open Access Journals (Sweden)

    Chen SJ

    2015-06-01

    Full Text Available Shijie Chen,1,* Zhiyuan Jian,2,* Linsheng Huang,2,* Wei Xu,3,* Shaohua Liu,4 Dajiang Song,3 Zongmiao Wan,3 Amanda Vaughn,5 Ruisen Zhan,1 Chaoyue Zhang,1 Song Wu,1 Minghua Hu,6 Jinsong Li1 1Department of Orthopaedics, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2The First General Surgery Department of Shiyan Taihe Hospital Affiliated to Hubei University of Medicine, Shiyan, People’s Republic of China; 3Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, People’s Republic of China; 4Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 5Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA; 6Department of Anthropotomy, Changsha Medical College, Changsha, Hunan, People’s Republic of China *These authors contributed equally to this work Abstract: A mesoporous bioactive glass (MBG surface modified with poly(lactic-co-glycolic acid (PLGA electrospun fibrous scaffold for bone regeneration was prepared by dip-coating a PLGA electrospun fibrous scaffold into MBG precursor solution. Different surface structures and properties were acquired by different coating times. Surface morphology, chemical composition, microstructure, pore size distribution, and hydrophilicity of the PLGA-MBG scaffold were characterized. Results of scanning electron microscopy indicated that MBG surface coating made the scaffold rougher with the increase of MBG content. Scaffolds after MBG modification possessed mesoporous architecture on the surface. The measurements of the water contact angles suggested that the incorporation of MBG into the PLGA scaffold improved the surface hydrophilicity. An energy dispersive spectrometer evidenced that calcium-deficient carbonated hydroxyapatite formed on the PLGA-MBG scaffolds

  19. Photo-induced regeneration of hormones by electron transfer processes: Potential biological and medical consequences

    Science.gov (United States)

    Getoff, Nikola; Hartmann, Johannes; Schittl, Heike; Gerschpacher, Marion; Quint, Ruth Maria

    2011-08-01

    Based on the previous results concerning electron transfer processes in biological substances, it was of interest to investigate if hormone transients resulting by e.g. electron emission can be regenerated. The presented results prove for the first time that the hormone transients originating by the electron emission process can be successfully regenerated by the transfer of electrons from a potent electron donor, such as vitamin C (VitC). Investigations were performed using progesterone (PRG), testosterone (TES) and estrone (E1) as representatives of hormones. By irradiation with monochromatic UV light (λ=254 nm) in a media of 40% water and 60% ethanol, the degradation as well as the regeneration of the hormones was studied with each hormone individually and in the mixture with VitC as a function of the absorbed UV dose, using HPLC. Calculated from the obtained initial yields, the determined regeneration of PRG amounted to 52.7%, for TES to 58.6% and for E1 to 90.9%. The consumption of VitC was determined in the same way. The reported results concerning the regeneration of hormones by the transfer of electrons from an electron donor offer a new, promising method for the therapy with hormones. As a consequence of the regeneration of hormones, a decreased formation of carcinogenic metabolites is expected.

  20. Photo-induced regeneration of hormones by electron transfer processes: Potential biological and medical consequences

    Energy Technology Data Exchange (ETDEWEB)

    Getoff, Nikola, E-mail: nikola.getoff@univie.ac.a [Section of Radiation Biology, Faculty of Life Sciences, University of Vienna, A-1090 Vienna (Austria); Hartmann, Johannes [Department of Gynecologic Endocrinology and Reproduction, Medical University of Vienna, A-1090 Vienna (Austria); Schittl, Heike [Section of Radiation Biology, Faculty of Life Sciences, University of Vienna, A-1090 Vienna (Austria); Gerschpacher, Marion [Department of Gynecologic Endocrinology and Reproduction, Medical University of Vienna, A-1090 Vienna (Austria); Quint, Ruth Maria [Section of Radiation Biology, Faculty of Life Sciences, University of Vienna, A-1090 Vienna (Austria)

    2011-08-15

    Based on the previous results concerning electron transfer processes in biological substances, it was of interest to investigate if hormone transients resulting by e.g. electron emission can be regenerated. The presented results prove for the first time that the hormone transients originating by the electron emission process can be successfully regenerated by the transfer of electrons from a potent electron donor, such as vitamin C (VitC). Investigations were performed using progesterone (PRG), testosterone (TES) and estrone (E1) as representatives of hormones. By irradiation with monochromatic UV light ({lambda}=254 nm) in a media of 40% water and 60% ethanol, the degradation as well as the regeneration of the hormones was studied with each hormone individually and in the mixture with VitC as a function of the absorbed UV dose, using HPLC. Calculated from the obtained initial yields, the determined regeneration of PRG amounted to 52.7%, for TES to 58.6% and for E1 to 90.9%. The consumption of VitC was determined in the same way. The reported results concerning the regeneration of hormones by the transfer of electrons from an electron donor offer a new, promising method for the therapy with hormones. As a consequence of the regeneration of hormones, a decreased formation of carcinogenic metabolites is expected.

  1. Photo-induced regeneration of hormones by electron transfer processes: Potential biological and medical consequences

    International Nuclear Information System (INIS)

    Getoff, Nikola; Hartmann, Johannes; Schittl, Heike; Gerschpacher, Marion; Quint, Ruth Maria

    2011-01-01

    Based on the previous results concerning electron transfer processes in biological substances, it was of interest to investigate if hormone transients resulting by e.g. electron emission can be regenerated. The presented results prove for the first time that the hormone transients originating by the electron emission process can be successfully regenerated by the transfer of electrons from a potent electron donor, such as vitamin C (VitC). Investigations were performed using progesterone (PRG), testosterone (TES) and estrone (E1) as representatives of hormones. By irradiation with monochromatic UV light (λ=254 nm) in a media of 40% water and 60% ethanol, the degradation as well as the regeneration of the hormones was studied with each hormone individually and in the mixture with VitC as a function of the absorbed UV dose, using HPLC. Calculated from the obtained initial yields, the determined regeneration of PRG amounted to 52.7%, for TES to 58.6% and for E1 to 90.9%. The consumption of VitC was determined in the same way. The reported results concerning the regeneration of hormones by the transfer of electrons from an electron donor offer a new, promising method for the therapy with hormones. As a consequence of the regeneration of hormones, a decreased formation of carcinogenic metabolites is expected.

  2. Acellular dermal matrix loading with bFGF achieves similar acceleration of bone regeneration to BMP-2 via differential effects on recruitment, proliferation and sustained osteodifferentiation of mesenchymal stem cells

    International Nuclear Information System (INIS)

    Du, Mi; Zhu, Ting; Duan, Xiaoqi; Ge, Shaohua; Li, Ning; Sun, Qinfeng; Yang, Pishan

    2017-01-01

    New generation of barrier membranes has been developed, which not only act as barriers but also as delivery devices to release specific growth factors. This study observed biological behaviors of bone morrow mesenchymal stem cells (BMMSCs) pretreated by bFGF or BMP-2 in vitro and evaluated differential bone regeneration process induced by bFGF and BMP-2 loaded acellular dermal matrix (ADM) membrane using critical-size rat calvarial defect model in vivo. The results showed that the proliferation capability of BMMSCs pretreated by bFGF was stronger than that by BMP-2, while there was temporally differential effect of bFGF and BMP-2 pretreatment on MSC osteogenic differentiation potentials. During healing process of rat calvarial defects, 2-fold more CD34 −/CD90 + MSCs in group of bFGF-ADM was observed than in any other treatment group at 2 weeks. However, there were similar amount of new bone formation and expression of osteopotin in newly-formed bone tissue in groups of bFGF- and BMP-2-ADM at 8 weeks, which were more than those in ADM alone and blank control. Taken together, bFGF-ADM guided similar bone regeneration to BMP-2 through more efficient recruitment of MSCs, and moreover, BMMSCs pretreated by bFGF showed stronger proliferation at 1–5 days and osteogenic differentiation potentials at 14 days compared with BMP-2 pretreatment. - Highlights: • An improved barrier membrane used in the field of bone tissue engineering was proposed, which is acellular dermal matrix (ADM) loaded with growth factors. • It is generally agreed that BMP-2 and -7 provide the greatest bone regeneration potentials, however, we found that ADM loading with bFGF could guide similar bone regeneration to BMP-2. • Compared with BMP-2, bFGF could more effectively recruit MSCs and moreover, BMMSCs pretreated by bFGF showed out stronger proliferation at 1-5 days and osteogenic differentiation potentials at 14 days.

  3. Off-label use of rhBMP-2 as bone regeneration strategies in mandibular ameloblastoma unicystic.

    Science.gov (United States)

    Silva, Henrique Celestino Lima E; Cheim, Adonai Peixoto; Moreno, Roberto; Miranda, Sérgio Luis de

    2017-01-01

    Jawbone reconstruction after tumor resection is one of the most challenging clinical tasks for maxillofacial surgeons. Osteogenic, osteoinductive, osteoconductive and non-antigenic properties of autogenous bone place this bone as the gold standard for solving problems of bone availability. However, the need for a second surgical site to harvest the bone graft increases significantly both the cost and the morbidity associated with the reconstructive procedures. Bone grafting gained an important tool with the discovery of bone morphogenetic proteins in 1960. Benefit of obtaining functional and real bone matrix without need of second surgical site seems to be the great advantage of use bone morphogenetic proteins. This study analyzed the use of rhBMP-2 in unicystic ameloblastoma of the mandible, detailing its structure, mechanisms of cell signaling and biological efficacy, in addition to present possible advantages and disadvantages of clinical use of rhBMP-2 as bone regeneration strategy. RESUMO A reconstrução óssea dos maxilares após ressecções tumorais é uma das tarefas mais difíceis para o cirurgião maxilofacial. As propriedades osteogênicas, osteoindutoras, osteocondutoras e não antigênicas do osso autógeno o colocam como o padrão-ouro para a solução de problemas de disponibilidade óssea. Entretanto a coleta do enxerto ósseo necessita de um segundo sítio cirúrgico, aumentando significativamente o custo e a morbidade associados ao procedimento reconstrutivo. A enxertia óssea ganhou uma excelente ferramenta com a descoberta das proteínas ósseas morfogenéticas na década de 1960. O benefício da obtenção de matriz óssea verdadeira e funcional, sem a necessidade de um segundo sítio cirúrgico, parece ser a grande vantagem do uso das proteínas ósseas morfogenéticas. Neste contexto, o objetivo deste estudo foi analisar a utilização da rhBMP-2 na regeneração óssea de ameloblastoma mandibular unicístico, detalhando sua estrutura, seus

  4. Bone regeneration potential of stem cells derived from periodontal ligament or gingival tissue sources encapsulated in RGD-modified alginate scaffold.

    Science.gov (United States)

    Moshaverinia, Alireza; Chen, Chider; Xu, Xingtian; Akiyama, Kentaro; Ansari, Sahar; Zadeh, Homayoun H; Shi, Songtao

    2014-02-01

    Mesenchymal stem cells (MSCs) provide an advantageous alternative therapeutic option for bone regeneration in comparison to current treatment modalities. However, delivering MSCs to the defect site while maintaining a high MSC survival rate is still a critical challenge in MSC-mediated bone regeneration. Here, we tested the bone regeneration capacity of periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) encapsulated in a novel RGD- (arginine-glycine-aspartic acid tripeptide) coupled alginate microencapsulation system in vitro and in vivo. Five-millimeter-diameter critical-size calvarial defects were created in immunocompromised mice and PDLSCs and GMSCs encapsulated in RGD-modified alginate microspheres were transplanted into the defect sites. New bone formation was assessed using microcomputed tomography and histological analyses 8 weeks after transplantation. Results confirmed that our microencapsulation system significantly enhanced MSC viability and osteogenic differentiation in vitro compared with non-RGD-containing alginate hydrogel microspheres with larger diameters. Results confirmed that PDLSCs were able to repair the calvarial defects by promoting the formation of mineralized tissue, while GMSCs showed significantly lower osteogenic differentiation capability. Further, results revealed that RGD-coupled alginate scaffold facilitated the differentiation of oral MSCs toward an osteoblast lineage in vitro and in vivo, as assessed by expression of osteogenic markers Runx2, ALP, and osteocalcin. In conclusion, these results for the first time demonstrated that MSCs derived from orofacial tissue encapsulated in RGD-modified alginate scaffold show promise for craniofacial bone regeneration. This treatment modality has many potential dental and orthopedic applications.

  5. Handling zone dividing method in packed bed liquid desiccant dehumidification/regeneration