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Sample records for bone regeneration gbr

  1. Comparison of the performance of natural latex membranes prepared with different procedures and PTFE membrane in guided bone regeneration (GBR) in rabbits.

    PubMed

    Moura, Jonas M L; Ferreira, Juliana F; Marques, Leonardo; Holgado, Leandro; Graeff, Carlos F O; Kinoshita, Angela

    2014-09-01

    This work assessed the performance of membranes made of natural latex extracted from Hevea brasiliensis prepared with three different methods: polymerized immediately after collection without the use of ammonia (L1); polymerized after preservation in ammonia solution (L2); and polymerized after storage in ammonia, followed by Soxhlet technique for the extraction of substances (L3). Polytetrafluoroethylene (PTFE) membrane was used as control. Two 10-mm diameter bone defects were surgically made in the calvaria of thirty adult male New Zealand rabbits. Defects (total n = 60) were treated with guided bone regeneration (GBR) using L1, L2, L3 or PTFE membranes (n = 15 for each membrane). Ten animals were euthanized after 7, 20 and 60 days postoperatively so that five samples (n = 5) of each treatment were collected at each time, and bone regeneration was assessed microscopically. The microscopic analysis revealed defects filled with blood clot and new bone formation at the margins of the defect in all 7-day samples, while 20-day defects were mainly filled with fibrous connective tissue. After 60 days defects covered with L1 membranes showed a significantly larger bone formation area in comparison to the other groups (P < 0.05, ANOVA, Tukey). Additionally, bone tissue hypersensitization for L1 and PTFE membranes was also investigated in six additional rabbits. The animals were subjected to the same surgical procedure for the confection of one 10-mm diameter bone defect that was treated with L1 (n = 3) or PTFE (n = 3). Fifty-three days later, a second surgery was performed to make a second defect, which was treated with the same type of membrane used in the first surgery. Seven days later, the animals were euthanized and samples analyzed. No differences among L1 and PTFE samples collected from sensitized and non-sensitized animals were found (P > 0.05, Kruskal-Wallis). Therefore, the results demonstrated that latex membranes presented performance

  2. Mechanisms of Guided Bone Regeneration: A Review

    PubMed Central

    Liu, Jie; Kerns, David G

    2014-01-01

    Post-extraction crestal bone resorption is common and unavoidable which can lead to significant ridge dimensional changes. To regenerate enough bone for successful implant placement, Guided Bone Regeneration (GBR) is often required. GBR is a surgical procedure that uses barrier membranes with or without particulate bone grafts or/and bone substitutes. There are two approaches of GBR in implant therapy: GBR at implant placement (simultaneous approach) and GBR before implant placement to increase the alveolar ridge or improve ridge morphology (staged approach). Angiogenesis and ample blood supply play a critical role in promoting bone regeneration. PMID:24894890

  3. Assessment of bone healing on tibial fractures treated with wire osteosynthesis associated or not with infrared laser light and biphasic ceramic bone graft (HATCP) and guided bone regeneration (GBR): Raman spectroscopy study

    NASA Astrophysics Data System (ADS)

    Bastos de Carvalho, Fabíola; Aciole, Gilberth Tadeu S.; Aciole, Jouber Mateus S.; Silveira, Landulfo, Jr.; Nunes dos Santos, Jean; Pinheiro, Antônio L. B.

    2011-03-01

    The aim of this study was to evaluate, through Raman spectroscopy, the repair of complete tibial fracture in rabbits fixed with wire osteosynthesis - WO, treated or not with infrared laser light (λ 780nm, 50mW, CW) associated or not to the use of HATCP and GBR. Surgical fractures were created under general anesthesia (Ketamine 0.4ml/Kg IP and Xilazine 0.2ml/Kg IP), on the tibia of 15 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 WO. Animals of groups III and V were grafted with hydroxyapatite + GBR technique. Animals of groups IV and V were irradiated at every other day during two weeks (16J/cm2, 4 x 4J/cm2). Observation time was that of 30 days. After animal death the specimens were kept in liquid nitrogen for further analysis by Raman spectroscopy. Raman spectroscopy showed significant differences between groups (p<0.001). 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 calcium hydroxyapatite.

  4. Effect of biological/physical stimulation on guided bone regeneration through asymmetrically porous membrane.

    PubMed

    Kim, Tae Ho; Oh, Se Heang; Na, Seung Yeon; Chun, So Young; Lee, Jin Ho

    2012-06-01

    Asymmetrically porous polycaprolactone (PCL)/Pluronic F127 guided bone regeneration (GBR) membranes were fabricated. The top surface of the membrane had nanosize pores (∼10 nm) which can effectively prevent invasion by fibrous connective tissue but permeate nutrients, whereas the bottom surface had microsize pores (∼200 μm) which can enhance the adhesiveness with bone tissue. Ultrasound was applied to a bone morphogenetic protein (BMP-2)-immobilized PCL/F127 GBR membrane to investigate the feasibility of using dual biological (BMP-2) and physical (ultrasound) stimulation for enhancing bone regeneration through the membrane. In an animal study using SD rats (cranial defect model), the bone regeneration behavior that occurred when using BMP-2-loaded GBR membranes with ultrasound treatment (GBR/BMP-2/US) was much faster than when the same GBR membrane was used without the ultrasound treatment (GBR/BMP-2), as well as when GBR membranes were used without stimulations (GBR). The enhanced bone regeneration of the GBR/BMP-2/US group can be interpreted as resulting from the synergistic or additive effect of the asymmetrically porous PCL/F127 membrane with unique properties (selective permeability, hydrophilicity, and osteoconductivity) and the stimulatory effects of BMP-2 and ultrasound (osteoinductivity). The asymmetrically porous GBR membrane with dual BMP-2 and ultrasound stimulation may be promising for the clinical treatment of delayed and insufficient bone healing. PMID:22408081

  5. Nanomaterials and bone regeneration

    PubMed Central

    Gong, Tao; Xie, Jing; Liao, Jinfeng; Zhang, Tao; Lin, Shiyu; Lin, Yunfeng

    2015-01-01

    The worldwide incidence of bone disorders and conditions has been increasing. Bone is a nanomaterials composed of organic (mainly collagen) and inorganic (mainly nano-hydroxyapatite) components, with a hierarchical structure ranging from nanoscale to macroscale. In consideration of the serious limitation in traditional therapies, nanomaterials provide some new strategy in bone regeneration. Nanostructured scaffolds provide a closer structural support approximation to native bone architecture for the cells and regulate cell proliferation, differentiation, and migration, which results in the formation of functional tissues. In this article, we focused on reviewing the classification and design of nanostructured materials and nanocarrier materials for bone regeneration, their cell interaction properties, and their application in bone tissue engineering and regeneration. Furthermore, some new challenges about the future research on the application of nanomaterials for bone regeneration are described in the conclusion and perspectives part. PMID:26558141

  6. Postloading behavior of regenerated tissues in GBR-treated implant sites.

    PubMed

    Cordioli, G; Majzoub, Z; Riachi, F

    1999-02-01

    The objective of this study was to assess, using reentry procedures, the capacity of regenerated tissues in implant-associated defects to respond to occlusal loading. Two groups of patients treated with membrane-augmented osseointegrated implants were included in the study. In group A (7 patients), a total of 9 implant-associated defects, including 6 dehiscences and 3 immediate extraction sites, were prospectively followed up 6 months following prosthesis connection. In group B (3 patients), 4 dehiscence defects were retrospectively evaluated 5 years after prosthetic loading. All defects in both groups had an uneventful healing period beyond the 6 months following implant insertion and showed complete fill with bone-like hard tissues at abutment connection surgery. A second surgical reentry was carried out to evaluate the quantitative changes in the regenerated tissues at the membrane-treated sites; it was carried out 6 months following prosthesis connection in group A, and 5 years postloading in group B. At the second reentry procedure, the mean percentage of defect fill at the dehiscence sites was 82% +/- 12.8% in group A and 83% +/- 7.3% in group B. In the 3 immediate extraction sites in group A, the most apical bone-implant contact around the implant was consistently located at about 1 mm, relative to the coronal aspect of the implant shoulder, as evidenced both radiographically and during the second reentry. The trends noted in this investigation suggest that tissues regenerated in successfully treated implant-associated defects can be maintained in the short-term and long-term periods following prosthetic loading. PMID:10379286

  7. Osteogenesis effect of guided bone regeneration combined with alveolar cleft grafting: assessment by cone beam computed tomography.

    PubMed

    Xiao, W-L; Zhang, D-Z; Chen, X-J; Yuan, C; Xue, L-F

    2016-06-01

    Cone beam computed tomography (CBCT) allows for a significantly lower radiation dose than conventional computed tomography (CT) scans and provides accurate images of the alveolar cleft area. The osteogenic effect of guided bone regeneration (GBR) vs. conventional alveolar bone grafting alone for alveolar cleft defects was evaluated in this study. Sixty alveolar cleft patients were divided randomly into two groups. One group underwent GBR using acellular dermal matrix film combined with alveolar bone grafting using iliac crest bone grafts (GBR group), while the other group underwent alveolar bone grafting only (non-GBR group). CBCT images were obtained at 1 week and at 3 months following the procedure. Using Simplant 11.04 software, the bone resorption rate was calculated and compared between the two groups. The bone resorption rate from 1 week to 3 months following bone grafting without the GBR technique was 36.50±5.04%, whereas the bone resorption rate using the GBR technique was 31.69±5.50% (P=0.017). The application of autogenous iliac bone combined with the GBR technique for alveolar bone grafting of alveolar cleft patients can reduce bone resorption and result in better osteogenesis. PMID:26876144

  8. Effects of cortical bone perforation on experimental guided bone regeneration.

    PubMed

    Nishimura, Ichiro; Shimizu, Yoshinaka; Ooya, Kiyoshi

    2004-06-01

    This study was designed to evaluate the effects of cortical bone perforation histologically and histomorphometrically on guided bone regeneration (GBR) in rabbits. After elimination of the periosteum, cortical bone defects of two sizes were made in the external cortical plate of the frontal bone (Group A: 1 x 15 mm; Group B: 3 x 15 mm). A non-resorbable membrane filled with autogenous blood was placed in the experimental area and secured with titanium pins. After 1 and 2 weeks, vascularized connective tissue and new bone were generated in the space surrounding the defects in both the groups. The amount of vascularized connective tissue generated in Group B was greater than that in Group A at 1 week. Alkaline phosphatase (ALP) was expressed on the bone surrounding the perforation. The expression of ALP was more extensive in Group B than in Group A and was proportional to the breadth of perforation. At 2 weeks, the perforated region was almost covered with new bone in Group A. ALP was expressed at the periphery of newly formed bone. The expression of ALP was proportional to the breadth and height of perforation. At 6 weeks, semicircular outgrowth of bone towards the periphery of the perforated region was observed in both the groups. Newly formed bone volume and ALP expression in Group B were more extensive than those in Group A. At 12 weeks, the space was filled with bone and connective tissue in both the groups. There was no difference in ALP expression between Groups A and B. Histomorphometric analysis showed significant differences between both the groups (two-way ANOVA, P<0.01). We conclude that a larger perforation is associated with prompter bone formation in the secluded space during GBR. PMID:15142091

  9. Asymmetric Collagen/chitosan Membrane Containing Minocycline-loaded Chitosan Nanoparticles for Guided Bone Regeneration.

    PubMed

    Ma, Shiqing; Adayi, Aidina; Liu, Zihao; Li, Meng; Wu, Mingyao; Xiao, Linghao; Sun, Yingchun; Cai, Qing; Yang, Xiaoping; Zhang, Xu; Gao, Ping

    2016-01-01

    Infections caused by pathogens colonization at wound sites in the process of bone healing are considered as one of the major reasons for the failure of guided bone regeneration (GBR). The objective of this study was to prepare a novel asymmetric collagen/chitosan GBR membrane containing minocycline-loaded chitosan nanoparticles. The morphologies of the membranes and nanoparticles were observed by SEM and TEM, respectively. The characterization and biocompatibility of the membranes was evaluated. The effect of the membrane on bone regeneration was assessed using the critical-size at cranial defect model. TEM images showed the spherical morphology of the nanoparticles. The results of SEM indicated that the asymmetric membrane contained a dense collagen layer and a loose chitosan layer. An in vitro experiment showed that the membrane can inhibit bacterial growth and promote osteoblasts and fibroblasts growth. The membrane showed the ability to promote angiogenesis and enhance bone regeneration in vivo. An asymmetric collagen/chitosan GBR membrane can be fabricated by loading minocycline encapsulated chitosan nanoparticles, and shows satisfactory biocompatibility and barrier function, which enhances bone regeneration. Therefore, this antibacterial GBR membrane is a promising therapeutic approach to prevent infection and guide bone regeneration. PMID:27546177

  10. Asymmetric Collagen/chitosan Membrane Containing Minocycline-loaded Chitosan Nanoparticles for Guided Bone Regeneration

    PubMed Central

    Ma, Shiqing; Adayi, Aidina; Liu, Zihao; Li, Meng; Wu, Mingyao; Xiao, Linghao; Sun, Yingchun; Cai, Qing; Yang, Xiaoping; Zhang, Xu; Gao, Ping

    2016-01-01

    Infections caused by pathogens colonization at wound sites in the process of bone healing are considered as one of the major reasons for the failure of guided bone regeneration (GBR). The objective of this study was to prepare a novel asymmetric collagen/chitosan GBR membrane containing minocycline-loaded chitosan nanoparticles. The morphologies of the membranes and nanoparticles were observed by SEM and TEM, respectively. The characterization and biocompatibility of the membranes was evaluated. The effect of the membrane on bone regeneration was assessed using the critical-size at cranial defect model. TEM images showed the spherical morphology of the nanoparticles. The results of SEM indicated that the asymmetric membrane contained a dense collagen layer and a loose chitosan layer. An in vitro experiment showed that the membrane can inhibit bacterial growth and promote osteoblasts and fibroblasts growth. The membrane showed the ability to promote angiogenesis and enhance bone regeneration in vivo. An asymmetric collagen/chitosan GBR membrane can be fabricated by loading minocycline encapsulated chitosan nanoparticles, and shows satisfactory biocompatibility and barrier function, which enhances bone regeneration. Therefore, this antibacterial GBR membrane is a promising therapeutic approach to prevent infection and guide bone regeneration. PMID:27546177

  11. Guided Bone Regeneration of an Atrophic Mandible with a Heterologous Bone Block.

    PubMed

    Di Stefano, Danilo Alessio; Greco, Gian Battista; Riboli, Francesco

    2016-03-01

    The aim of this work was to test the effectiveness of using enzymatically deantigenated equine bone block as a scaffold for guided bone regeneration (GBR) during a horizontal augmentation of the lower jaw. A partially edentulous atrophic mandible was augmented using an equine-derived block with an expanded polytetrafluoroethylene membrane. After 8.5 months, two bone core samples were collected at the augmentation site, and implants were placed. A definitive prosthesis delivered 6 months after implant placement provided excellent functional and aesthetic rehabilitation throughout the follow-up period. Histological and histomorphometrical analysis of the biopsies showed newly formed bone to be present and the residual biomaterial was still undergoing remodeling. Comparison of cone beam computed tomography scans taken before augmentation and 26 months later showed maintenance of ridge width and possible corticalization of the vestibular augmented ridge side. The equine-derived bone block placed in accordance with GBR principles provided a successful clinical, radiographic, and histological outcome. PMID:26889354

  12. Nanocomposites and bone regeneration

    NASA Astrophysics Data System (ADS)

    James, Roshan; Deng, Meng; Laurencin, Cato T.; Kumbar, Sangamesh G.

    2011-12-01

    This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite (HA) and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA (reduced grain size), one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

  13. Antibacterial Nanostructured Polyhydroxybutyrate Membranes for Guided Bone Regeneration.

    PubMed

    Karahaliloğlu, Zeynep; Ercan, Batur; Taylor, Erik N; Chung, Stanley; Denkbaş, Emir B; Webster, Thomas J

    2015-12-01

    The principle of guided bone regeneration (GBR) in orthopedic, cranio-maxillofacial and dental tissue engineering applications is to create a secluded space for the treatment of large bone defects while excluding fibrous connective tissue formation at the defect area. In dental surgeries, a GBR membrane is placed near the dental implant in post-extraction sockets to grow new bone at the implant site, along with inhibiting infection due to the microbial nature of the mouth flora. Poly[(R)-3-hydroxybutyric acid] (PHB) is a natural polyester synthesized by a wide variety of microorganisms which has been proposed for various biomedical applications. In this study, to improve the performance of PHB as a GBR, a NaOH based alkaline treatment was designed to create nanofeatured PHB membranes. The newly fabricated nanofeatured PHB membranes were investigated for GBR applications. The results showed that a quick, simple, and inexpensive sodium hydroxide treatment modified the nanostructured surface morphology and chemistry of the PHB membranes by inducing hydrolysis of the ester bonds in the PHB backbone creating carboxylic surface functional groups, which increased the hydrophilicity of the PHB surfaces. Cytocompatibility studies showed increased proliferation of human osteoblasts (bone forming cells) on the NaOH treated PHB membranes compared to the untreated ones. Importantly, in vitro bacterial studies with Staphylococcus aureus (S. aureus) indicated that the NaOH-treated PHB surfaces inhibited S. aureus growth more than 60% after 48 hours of culture compared to the untreated PHB membrane. Thus, this study, for the first time, showed that nanofeatured PHB membranes modified with a NaOH treatment may be a useful anti-bacterial, osteoconductive GBR membrane for numerous orthopedic, cranio-maxillofacial and dental tissue engineering applications. PMID:26510318

  14. GBR using bovine bone matrix and resorbable and nonresorbable membranes. Part 1: histologic results.

    PubMed

    Fugazzotto, Paul A

    2003-08-01

    Ninety sites were treated with either sinus augmentation therapy using only Bio-Oss (31 sites), or extraction socket and ridge augmentation therapy using only Bio-Oss beneath secured resorbable or titanium-reinforced nonresorbable membranes (59 sites). Core biopsies were taken at intervals ranging from 4 to 13 months. The 12 core biopsies taken 12 to 13 months postoperative (five sinus augmentation sites and seven extraction socket/ridge augmentation sites) demonstrated distinct Bio-Oss particles in an average of only 0.13% of the core biopsy volume. Bone regeneration was evident in all specimens. PMID:12956480

  15. Vertical Guided Bone Regeneration using Titanium-reinforced d-PTFE Membrane and Prehydrated Corticocancellous Bone Graft

    PubMed Central

    Cucchi, Alessandro; Ghensi, Paolo

    2014-01-01

    Guided bone regeneration (GBR) standard protocols call for filling the space underneath the membrane with autogenous bone or a mixture composed of autogenous bone particles and allogeneic bone tissue or heterologous biomaterials. This work describes the case of a GBR performed to restore a vertical bone defect with simultaneous placement of a dental implant in the posterior mandible that was carried out using a high density d-PTFE membrane and corticocancellous porcine-derived bone without the addition of any autogenous bone. Bone regeneration was assessed by histological analysis of a biopsy sample collected from the grafted site nine months after the surgery. Intraoral radiographs taken at follow-up visits showed complete maintenance of the peri-implant bone levels for up to two years after prosthesis delivery. The regenerated site successfully supported functional loading of the implant. The present case report suggests that the use of a heterologous bone substitute alone to restore a vertical defect in a GBR procedure can be as effective as the standard protocol, while avoiding the drawbacks associated with a second surgical site opening. PMID:25419250

  16. Maintenance of soft tissue closure following guided bone regeneration: technical considerations and report of 723 cases.

    PubMed

    Fugazzotto, P A

    1999-09-01

    The purpose of this paper is to present simple clinical techniques which have been utilized in a significant number of consecutive cases to maintain primary closure throughout the course of regeneration. The maintenance of soft tissue primary closure following guided bone regeneration (GBR) therapy, while considered a considerable challenge, is recognized as contributing to the maximization of therapeutic results. A retrospective analysis of the maintenance of such soft tissue primary closure following the utilization of specific mucoperiosteal flap designs during GBR surgery in 723 consecutively treated cases was carried out. Soft tissue closure was maintained over the membranes for the course of regeneration (a minimum of 6 months) in 695 cases (96.1%). The maintenance of soft tissue primary closure following GBR therapy may be predictably attained through proper surgical planning, technical care, and appropriate postoperative management. PMID:10505812

  17. GBR and autogenous cortical bone particulate by bone scraper for alveolar ridge augmentation: a 2-case report.

    PubMed

    Trombelli, Leonardo; Farina, Roberto; Marzola, Andrea; Itro, Angelo; Calura, Giorgio

    2008-01-01

    Scientific literature describes autogenous bone as the gold standard among graft materials for alveolar reconstructive procedures. Alveolar ridge augmentation has been clinically achieved with different forms of autogenous bone, including autogenous cortical bone particulate (ACBP). However, few histologic studies demonstrating the biologic potential and healing dynamics following the use of ACBP are currently available. This case report presents 2 patients in whom atrophic edentulous alveolar crests were submitted to a vertical/lateral ridge augmentation prior to implant placement. The technique was performed through the use of a titanium-reinforced expanded polytetrafluoroethylene (e-PTFE) membrane with an ACBP graft obtained from the retromolar region with a specially designed bone scraper. Bone biopsy specimens were harvested at 9 months after graft placement. Analysis of the reconstructed bone revealed bone with a lamellar quality characterized by a mature osteonic structure. Sparse particles of grafted bone were evident in direct contact with the regenerated bone. Marrow spaces showed a normal stromal component with limited grafted particles. PMID:18416419

  18. Dental implants with versus without peri-implant bone defects treated with guided bone regeneration

    PubMed Central

    Peñarrocha-Oltra, David; Peñarrocha-Diago, Maria; Peñarrocha-Diago, Miguel

    2015-01-01

    Background The guided bone regeneration (GBR) technique is highly successful for the treatment of peri-implant bone defects. The aim was to determine whether or not implants associated with GBR due to peri-implant defects show the same survival and success rates as implants placed in native bone without defects. Material and Methods Patients with a minimum of two submerged dental implants: one suffering a dehiscence or fenestration defect during placement and undergoing simultaneous guided bone regeneration (test group), versus the other entirely surrounded by bone (control group) were treated and monitored annually for three years. Complications with the healing procedure, implant survival, implant success and peri-implant marginal bone loss were assessed. Statistical analysis was performed with non-parametric tests setting an alpha value of 0.05. Results Seventy-two patients and 326 implants were included (142 test, 184 control). One hundred and twenty-five dehiscences (average height 1.92±1.11) and 18 fenestrations (average height 3.34±2.16) were treated. At 3 years post-loading, implant survival rates were 95.7% (test) and 97.3% (control) and implant success rates were 93.6% and 96.2%, respectively. Mean marginal bone loss was 0.54 (SD 0.26 mm) for the test group and 0.43 (SD 0.22 mm) for the control group. No statistically significant differences between both groups were found. Conclusions Within the limits of this study, implants with peri-implant defects treated with guided bone regeneration exhibited similar survival and success rates and peri-implant marginal bone loss to implants without those defects. Large-scale randomized controlled studies with longer follow-ups involving the assessment of esthetic parameters and hard and soft peri-implant tissue stability are needed. Key words:Guided bone regeneration, peri-implant defects, dental implants, marginal bone level, success rate, survival rate. PMID:26330931

  19. Biocompatibility, resorption and biofunctionality of a new synthetic biodegradable membrane for guided bone regeneration.

    PubMed

    Hoornaert, Alain; d'Arros, Cyril; Heymann, Marie-Francoise; Layrolle, Pierre

    2016-01-01

    Membranes for guided bone regeneration (GBR) were prepared from the synthetic biodegradable polymer poly-D,L-lactic/glycolic acid (PLGA). This GBR membrane has a bi-layered structure with a dense film to prevent gingival fibroblast ingrowth and ensure mechanical function, and a micro-fibrous layer to support colonization by osteogenic cells and promote bone regeneration. Hydrolysis and biodegradation were both studied in vitro through soaking in phosphate buffered saline (PBS) and in vivo by implantation in the subcutis of rats for 4, 8, 16, 26, 48 and 52 weeks. Histology revealed an excellent colonization of the micro-fibrous layer by cells with a minimal inflammatory reaction during resorption. GBR using the synthetic PLGA membrane was evaluated on critical-size calvaria defects in rats for 4 and 8 weeks. Radiographs, micro-computed tomography and histology showed bone regeneration with the PLGA membrane, while the defects covered with a collagen membrane showed a limited amount of mineralized bone, similar to that of the defect left empty. The biofunctionality of the PLGA membranes was also compared to collagen membranes in mandible defects in rabbits, associated or not with beta-tricalcium phosphate granules. This study revealed that the bi-layered synthetic membrane made of PLGA was safer, more biocompatible, and had a greater controlled resorption rate and bone regeneration capacity than collagen membranes. This new PLGA membrane could be used in pre-implantology and peri-odontology surgery. PMID:27509180

  20. Improving gingival smile by means of guided bone regeneration principles

    PubMed Central

    Ferreira, Carlos Eduardo de Almeida; Brandão, Roberto Carlos Bodart; Martinelli, Carolina Borges; Pignaton, Túlio Bonna

    2016-01-01

    ABSTRACT Objective: This study evaluated the effectiveness of guided bone regeneration (GBR) carried out with xenogenic bone substitute (Bio-OssTM) and collagen resorbable membrane (Bio-GideTM) to improve gingival smile (GS) in patients with excessive vertical maxillary growth (EVMG). Methods: Twelve healthy women aged between 20 and 49 years old (mean age of 26 years), with 5 mm or more of gingival exposure during fully posed smile (FPS) due to EVMG, were included. Baseline digital photographs were taken with standardized head position at rest and FPS. In eight out of 12 cases, crown lengthening procedure was indicated and the initial incision was made 2 to 4 mm from the gingival margin. In four cases, with no indication for crown lengthening procedure, a sulcular incision was performed. GBR was performed in all cases, using micro screws and/or titanium mesh associated with Bio-OssTM and Bio-GideTM. After 10 days, sutures were removed. Recall appointments were scheduled at 1, 6, and 12 months when standardized photographs were again taken. ImageToolTM software was used to measure the gingival exposure (GE) during FPS from the standardized close-up smile photographs at baseline and 12 months. Results: GE mean at baseline was 275.44 mm2. After 12 months, patients who undergone exclusively GBR procedure, presented GE reduction of 40.7%, ∆ = 112.01 mm2 (statistically significant, p = 0.12), and patients who had crown lengthening associated with the graft had a reduction of 60%, ∆ = 167.01 mm2. Conclusion: Our results using GBR to improve GS in cases of EVMG showed an exceptionally high patient acceptance and satisfaction. One-year follow-up confirmed stable results. PMID:27409660

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

    PubMed Central

    Ferroni, Letizia; Guazzo, Riccardo; Sbricoli, Luca; De Benedictis, Giulia; Finotti, Luca; Isola, Maurizio; Bressan, Eriberto; Zavan, Barbara

    2015-01-01

    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. PMID:26191793

  2. GBR using bovine bone matrix and resorbable and nonresorbable membranes. Part 2: Clinical results.

    PubMed

    Fugazzotto, Paul A

    2003-12-01

    Ninety sites were treated by sinus augmentation therapy using only Bio-Oss (31 sites) or extraction socket and ridge augmentation therapy using only Bio-Oss beneath secured resorbable or titanium-reinforced nonresorbable membranes (59 sites). The results of core biopsies taken at different intervals were discussed in part 1 of this study. A discussion of the use of resorbable versus reinforced nonresorbable membranes as a function of defect morphology is undertaken in part 2. Secured titanium-reinforced membranes were shown to be the most ideal means by which to ensure the final morphology of the regenerated hard tissues. PMID:14703764

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

    NASA Astrophysics Data System (ADS)

    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.

  4. A novel silk fibroin nanofibrous membrane for guided bone regeneration: a study in rat calvarial defects

    PubMed Central

    Lu, Shijun; Wang, Peng; Zhang, Feng; Zhou, Xichao; Zuo, Baoqi; You, Xinran; Gao, Yang; Liu, Hongchen; Tang, Hailiang

    2015-01-01

    A novel membrane for guided bone regeneration (GBR), constituting silk fibroin (SF) nanofiber from native silk nanofibril solution, was prepared by electrospinning process. Another barrier membrane, a collagen-type membrane (Bio-Gide®), was used as a comparative sample. Twelve healthy male Sprague-Dawley rats were used in this study. Bilateral round defects were created in the calvarial bone. The bone regenerative efficacy was evaluated in rat calvarial defects. Animals were killed at 4 and 12 weeks. Bone regeneration was analyzed using micro-computed tomography and histological analysis. The SF nanofibrous membrane showed superior results with regard to mechanical tensile properties. At 4 weeks, the bone volume and collagen I positive areas in the SF group were greater than in the Bio-Gide group. At 12 weeks, the defect had completely healed with new bone in both the groups. In conclusion, the SF nanofibrous membranes showed satisfactory mechanical stability, good biocompatibility, slow degradability, and improved new bone regeneration without any adverse inflammatory reactions. Considering the low cost and low risk of disease transmission, the SF nanofibrous membrane is a potential candidate for GBR therapy compared with the widely used collagen membranes. PMID:26807172

  5. Scaffold Design for Bone Regeneration

    PubMed Central

    Polo-Corrales, Liliana; Latorre-Esteves, Magda; Ramirez-Vick, Jaime E.

    2014-01-01

    The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate lost bone, as demonstrated by the large number of bone graft procedures performed worldwide. The most common of these is the autograft, however, its use can lead to complications such as pain, infection, scarring, blood loss, and donor-site morbidity. The alternative is allografts, but they lack the osteoactive capacity of autografts and carry the risk of carrying infectious agents or immune rejection. Other approaches, such as the bone graft substitutes, have focused on improving the efficacy of bone grafts or other scaffolds by incorporating bone progenitor cells and growth factors to stimulate cells. An ideal bone graft or scaffold should be made of biomaterials that imitate the structure and properties of natural bone ECM, include osteoprogenitor cells and provide all the necessary environmental cues found in natural bone. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. This focus of this review is on the evolution of these scaffolds as bone graft substitutes in the process of recreating the bone tissue microenvironment, including biochemical and biophysical cues. PMID:24730250

  6. Infection, Inflammation, and Bone Regeneration

    PubMed Central

    Thomas, M.V.; Puleo, D.A.

    2011-01-01

    Various strategies have been developed to promote bone regeneration in the craniofacial region. Most of these interventions utilize implantable materials or devices. Infections resulting from colonization of these implants may result in local tissue destruction in a manner analogous to periodontitis. This destruction is mediated via the expression of various inflammatory mediators and tissue-destructive enzymes. Given the well-documented association among microbial biofilms, inflammatory mediators, and tissue destruction, it seems reasonable to assume that inflammation may interfere with bone healing and regeneration. Paradoxically, recent evidence also suggests that the presence of certain pro-inflammatory mediators is actually required for bone healing. Bone injury (e.g., subsequent to a fracture or surgical intervention) is followed by a choreographed cascade of events, some of which are dependent upon the presence of pro-inflammatory mediators. If inflammation resolves promptly, then proper bone healing may occur. However, if inflammation persists (which might occur in the presence of an infected implant or graft material), then the continued inflammatory response may result in suboptimal bone formation. Thus, the effect of a given mediator is dependent upon the temporal context in which it is expressed. Better understanding of this temporal sequence may be used to optimize regenerative outcomes. PMID:21248364

  7. Clinical and histological evaluation of alloderm GBR and BioOss in the treatment of Siebert's class I ridge deficiency

    PubMed Central

    Sudarsan, Sabitha; Arun, K. V.; Priya, M. S.; Arun, Ramya

    2008-01-01

    Complete prosthetic rehabilitation using implants require the presence of adequate dimensions of alveolar bone. Ridge augmentation procedures include the use of guided bone regeneration (GBR) procedures where the barrier membrane provides cell occlusion and space for the regenerating tissues. Alloderm GBR has been introduced for the purpose of augmenting bone and has been postulated to have the additionally ability to integrate into soft tissues. Twenty-two patients with Siebert's class I ridge deficiency were treated with BioOss and Alloderm GBR and followed up for a period of nine months. Significant increase in ridge dimensions of both hard and soft tissues were observed at six months period itself, suggesting that it as an effective method of augmenting deficient ridges. PMID:20142949

  8. Guided bone regeneration is promoted by the molecular events in the membrane compartment.

    PubMed

    Turri, Alberto; Elgali, Ibrahim; Vazirisani, Forugh; Johansson, Anna; Emanuelsson, Lena; Dahlin, Christer; Thomsen, Peter; Omar, Omar

    2016-04-01

    The working hypothesis of guided bone regeneration (GBR) is that the membrane physically excludes non-osteogenic tissues from interfering with bone healing. However, the underlying mechanisms are insufficiently explained. This study aimed to investigate the molecular and structural pattern of bone healing in trabecular bone defects, with and without naturally derived resorbable membrane. Defects were created in rat femurs and treated with the membrane or left empty (sham). After 3d, 6d and 28d, the defect sites and membranes were harvested and analyzed with histology, histomorphometry, quantitative-polymerase chain reaction (qPCR), Western blot (WB) and immunohistochemistry (IHC). Histomorphometry demonstrated that the presence of the membrane promoted bone formation in early and late periods. This was in parallel with upregulation of cell recruitment and coupled bone remodeling genes in the defect. Cells recruited into the membrane expressed signals for bone regeneration (BMP-2, FGF-2, TGF-β1 and VEGF). Whereas the native membrane contained FGF-2 but not BMP-2, an accumulation of FGF-2 and BMP-2 proteins and immunoreactive cells were demonstrated by WB and IHC in the in vivo implanted membrane. The results provide cellular and molecular evidence suggesting a novel role for the membrane during GBR, by acting as a bioactive compartment rather than a passive barrier. PMID:26828682

  9. Bone regeneration and stem cells

    PubMed Central

    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

  10. Comparable efficacy of silk fibroin with the collagen membranes for guided bone regeneration in rat calvarial defects

    PubMed Central

    Kim, Jwa-Young; Yang, Byoung-Eun; Ahn, Jin-Hee; Park, Sang O

    2014-01-01

    PURPOSE Silk fibroin (SF) is a new degradable barrier membrane for guided bone regeneration (GBR) that can reduce the risk of pathogen transmission and the high costs associated with the use of collagen membranes. This study compared the efficacy of SF membranes on GBR with collagen membranes (Bio-Gide®) using a rat calvarial defect model. MATERIALS AND METHODS Thirty-six male Sprague Dawley rats with two 5 mm-sized circular defects in the calvarial bone were prepared (n=72). The study groups were divided into a control group (no membrane) and two experimental groups (SF membrane and Bio-Gide®). Each group of 24 samples was subdivided at 2, 4, and 8 weeks after implantation. New bone formation was evaluated using microcomputerized tomography and histological examination. RESULTS Bone regeneration was observed in the SF and Bio-Gide®-treated groups to a greater extent than in the control group (mean volume of new bone was 5.49 ± 1.48 mm3 at 8 weeks). There were different patterns of bone regeneration between the SF membrane and the Bio-Gide® samples. However, the absolute volume of new bone in the SF membrane-treated group was not significantly different from that in the collagen membrane-treated group at 8 weeks (8.75 ± 0.80 vs. 8.47 ± 0.75 mm3, respectively, P=.592). CONCLUSION SF membranes successfully enhanced comparable volumes of bone regeneration in calvarial bone defects compared with collagen membranes. Considering the lower cost and lesser risk of infectious transmission from animal tissue, SF membranes are a viable alternative to collagen membranes for GBR. PMID:25551015

  11. Efficacy of rhBMP-2 loaded PCL/PLGA/β-TCP guided bone regeneration membrane fabricated by 3D printing technology for reconstruction of calvaria defects in rabbit.

    PubMed

    Shim, Jin-Hyung; Yoon, Min-Chul; Jeong, Chang-Mo; Jang, Jinah; Jeong, Sung-In; Cho, Dong-Woo; Huh, Jung-Bo

    2014-12-01

    We successfully fabricated a three-dimensional (3D) printing-based PCL/PLGA/β-TCP guided bone regeneration (GBR) membrane that slowly released rhBMP-2. To impregnate the GBR membrane with intact rhBMP-2, collagen solution encapsulating rhBMP-2 (5 µg ml(-1)) was infused into pores of a PCL/PLGA/β-TCP membrane constructed using a 3D printing system with four dispensing heads. In a release profile test, sustained release of rhBMP-2 was observed for up to 28 d. To investigate the efficacy of the GBR membrane on bone regeneration, PCL/PLGA/β-TCP membranes with or without rhBMP-2 were implanted in an 8 mm calvaria defect of rabbits. Bone formation was evaluated at weeks 4 and 8 histologically and histomorphometrically. A space making ability of the GBR membrane was successfully maintained in both groups, and significantly more new bone was formed at post-implantation weeks 4 and 8 by rhBMP-2 loaded GBR membranes. Interestingly, implantation with rhBMP-2 loaded GBR membranes led to almost entire healing of calvaria defects within 8 weeks. PMID:25384105

  12. Enhanced bioactivity of polyvinylidene chloride films using argon ion bombardment for guided bone regeneration.

    PubMed

    Kobayashi, Shuichiro; Hayashi, Tatsuhide; Asakura, Masaki; Hamajima, Soichiro; Sato, Yamato; Sasaki, Keisuke; Okabe, Eijiro; Kawase, Mayu; Ando, Masahiko; Kawai, Tatsushi; Noguchi, Toshihide

    2014-09-01

    Polyvinylidene chloride (PVDC) is a long chain carbon synthetic polymer. The objective of this study was to improve the bioactivity of PVDC films through surface modification using argon (Ar) ion bombardment to create Ar-modified PVDC films (Ar-PVDC) to address the clinical problems of guided bone regeneration (GBR), which is technique-sensitive, and low bone regenerative ability. First, the effects of Ar ion bombardment, a low temperature plasma etching technique widely used in industry, on PVDC film wettability, surface chemistry, and morphology were confirmed. Next, fibroblast-like and osteoblast-like cell attachment and proliferation on Ar-PVDC were assessed. As a preclinical in vivo study, Ar-PVDC was used to cover a critical-sized bone defect on rat calvaria and osteoconductivity was evaluated by micro-computed tomography analysis and histological examinations. We found that the contact angle of PVDC film decreased by 50° because of the production of -OH groups on the PVDC film surface, though surface morphological was unchanged at 30 min after Ar ion bombardment. We demonstrated that cell attachment increased by about 40% and proliferation by more than 140% because of increased wettability, and 2.4 times greater bone regeneration was observed at week 3 with Ar-PVDC compared with untreated PVDC films. These results suggest that Ar ion bombardment modification of PVDC surfaces improves osteoconductivity, indicating its potential to increase bone deposition during GBR. PMID:24893861

  13. Engineered matrices for bone regeneration

    NASA Astrophysics Data System (ADS)

    Winn, Shelley R.; Hu, Yunhua; Pugh, Amy; Brown, Leanna; Nguyen, Jesse T.; Hollinger, Jeffrey O.

    2000-06-01

    Traditional therapies of autografts and allogeneic banked bone can promote reasonable clinical outcome to repair damaged bone. However, under certain conditions the success of these traditional approaches plummets, providing the incentive for researchers to develop clinical alternatives. The evolving field of tissue engineering in the musculoskeletal system attempts to mimic many of the components from the intact, healthy subject. Those components consist of a biologic scaffold, cells, extracellular matrix, and signaling molecules. The bone biomimetic, i.e., an engineered matrix, provides a porous structural architecture for the regeneration and ingrowth of osseous tissue at the site of injury. To further enhance the regenerative cascade, our strategy has involved porous biodegradable scaffolds containing and releasing signaling molecules and providing a suitable environment for cell attachment, growth and differentiation. In addition, the inclusion of genetically modified osteogenic precursor cells has brought the technology closer to developing a tissue-engineered equivalent. The presentation will describe various formulations and the methods utilized to evaluate the clinical utility of these biomimetics.

  14. The effect of bacterial cellulose membrane compared with collagen membrane on guided bone regeneration

    PubMed Central

    Lim, Youn-Mook; Jeong, Sung In; An, Sung-Jun; Kang, Seong-Soo

    2015-01-01

    PURPOSE This study was to evaluate the effects of bacterial cellulose (BC) membranes as a barrier membrane on guided bone regeneration (GBR) in comparison with those of the resorbable collagen membranes. MATERIALS AND METHODS BC membranes were fabricated using biomimetic technology. Surface properties were analyzed, Mechanical properties were measured, in vitro cell proliferation test were performed with NIH3T3 cells and in vivo study were performed with rat calvarial defect and histomorphometric analysis was done. The Mann-Whitney U test and the Wilcoxon signed rank test was used (α<.05). RESULTS BC membrane showed significantly higher mechanical properties such as wet tensile strength than collagen membrane and represented a three-dimensional multilayered structure cross-linked by nano-fibers with 60 % porosity. In vitro study, cell adhesion and proliferation were observed on BC membrane. However, morphology of the cells was found to be less differentiated, and the cell proliferation rate was lower than those of the cells on collagen membrane. In vivo study, the grafted BC membrane did not induce inflammatory response, and maintained adequate space for bone regeneration. An amount of new bone formation in defect region loaded with BC membrane was significantly similar to that of collagen membrane application. CONCLUSION BC membrane has potential to be used as a barrier membrane, and efficacy of the membrane on GBR is comparable to that of collagen membrane. PMID:26816579

  15. Novel naturally crosslinked electrospun nanofibrous chitosan mats for guided bone regeneration membranes: material characterization and cytocompatibility.

    PubMed

    Norowski, Peter A; Fujiwara, Tomoko; Clem, William C; Adatrow, Pradeep C; Eckstein, Eugene C; Haggard, Warren O; Bumgardner, Joel D

    2015-05-01

    Guided bone regeneration (GBR) barrier membranes are used to prevent soft tissue infiltration into the graft space during dental procedures that involve bone grafting. Chitosan materials have shown promise as GBR barrier membranes, due to their biocompatibility and predictable biodegradability, but degradation rates may still be too high for clinical applications. In this study, chitosan GBR membranes were electrospun using chitosan (70% deacetylated, 312 kDa, 5.5 w/v%), with or without the addition of 5 or 10 mm genipin, a natural crosslinking agent, in order to extend the degradation to meet the clinical target time frame of 4-6 months. Membranes were evaluated for fibre diameter, tensile strength, biodegradation rate, bond structure and cytocompatibility. Genipin addition, at 5 or 10 mm, resulted in median fibre diameters 184, 144 and 154 nm for uncrosslinked, 5 mm and 10 mm crosslinked, respectively. Crosslinking, examined by Fourier transform infrared spectroscopy, showed a decrease in N-H stretch as genipin levels were increased. Genipin-crosslinked mats exhibited only 22% degradation based on mass loss, as compared to 34% for uncrosslinked mats at 16 weeks in vitro. The ultimate tensile strength of the mats was increased by 165% to 32 MPa with 10 mm crosslinking as compared to the uncrosslinked mats. Finally, genipin-crosslinked mats supported the proliferation of SAOS-2 cells in a 5 day growth study, similar to uncrosslinked mats. These results suggest that electrospun chitosan mats may benefit from genipin crosslinking and have the potential to meet clinical degradation time frames for GBR applications. PMID:23166109

  16. Risk Factors for Wound Dehiscence after Guided Bone Regeneration in Dental Implant Surgery

    PubMed Central

    Kim, Young-Kyun; Yun, Pil-Young

    2014-01-01

    Purpose: The purpose of this study was to evaluate risks for wound dehiscence after guided bone regeneration (GBR) in dental implant surgery. Methods: Patients who received dental implant therapy with GBR procedure at Seoul National University Bundang Hospital (Seongnam, Korea) from June 2004 to May 2007 were included. The clinical outcome of interest was complications related to dental implant surgery. The factors influencing wound dehiscence, classified into patient-related factors, surgery-related factors and material-related factors, were evaluated. Results: One hundred and fifteen cases (202 implants) were included in this study. Wound dehiscence (19.1%) was considered a major complication. The risk of wound dehiscence was higher in males than in females (odds ratio=4.279, P =0.014). In the main graft, the allogenic group had the lowest risk of wound dehiscence (odds ratio=0.106, P =0.006). Though the external connection group had a higher risk of wound dehiscence than the internal connection group (odds ratio=2.381), the difference was not significant (P =0.100). Conclusion: In this study, male gender and main graft have the highest risk of wound dehiscence. To reduce wound dehiscence after GBR, instructions on postoperative care with supplementary procedure for the protection of the wound dehiscence is recommended, especially to male patients. A main graft with a gel base can reduce the risk of wound dehiscence. PMID:27489821

  17. In vitro and in vivo evaluation of chitosan/β-glycerol phosphate composite membrane for guided bone regeneration.

    PubMed

    Cui, Jun; Liang, Jie; Wen, Yong; Sun, Xiaoning; Li, Tiejun; Zhang, Gairong; Sun, Kangning; Xu, Xin

    2014-09-01

    Chitosan and β-glycerol phosphate (CS/β-GP) composite, with a thermosensitive sol-gel transition behavior, has been tested as one of the viable materials for barrier membrane fabrication. These studies have provided us with a new concept for a guided bone regeneration (GBR) membrane design. The composition, porous structure of the membrane, and the neutral mild preparation procedures make the CS/β-GP membrane a potentially active guide for bone regeneration. In this study, the CS/β-GP composite membrane, with different concentrations of β-GP, was studied to assess their potential utility in GBR application. The initial attachment of the ST2 stromal cell line to the CS/β-GP composite membrane was better than their attachment to the pure CS membrane. The proliferation and osteoblastic differentiation of the cells were much higher on the CS/β-GP composite membrane as compared to the pure CS membrane (p < 0.05). A mild inflammatory response was observed around the implanted CS/β-GP composite membrane without any foreign body reaction that continued up to 4 weeks of postsurgery. This primary study indicated that the in vitro and in vivo bioactivities of the CS/β-GP composite membrane fulfilled the requirements for GBR technique. PMID:23894020

  18. Bone Regeneration in Iliac Crestal Defects: An Experimental Study on Sheep

    PubMed Central

    Lorusso, Felice; Ravera, Lorenzo; Mortellaro, Carmen; Piattelli, Adriano

    2016-01-01

    Background. Oral rehabilitation of partially fully edentulous patients with dental implants has become a routine procedure in clinical practice. In a site with a lack of bone GBR is a surgical procedure that provides an augmentation in terms of volume for the insertion of dental implants. Materials and Methods. In the iliac crest of six sheep 4 defects were created where an implant was inserted, three of them with different biomaterials and a control site. All animals were sacrificed after a 4-month healing period. All specimens were processed and analyzed with histomorphometry. Statistical evaluation was done to evaluate percentage of bone defect filled by new bone. Results. All experimental groups showed an increase of the new bone. Higher and highly statistically significant differences were found in the percentages of bone defect filled by new bone in group filled with corticocancellous 250–1000 microns particulate porcine bone mix. Conclusions. This study demonstrates that particulate porcine bone mix and porcine corticocancellous collagenate prehydrated bone mix when used as scaffold are able to induce bone regeneration. Moreover, these data suggest that these biomaterials have higher biocompatibility and are capable of inducing faster and greater bone formation. PMID:27413746

  19. MicroRNAs and Bone Regeneration

    PubMed Central

    Nakasa, Tomoyuki; Yoshizuka, Masaaki; Andry Usman, Muhammad; Elbadry Mahmoud, Elhussein; Ochi, Mitsuo

    2015-01-01

    Bone has multiple functions, both morphologically and physiologically, and it frequently features in the pathological condition, including fracture and osteoporosis. For bone regeneration therapy, the regulation of osteoblast differentiation is important. MicroRNA (miRNA)s are short noncoding RNA which regulate gene expression at the post-transcriptional level. MiRNAs play an important role not only in a variety of other cellular processes including differentiation, proliferation, and apoptosis but also in the pathogenesis of human diseases. Recently, miRNAs have been known to participate in osteoblast differentiation by regulating several signaling pathways including transcription factors. New insight into the mechanism during osteogenes is affected by miRNAs has been gained. Moreover, therapeutic trials for bone diseases including osteoporosis, fracture and bone defects targeting miRNAs have been examined in animal models. MiRNA therapy will enable development of a bone regeneration therapy. PMID:27019619

  20. Gene therapy approaches to regenerating bone

    PubMed Central

    Bleich, Nadav Kimelman; Kallai, Ilan; Lieberman, Jay R.; Schwarz, Edward M.; Pelled, Gadi; Gazit, Dan

    2013-01-01

    Bone formation and regeneration therapies continue to require optimization and improvement because many skeletal disorders remain undertreated. Clinical solutions to nonunion fractures and osteoporotic vertebral compression fractures, for example, remain suboptimal and better therapeutic approaches must be created. The widespread use of recombinant human bone morphogenetic proteins (rhBMPs) for spine fusion was recently questioned by a series of reports in a special issue of The Spine Journal, which elucidated the side effects and complications of direct rhBMP treatments. Gene therapy—both direct (in vivo) and cell-mediated (ex vivo)—has long been studied extensively to provide much needed improvements in bone regeneration. In this article, we review recent advances in gene therapy research whose aims are in vivo or ex vivo bone regeneration or formation. We examine appropriate vectors, safety issues, and rates of bone formation. The use of animal models and their relevance for translation of research results to the clinical setting are also discussed in order to provide the reader with a critical view. Finally, we elucidate the main challenges and hurdles faced by gene therapy aimed at bone regeneration as well as expected future trends in this field. PMID:22429662

  1. [Fibrin glue and bone regeneration].

    PubMed

    Zilch, H; Wolff, R

    1987-01-01

    The osteoinductive property of fibrin glue with and without admixture of aprotinin was proven in animal model. Aprotinin as an inhibitor of the fibrinolysis is supposed to be an inhibitor of the osteogenesis, too. Three holes of 4 mm diameter and 2 mm depth were placed into the diaphysis of both femura in 12 adults dogs. The defects were filled with either pure fibrin glue or with glue containing aprotinin (3000 KIE), or with nothing (vacant). After 8 weeks the quantity of the new built woven-bone was examined by plane geometry and the "Bone Metabolising Unit (BMU)" (Frost) which are crossing the border of lamellar bone and new woven bone were counted out. There was seen no statistical significantly between the three groups neither in the quantity of new bone nor in the BMU. Therefore the fibrin glue has no osteoinductive property. PMID:2441537

  2. Novel applications of statins for bone regeneration

    PubMed Central

    Shah, Sarita R.; Werlang, Caroline A.; Kasper, F. Kurtis; Mikos, Antonios G.

    2015-01-01

    The use of statins for bone regeneration is a promising and growing area of research. Statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. Because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. In particular, statins can greatly affect the process of bone turnover and regeneration via effects on important cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts. Statins have also been shown to have anti-inflammatory and antimicrobial properties that may be useful since infection can derail normal bone healing. This review will explore the pleiotropic effects of statins, discuss the current use of statins for bone regeneration, particularly with regard to biomaterials-based controlled delivery, and offer perspectives on the challenges and future directions of this emerging area of bone tissue engineering. PMID:26543666

  3. Effortless effort in bone regeneration: a review.

    PubMed

    Nazirkar, Girish; Singh, Shailendra; Dole, Vinaykumar; Nikam, Akhilesh

    2014-06-01

    Since the beginning of the 20th century, the concept of osteoconduction in bony changes in the oral cavity showed a wide range of biomaterials and their osteoinductive potential that emerged gradually and has to a large extent improved the quality of the bone prior to the placement of an implant. Alveolar bone loss is a major concern after tooth extraction in patients and therefore atraumatic extraction procedures should be followed to avoid further bone loss. To overcome the alveolar bone loss and to augment support for placing dental implants, many bone regenerative substitutes are available such as allografts, autografts, xenografts, synthetic biomaterials and osteoactive agents. In light of the steady progress in bone grafting techniques and graft materials, it has become possible to improve the volume, width, and height of bone in deficient areas of the oral cavity. These advances in regenerative dentistry thus facilitate an easy and convenient placement of an implant in an ideal position and angulations resulting in superior esthetics and function. Bone grafting materials and their substitutes are the alternative filler materials, which facilitate to reduce additional surgical procedures, risks, chances of cross infection involved in placing autografts and allografts into the bony structures. This review literature highlights various biomaterials that are helpful in bone healing and thus create an anatomically favorable base for ideal implant placement. How to cite the article: Nazirkar G, Singh S, Dole V, Nikam A. Effortless effort in bone regeneration: A review. J Int Oral Health 2014;6(3):120-4. PMID:25083047

  4. Effortless Effort in Bone Regeneration: A Review

    PubMed Central

    Nazirkar, Girish; Singh, Shailendra; Dole, Vinaykumar; Nikam, Akhilesh

    2014-01-01

    Since the beginning of the 20th century, the concept of osteoconduction in bony changes in the oral cavity showed a wide range of biomaterials and their osteoinductive potential that emerged gradually and has to a large extent improved the quality of the bone prior to the placement of an implant. Alveolar bone loss is a major concern after tooth extraction in patients and therefore atraumatic extraction procedures should be followed to avoid further bone loss. To overcome the alveolar bone loss and to augment support for placing dental implants, many bone regenerative substitutes are available such as allografts, autografts, xenografts, synthetic biomaterials and osteoactive agents. In light of the steady progress in bone grafting techniques and graft materials, it has become possible to improve the volume, width, and height of bone in deficient areas of the oral cavity. These advances in regenerative dentistry thus facilitate an easy and convenient placement of an implant in an ideal position and angulations resulting in superior esthetics and function. Bone grafting materials and their substitutes are the alternative filler materials, which facilitate to reduce additional surgical procedures, risks, chances of cross infection involved in placing autografts and allografts into the bony structures. This review literature highlights various biomaterials that are helpful in bone healing and thus create an anatomically favorable base for ideal implant placement. How to cite the article: Nazirkar G, Singh S, Dole V, Nikam A. Effortless effort in bone regeneration: A review. J Int Oral Health 2014;6(3):120-4. PMID:25083047

  5. Dimensionally stable and bioactive membrane for guided bone regeneration: An in vitro study.

    PubMed

    Rowe, Matthew J; Kamocki, Krzysztof; Pankajakshan, Divya; Li, Ding; Bruzzaniti, Angela; Thomas, Vinoy; Blanchard, Steve B; Bottino, Marco C

    2016-04-01

    Composite fibrous electrospun membranes based on poly(dl-lactide) (PLA) and poly(ε-caprolactone) (PCL) were engineered to include borate bioactive glass (BBG) for the potential purposes of guided bone regeneration (GBR). The fibers were characterized using scanning and transmission electron microscopies, which respectively confirmed the submicron fibrous arrangement of the membranes and the successful incorporation of BBG particles. Selected mechanical properties of the membranes were evaluated using the suture pullout test. The addition of BBG at 10 wt % led to similar stiffness, but more importantly, it led to a significantly stronger (2.37 ± 0.51 N mm) membrane when compared with the commercially available Epiguide® (1.06 ± 0.24 N mm) under hydrated conditions. Stability (shrinkage) was determined after incubation in a phosphate buffer solution from 24 h up to 9 days. The dimensional stability of the PLA:PCL-based membranes with or without BBG incorporation (10.07-16.08%) was similar to that of Epiguide (14.28%). Cell proliferation assays demonstrated a higher rate of preosteoblasts proliferation on BBG-containing membranes (6.4-fold) over BBG-free membranes (4- to 5.8-fold) and EpiGuide (4.5-fold), following 7 days of in vitro culture. Collectively, our results demonstrated the ability to synthesize, via electrospinning, stable, polymer-based submicron fibrous BBG-containing membranes capable of sustaining osteoblastic attachment and proliferation-a promising attribute in GBR. PMID:25953329

  6. Candidates Cell Sources to Regenerate Alveolar Bone from Oral Tissue

    PubMed Central

    Nishimura, Masahiro; Takase, Kazuma; Suehiro, Fumio; Murata, Hiroshi

    2012-01-01

    Most of the cases of dental implant surgery, especially the bone defect extensively, are essential for alveolar ridge augmentation. As known as cell therapy exerts valuable effects on bone regeneration, numerous reports using various cells from body to regenerate bone have been published, including clinical reports. Mesenchymal cells that have osteogenic activity and have potential to be harvested from intra oral site might be a candidate cells to regenerate alveolar bone, even dentists have not been harvested the cells outside of mouth. This paper presents a summary of somatic cells in edentulous tissues which could subserve alveolar bone regeneration. The candidate tissues that might have differentiation potential as mesenchymal cells for bone regeneration are alveolar bone chip, bone marrow from alveolar bone, periosteal tissue, and gingival tissue. Understanding their phenotype consecutively will provide a rational approach for alveolar ridge augmentation. PMID:22505911

  7. Bone Adaptation and Regeneration - New Developments

    NASA Astrophysics Data System (ADS)

    Klein-Nulend, Jenneke; Bacabac, Rommel Gaud

    osteocytes sensing different canalicular flow patterns around cutting cone and reversal zone during loading, thus determining the bone's structure. Disturbances in architecture and permeability of the 3D porous network will affect transduction of mechanical loads to the mechanosensors. Uncovering the cellular and mechanical basis of the osteocyte's response to loading represents a significant challenge to our understanding of cellular mechanotransduction and bone remodeling. In view of the importance of mechanical stress for maintaining bone strength, mechanical stimuli have great potential for providing a therapeutic approach for bone (re)generation.

  8. Proresolving Nanomedicines Activate Bone Regeneration in Periodontitis

    PubMed Central

    Hasturk, H.; Kantarci, A.; Freire, M.O.; Nguyen, D.; Dalli, J.; Serhan, C.N.

    2015-01-01

    Therapies to reverse tissue damage from osteolytic inflammatory diseases are limited by the inability of current tissue-engineering procedures to restore lost hard and soft tissues. There is a critical need for new therapeutics in regeneration. In addition to scaffolds, cells, and soluble mediators necessary for tissue engineering, control of endogenous inflammation is an absolute requirement for success. Although significant progress has been made in understanding natural resolution of inflammation pathways to limit uncontrolled inflammation in disease, harnessing the biomimetic properties of proresolving lipid mediators has not been demonstrated. Here, we report the use of nano-proresolving medicines (NPRM) containing a novel lipoxin analog (benzo-lipoxin A4, bLXA4) to promote regeneration of hard and soft tissues irreversibly lost to periodontitis in the Hanford miniature pig. In this proof-of-principle experiment, NPRM-bLXA4 dramatically reduced inflammatory cell infiltrate into chronic periodontal disease sites treated surgically and dramatically increased new bone formation and regeneration of the periodontal organ. These findings indicate that NPRM-bLXA4 is a mimetic of endogenous resolving mechanisms with potent bioactions that offers a new therapeutic tissue-engineering approach for the treatment of chronic osteolytic inflammatory diseases. PMID:25389003

  9. Bone Repair Cells for Craniofacial Regeneration

    PubMed Central

    Pagni, G; Kaigler, D; Rasperini, G; Avila-Ortiz, G; Bartel, R; Giannobile, WV

    2012-01-01

    Reconstruction of complex craniofacial deformities is a clinical challenge in situations of injury, congenital defects or disease. The use of cell-based therapies represents one of the most advanced methods for enhancing the regenerative response for craniofacial wound healing. Both Somatic and Stem Cells have been adopted in the treatment of complex osseous defects and advances have been made in finding the most adequate scaffold for the delivery of cell therapies in human regenerative medicine. As an example of such approaches for clinical application for craniofacial regeneration, Ixmyelocel-T or bone repair cells are a source of bone marrow derived stem and progenitor cells. They are produced through the use of single pass perfusion bioreactors for CD90+ mesenchymal stem cells and CD14+ monocyte/macrophage progenitor cells. The application of ixmyelocel-T has shown potential in the regeneration of muscular, vascular, nervous and osseous tissue. The purpose of this manuscript is to highlight cell therapies used to repair bony and soft tissue defects in the oral and craniofacial complex. The field at this point remains at an early stage, however this review will provide insights into the progress being made using cell therapies for eventual development into clinical practice. PMID:22433781

  10. Biological Evaluation (In Vitro and In Vivo) of Bilayered Collagenous Coated (Nano Electrospun and Solid Wall) Chitosan Membrane for Periodontal Guided Bone Regeneration.

    PubMed

    Lotfi, Ghogha; Shokrgozar, Mohammad Ali; Mofid, Rasoul; Abbas, Fatemeh Mashhadi; Ghanavati, Farzin; Baghban, Alireza Akbarzadeh; Yavari, Seyedeh Kimia; Pajoumshariati, Seyedramin

    2016-07-01

    The application of barrier membranes in guided bone regeneration (GBR) has become a commonly used surgical technique in periodontal research. The objectives of this study were to evaluate the in vitro biocompatibility and osteogenic differentiation of mesenchymal stem cells (MSCs) on two different collagenous coatings (nano electrospun fibrous vs. solid wall) of bilayered collagen/chitosan membrane and their histological evaluation on bone regeneration in rabbit calvarial defects. It was found that chitosan-nano electrospun collagen (CNC) membranes had higher proliferation/metabolic activity compared to the chitosan-collagen (CC) and pristine chitosan membranes. The qRT-PCR analysis demonstrated the CNC membranes induced significant expression of osteogenic genes (Osteocalcin, RUNX2 and Col-α1) in MSCs. Moreover, higher calcium content and alkaline phosphatase activity of MSCs were observed compared to the other groups. Histologic and histomorphometric evaluations were performed on the uncovered (negative control) as well as covered calvarial defects of ten adult white rabbits with different membranes (CNC, CC, BioGide (BG, positive control)) at 1 and 2 months after surgery. More bone formation was detected in the defects covered with CNC and BG membranes than those covered by CC and the negative control. No inflammation and residual biomaterial particles were observed on the membrane surface or in the surrounding tissues in the surgical areas. These results suggest that bilayer CNC membrane can have the potential for use as a GBR membrane material facilitating bone formation. PMID:26586588

  11. The use of demineralized laminar bone sheets in guided bone regeneration procedures: report of three cases.

    PubMed

    Fugazzotto, P A

    1996-01-01

    Demineralized laminar bone sheets were utilized as membranes to affect guided bone regeneration around five implants in two patients and to perform a ridge augmentation procedure in one patient. In all cases, significant regeneration of hard tissues occurred, and no complications were encountered. The regenerated hard tissues have been in function for up to 32 months with no clinical signs of breakdown. PMID:8666457

  12. Tissue engineering strategies for promoting vascularized bone regeneration.

    PubMed

    Almubarak, Sarah; Nethercott, Hubert; Freeberg, Marie; Beaudon, Caroline; Jha, Amit; Jackson, Wesley; Marcucio, Ralph; Miclau, Theodore; Healy, Kevin; Bahney, Chelsea

    2016-02-01

    This review focuses on current tissue engineering strategies for promoting vascularized bone regeneration. We review the role of angiogenic growth factors in promoting vascularized bone regeneration and discuss the different therapeutic strategies for controlled/sustained growth factor delivery. Next, we address the therapeutic uses of stem cells in vascularized bone regeneration. Specifically, this review addresses the concept of co-culture using osteogenic and vasculogenic stem cells, and how adipose derived stem cells compare to bone marrow derived mesenchymal stem cells in the promotion of angiogenesis. We conclude this review with a discussion of a novel approach to bone regeneration through a cartilage intermediate, and discuss why it has the potential to be more effective than traditional bone grafting methods. PMID:26608518

  13. Photocrosslinkable and elastomeric hydrogels for bone regeneration.

    PubMed

    Thakur, Teena; Xavier, Janet R; Cross, Lauren; Jaiswal, Manish K; Mondragon, Eli; Kaunas, Roland; Gaharwar, Akhilesh K

    2016-04-01

    Nanocomposite biomaterials are extensively investigated for cell and tissue engineering applications due their unique physical, chemical and biological characteristics. Here, we investigated the mechanical, rheological, and degradation properties of photocrosslinkable and elastomeric nanocomposite hydrogels from nanohydroxyapatite (nHAp) and gelatin methacryloyl (GelMA). The addition of nHAp resulted in a significant increase in mechanical stiffness and physiological stability. Cells readily adhere and proliferate on the nanocomposite surfaces. Cyclic stretching of cells on the elastomeric nanocomposites revealed that nHAp elicited a stronger alignment response in the direction of strain. In vitro studies highlight enhanced bioactivity of nanocomposites as determined by alkaline phosphate (ALP) activity. Overall, the elastomeric and photocrosslinkable nanocomposite hydrogels can be used for minimally invasive therapy for bone regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 879-888, 2016. PMID:26650507

  14. On-Demand Guided Bone Regeneration with Microbial Protection of Ornamented SPU Scaffold with Bismuth-Doped Single Crystalline Hydroxyapatite: Augmentation and Cartilage Formation.

    PubMed

    Selvakumar, M; Srivastava, Priyanka; Pawar, Harpreet Singh; Francis, Nimmy K; Das, Bodhisatwa; Sathishkumar, G; Subramanian, Bhuvaneshwaran; Jaganathan, Saravana Kumar; George, Gibin; Anandhan, S; Dhara, Santanu; Nando, Golok B; Chattopadhyay, Santanu

    2016-02-17

    Guided bone regeneration (GBR) scaffolds are futile in many clinical applications due to infection problems. In this work, we fabricated GBR with an anti-infective scaffold by ornamenting 2D single crystalline bismuth-doped nanohydroxyapatite (Bi-nHA) rods onto segmented polyurethane (SPU). Bi-nHA with high aspect ratio was prepared without any templates. Subsequently, it was introduced into an unprecedented synthesized SPU matrix based on dual soft segments (PCL-b-PDMS) of poly(ε-caprolactone) (PCL) and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, undoped pristine nHA rods were also ornamented into it. The enzymatic ring-opening polymerization technique was adapted to synthesize soft segments of PCL-b-PDMS copolymers of SPU. Structure elucidation of the synthesized polymers is done by nuclear magnetic resonance spectroscopy. Sparingly, Bi-nHA ornamented scaffolds exhibit tremendous improvement (155%) in the mechanical properties with excellent antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast cells (in vitro), the scaffolds were implanted in rabbits by subcutaneous and intraosseous (tibial) sites. Various histological sections reveal the signatures of early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks of the critical defects filled with ornamented scaffold compared to SPU scaffold. This implies osteogenic potential and ability to provide an adequate biomimetic microenvironment for mineralization for GBR of the scaffolds. Organ toxicity studies further confirm that no tissue architecture abnormalities were observed in hepatic, cardiac, and renal tissue sections. This finding manifests the feasibility of fabricating a mechanically adequate nanofibrous SPU scaffold by a biomimetic strategy and the advantages of Bi

  15. Bone regenerates via dedifferentiation of osteoblasts in the zebrafish fin.

    PubMed

    Knopf, Franziska; Hammond, Christina; Chekuru, Avinash; Kurth, Thomas; Hans, Stefan; Weber, Christopher W; Mahatma, Gina; Fisher, Shannon; Brand, Michael; Schulte-Merker, Stefan; Weidinger, Gilbert

    2011-05-17

    While mammals have a limited capacity to repair bone defects, zebrafish can completely regenerate amputated bony structures of their fins. Fin regeneration is dependent on formation of a blastema, a progenitor cell pool accumulating at the amputation plane. It is unclear which cells the blastema is derived from, whether it forms by dedifferentiation of mature cells, and whether blastema cells are multipotent. We show that mature osteoblasts dedifferentiate and form part of the blastema. Osteoblasts downregulate expression of intermediate and late bone differentiation markers and induce genes expressed by bone progenitors. Dedifferentiated osteoblasts proliferate in a FGF-dependent manner and migrate to form part of the blastema. Genetic fate mapping shows that osteoblasts only give rise to osteoblasts in the regenerate, indicating that dedifferentiation is not associated with the attainment of multipotency. Thus, bone can regenerate from mature osteoblasts via dedifferentiation, a finding with potential implications for human bone repair. PMID:21571227

  16. Recent advances in bone regeneration using adult stem cells.

    PubMed

    Zigdon-Giladi, Hadar; Rudich, Utai; Michaeli Geller, Gal; Evron, Ayelet

    2015-04-26

    Bone is a highly vascularized tissue reliant on the close spatial and temporal association between blood vessels and bone cells. Therefore, cells that participate in vasculogenesis and osteogenesis play a pivotal role in bone formation during prenatal and postnatal periods. Nevertheless, spontaneous healing of bone fracture is occasionally impaired due to insufficient blood and cellular supply to the site of injury. In these cases, bone regeneration process is interrupted, which might result in delayed union or even nonunion of the fracture. Nonunion fracture is difficult to treat and have a high financial impact. In the last decade, numerous technological advancements in bone tissue engineering and cell-therapy opened new horizon in the field of bone regeneration. This review starts with presentation of the biological processes involved in bone development, bone remodeling, fracture healing process and the microenvironment at bone healing sites. Then, we discuss the rationale for using adult stem cells and listed the characteristics of the available cells for bone regeneration. The mechanism of action and epigenetic regulations for osteogenic differentiation are also described. Finally, we review the literature for translational and clinical trials that investigated the use of adult stem cells (mesenchymal stem cells, endothelial progenitor cells and CD34(+) blood progenitors) for bone regeneration. PMID:25914769

  17. Hyperbaric Oxygen Promotes Proximal Bone Regeneration and Organized Collagen Composition during Digit Regeneration

    PubMed Central

    Sammarco, Mimi C.; Simkin, Jennifer; Cammack, Alexander J.; Fassler, Danielle; Gossmann, Alexej; Marrero, Luis; Lacey, Michelle; Van Meter, Keith; Muneoka, Ken

    2015-01-01

    Oxygen is critical for optimal bone regeneration. While axolotls and salamanders have retained the ability to regenerate whole limbs, mammalian regeneration is restricted to the distal tip of the digit (P3) in mice, primates, and humans. Our previous study revealed the oxygen microenvironment during regeneration is dynamic and temporally influential in building and degrading bone. Given that regeneration is dependent on a dynamic and changing oxygen environment, a better understanding of the effects of oxygen during wounding, scarring, and regeneration, and better ways to artificially generate both hypoxic and oxygen replete microenvironments are essential to promote regeneration beyond wounding or scarring. To explore the influence of increased oxygen on digit regeneration in vivo daily treatments of hyperbaric oxygen were administered to mice during all phases of the entire regenerative process. Micro-Computed Tomography (μCT) and histological analysis showed that the daily application of hyperbaric oxygen elicited the same enhanced bone degradation response as two individual pulses of oxygen applied during the blastema phase. We expand past these findings to show histologically that the continuous application of hyperbaric oxygen during digit regeneration results in delayed blastema formation at a much more proximal location after amputation, and the deposition of better organized collagen fibers during bone formation. The application of sustained hyperbaric oxygen also delays wound closure and enhances bone degradation after digit amputation. Thus, hyperbaric oxygen shows the potential for positive influential control on the various phases of an epimorphic regenerative response. PMID:26452224

  18. Preparation and preliminary in vitro evaluation of a bFGF-releasing heparin-conjugated poly(ε-caprolactone) membrane for guided bone regeneration.

    PubMed

    Cao, Cong; Song, Ying; Yao, Qianqian; Yao, Yang; Wang, Tianlu; Huang, Bo; Gong, Ping

    2015-01-01

    In an effort to improve guided bone regeneration (GBR), we successfully fabricated a novel basic fibroblast growth factor (bFGF)-releasing heparin-conjugated poly(ε-caprolactone) membrane (hep-PCL/bFGF). This material has a porous microstructure with smooth and rough pore walls before and after heparinization, respectively. Our FTIR analyses indicated that chemical bonds were formed between PCL and heparin with a new amide C=O band at 1660 cm(-1) and a band at 3400 cm(-1) that can be attributed to -OH stretching in cross-linked heparin. We showed that bFGF was released from hep-PCL/bFGF in a continuous pattern, which remained for 3 weeks. We evaluated MG63 cell proliferation and biocompatibility of GBR membrane by a CCK-8 assay and a live/dead assay. The CCK-8 results revealed that the hep-PCL/bFGF group had superiority compared to other groups. Furthermore, cell morphology of hep-PCL membrane exhibited larger projected areas than those of PCL surfaces based on scanning electron microscopy analysis and immunofluorescent staining of cell cytoskeleton and vinculin expression. Our alkaline phosphatase activity assay also confirmed better performance of the hep-PCL/bFGF group. These results suggested that this novel hep-PCL/bFGF membrane is suitable for osteoblast-like cells to attach, proliferate, and differentiate. Therefore, the hep-PCL/bFGF membrane has potential to be a biodegradable membrane for GBR and warrants further investigation. PMID:26065539

  19. Bioactive and Biodegradable Nanocomposites and Hybrid Biomaterials for Bone Regeneration

    PubMed Central

    Allo, Bedilu A.; Costa, Daniel O.; Dixon, S. Jeffrey; Mequanint, Kibret; Rizkalla, Amin S.

    2012-01-01

    Strategies for bone tissue engineering and regeneration rely on bioactive scaffolds to mimic the natural extracellular matrix and act as templates onto which cells attach, multiply, migrate and function. Of particular interest are nanocomposites and organic-inorganic (O/I) hybrid biomaterials based on selective combinations of biodegradable polymers and bioactive inorganic materials. In this paper, we review the current state of bioactive and biodegradable nanocomposite and O/I hybrid biomaterials and their applications in bone regeneration. We focus specifically on nanocomposites based on nano-sized hydroxyapatite (HA) and bioactive glass (BG) fillers in combination with biodegradable polyesters and their hybrid counterparts. Topics include 3D scaffold design, materials that are widely used in bone regeneration, and recent trends in next generation biomaterials. We conclude with a perspective on the future application of nanocomposites and O/I hybrid biomaterials for regeneration of bone. PMID:24955542

  20. Harnessing and Modulating Inflammation in Strategies for Bone Regeneration

    PubMed Central

    Mountziaris, Paschalia M.; Spicer, Patrick P.; Kasper, F. Kurtis

    2011-01-01

    Inflammation is an immediate response that plays a critical role in healing after fracture or injury to bone. However, in certain clinical contexts, such as in inflammatory diseases or in response to the implantation of a biomedical device, the inflammatory response may become chronic and result in destructive catabolic effects on the bone tissue. Since our previous review 3 years ago, which identified inflammatory signals critical for bone regeneration and described the inhibitory effects of anti-inflammatory agents on bone healing, a multitude of studies have been published exploring various aspects of this emerging field. In this review, we distinguish between regenerative and damaging inflammatory processes in bone, update our discussion of the effects of anti-inflammatory agents on bone healing, summarize recent in vitro and in vivo studies demonstrating how inflammation can be modulated to stimulate bone regeneration, and identify key future directions in the field. PMID:21615330

  1. Guided bone regeneration in distal mandibular atrophy by means of a preformed titanium foil: a case series.

    PubMed

    Andreasi Bassi, M; Andrisani, C; Lopez, M A; Gaudio, R M; Lombardo, L; Lauritano, D

    2016-01-01

    The aim of this case series was to evaluate the clinical outcome of preformed titanium foil (PTF) to perform guided bone regeneration (GBR) in posterior mandibular atrophies. Thirteen patients (4 male; 9 female; mean age 58.85±10.16 years), with class II division C atrophy, according to Misch, were selected to perform GBR by means of PTF, using a moldable allograft paste as graft material. The devices, made of a 0.2mm thick pure titanium foil, were pre-shaped using stereolithographic models obtained from CT-scan of the patients’ recipient sites. In the second stage, performed at 6.35±2.15 months, 23 cylindrical two-piece implants were placed and the devices removed. At four months, the implants were exposed and submitted to progressive prosthetic load for a span of 4 months. The cases were finalized by means of metal-ceramic cementable restorations. The post finalization follow-up was at 12 months. Survival rate (i.e. SVR) was 100% since no fixtures were lost. At the one-year follow up, the clinical appearance of the soft tissues was optimal and no pathological signs on probing were recorded. The success rate (i.e. SCR) was 82.6% and the average peri-implant bone reabsorption was 0.99±0.59 mm. The results suggest good potentialities of this method for bone volume augmentation in distal mandibular atrophies, allowing to maximize the outcome and simplifying the surgical phase. PMID:27469550

  2. Maxillofacial-derived stem cells regenerate critical mandibular bone defect.

    PubMed

    Steinhardt, Yair; Aslan, Hadi; Regev, Eran; Zilberman, Yoram; Kallai, Ilan; Gazit, Dan; Gazit, Zulma

    2008-11-01

    Stem cell-based bone tissue regeneration in the maxillofacial complex is a clinical necessity. Genetic engineering of mesenchymal stem cells (MSCs) to follow specific differentiation pathways may enhance the ability of these cells to regenerate and increase their clinical relevance. MSCs isolated from maxillofacial bone marrow (BM) are good candidates for tissue regeneration at sites of damage to the maxillofacial complex. In this study, we hypothesized that MSCs isolated from the maxillofacial complex can be engineered to overexpress the bone morphogenetic protein-2 gene and induce bone tissue regeneration in vivo. To demonstrate that the cells isolated from the maxillofacial complex were indeed MSCs, we performed a flow cytometry analysis, which revealed a high expression of mesenchyme-related markers and an absence of non-mesenchyme-related markers. In vitro, the MSCs were able to differentiate into osteogenic, chondrogenic, and adipogenic lineages. Gene delivery of the osteogenic gene BMP2 via an adenoviral vector revealed high expression levels of BMP2 protein that induced osteogenic differentiation of these cells in vitro and induced bone formation in an ectopic site in vivo. In addition, implantation of genetically engineered maxillofacial BM-derived MSCs into a mandibular defect led to regeneration of tissue at the site of the defect; this was confirmed by performing micro-computed tomography analysis. Histological analysis of the mandibles revealed osteogenic differentiation of implanted cells as well as bone tissue regeneration. We conclude that maxillofacial BM-derived MSCs can be genetically engineered to induce bone tissue regeneration in the maxillofacial complex and that this finding may be clinically relevant. PMID:18636943

  3. Adverse Effects of Hyperlipidemia on Bone Regeneration and Strength

    PubMed Central

    Pirih, F; Lu, J; Ye, F; Bezouglaia, O; Atti, E; Ascenzi, MG; Tetradis, S; Demer, LL; Aghaloo, T; Tintut, Y

    2011-01-01

    Hyperlipidemia increases the risk for generation of lipid oxidation products, which accumulate in the subendothelial spaces of vasculature and bone. Atherogenic high-fat diets increase serum levels of oxidized lipids, which are known to attenuate osteogenesis in culture and to promote bone loss in mice. In this study, we investigated whether oxidized lipids affect bone regeneration and mechanical strength. Wild type and hyperlipidemic (Ldlr−/−) mice were placed on a high-fat (HF) diet for 13 weeks. Bilateral cranial defects were introduced on each side of the sagittal suture, and 5 weeks post-surgery on the respective diets, the repair/regeneration of cranial bones and mechanical properties of femoral bones were assessed. MicroCT and histological analyses demonstrated that bone regeneration was significantly impaired by the HF diet in WT and Ldlr−/− mice. In femoral bone, cortical bone volume fraction (BV/TV) was significantly reduced while cortical porosity was increased by the HF diet in Ldlr−/− but not in WT mice. Femoral bone strength and stiffness, measured by three-point bending analysis, were significantly reduced by the HF diet in Ldlr−/−, but not in WT mice. Serum analysis showed that the HF diet significantly increased levels of parathyroid hormone, TNF-alpha, calcium and phosphorus, whereas it reduced procollagen type I N-terminal propeptide, a serum marker of bone formation, in Ldlr−/−, but not in WT mice. The serum level of carboxyl-terminal collagen crosslinks, a marker for bone resorption, was also 1.7-fold greater in Ldlr−/− mice. These findings suggest that hyperlipidemia induces secondary hyperparathyroidism and impairs bone regeneration and mechanical strength. PMID:21987408

  4. Biomechanical characteristics of regenerated cortical bone in the canine mandible

    PubMed Central

    Zapata, Uriel; Opperman, Lynne A.; Kontogiorgos, Elias; Elsalanty, Mohammed E.; Dechow, Paul C.

    2010-01-01

    To test the mechanical properties of regenerate cortical bone created using Mandibular Bone Transport (MBT) distraction, five adult male American foxhound dogs underwent unilateral distraction of the mandible with a novel MBT device placed to linearly repair a 30-35 mm bone defect. The animals were sacrificed 12 weeks after the beginning of the consolidation period. Fourteen cylindrical specimens were taken from the inner (lingual) and outer (buccal) plates of the reconstructed mandible and 21 control specimens were removed from the contralateral aspect of the mandible. The mechanical properties of the 35 cylindrical cortical bone specimens were assessed by using a non-destructive pulse ultrasound technique. Results showed that all of the cortical mechanical properties exhibit higher numerical values on the control side than the MBT regenerate side. In addition, both densities and the elastic moduli in the direction of maximum stiffness of the regenerate cortical bone specimens are higher on the lingual side than the buccal side. Interestingly, there is no statistical difference between elastic modulus (E1 and E2) in orthogonal directions throughout the 35 cortical specimens. The data suggest that the regenerate canine cortical bone is not only heterogeneous, but the elastic mechanical properties tend to approximate transverse isotropy at a tissue level as opposed to control cortical bone that is orthotropic. In addition, the elastic mechanical properties are not only higher on the control side but also in the lingual anatomical position, suggesting a stress shielding effect from the presence of the reconstruction plate. PMID:21695796

  5. Nell-1-induced bone regeneration in calvarial defects.

    PubMed

    Aghaloo, Tara; Cowan, Catherine M; Chou, Yu-Fen; Zhang, Xinli; Lee, Haofu; Miao, Steve; Hong, Nichole; Kuroda, Shun'ichi; Wu, Benjamin; Ting, Kang; Soo, Chia

    2006-09-01

    Many craniofacial birth defects contain skeletal components requiring bone grafting. We previously identified the novel secreted osteogenic molecule NELL-1, first noted to be overexpressed during premature bone formation in calvarial sutures of craniosynostosis patients. Nell-1 overexpression significantly increases differentiation and mineralization selectively in osteoblasts, while newborn Nell-1 transgenic mice significantly increase premature bone formation in calvarial sutures. In the current study, cultured calvarial explants isolated from Nell-1 transgenic newborn mice (with mild sagittal synostosis) demonstrated continuous bone growth and overlapping sagittal sutures. Further investigation into gene expression cascades revealed that fibroblast growth factor-2 and transforming growth factor-beta1 stimulated Nell-1 expression, whereas bone morphogenetic protein (BMP)-2 had no direct effect. Additionally, Nell-1-induced osteogenesis in MC3T3-E1 osteoblasts through reduction in the expression of early up-regulated osteogenic regulators (OSX and ALP) but induction of later markers (OPN and OCN). Grafting Nell-1 protein-coated PLGA scaffolds into rat calvarial defects revealed the osteogenic potential of Nell-1 to induce bone regeneration equivalent to BMP-2, whereas immunohistochemistry indicated that Nell-1 reduced osterix-producing cells and increased bone sialoprotein, osteocalcin, and BMP-7 expression. Insights into Nell-1-regulated osteogenesis coupled with its ability to stimulate bone regeneration revealed a potential therapeutic role and an alternative to the currently accepted techniques for bone regeneration. PMID:16936265

  6. Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration

    PubMed Central

    Zhang, Xingdi; Zeng, Deliang; Li, Nan; Wen, Jin; Jiang, Xinquan; Liu, Changsheng; Li, Yongsheng

    2016-01-01

    Mesoporous bioactive glass (MBG), which possesses excellent bioactivity, biocompatibility and osteoconductivity, has played an important role in bone tissue regeneration. However, it is difficult to prepare MBG scaffolds with high compressive strength for applications in bone regeneration; this difficulty has greatly hindered its development and use. To solve this problem, a simple powder processing technique has been successfully developed to fabricate a novel type of MBG scaffold (MBGS). Furthermore, amino or carboxylic groups could be successfully grafted onto MBGSs (denoted as N-MBGS and C-MBGS, respectively) through a post-grafting process. It was revealed that both MBGS and the functionalized MBGSs could significantly promote the proliferation and osteogenic differentiation of bMSCs. Due to its positively charged surface, N-MBGS presented the highest in vitro osteogenic capability of the three samples. Moreover, in vivo testing results demonstrated that N-MBGS could promote higher levels of bone regeneration compared with MBGS and C-MBGS. In addition to its surface characteristics, it is believed that the decreased degradation rate of N-MBGS plays a vital role in promoting bone regeneration. These findings indicate that MBGSs are promising materials with potential practical applications in bone regeneration, which can be successfully fabricated by combining a powder processing technique and post-grafting process. PMID:26763311

  7. Organ printing: the future of bone regeneration?

    PubMed

    Fedorovich, Natalja E; Alblas, Jacqueline; Hennink, Wim E; Oner, F Cumhur; Dhert, Wouter J A

    2011-12-01

    In engineered bone grafts, the combined actions of bone-forming cells, matrix and bioactive stimuli determine the eventual performance of the implant. The current notion is that well-built 3D constructs include the biological elements that recapitulate native bone tissue structure to achieve bone formation once implanted. The relatively new technology of organ/tissue printing now enables the accurate 3D organization of the components that are important for bone formation and also addresses issues, such as graft porosity and vascularization. Bone printing is seen as a great promise, because it combines rapid prototyping technology to produce a scaffold of the desired shape and internal structure with incorporation of multiple living cell types that can form the bone tissue once implanted. PMID:21831463

  8. A histological evaluation for guided bone regeneration induced by a collagenous membrane.

    PubMed

    Taguchi, Yuya; Amizuka, Norio; Nakadate, Masayoshi; Ohnishi, Hideo; Fujii, Noritaka; Oda, Kimimitsu; Nomura, Shuichi; Maeda, Takeyasu

    2005-11-01

    This study was designed to evaluate the histological changes during ossification and cellular events including osteogenic differentiation responding to collagenous bioresorbable membranes utilized for GBR. Standardized artificial bony defects were prepared at rat maxillae, and covered with a collagenous bioresorbable membrane. These animals were sacrificed at 1, 2, 3 and 4 weeks after the GBR-operation. The paraffin sections were subject to tartrate resistant acid phosphatase (TRAP) enzyme histochemistry and immunohistochemistry for alkaline phosphatase (ALP), osteopontin (OP) and osteocalcin (OC). In the first week of the experimental group, woven bone with ALP-positive osteoblasts occupied the lower half of the cavity. The collagenous membrane included numerous ALP-negative cells and OP-immunoreactive extracellular matrices. At 2 weeks, the ALP-, OP- and OC-immunoreactivity came to be recognizable in the region of collagenous membrane. Since ALP-negative soft tissue separated the collagenous membrane and the new bone originating from the cavity bottom, the collagenous membrane appeared to induce osteogenesis in situ. At 3 weeks, numerous collagen fibers of the membrane were embedded in the adjacent bone matrix. At 4 weeks, the membrane-associated and the cavity-derived bones had completely integrated, showing the same height of the periosteal ridge as the surrounding alveolar bones. The collagen fibers of a GBR-membrane appear to participate in osteogenic differentiation. PMID:15885767

  9. Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo micro-computed tomographic and histologic experiment in rats.

    PubMed

    Al-Hezaimi, Khalid; Ramalingam, Sundar; Al-Askar, Mansour; ArRejaie, Aws S; Nooh, Nasser; Jawad, Fawad; Aldahmash, Abdullah; Atteya, Muhammad; Wang, Cun-Yu

    2016-01-01

    The aim of the present real time in vivo micro-computed tomography (µCT) and histologic experiment was to assess the efficacy of guided bone regeneration (GBR) around standardized calvarial critical size defects (CSD) using bone marrow-derived mesenchymal stem cells (BMSCs), and collagen membrane (CM) with and without tricalcium phosphate (TCP) graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD (diameter 4.6 mm) were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone (NFB) and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo µCT. At the 10th week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups 1 and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical "lock" between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adjunct BMSC therapy. PMID:27025260

  10. Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo micro-computed tomographic and histologic experiment in rats

    PubMed Central

    Al-Hezaimi, Khalid; Ramalingam, Sundar; Al-Askar, Mansour; ArRejaie, Aws S; Nooh, Nasser; Jawad, Fawad; Aldahmash, Abdullah; Atteya, Muhammad; Wang, Cun-Yu

    2016-01-01

    The aim of the present real time in vivo micro-computed tomography (µCT) and histologic experiment was to assess the efficacy of guided bone regeneration (GBR) around standardized calvarial critical size defects (CSD) using bone marrow-derived mesenchymal stem cells (BMSCs), and collagen membrane (CM) with and without tricalcium phosphate (TCP) graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD (diameter 4.6 mm) were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone (NFB) and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo µCT. At the 10th week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups 1 and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical “lock” between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adjunct BMSC therapy. PMID:27025260

  11. Tracheal cartilage regeneration and new bone formation by slow release of bone morphogenetic protein (BMP)-2.

    PubMed

    Igai, Hitoshi; Chang, Sung Soo; Gotoh, Masashi; Yamamoto, Yasumichi; Yamamoto, Masaya; Tabata, Yasuhiko; Yokomise, Hiroyasu

    2008-01-01

    We investigated the efficiency of bone morphogenetic protein (BMP)-2 released slowly from gelatin sponge for tracheal cartilage regeneration. A 1-cm gap was made in the mid-ventral portion of each of 10 consecutive tracheal cartilages. In the control group (n = 4), the resulting gap was left untreated. In the gelatin group (n = 4), plain gelatin was implanted in the gap. In the BMP-2 group (n = 4), gelatin containing 100 microg BMP-2 was implanted. We euthanatized all dogs in each group at 1, 3, 6, and 12 months after the implantation, respectively, and then examined the implant site macro- and microscopically. In the BMP-2 group, regenerated fibrous cartilage and newly formed bone were observed at 1 and 12 months. Regenerated cartilage was observed at the ends of the host cartilage stumps, with newly formed bone in the middle portion. The gaps were filled with regenerated cartilage and newly formed bone. At 3 and 6 months, regenerated cartilage, but not newly formed bone, was evident. The regenerated cartilage was covered with perichondrium and showed continuity with the host cartilage. We succeeded in inducing cartilage regeneration and new bone formation in canine trachea by slow release of 100 microg BMP-2 from gelatin. PMID:18204324

  12. Stem Cells and Calcium Phosphate Cement Scaffolds for Bone Regeneration

    PubMed Central

    Wang, P.; Zhao, L.; Chen, W.; Liu, X.; Weir, M.D.; Xu, H.H.K.

    2014-01-01

    Calcium phosphate cements (CPCs) have excellent biocompatibility and osteoconductivity for dental, craniofacial, and orthopedic applications. This article reviews recent developments in stem cell delivery via CPC for bone regeneration. This includes: (1) biofunctionalization of the CPC scaffold, (2) co-culturing of osteoblasts/endothelial cells and prevascularization of CPC, (3) seeding of CPC with different stem cell species, (4) human umbilical cord mesenchymal stem cell (hUCMSC) and bone marrow MSC (hBMSC) seeding on CPC for bone regeneration, and (5) human embryonic stem cell (hESC) and induced pluripotent stem cell (hiPSC) seeding with CPC for bone regeneration. Cells exhibited good attachment/proliferation in CPC scaffolds. Stem-cell-CPC constructs generated more new bone and blood vessels in vivo than did the CPC control without cells. hUCMSCs, hESC-MSCs, and hiPSC-MSCs in CPC generated new bone and blood vessels similar to those of hBMSCs; hence, they were viable cell sources for bone engineering. CPC with hESC-MSCs and hiPSC-MSCs generated new bone two- to three-fold that of the CPC control. Therefore, this article demonstrates that: (1) CPC scaffolds are suitable for delivering cells; (2) hUCMSCs, hESCs, and hiPSCs are promising alternatives to hBMSCs, which require invasive procedures to harvest with limited cell quantity; and (3) stem-cell-CPC constructs are highly promising for bone regeneration in dental, craniofacial, and orthopedic applications. PMID:24799422

  13. Stem Cells and Calcium Phosphate Cement Scaffolds for Bone Regeneration.

    PubMed

    Wang, P; Zhao, L; Chen, W; Liu, X; Weir, M D; Xu, H H K

    2014-07-01

    Calcium phosphate cements (CPCs) have excellent biocompatibility and osteoconductivity for dental, craniofacial, and orthopedic applications. This article reviews recent developments in stem cell delivery via CPC for bone regeneration. This includes: (1) biofunctionalization of the CPC scaffold, (2) co-culturing of osteoblasts/endothelial cells and prevascularization of CPC, (3) seeding of CPC with different stem cell species, (4) human umbilical cord mesenchymal stem cell (hUCMSC) and bone marrow MSC (hBMSC) seeding on CPC for bone regeneration, and (5) human embryonic stem cell (hESC) and induced pluripotent stem cell (hiPSC) seeding with CPC for bone regeneration. Cells exhibited good attachment/proliferation in CPC scaffolds. Stem-cell-CPC constructs generated more new bone and blood vessels in vivo than did the CPC control without cells. hUCMSCs, hESC-MSCs, and hiPSC-MSCs in CPC generated new bone and blood vessels similar to those of hBMSCs; hence, they were viable cell sources for bone engineering. CPC with hESC-MSCs and hiPSC-MSCs generated new bone two- to three-fold that of the CPC control. Therefore, this article demonstrates that: (1) CPC scaffolds are suitable for delivering cells; (2) hUCMSCs, hESCs, and hiPSCs are promising alternatives to hBMSCs, which require invasive procedures to harvest with limited cell quantity; and (3) stem-cell-CPC constructs are highly promising for bone regeneration in dental, craniofacial, and orthopedic applications. PMID:24799422

  14. Enhanced initial bone regeneration with inorganic polyphosphate-adsorbed hydroxyapatite.

    PubMed

    Morita, K; Doi, K; Kubo, T; Takeshita, R; Kato, S; Shiba, T; Akagawa, Y

    2010-07-01

    Inorganic polyphosphate (poly(P)) can promote binding between fibroblast growth factors and their receptors and enhance osteoblastic cell differentiation and calcification. This study evaluated the possibilities for poly(P) adsorbed onto interconnected porous calcium hydroxyapatite (IP-CHA) as a new bone regeneration material. Prepared 1%, 5%, 25% and 50% poly(P)/IP-CHA composites showed the elution peak of poly(P) between 15 and 20 min, respectively, with the highest value from 50% poly(P)/IP-CHA in vitro. Histologically, at 1 week of placement into the femur of rabbits, granulation tissue had penetrated into the pores in all composites and IP-CHA as a control. In contrast, at 2 weeks of placement, newly formed lamellar bone was found in all groups, although a higher amount of bone regeneration was obviously formed in the 25% and 50% poly(P)/IP-CHA with a significantly higher value of bone regeneration ratio of 50% poly(P)/IP-CHA. These results indicate that 25% and 50% poly(P)/IP-CHA composites may enhance initial bone regeneration. PMID:20056175

  15. [The importance of lactoferrin in bone regeneration].

    PubMed

    Włodarski, Krzysztof H; Galus, Ryszard; Brodzikowska, Aniela; Włodarski, Paweł K; Wojtowicz, Andrzej

    2014-07-01

    Lactoferrin is an iron-binding protein secreted by mammary gland, thus present in milk and in colostrum, which are a cheap and easy to obtain sources of this protein. Lactoferrin is also present in specific granules of neutrophils. Lactoferrin is a multifunctional agent involved, among others in the immune response and in the regulation of bone metabolism. Lactoferrin actives of osteoblast proliferation and bone matrix secretion, and inhibits apoptosis of osteoblast and osteoclastogenesis. Lactoferrin administered to rodents accelerates bone healing and prevents bone loss induced by ovariectomy. Therefore the use of lactoferrin or milk whey in osteoporosis treatment and prevention is postulated. PMID:25154204

  16. BONE REGENERATION AND DOCKING SITE HEALING AFTER BONE TRANSPORT DISTRACTION OSTEOGENESIS IN THE CANINE MANDIBLE

    PubMed Central

    Nagashima, Lucy K; Newby, Michelle Rondon; Zakhary, Ibrahim E; Nagy, William W; Zapata, Uriel; Dechow, Paul C; Opperman, Lynne A; Elsalanty, Mohammed E

    2011-01-01

    Purpose Bone transport distraction osteogenesis (BTDO) provides a promising alternative to traditional grafting techniques. However, existing BTDO devices have many limitations. The purpose of this research was to test a new device, the mandibular bone transport reconstruction plate (BTRP), in an animal model with comparable mandible size to humans and to histologically and mechanically examine the regenerate bone. Materials and methods Eleven adult foxhound dogs were divided into an unreconstructed control group of 5 animals, and an experimental group of 6 animals. In each animal, a 34 mm segmental defect was created in the mandible. The defect was reconstructed with BTRP. Histological and biomechanical characteristics of the regenerate and un-repaired defect were analyzed and compared to bone on the contralateral side of the mandible after 4 weeks of consolidation. Results The reconstructed defect was bridged with new bone, with little bone in the control defect. Regenerate density and microhardness were 22.3% and 42.6% lower than the contralateral normal bone, respectively. Likewise, the anisotropy of the experimental group was statistically lower than in the contralateral bone. Half the experimental animals showed non-union at the docking site. Conclusion The device was very stable and easy to install and activate. After one month of consolidation, the defect has been bridged with new bone with evidence of active bone formation. Regenerate bone was less mature than the control bone. Studies are underway to identify when the regenerate properties compare to normal bone, and to identify methods to augment bone union at the docking site. PMID:21601342

  17. Nanocomposite Membranes Enhance Bone Regeneration Through Restoring Physiological Electric Microenvironment.

    PubMed

    Zhang, Xuehui; Zhang, Chenguang; Lin, Yuanhua; Hu, Penghao; Shen, Yang; Wang, Ke; Meng, Song; Chai, Yuan; Dai, Xiaohan; Liu, Xing; Liu, Yun; Mo, Xiaoju; Cao, Cen; Li, Shue; Deng, Xuliang; Chen, Lili

    2016-08-23

    Physiological electric potential is well-known for its indispensable role in maintaining bone volume and quality. Although implanted biomaterials simulating structural, morphological, mechanical, and chemical properties of natural tissue or organ has been introduced in the field of bone regeneration, the concept of restoring physiological electric microenvironment remains ignored in biomaterials design. In this work, a flexible nanocomposite membrane mimicking the endogenous electric potential is fabricated to explore its bone defect repair efficiency. BaTiO3 nanoparticles (BTO NPs) were first coated with polydopamine. Then the composite membranes are fabricated with homogeneous distribution of Dopa@BTO NPs in poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix. The surface potential of the nanocomposite membranes could be tuned up to -76.8 mV by optimizing the composition ratio and corona poling treatment, which conform to the level of endogenous biopotential. Remarkably, the surface potential of polarized nanocomposite membranes exhibited a dramatic stability with more than half of original surface potential remained up to 12 weeks in the condition of bone defect. In vitro, the membranes encouraged bone marrow mesenchymal stem cells (BM-MSCs) activity and osteogenic differentiation. In vivo, the membranes sustainably maintained the electric microenvironment giving rise to rapid bone regeneration and complete mature bone-structure formation. Our findings evidence that physiological electric potential repair should be paid sufficient attention in biomaterials design, and this concept might provide an innovative and well-suited strategy for bone regenerative therapies. PMID:27389708

  18. Biomimetic Strategies for Bone Repair and Regeneration

    PubMed Central

    Raucci, Maria G.; Guarino, Vincenzo; Ambrosio, Luigi

    2012-01-01

    The osseointegration rate of implants is related to their composition and surface roughness. Implant roughness favors both bone anchoring and biomechanical stability. Osteoconductive calcium phosphate (Ca-P) coatings promote bone healing and apposition, leading to the rapid biological fixation of implants. It has been clearly shown in many publications that Ca-P coating accelerates bone formation around the implant. This review discusses two main routes for the manufacturing of polymer-based osteoconductive scaffolds for tissue engineering, namely the incorporation of bioceramic particles in the scaffold and the coating of a scaffold with a thin layer of apatite through a biomimetic process. PMID:24955638

  19. Mechanical testing of recombinant human bone morphogenetic protein-7 regenerated bone in sheep mandibles.

    PubMed

    Kontaxis, A; Abu-Serriah, M; Ayoub, A F; Barbenel, J C

    2004-01-01

    A new method was developed in this study for testing excised sheep mandibles as a cantilever. The method was used to determine the strength and stiffness of sheep hemi-mandibles including a 35 mm defect bridged by regenerated bone. Recombinant human bone morphogenetic protein-7 (rhBMP-7) in a bovine collagen type-I carrier was used for the bone regeneration. Initial tests on ten intact sheep mandibles confirmed that the strength, stiffness and area beneath the load-deformation curves of the right and left hemi-mandibles were not significantly different, confirming the validity of using the contra-lateral hemi-mandible as a control side. Complete bone regeneration occurred in six hemi-mandibles treated with rhBMP, but the quality and mechanical properties of the bone were very variable. The new bone in three samples contained fibrous tissue and was weaker and less stiff than the contra-lateral side (strength, 10-20 per cent; stiffness, 6-15 per cent). The other half had better-quality bone and was significantly stiffer and stronger (p < 0.05), with strength 45-63 per cent and stiffness 35-46 per cent of the contra-lateral side. Hemi-mandibles treated with collagen alone had no regenerated bone bridge suggesting that 35 mm is a critical-size bone defect. PMID:15648662

  20. Physiological bases of bone regeneration I. Histology and physiology of bone tissue.

    PubMed

    Fernández-Tresguerres-Hernández-Gil, Isabel; Alobera-Gracia, Miguel Angel; del-Canto-Pingarrón, Mariano; Blanco-Jerez, Luis

    2006-01-01

    Bone is the only body tissue capable of regeneration, allowing the restitutio ad integrum following trauma. In the event of a fracture or bone graft, new bone is formed, which following the remodeling process is identical to the pre-existing. Bone is a dynamic tissue in constant formation and resorption. This balanced phenomena, known as the remodeling process, allows the renovation of 5-15% of the total bone mass per year under normal conditions. Bone remodeling consists of the resorption of a certain amount of bone by osteoclasts, likewise the formation of osteoid matrix by osteoblasts, and its subsequent mineralization. This phenomenon occurs in small areas of the cortical bone or the trabecular surface, called Basic Multicellular Units (BMU). Treatment in Traumatology, Orthopedics, Implantology, and Maxillofacial and Oral Surgery, is based on the biologic principals of bone regeneration, in which cells, extracellular matrix, and osteoinductive signals are involved. The aim of this paper is to provide an up date on current knowledge on the biochemical and physiological mechanisms of bone regeneration, paying particular attention to the role played by the cells and proteins of the bone matrix. PMID:16388294

  1. Bone marrow-derived cell regulation of skeletal muscle regeneration.

    PubMed

    Sun, Dongxu; Martinez, Carlo O; Ochoa, Oscar; Ruiz-Willhite, Lourdes; Bonilla, Jose R; Centonze, Victoria E; Waite, Lindsay L; Michalek, Joel E; McManus, Linda M; Shireman, Paula K

    2009-02-01

    Limb regeneration requires the coordination of multiple stem cell populations to recapitulate the process of tissue formation. Therefore, bone marrow (BM) -derived cell regulation of skeletal muscle regeneration was examined in mice lacking the CC chemokine receptor 2 (CCR2). Myofiber size, numbers of myogenic progenitor cells (MPCs), and recruitment of BM-derived cells and macrophages were assessed after cardiotoxin-induced injury of chimeric mice produced by transplanting BM from wild-type (WT) or CCR2(-/-) mice into irradiated WT or CCR2(-/-) host mice. Regardless of the host genotype, muscle regeneration and recruitment of BM-derived cells and macrophages were similar in mice replenished with WT BM, whereas BM-derived cells and macrophage accumulation were decreased and muscle regeneration was impaired in all animals receiving CCR2(-/-) BM. Furthermore, numbers of MPCs (CD34(+)/Sca-1(-)/CD45(-) cells) were significantly increased in mice receiving CCR2(-/-) BM despite the decreased size of regenerated myofibers. Thus, the expression of CCR2 on BM-derived cells regulated macrophage recruitment into injured muscle, numbers of MPC, and the extent of regenerated myofiber size, all of which were independent of CCR2 expression on host-derived cells. Future studies in regenerative medicine must include consideration of the role of BM-derived cells, possibly macrophages, in CCR2-dependent events that regulate effective skeletal muscle regeneration. PMID:18827026

  2. [Contribution of low-intensity pulsed ultrasounds to bone regeneration].

    PubMed

    Gleizal, A; Lavandier, B; Paris, M; Béra, J-C

    2011-09-01

    A maxillo-facial surgeon manages patients with bone defects due to trauma, malformations or of iatrogenic origin. The surgical management has potentially deleterious effects and its cost for society is increasing. Hence, it is crucial to develop techniques stimulating bone growth, stimulating the regeneration of a fracture or filling bone deficit. Ultrasounds (US), vibrations of the same nature as sound but with frequencies above the highest audible frequency for men (above 20 kHz), are used in many fields, particularly in medicine, usually at frequencies of around 0.5 to 5 MHz (million cycles per second). Their biological effects are not fully understood yet, but it is well known that US have effects on organic tissues when their mechanical energy is converted into thermic energy. These effects induce vasodilation and modification of membrane permeability. Several publications present the benefit of US for the stimulation of bone regeneration after a fracture. We present an overview of current knowledge on the effect of pulsed ultrasound on craniofacial bone regeneration, with study results conducted within Inserm unit U1032 in Lyon, the current reference lab on this issue. PMID:21820690

  3. Novel electrospun nanotholits/PHB scaffolds for bone tissue regeneration.

    PubMed

    Xavier Filho, Lauro; Olyveira, Gabriel Molina; Basmaji, Pierre; Costa, Ligia Maria Manzine

    2013-07-01

    Nanotholits is an osteoinductor or be, stimulates the bone regeneration, enabling bigger migration of the cells for formation of the bone tissue regeneration mainly because nanotholits are rich in minerals considered essential to the bone mineralization process on a protein matrix (otolin) as hydroxiapatite. In order to improve its biodegrability and bioresorption in new platforms for tissue engineering, it was electrospun PHB/nanotholits from aqueous solutions of this polymer at concentrations of nanotholits 1% (w/v) and compared morphological and thermal properties with PHB/nanotholits casting films. Electrospun PHB/nanotholits mats presents more symmetric nanopore structure than casting films mats observed by SEM images mainly because the orientation of pores along the longitudinal direction of the electrospun fibers. Nanotholits influences in PHB electrospun/casting was analyzed using transmission infrared spectroscopy (FTIR). TGA showed similar thermal properties but DSC showed distinct thermal properties and crystallinity process of the developed bionanocomposite mainly because of different processing. PMID:23901495

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

    PubMed

    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. PMID:24220423

  5. Pullulan microcarriers for bone tissue regeneration.

    PubMed

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

    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. PMID:27040238

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

    PubMed

    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

  7. Development of laminated fiber-reinforced nanocomposites for bone regeneration

    NASA Astrophysics Data System (ADS)

    Xu, Weijie

    There have been numerous efforts to develop synthetic and/or natural tissue engineering scaffolds that are suitable for bone regeneration applications to replace autograft and allograft bones. Current biomaterials as a scaffold for bone regeneration are limited by the extent of degradation concurrent with bone formation, mechanical strength, and the extent of osteogenic differentiation of marrow stromal cells migrating from the surrounding tissues. In this project, a novel laminated nanocomposite scaffold is fabricated, consisting of poly (L-lactide ethylene oxide fumarate) (PLEOF) hydrogel reinforced with poly (L-lactic acid) (PLLA) electrospun nanofibers and hydroxyapatite (HA) nanoparticles. PLEOF is a novel in situ crosslinkable macromer synthesized from biocompatible building units which can be functionalized with bioactive peptides like the cell-adhesive Arg--Gly--Asp (RGD) amino acid sequence. The hydrophilicity and degradation rate of the macromer can be tailored to a particular application by controlling the ratio of PEG to PLA blocks in the macromer and the unsaturated fumarate units can be used for in-situ crosslinking. The PLLA nanofibers were electrospun from high molecular weight PLLA. The laminated nanocomposites were fabricated by dry-hand lay up technique followed by compression molding and thermal crosslinking. The laminated nanocomposites were evaluated with respect to degradation, water uptake, mechanical strength, and the extent of osteogenic differentiation of bone marrow stromal (BMS) cells. Laminates with or without HA nanoparticles showed modulus values much higher than that of trabecular bone (50-100 MPa). The effect of laminated nanocomposites on osteogenic differentiation of BMS cells was determined in terms of cell number, ALPase activity and calcium content. Our results demonstrate that grafting RGD peptide and HA nanoparticles to a PLEOF hydrogel reinforced with PLLA nanofibers synergistically enhance osteogenic differentiation of BMS

  8. Infection, inflammation, and bone regeneration: a paradoxical relationship.

    PubMed

    Thomas, M V; Puleo, D A

    2011-09-01

    Various strategies have been developed to promote bone regeneration in the craniofacial region. Most of these interventions utilize implantable materials or devices. Infections resulting from colonization of these implants may result in local tissue destruction in a manner analogous to periodontitis. This destruction is mediated via the expression of various inflammatory mediators and tissue-destructive enzymes. Given the well-documented association among microbial biofilms, inflammatory mediators, and tissue destruction, it seems reasonable to assume that inflammation may interfere with bone healing and regeneration. Paradoxically, recent evidence also suggests that the presence of certain pro-inflammatory mediators is actually required for bone healing. Bone injury (e.g., subsequent to a fracture or surgical intervention) is followed by a choreographed cascade of events, some of which are dependent upon the presence of pro-inflammatory mediators. If inflammation resolves promptly, then proper bone healing may occur. However, if inflammation persists (which might occur in the presence of an infected implant or graft material), then the continued inflammatory response may result in suboptimal bone formation. Thus, the effect of a given mediator is dependent upon the temporal context in which it is expressed. Better understanding of this temporal sequence may be used to optimize regenerative outcomes. PMID:21248364

  9. Heat-treated membranes with bioelectricity promote bone regeneration.

    PubMed

    Qu, Yili; Wang, Yanying; Kong, Xiangli; Li, Jidong; Zuo, Yi; Zou, Qin; Gong, Ping; Man, Yi

    2014-01-01

    The barrier membranes maintain a secluded space to prevent the ingrowth of connective tissue and direct the growth of new bone into a desired site; however, they do not stimulate or induce bone regeneration. To enhance the bone bioactivities of membranes, we developed chitosan electret membranes with bioelectricity by grid-controlled constant voltage corona charging. The electret membranes charged with heat treatment (HT electret membranes) exhibited superior electret charge storage stability than the ones charged without heat treatment (RT electret membranes). Human bone marrow stromal cells (hBMSCs) demonstrated better growth on HT electrets membrane. Moreover, hBMSCs osteoblastic differentiation was enhanced on HT electret membranes, as evidenced by osteocalcin and osteopontin expression as assessed by immunocytochemistry, quantitative RT-PCR and western blot analysis. The rabbit calvarial defect model demonstrated that HT electret membranes induced a significantly enhanced bone regeneration compared with RT electret membranes. New bone formation was found at both the periphery and in the center of the defects four weeks after implantation. These results indicated that the chitosan electret membrane has osteogenic potential and could be applied as a novel barrier membrane. PMID:24147762

  10. Negative pressure technology enhances bone regeneration in rabbit skull defects

    PubMed Central

    2013-01-01

    Background Bone is a slowly regenerating tissue influenced by various physiological processes, including proliferation, differentiation, and angiogenesis, under the control of growth factors. Shortening this healing time is an important and popular clinical research focus in orthopedics. Negative pressure can stimulate angiogenesis, improve blood circulation, promote granulation tissue growth and accelerate tissue wound healing. We sought to determine whether negative pressure could reduce bone healing time in a rabbit cranial defect model. Methods Four symmetrical holes (diameter, 3.5 mm) were drilled into the skulls of 42 New Zealand white rabbits, with two holes in each parietal bone. For each rabbit, the two sides were then randomly assigned into experimental and control groups. Using negative pressure suction tubes, experimental holes were treated with −50 kPa for 15 minutes, four times per day, whereas the control holes remained untreated. After 4 weeks, the negative pressure suction tubes were removed. At 2, 4, 6 and 8 weeks, three-dimensional (3D) reconstruction computed tomography (CT), X-ray radiopacity, and two-photon absorptiometry were used to evaluate new bone formation. Histological changes were determined by hematoxylin and eosin (H.E) staining. At weekly intervals until 6 weeks, the mRNA expression levels of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-2 were evaluated by RT-PCR. A paired student’s t-test was employed to compare X-ray radiopacity and bone density measurements between the experimental and control groups. Results 3D-reconstruction CT showed that new bone regeneration in the experimental group was greater than that in the control group at 4 and 6 weeks. At these time points, the experimental group presented with higher X-ray radiopacity and increased bone density (P < 0.05) as compared with the control group. Cartilage islands and new bone were observed by H.E staining at 2

  11. Excavating the Role of Aloe Vera Wrapped Mesoporous Hydroxyapatite Frame Ornamentation in Newly Architectured Polyurethane Scaffolds for Osteogenesis and Guided Bone Regeneration with Microbial Protection.

    PubMed

    Selvakumar, M; Pawar, Harpreet Singh; Francis, Nimmy K; Das, Bodhisatwa; Dhara, Santanu; Chattopadhyay, Santanu

    2016-03-01

    Guided bone regeneration (GBR) scaffolds are unsuccessful in many clinical applications due to a high incidence of postoperative infection. The objective of this work is to fabricate GBR with an anti-infective electrospun scaffold by ornamenting segmented polyurethane (SPU) with two-dimensional Aloe vera wrapped mesoporous hydroxyapatite (Al-mHA) nanorods. The antimicrobial characteristic of the scaffold has been retrieved from the prepared Al-mHA frame with high aspect ratio (∼14.2) via biosynthesis route using Aloe vera (Aloe barbadensis miller) extract. The Al-mHA frame was introduced into an unprecedented SPU matrix (solution polymerized) based on combinatorial soft segments of poly(ε-caprolactone) (PCL), poly(ethylene carbonate) (PEC), and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, pristine mHA nanorods are also ornamented into it. An enzymatic ring-opening polymerization technique was adapted to synthesize soft segment of (PCL-PEC-b-PDMS). Structure elucidation of the synthesized polymers is established by nuclear magnetic resonance spectroscopy. Sparingly, Al-mHA ornamented scaffolds exhibit tremendous improvement (175%) in the mechanical properties with promising antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast-like MG63 cells (in vitro), the scaffolds were implanted in rabbits as an animal model by subcutaneous and intraosseous (tibial) sites. Improved in vivo biocompatibilities, biodegradation, osteoconductivity, and the ability to provide an adequate biomimetic environment for biomineralization for GBR of the scaffolds (SPU and ornamented SPUs) have been found from the various histological sections. Early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks were found in the defects filled with Al-mHA ornamented

  12. Multifunctional Chitosan-45S5 Bioactive Glass-Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Microsphere Composite Membranes for Guided Tissue/Bone Regeneration.

    PubMed

    Li, Wei; Ding, Yaping; Yu, Shanshan; Yao, Qingqing; Boccaccini, Aldo R

    2015-09-23

    Novel multifunctional chitosan-45S5 bioactive glass-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microsphere (CS-BG-MS) composite membranes were developed with applicability in guided tissue/bone regeneration (GTR/GBR). The incorporation of 45S5 BG and PHBV MS into CS membranes not only provided the membranes with favorable surface roughness, hydrophilicity, and flexibility but also slowed down their degradation rate. Moreover, the CS membranes became bioactive after the incorporation of 45S5 BG and capable of releasing drugs of different physicochemical properties in a controlled and sustained manner with the addition of PHBV MS. Cell culture tests showed that osteoblast-like MG-63 human osteosarcoma cells had significantly higher adhesion, cell proliferation, and alkaline phosphatase (ALP) activity on CS-BG and CS-BG-MS membranes than on neat CS membranes. Therefore, the developed bioactive CS-BG-MS membranes with potential multidrug (e.g., antibacterial and antiosteoporosis drugs) delivery capability are promising candidate membranes for GTR/GBR applications. PMID:26317326

  13. Cellular compatibility of a gamma-irradiated modified siloxane-poly(lactic acid)-calcium carbonate hybrid membrane for guided bone regeneration.

    PubMed

    Takeuchi, Naoshi; Machigashira, Miho; Yamashita, Daisuke; Shirakata, Yoshinori; Kasuga, Toshihiro; Noguchi, Kazuyuki; Ban, Seiji

    2011-01-01

    A bi-layered silicon-releasable membrane consisting of a siloxane-poly(lactic acid) (PLA)-vaterite hybrid material (Si-PVH) microfiber mesh and a PLA microfiber mesh has been developed by an electrospinning method for guided bone regeneration (GBR) application. The bi-layered membrane was modified to a three-laminar structure by sandwiching an additional PLA microfiber mesh between the Si-PVH and PLA microfiber meshes (Si-PVH/PLA membrane). In this study, the influence of gamma irradiation, used for sterilization, on biological properties of the Si-PVH/PLA membrane was evaluated with osteoblasts and fibroblasts. After gamma irradiation, while the average molecular weight of the Si-PVH/PLA membrane decreased, the Si-PVH/PLA membrane promoted cell proliferation and differentiation (alkaline phosphatase activity and calcification) of osteoblasts, compared with the poly(lactide-co-glycolide) membrane. These results suggest that the gamma-irradiated Si-PVH/PLA membrane is biocompatible with both fibroblasts and osteoblasts, and may have an application for GBR. PMID:21946495

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

    NASA Astrophysics Data System (ADS)

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

    2011-09-01

    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.

  15. Bone Regeneration from PLGA Micro-Nanoparticles.

    PubMed

    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. PMID:26509156

  16. Bone Regeneration from PLGA Micro-Nanoparticles

    PubMed Central

    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. PMID:26509156

  17. MicroRNAs Regulate Bone Development and Regeneration

    PubMed Central

    Fang, Sijie; Deng, Yuan; Gu, Ping; Fan, Xianqun

    2015-01-01

    MicroRNAs (miRNAs) are endogenous small noncoding ~22-nt RNAs, which have been reported to play a crucial role in maintaining bone development and metabolism. Osteogenesis originates from mesenchymal stem cells (MSCs) differentiating into mature osteoblasts and each period of bone formation is inseparable from the delicate regulation of various miRNAs. Of note, apprehending the sophisticated circuit between miRNAs and osteogenic homeostasis is of great value for artificial skeletal regeneration for severe bone defects. In this review, we highlight how different miRNAs interact with diverse osteo-related genes and endeavor to sketch the contours of potential manipulations of miRNA-modulated bone repair. PMID:25872144

  18. Pulsed Electromagnetic Fields Enhance Bone Morphogenetic Protein-2 Dependent-Bone Regeneration.

    PubMed

    Yang, Hoon Joo; Kim, Ri Youn; Hwang, Soon Jung

    2015-10-01

    The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for the purpose of promoting bone regeneration is emerging; however, the high dose of rhBMP-2 required in humans is accompanied by several limitations, including bone resorption and swelling. To reduce the dose of rhBMP-2 required, the applicability of pulsed electromagnetic fields (PEMF) was evaluated using a rat calvarial defect model. After creating an 8-mm-diameter calvarial bone defect, a collagen sponge soaked in different concentrations (0, 2.5, 5, 10 μg) of rhBMP-2 was implanted at the defect area. One week after surgery, PEMF was applied for 8 h/day over 5 days in an experimental group of animals (n = 28) using a width of 12 μs, a pulse frequency of 60 Hz, and a magnetic intensity of 10 G. Animals were sacrificed 4 weeks after surgery and assessed by microcomputed tomography and histological and immunohistochemical analyses. In the absence of application of PEMF, bone volume, bone mineral density, trabecular thickness, trabecular number, and trabecular separation, all showed statistically significant differences, depending on the concentration of rhBMP-2 utilized (p < 0.001). PEMF accelerated bone regeneration in the groups that received 0, 2.5, and 5 μg rhBMP-2 (p < 0.05). In contrast, administration of 10 μg rhBMP-2 resulted in no additive effect on bone regeneration in combination with PEMF. Groups receiving no rhBMP-2 showed distinct bone regeneration in the central zone of the bone defect when treated with PEMF, whereas they failed to bridge the defect space without PEMF. Among the groups without PEMF, soft tissue infiltrations from the outer surface on the skin side were common. Among groups with PEMF, the groups receiving 5 and 10 μg rhBMP-2 displayed denser bone with significantly reduced dead spaces. The application of PEMF did not result in an accelerated effect on bone regeneration in groups treated with 10 μg rhBMP-2. Therefore, our data

  19. Nanobioengineered electrospun composite nanofibers and osteoblasts for bone regeneration.

    PubMed

    Venugopal, Jayarama Reddy; Low, Sharon; Choon, Aw Tar; Kumar, A Bharath; Ramakrishna, Seeram

    2008-05-01

    Bone defects represent a medical and socioeconomic challenge. Engineering bioartificial bone tissues may help to solve problems related to donor site morbidity and size limitations. Nanofibrous scaffolds were electrospun into a blend of synthetic biodegradable polycaprolactone (PCL) with hydroxyapatite (HA) and natural polymer gelatin (Gel) at a ratio of 1:1:2 (PCL/HA/Gel) compared to PCL (9%), PCL/HA (1:1), and PCL/Gel (1:2) nanofibers. These fiber diameters were around 411 +/- 158 to 856 +/- 157 nm, and the pore size and porosity around 5-35 microm and 76-93%, respectively. The interconnecting porous structure of the nanofibrous scaffolds provides large surface area for cell attachment and sufficient space for nutrient transportation. The tensile property of composite nanofibrous scaffold (PCL/HA/Gel) was highly flexible and allows penetrating osteoblasts inside the scaffolds for bone tissue regeneration. Fourier transform infrared analysis showed that the composite nanofiber contains an amino group, a phosphate group, and carboxyl groups for inducing proliferation and mineralization of osteoblasts for in vitro bone formation. The cell proliferation (88%), alkaline phosphatase activity (77%), and mineralization (66%) of osteoblasts were significantly (P < 0.001) increased in composite nanofibrous scaffold compared to PCL nanofibrous scaffolds. Field emission scanning electron microscopic images showed that the composite nanofibers supported the proliferation and mineralization of osteoblast cells. These results show that the fabrication of electrospun PCL/HA/Gel composite nanofibrous scaffolds has potential for the proliferation and mineralization of osteoblasts for bone regeneration. PMID:18471168

  20. Stromal cells and stem cells in clinical bone regeneration

    PubMed Central

    Grayson, Warren L.; Bunnell, Bruce A.; Martin, Elizabeth; Frazier, Trivia; Hung, Ben P.; Gimble, Jeffrey M.

    2015-01-01

    Stem-cell-mediated bone repair has been used in clinical trials for the regeneration of large craniomaxillofacial defects, to slow the process of bone degeneration in patients with osteonecrosis of the femoral head and for prophylactic treatment of distal tibial fractures. Successful regenerative outcomes in these investigations have provided a solid foundation for wider use of stromal cells in skeletal repair therapy. However, employing stromal cells to facilitate or enhance bone repair is far from being adopted into clinical practice. Scientific, technical, practical and regulatory obstacles prevent the widespread therapeutic use of stromal cells. Ironically, one of the major challenges lies in the limited understanding of the mechanisms via which transplanted cells mediate regeneration. Animal models have been used to provide insight, but these models largely fail to reproduce the nuances of human diseases and bone defects. Consequently, the development of targeted approaches to optimize cell-mediated outcomes is difficult. In this Review, we highlight the successes and challenges reported in several clinical trials that involved the use of bone-marrow-derived mesenchymal or adipose-tissue-derived stromal cells. We identify several obstacles blocking the mainstream use of stromal cells to enhance skeletal repair and highlight technological innovations or areas in which novel techniques might be particularly fruitful in continuing to advance the field of skeletal regenerative medicine. PMID:25560703

  1. Bacterial Cellulose-Hydroxyapatite Nanocomposites for Bone Regeneration

    PubMed Central

    Saska, S.; Barud, H. S.; Gaspar, A. M. M.; Marchetto, R.; Ribeiro, S. J. L.; Messaddeq, Y.

    2011-01-01

    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. PMID:21961004

  2. A novel oxysterol promotes bone regeneration in rabbit cranial bone defects.

    PubMed

    Hokugo, Akishige; Sorice, Sarah; Parhami, Farhad; Yalom, Anisa; Li, Andrew; Zuk, Patricia; Jarrahy, Reza

    2016-07-01

    Bone morphogenetic proteins (BMPs) have played a central role in the development of regenerative therapies for bone reconstruction. However, the high cost and side-effect profile of BMPs limits their broad application. Oxysterols, naturally occurring products of cholesterol oxidation, are promising osteogenic agents alternative to BMPs. The osteogenic capacity of these non-toxic and relatively inexpensive molecules has been documented in rodent models. We studied the impact of Oxy49, a novel oxysterol analogue, on the osteogenic differentiation of rabbit bone marrow stromal cells (BMSCs). Moreover, we evaluated the capacity for in vivo bone regeneration with Oxy49 in rabbit cranial bone defects. We found that rabbit BMSCs treated with Oxy49 demonstrated differentiation along osteogenic pathways, and that complete bone regeneration occurred when cranial defects were treated with Oxy49. Collectively, these results demonstrate that Oxy49 has the ability to induce osteogenic differentiation in rabbit BMSCs with an efficacy comparable to that of BMP-2 and to promote significant bone regeneration in cranial defects. Oxysterols may be a viable novel agent in bone tissue engineering. Copyright © 2016 John Wiley & Sons, Ltd. PMID:23997014

  3. Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration.

    PubMed

    Colnot, Céline

    2009-02-01

    Bone repair requires the mobilization of adult skeletal stem cells/progenitors to allow deposition of cartilage and bone at the injury site. These stem cells/progenitors are believed to come from multiple sources including the bone marrow and the periosteum. The goal of this study was to establish the cellular contributions of bone marrow and periosteum to bone healing in vivo and to assess the effect of the tissue environment on cell differentiation within bone marrow and periosteum. Results show that periosteal injuries heal by endochondral ossification, whereas bone marrow injuries heal by intramembranous ossification, indicating that distinct cellular responses occur within these tissues during repair. [corrected] Next, lineage analyses were used to track the fate of cells derived from periosteum, bone marrow, and endosteum, a subcompartment of the bone marrow. Skeletal progenitor cells were found to be recruited locally and concurrently from periosteum and/or bone marrow/endosteum during bone repair. Periosteum and bone marrow/endosteum both gave rise to osteoblasts, whereas the periosteum was the major source of chondrocytes. Finally, results show that intrinsic and environmental signals modulate cell fate decisions within these tissues. In conclusion, this study sheds light into the origins of skeletal stem cells/progenitors during bone regeneration and indicates that periosteum, endosteum, and bone marrow contain pools of stem cells/progenitors with distinct osteogenic and chondrogenic potentials that vary with the tissue environment. PMID:18847330

  4. Preparation and In Vitro Biological Evaluation of Octacalcium Phosphate/Bioactive Glass-Chitosan/ Alginate Composite Membranes Potential for Bone Guided Regeneration.

    PubMed

    Xu, Sanzhong; Chen, Xiaoyi; Yang, Xianyan; Zhang, Lei; Yang, Guojing; Shao, Huifeng; He, Yong; Gou, Zhongru

    2016-06-01

    The chitosan/alginate-trace element-codoped octacalcium phosphate/nano-sized bioactive glass (CS/ALG-teOCP/nBG) composite membranes were prepared by a layer-by-layer coating method for the functional requirement of guided bone regeneration (GBR). The morphology, mechanical properties and moisture content of the membranes was studied by scanning electron microscopy (SEM) observation, mechanical and swelling test. The results showed that the teOCP/nBG distributed uniformly in the composite membranes, and such as-prepared composite membrane exhibited an excellent tensile strength, accompanying with mechanical decay with immersion in aqueous medium. Cell culture and MTT assays showed that the surface microstructure and the ion dissolution products from teOCP/nBG components could enhance the cell proliferation, and especially the composite membranes was suitable for supporting the adhesion and growth behavior of human bone marrow mesenchymal stem cells (hBMSCs) in comparison with the CS/ALG pure polymer membranes. These results suggest that the new CS/ALG-teOCP/nBG composite membrane is highly bioactive and biodegradable, and favorable for guiding bone regeneration. PMID:27427599

  5. Porous calcium phosphate cement for alveolar bone regeneration.

    PubMed

    Félix Lanao, R P; Hoekstra, J W M; Wolke, J G C; Leeuwenburgh, S C G; Plachokova, A S; Boerman, O C; van den Beucken, J J J P; Jansen, J A

    2014-06-01

    The present study aimed to provide information on material degradation and subsequent alveolar bone formation, using composites consisting of calcium phosphate cement (CPC) and poly(lactic-co-glycolic) acid (PLGA) with different microsphere morphology (hollow vs dense). In addition to the plain CPC-PLGA composites, loading the microspheres with the growth factors platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF) was investigated. A total of four different CPC composites were applied into one-wall mandible bone defects in beagle dogs in order to evaluate them as candidates for alveolar bone regeneration. These composites consisted of CPC and hollow or dense PLGA microspheres, with or without the addition of PDGF-IGF growth factor combination (CPC-hPLGA, CPC-dPLGA, CPC-hPLGAGF , CPC-dPLGAGF ). Histological evaluation revealed significantly more bone formation in CPC-dPLGA than in CPC-hPLGA composites. The combination PDGF-IGF enhanced bone formation in CPC-hPLGA materials, but significantly more bone formation occurred when CPC-dPLGA was used, with or without the addition of growth factors. The findings demonstrated that CPC-dPLGA composite was the biologically superior material for use as an off-the-shelf material, due to its good biocompatibility, enhanced degradability and superior bone formation. PMID:22777771

  6. Efficacy of Mucograft vs Conventional Resorbable Collagen Membranes in Guided Bone Regeneration Around Standardized Calvarial Defects in Rats: A Histologic and Biomechanical Assessment.

    PubMed

    Ramalingam, Sundar; Babay, Nadir; Al-Rasheed, Abdulaziz; Nooh, Nasser; Naghshbandi, Jafar; Aldahmash, Abdullah; Atteya, Muhammad; Al-Hezaimi, Khalid

    2016-01-01

    Guided bone regeneration (GBR) using a porcine-derived collagen matrix (Mucograft [MG], Geistlich) has not yet been reported. The aim of this histologic and biomechanical study was to compare the efficacy of MG versus resorbable collagen membranes (RCMs) in facilitating GBR around standardized rat calvarial defects. Forty female Wistar albino rats with a mean age and weight of 6 to 9 weeks and 250 to 300 g, respectively, were used. With the rats under general anesthesia, the skin over the calvaria was exposed using a full-thickness flap. A 4.6-mm-diameter standardized calvarial defect was created in the left parietal bone. For treatment, the rats were randomly divided into four groups (n = 10 per group): (1) MG group: the defect was covered with MG; (2) RCM group: the defect was covered with an RCM; (3) MG + bone group: the defect was filled with bone graft particles and covered by MG; and (4) RCM + bone group: the defect was filled with bone graft particles and covered by an RCM. Primary closure was achieved using interrupted resorbable sutures. The animals were sacrificed at 8 weeks after the surgical procedures. Qualitative histologic analysis and biomechanical assessment to identify hardness and elastic modulus of newly formed bone (NFB) were performed. Collected data were statistically analyzed using one-way analysis of variance. Histologic findings revealed NFB with fibrous connective tissue in all groups. The quantity of NFB was highest in the RCM + bone group. Statistically significant differences in the hardness (F = 567.69, dfN = 3, dfD = 36, P < .001) and elastic modulus (F = 294.19, dfN = 3, dfD = 36, P < .001) of NFB were found between the groups. Although the RCM + bone group had the highest mean ± standard deviation (SD) hardness of NFB (531.4 ± 24.9 MPa), the RCM group had the highest mean ± SD elastic modulus of NFB (18.63 ± 1.89 GPa). The present study demonstrated that RCMs are better than MG at enhancing new bone formation in standardized

  7. Hierarchically engineered fibrous scaffolds for bone regeneration

    PubMed Central

    Sachot, Nadège; Castaño, Oscar; Mateos-Timoneda, Miguel A.; Engel, Elisabeth; Planell, Josep A.

    2013-01-01

    Surface properties of biomaterials play a major role in the governing of cell functionalities. It is well known that mechanical, chemical and nanotopographic cues, for example, influence cell proliferation and differentiation. Here, we present a novel coating protocol to produce hierarchically engineered fibrous scaffolds with tailorable surface characteristics, which mimic bone extracellular matrix. Based on the sol–gel method and a succession of surface treatments, hollow electrospun polylactic acid fibres were coated with a silicon–calcium–phosphate bioactive organic–inorganic glass. Compared with pure polymeric fibres that showed a completely smooth surface, the coated fibres exhibited a nanostructured topography and greater roughness. They also showed improved hydrophilic properties and a Young's modulus sixfold higher than non-coated ones, while remaining fully flexible and easy to handle. Rat mesenchymal stem cells cultured on these fibres showed great cellular spreading and interactions with the material. This protocol can be transferred to other structures and glasses, allowing the fabrication of various materials with well-defined features. This novel approach represents therefore a valuable improvement in the production of artificial matrices able to direct stem cell fate through physical and chemical interactions. PMID:23985738

  8. Real-Time Assessment of Guided Bone Regeneration in Standardized Calvarial Defects Using a Combination of Bone Graft and Platelet-Derived Growth Factor With and Without Collagen Membrane: An In Vivo Microcomputed Tomographic and Histologic Experiment in Rats.

    PubMed

    Alrasheed, Abdulaziz; Al-Ahmari, Fatemah; Ramalingam, Sundar; Nooh, Nasser; Wang, Cun-Yu; Al-Hezaimi, Khalid

    2016-01-01

    The aim of the present in vivo microcomputed tomography (μCT) and histologic experiment was to assess the efficacy of guided bone regeneration (GBR) around standardized calvarial defects using recombinant human platelet-derived growth factor (rhPDGF) with and without resorbable collagen membrane (RCM). A total of 50 female Wistar albino rats with a mean age of 7.5 months and mean weight of 275 g were used. The calvarium was exposed following midsagittal scalp incision and flap reflection. A full-thickness standardized calvarial defect (4.6 mm diameter) was created. Study animals were randomly divided into five groups based on biomaterials used for GBR within the defect: (1) no treatment (negative control), (2) bone graft alone (BG), (3) bone graft covered by RCM (BG + RCM), (4) bone graft soaked in rhPDGF (BG + rhPDGF), and (5) bone graft soaked in rhPDGF and covered with RCM (BG + rhPDGF + RCM). In vivo μCT for determination of newly formed bone volume (NFBV) and mineral density (NFBMD) and remnant bone particles volume (RBPV) and mineral density (RBPMD) was done at baseline and at 2, 4, 6, and 8 weeks postoperatively. Eight weeks following surgery, the animals were sacrificed and harvested calvarial specimens were subjected to histologic and biomechanical analysis. There was an increase in NFBV and NFBMD associated with a corresponding decrease in RBPV and RBPMD in all the study groups. Two-way analysis of variance revealed significant differences in the measured values within and between the groups across the timelines examined during the study period (P < .05). While the NFBV was significantly higher in the bone graft, BG + RCM, and BG + rhPDGF + RCM groups, the NFBMD was similar in all the groups except negative control. The greatest decreases in RBPV and RBPMD were observed in the BG + rhPDGF + RCM group in comparison to the other groups. Similarly, BG + rhPDGF + RCM groups had hardness and elastic modulus similar to that of natural bone. The in vivo

  9. Variations to the Nanotube Surface for Bone Regeneration

    PubMed Central

    Frandsen, Christine J.; Brammer, Karla S.; Jin, Sungho

    2013-01-01

    The complex mechanisms of the bone cell-surface interactions are yet to be completely understood, and researchers continue to strive to uncover the fully optimized implant material for perfect osseointegration. A particularly fascinating area of research involves the study of nanostructured surfaces, which are believed to enhance osteogenic behavior, possibly due to the mimicry of components of the extracellular matrix of bone. There is a growing body of data that emphasizes the promise of the titanium oxide (TiO2) nanotube architecture as an advanced orthopedic implant material. The review herein highlights findings regarding TiO2 nanotube surfaces for bone regeneration and the osteogenic effects of minute changes to the surface such as tube size and surface chemistry. PMID:23710182

  10. Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction Osteogenesis via Endochondral Bone Formation

    PubMed Central

    Kim, Ji-Beom; Seo, Sang Gyo; Kim, Eo Jin; Kim, Ji Hye; Yoo, Won Joon; Cho, Tae-Joon; Choi, In Ho

    2015-01-01

    Background Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction. Methods The immature rabbit tibial DO model (20 mm length-gain) was used. Twenty-eight animals received DBM 100 mg percutaneously at the end of distraction. Another 22 animals were left without further procedure (control). Plain radiographs were taken every week. Postmortem bone dual-energy X-ray absorptiometry and micro-computed tomography (micro-CT) studies were performed at the third and sixth weeks of the consolidation period and histological analysis was performed. Results The regenerate bone mineral density was higher in the DBM group when compared with that in the saline injection control group at the third week postdistraction. Quantitative analysis using micro-CT revealed larger trabecular bone volume, higher trabecular number, and less trabecular separation in the DBM group than in the saline injection control group. Cross-sectional area and cortical thickness at the sixth week postdistraction, assessed using micro-CT, were greater in the regenerates of the DBM group compared with the control group. Histological evaluation revealed higher trabecular bone volume and trabecular number in the regenerate of the DBM group. New bone formation was apparently enhanced, via endochondral ossification, at the site and in the vicinity of the injected DBM. DBM was absorbed slowly, but it remained until the sixth postoperative week after injection. Conclusions DBM administration into the distraction gap at the end of the distraction period resulted in a significantly greater regenerate bone area, trabecular number, and cortical thickness in the

  11. Evaluation of Bone Regeneration on Polyhydroxyethyl-polymethyl Methacrylate Membrane in a Rabbit Calvarial Defect Model.

    PubMed

    Kim, Somin; Hwang, Yawon; Kashif, Muhammad; Jeong, Dosun; Kim, Gonhyung

    This study was conducted to evaluate the capacity of guiding bone regeneration of polyhydroxyethyl-polymethyl methacrylate (PHEMA-PMMA) membrane as a guided tissue regeneration membrane for bone defects. Two 8-mm diameter transosseous round defects were made at the parietal bone of 18 New Zealand White rabbits. Defects were covered with or without PHEMA-PMMA membrane. Radiological and histological evaluation revealed that the bone tissue over the defect was more regenerated with time in both groups. However, there was significantly more bone regeneration at 8 weeks in the experimental group than the control group (p<0.05). There was no sign of membrane degradation or tissue inflammation and no invasion of muscle and fibrous tissue into defects. PHEMA-PMMA is a potential material for guided tissue regeneration membrane as it induces no adverse tissue reaction and effectively supports selective bone regeneration. PMID:27566076

  12. Salicylic Acid-Based Polymers for Guided Bone Regeneration Using Bone Morphogenetic Protein-2

    PubMed Central

    Subramanian, Sangeeta; Mitchell, Ashley; Yu, Weiling; Snyder, Sabrina; Uhrich, Kathryn

    2015-01-01

    Bone morphogenetic protein-2 (BMP-2) is used clinically to promote spinal fusion, treat complex tibia fractures, and to promote bone formation in craniomaxillofacial surgery. Excessive bone formation at sites where BMP-2 has been applied is an established complication and one that could be corrected by guided tissue regeneration methods. In this study, anti-inflammatory polymers containing salicylic acid [salicylic acid-based poly(anhydride-ester), SAPAE] were electrospun with polycaprolactone (PCL) to create thin flexible matrices for use as guided bone regeneration membranes. SAPAE polymers hydrolyze to release salicylic acid, which is a nonsteroidal anti-inflammatory drug. PCL was used to enhance the mechanical integrity of the matrices. Two different SAPAE-containing membranes were produced and compared: fast-degrading (FD-SAPAE) and slow-degrading (SD-SAPAE) membranes that release salicylic acid at a faster and slower rate, respectively. Rat femur defects were treated with BMP-2 and wrapped with FD-SAPAE, SD-SAPAE, or PCL membrane or were left unwrapped. The effects of different membranes on bone formation within and outside of the femur defects were measured by histomorphometry and microcomputed tomography. Bone formation within the defect was not affected by membrane wrapping at BMP-2 doses of 12 μg or more. In contrast, the FD-SAPAE membrane significantly reduced bone formation outside the defect compared with all other treatments. The rapid release of salicylic acid from the FD-SAPAE membrane suggests that localized salicylic acid treatment during the first few days of BMP-2 treatment can limit ectopic bone formation. The data support development of SAPAE polymer membranes for guided bone regeneration applications as well as barriers to excessive bone formation. PMID:25813520

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

    PubMed

    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

    2015-05-01

    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 titanium is improved with a coating of osteostatin, an osteoinductive peptide that consists of the 107-111 domain of the parathyroid hormone (PTH)-related protein (PTHrP), and the effects of this osteostatin coating on bone regeneration were evaluated in vitro and in vivo. SLM-produced porous titanium received an alkali-acid-heat treatment and was coated with osteostatin through soaking in a 100 nM solution for 24 h or left uncoated. Osteostatin-coated scaffolds contained ∼0.1 μg peptide/g titanium, and in vitro 81% was released within 24 h. Human periosteum-derived osteoprogenitor cells cultured on osteostatin-coated scaffolds did not induce significant changes in osteogenic (alkaline phosphatase [ALP], collagen type 1 [Col1], osteocalcin [OCN], runt-related transcription factor 2 [Runx2]), or angiogenic (vascular endothelial growth factor [VEGF]) gene expression; however, it resulted in an upregulation of osteoprotegerin (OPG) gene expression after 24 h and a lower receptor activator of nuclear factor kappa-B ligand (RankL):OPG mRNA ratio. In vivo, osteostatin-coated, porous titanium implants increased bone regeneration in critical-sized cortical bone defects (p=0.005). Bone regeneration proceeded until 12 weeks, and femurs grafted with osteostatin-coated implants and uncoated implants recovered, respectively, 66% and 53% of the original femur torque strength (97±31 and 77±53 N·mm, not significant). In conclusion, the osteostatin coating improved bone regeneration of porous titanium. This effect was initiated after a short burst release and might be related to the observed in vitro upregulation of OPG gene expression by osteostatin in osteoprogenitor

  14. Bioactive and biodegradable silica biomaterial for bone regeneration.

    PubMed

    Wang, Shunfeng; Wang, Xiaohong; Draenert, Florian G; Albert, Olga; Schröder, Heinz C; Mailänder, Volker; Mitov, Gergo; Müller, Werner E G

    2014-10-01

    Biosilica, a biocompatible, natural inorganic polymer that is formed by an enzymatic, silicatein-mediated reaction in siliceous sponges to build up their inorganic skeleton, has been shown to be morphogenetically active and to induce mineralization of human osteoblast-like cells (SaOS-2) in vitro. In the present study, we prepared beads (microspheres) by encapsulation of β-tricalcium phosphate [β-TCP], either alone (control) or supplemented with silica or silicatein, into the biodegradable copolymer poly(d,l-lactide-co-glycolide) [PLGA]. Under the conditions used, ≈5% β-TCP, ≈9% silica, and 0.32μg/mg of silicatein were entrapped into the PLGA microspheres (diameter≈800μm). Determination of the biocompatibility of the β-TCP microspheres, supplemented with silica or silicatein, revealed no toxicity in the MTT based cell viability assay using SaOS-2 cells. The adherence of SaOS-2 cells to the surface of silica-containing microspheres was higher than for microspheres, containing only β-TCP. In addition, the silica-containing β-TCP microspheres and even more pronounced, a 1:1 mixture of microspheres containing β-TCP and silica, and β-TCP and silicatein, were found to strongly enhance the mineral deposition by SaOS-2 cells. Using these microspheres, first animal experiments with silica/biosilica were performed in female, adult New Zealand White rabbits to study the effect of the inorganic polymer on bone regeneration in vivo. The microspheres were implanted into 5mm thick holes, drilled into the femur of the animals, applying a bilateral comparison study design (3 test groups with 4-8 animals each). The control implant on one of the two hind legs contained microspheres with only β-TCP, while the test implant on the corresponding leg consisted either of microspheres containing β-TCP and silica, or a 1:1 mixture of microspheres, supplemented with β-TCP and silica, and β-TCP and silicatein. The results revealed that tissue/bone sections of silica

  15. Drug-eluting scaffolds for bone and cartilage regeneration.

    PubMed

    Huang, Charlotte L; Lee, Wei Li; Loo, Joachim S C

    2014-06-01

    The advances in strategies for bone and cartilage regeneration have been centered on a concept that describes the close relationship between osteogenic cells, osteoconductive scaffolds, delivery growth factors and the mechanical environment. The dynamic nature of the tissue repair process involves intricate mimicry of signals expressed in the biological system in response to an injury. Recently, synergistic strategies involving hybrid delivery systems that provide sequential dual delivery of biomolecules and relevant topological cues received great attention. Future advances in tissue regeneration will therefore depend on multidisciplinary strategies that encompass the crux of tissue repair aimed at constructing the ideal functional regenerative scaffold. Here, functional scaffolds delivering therapeutics are reviewed in terms of their controlled release and healing capabilities. PMID:24239726

  16. Evaluation of cross-linked chitosan microparticles for bone regeneration.

    PubMed

    Bhat, Archana; Dreifke, Michael B; Kandimalla, Yugandhar; Gomez, Carlos; Ebraheim, Nabil A; Jayasuriya, A Champa

    2010-10-01

    The objective of this preliminary study was to evaluate the applying of chitosan (CS)-based microparticles (MPs) in bone regeneration in vivo. The CS MPs were fabricated using our scale-up method, as previously described. Mesenchymal stem cells (MSC) were harvested from the femora and tibiae of Dark Agouti (DA) rats and seeded on CS MPs. An in vitro MSCs attachment experiment was conducted by trypsinizing the cells attached to the MPs at 5, 10, 20 and 30 h. Fluorescence images of MSCs attached to the MPs were taken at 24 and 48 h, using a LIVE/DEAD cell assay. The MSC/osteoblasts (OB) seeded on MPs were then cultured in vitro using osteogenic media and implanted into partial thickness bone defects in rat femurs. There were two groups of rats, including experimental animals and controls, for the in vivo studies. The experimental group were implanted with MSC-seeded MPs and observed at 4 and 8 weeks. The control group of rats did not receive any implant material except the stainless steel plate to support the defect. Four rats per group were used for the study. The femurs were extracted at 4 and 8 weeks post-implantation and bone formation at the defect site was analysed using radiography, microcomputed tomography (µCT) and histology. Among all groups, a significant increase in bone formation was observed in the experimental group at 8 weeks implantation. The results of this study suggested that CS MPs prove to be a successful biomaterial for bone regeneration. PMID:20872740

  17. Strontium borate glass: potential biomaterial for bone regeneration

    PubMed Central

    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.

    2010-01-01

    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 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. PMID:20031984

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

    PubMed Central

    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

  19. Direct or indirect stimulation of adenosine A2A receptors enhances bone regeneration as well as bone morphogenetic protein-2

    PubMed Central

    Mediero, Aránzazu; Wilder, Tuere; Perez-Aso, Miguel; Cronstein, Bruce N.

    2015-01-01

    Promoting bone regeneration and repair of bone defects is a need that has not been well met to date. We have previously found that adenosine, acting via A2A receptors (A2AR) promotes wound healing and inhibits inflammatory osteolysis and hypothesized that A2AR might be a novel target to promote bone regeneration. Therefore, we determined whether direct A2AR stimulation or increasing endogenous adenosine concentrations via purine transport blockade with dipyridamole regulates bone formation. We determined whether coverage of a 3 mm trephine defect in a mouse skull with a collagen scaffold soaked in saline, bone morphogenetic protein-2 (BMP-2; 200 ng), 1 μM CGS21680 (A2AR agonist, EC50 = 160 nM), or 1 μM dipyridamole (EC50 = 32 nM) promoted bone regeneration. Microcomputed tomography examination demonstrated that CGS21680 and dipyridamole markedly enhanced bone regeneration as well as BMP-2 8 wk after surgery (60 ± 2%, 79 ± 2%, and 75 ± 1% bone regeneration, respectively, vs. 32 ± 2% in control, P < 0.001). Blockade by a selective A2AR antagonist (ZM241385, 1 μM) or deletion of A2AR abrogated the effect of CGS21680 and dipyridamole on bone regeneration. Both CGS21680 and dipyridamole treatment increased alkaline phosphatase-positive osteoblasts and diminished tartrate resistance acid phosphatase-positive osteoclasts in the defects. In vivo imaging with a fluorescent dye for new bone formation revealed a strong fluorescent signal in treated animals that was equivalent to BMP-2. In conclusion, stimulation of A2AR by specific agonists or by increasing endogenous adenosine levels stimulates new bone formation as well as BMP-2 and represents a novel approach to stimulating bone regeneration.—Mediero, A., Wilder, T., Perez-Aso, M., Cronstein, B. N. Direct or indirect stimulation of adenosine A2A receptors enhances bone regeneration as well as bone morphogenetic protein-2. PMID:25573752

  20. Mechanical Regulation of Bone Regeneration: Theories, Models, and Experiments

    PubMed Central

    Betts, Duncan Colin; Müller, Ralph

    2014-01-01

    How mechanical forces influence the regeneration of bone remains an open question. Their effect has been demonstrated experimentally, which has allowed mathematical theories of mechanically driven tissue differentiation to be developed. Many simulations driven by these theories have been presented, however, validation of these models has remained difficult due to the number of independent parameters considered. An overview of these theories and models is presented along with a review of experimental studies and the factors they consider. Finally limitations of current experimental data and how this influences modeling are discussed and potential solutions are proposed. PMID:25540637

  1. Effect of preparation route on the degradation behavior and ion releasability of siloxane-poly(lactic acid)-vaterite hybrid nonwoven fabrics for guided bone regeneration.

    PubMed

    Wakita, Takashi; Nakamura, Jin; Ota, Yoshio; Obata, Akiko; Kasuga, Toshihiro; Ban, Seiji

    2011-01-01

    Two types of nonwoven fabric, consisting of siloxane-doped vaterite (SiV) and poly(lactic acid) (PLA), for guided bone regeneration (GBR) were prepared by an electrospinning. One of the fabrics, SiV-PLA(M), was derived from PLA mixed with the solution of SiV dispersed in chloroform. Another one, SiV-PLA(K), was derived from a composite prepared by kneading SiV and PLA while heating at 200°C. The SiV-PLA(K) fabric shows higher degradability in dilute NaOH aq. than the SiV-PLA(M) fabric. To improve the cellular compatibility of the fabric, the fibers were coated with hydroxyapatite (HA) by soaking in simulated body fluid. The HA-coated SiV-PLA(K) fabric showed the release of silicate ions; the amount was reduced by 1/5 to 1/8 compared with that of the HA-coated SiV-PLA(M) fabric, and the excessive release was controlled. The preparation route of kneading at 200°C led to formation of a fabric with degradation behavior and ion releasability effective for bone regeneration. PMID:21415554

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

    PubMed Central

    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

  3. Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration

    PubMed Central

    Huh, Jung-Bo; Yang, June-Jip; Choi, Kyung-Hee; Bae, Ji Hyeon; Lee, Jeong-Yeol; Kim, Sung-Eun; Shin, Sang-Wan

    2015-01-01

    Anorganic bovine bone matrix (Bio-Oss®) has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter) were formed in a white rabbit model and then implanted or not (controls) with Bio-Oss® or BMP-2/Bio-Oss®. The Bio-Oss® and BMP-2/Bio-Oss® groups had significantly greater new bone areas (expressed as percentages of augmented areas) than the non-implanted controls at four and eight weeks after surgery, and the BMP-2/Bio-Oss® group (16.50 ± 2.87 (n = 6)) had significantly greater new bone areas than the Bio-Oss® group (9.43 ± 3.73 (n = 6)) at four weeks. These findings suggest that rhBMP-2 treated heparinized Bio-Oss® markedly enhances bone regeneration. PMID:26184187

  4. Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration.

    PubMed

    Huh, Jung-Bo; Yang, June-Jip; Choi, Kyung-Hee; Bae, Ji Hyeon; Lee, Jeong-Yeol; Kim, Sung-Eun; Shin, Sang-Wan

    2015-01-01

    Anorganic bovine bone matrix (Bio-Oss®) has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter) were formed in a white rabbit model and then implanted or not (controls) with Bio-Oss® or BMP-2/Bio-Oss®. The Bio-Oss® and BMP-2/Bio-Oss® groups had significantly greater new bone areas (expressed as percentages of augmented areas) than the non-implanted controls at four and eight weeks after surgery, and the BMP-2/Bio-Oss® group (16.50 ± 2.87 (n = 6)) had significantly greater new bone areas than the Bio-Oss® group (9.43 ± 3.73 (n = 6)) at four weeks. These findings suggest that rhBMP-2 treated heparinized Bio-Oss® markedly enhances bone regeneration. PMID:26184187

  5. Investigation of potential injectable polymeric biomaterials for bone regeneration

    PubMed Central

    Dreifke, Michael B.; Ebraheim, Nabil A.; Jayasuriya, Ambalangodage C.

    2014-01-01

    This article reviews the potential injectable polymeric biomaterial scaffolds currently being investigated for application in bone tissue regeneration. Two types of injectable biomaterial scaffolds are focused in this review, including injectable microspheres and injectable gels. The injectable microspheres section covers several polymeric materials, including poly(l-lactide-co-glycolide)-PLGA, poly (propylene fumarate), and chitosan. The injectable gel section covers alginate gels, hyaluronan hydrogels, poly(ethylene-glycol)-PEG hydrogels, and PEG-PLGA copolymer hydrogels. This review focuses on the effect of cellular behaviorin vitro andin vivo in terms of material properties of polymers, such as biodegradation, biocompatibility, porosity, microsphere size, and cross-linking nature. Injectable polymeric biomaterials offer a major advantage for orthopedic applications by allowing the ability to use noninvasive or minimally invasive treatment methods. Therefore, combining injectable polymeric biomaterial scaffolds with cells have a significant potential to treat orthopedic bone defects, including spine fusion, and craniofacial and periodontal defects. PMID:23401336

  6. Generation of clinical grade human bone marrow stromal cells for use in bone regeneration.

    PubMed

    Robey, Pamela G; Kuznetsov, Sergei A; Ren, Jiaqiang; Klein, Harvey G; Sabatino, Marianna; Stroncek, David F

    2015-01-01

    In current orthopaedic practice, there is a need to increase the ability to reconstruct large segments of bone lost due to trauma, resection of tumors and skeletal deformities, or when normal regenerative processes have failed such as in non-unions and avascular necrosis. Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells), when used in conjunction with appropriate carriers, represent a means by which to achieve bone regeneration in such cases. While much has been done at the bench and in pre-clinical studies, moving towards clinical application requires the generation of clinical grade cells. What is described herein is an FDA-approved cell manufacturing procedure for the ex vivo expansion of high quality, biologically active human BMSCs. This article is part of a Special Issue entitled Stem Cells and Bone. PMID:25064527

  7. [The progress in application of parathyroid hormone in craniomaxillofacial bone regeneration study].

    PubMed

    Chen, X Y; Tang, Z L

    2016-06-01

    Parathyroid hormone(PTH)is synthesized and secreted by chief cell of Gley's glands which possesses dual functions of catabolism and anabolism. It regulates the proliferation and differentiation of multiple cell lines including osteoblast, osteoclast and skeletal lining cells. Furthermore, PTH activates various signaling pathways which control calcium, phosphorous' metabolism and bone conversion, accelerating the bone regeneration and reconstruction. However, the study of PTH in craniomaxillofacial bone regeneration is relatively less and whether the role of parathyroid glands and the mechanism of ossification are consistent with the long bone or not needs further investigation. This review focuses on the progress of PTH in craniomaxillofacial bone regeneration in recent years. PMID:27256534

  8. Mechanical properties of a biodegradable bone regeneration scaffold

    NASA Technical Reports Server (NTRS)

    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.

  9. Xylan hemicellulose improves chitosan hydrogel for bone tissue regeneration

    PubMed Central

    Bush, Joshua R.; Liang, Haixiang; Dickinson, Molly; Botchwey, Edward A.

    2016-01-01

    The hemicellulose xylan, which has immunomodulatory effects, has been combined with chitosan to form a composite hydrogel to improve the healing of bone fractures. This thermally responsive and injectable hydrogel, which is liquid at room temperature and gels at physiological temperature, improves the response of animal host tissue compared with similar pure chitosan hydrogels in tissue engineering models. The composite hydrogel was placed in a subcutaneous model where the composite hydrogel is replaced by host tissue within 1 week, much earlier than chitosan hydrogels. A tibia fracture model in mice showed that the composite encourages major remodeling of the fracture callus in less than 4 weeks. A non-union fracture model in rat femurs was used to demonstrate that the composite hydrogel allows bone regeneration and healing of defects that with no treatment are unhealed after 6 weeks. These results suggest that the xylan/chitosan composite hydrogel is a suitable bone graft substitute able to aid in the repair of large bone defects.

  10. Fibromodulin reprogrammed cells: A novel cell source for bone regeneration.

    PubMed

    Li, Chen-Shuang; Yang, Pu; Ting, Kang; Aghaloo, Tara; Lee, Soonchul; Zhang, Yulong; Khalilinejad, Kambiz; Murphy, Maxwell C; Pan, Hsin Chuan; Zhang, Xinli; Wu, Benjamin; Zhou, Yan-Heng; Zhao, Zhihe; Zheng, Zhong; Soo, Chia

    2016-03-01

    Pluripotent or multipotent cell-based therapeutics are vital for skeletal reconstruction in non-healing critical-sized defects since the local endogenous progenitor cells are not often adequate to restore tissue continuity or function. However, currently available cell-based regenerative strategies are hindered by numerous obstacles including inadequate cell availability, painful and invasive cell-harvesting procedures, and tumorigenesis. Previously, we established a novel platform technology for inducing a quiescent stem cell-like stage using only a single extracellular proteoglycan, fibromodulin (FMOD), circumventing gene transduction. In this study, we further purified and significantly increased the reprogramming rate of the yield multipotent FMOD reprogrammed (FReP) cells. We also exposed the 'molecular blueprint' of FReP cell osteogenic differentiation by gene profiling. Radiographic analysis showed that implantation of FReP cells into a critical-sized SCID mouse calvarial defect, contributed to the robust osteogenic capability of FReP cells in a challenging clinically relevant traumatic scenario in vivo. The persistence, engraftment, and osteogenesis of transplanted FReP cells without tumorigenesis in vivo were confirmed by histological and immunohistochemical staining. Taken together, we have provided an extended potency, safety, and molecular profile of FReP cell-based bone regeneration. Therefore, FReP cells present a high potential for cellular and gene therapy products for bone regeneration. PMID:26774565

  11. A Novel Nanosilver/Nanosilica Hydrogel for Bone Regeneration in Infected Bone Defects.

    PubMed

    Zhang, Shiwen; Guo, Yuchen; Dong, Yuliang; Wu, Yunshu; Cheng, Lei; Wang, Yongyue; Xing, Malcolm; Yuan, Quan

    2016-06-01

    Treating bone defects in the presence of infection is a formidable clinical challenge. The use of a biomaterial with the dual function of bone regeneration and infection control is a novel therapeutic approach to this problem. In this study, we fabricated an innovative, dual-function biocomposite hydrogel containing nanosilver and nanosilica (nAg/nSiO2) particles and evaluated its characteristics using FT-IR, SEM, swelling ratio, and stiffness assays. The in vitro antibacterial analysis showed that this nAg/nSiO2 hydrogel inhibited both Gram-positive and Gram-negative bacteria. In addition, this nontoxic material could promote osteogenic differentiation of rat bone marrow stromal cells (BMSCs). We then created infected bone defects in rat calvaria in order to evaluate the function of the hydrogel in vivo. The hydrogel demonstrated effective antibacterial ability while promoting bone regeneration in these defects. Our results indicate that this nAg/nSiO2 hydrogel has the potential to both control infection and to promote bone healing in contaminated defects. PMID:27167643

  12. Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area

    PubMed Central

    Watanabe, Satoko; Takabatake, Kiyofumi; Tsujigiwa, Hidetsugu; Watanabe, Toshiyuki; Tokuyama, Eijiro; Ito, Satoshi; Nagatsuka, Hitoshi; Kimata, Yoshihiro

    2016-01-01

    Artificial bone materials that exhibit high biocompatibility have been developed and are being widely used for bone tissue regeneration. However, there are no biomaterials that are minimally invasive and safe. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP) which has through-and-through holes and is able to mimic the bone microenvironment for bone tissue regeneration. In the present study, we investigated how the difference in hole-diameter of honeycomb β-TCP (hole-diameter: 75, 300, 500, and 1600 μm) influences bone tissue regeneration histologically. Its osteoconductivity was also evaluated by implantation into zygomatic bone defects in rats. The results showed that the maximum bone formation was observed on the β-TCP with hole-diameter 300μm, included bone marrow-like tissue and the pattern of bone tissue formation similar to host bone. Therefore, the results indicated that we could control bone tissue formation by creating a bone microenvironment provided by β-TCP. Also, in zygomatic bone defect model with honeycomb β-TCP, the result showed there was osseous union and the continuity was reproduced between the both edges of resected bone and β-TCP, which indicated the zygomatic bone reproduction fully succeeded. It is thus thought that honeycomb β-TCP may serve as an excellent biomaterial for bone tissue regeneration in the head, neck and face regions, expected in clinical applications. PMID:27279797

  13. Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area.

    PubMed

    Watanabe, Satoko; Takabatake, Kiyofumi; Tsujigiwa, Hidetsugu; Watanabe, Toshiyuki; Tokuyama, Eijiro; Ito, Satoshi; Nagatsuka, Hitoshi; Kimata, Yoshihiro

    2016-01-01

    Artificial bone materials that exhibit high biocompatibility have been developed and are being widely used for bone tissue regeneration. However, there are no biomaterials that are minimally invasive and safe. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP) which has through-and-through holes and is able to mimic the bone microenvironment for bone tissue regeneration. In the present study, we investigated how the difference in hole-diameter of honeycomb β-TCP (hole-diameter: 75, 300, 500, and 1600 μm) influences bone tissue regeneration histologically. Its osteoconductivity was also evaluated by implantation into zygomatic bone defects in rats. The results showed that the maximum bone formation was observed on the β-TCP with hole-diameter 300μm, included bone marrow-like tissue and the pattern of bone tissue formation similar to host bone. Therefore, the results indicated that we could control bone tissue formation by creating a bone microenvironment provided by β-TCP. Also, in zygomatic bone defect model with honeycomb β-TCP, the result showed there was osseous union and the continuity was reproduced between the both edges of resected bone and β-TCP, which indicated the zygomatic bone reproduction fully succeeded. It is thus thought that honeycomb β-TCP may serve as an excellent biomaterial for bone tissue regeneration in the head, neck and face regions, expected in clinical applications. PMID:27279797

  14. Bone regeneration over a poorly-positioned implant to correct an esthetic deformity: a case report.

    PubMed

    Fugazzotto, P A

    1993-11-01

    Guided tissue regeneration was employed to effect regeneration of a disfigured edentulous ridge, with a poorly positioned implant in place. Demineralized freeze dried bone and an expanded polytetrafluoroethylene membrane were utilized and resulted in growth of new, bone-like material in both a bucco-lingual and apico-occlusal dimension, totally submerging the unusable implant. PMID:8295097

  15. The efficacy of the use of IR laser phototherapy associated to biphasic ceramic graft and guided bone regeneration on surgical fractures treated with miniplates: a histological and histomorphometric study on rabbits.

    PubMed

    Pinheiro, Antonio L B; Aciole, Gilberth Tadeu Santos; Ramos, Thais Andrade; Gonzalez, Tayná Assunção; da Silva, Laís Nogueira; Soares, Luiz G Pinheiro; Aciole, Jouber Mateus Santos; dos Santos, Jean Nunes

    2014-01-01

    The aim of the present study was to assess, by light microscopy and histomorphometry, the repair of surgical fractures fixed with internal rigid fixation (IRF) treated or not with IR laser (λ780 nm, 50 mW, 4 × 4 J/cm(2) = 16 J/cm(2), ϕ = 0.5 cm(2), CW) associated or not to the use of hydroxyapatite and guided bone regeneration. Surgical tibial fractures were created under general anesthesia on 15 rabbits that were divided into 5 groups, maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet, and had water ad libidum. The fractures in groups II, III, IV, and V were fixed with miniplates. Animals in groups III and V were grafted with hydroxyapatite and GBR technique used. Animals in groups IV and V were irradiated at every other day during two weeks (4 × 4 J/cm(2), 16 J/cm(2) = 112 J/cm(2)). Observation time was that of 30 days. After animal death, specimens were taken, routinely processed to wax, cut and stained with HA and Sirius red, and used for histological assessment. The results of both analyses showed a better bone repair on all irradiated subjects especially when the biomaterial and GBR were used. In conclusion, the results of the present investigation are important clinically as they are suggestive that the association of hydroxyapatite, and laser light resulted in a positive and significant repair of complete tibial fractures treated with miniplates. PMID:23649614

  16. Use of osteoplastic material to guide bone tissue regeneration deffect.

    PubMed

    Machavariani, A; Mazmishvili, K; Grdzelidze, T; Menabde, G; Amiranashvili, I

    2011-12-01

    The goal of research was study of restoration processes in jaw-teeth bone defects by application of osteoplastic materials in the experiment. The experiment was performed over 32 white (6-12 month old) rats; the animals were divided into 2 groups; 16 animals were enrolled in the first group; the section was performed in the edge of lower jaw; the lower jaw body was revealed. Under the effect of the dental drilling machine and the # 1 cooling mean by the fissure bohrium (distilled water) the defect of the dimension of 2x2 mm was created; the defect was washed by 0/9% saline to remove the bone sawdust; the wound was sutured tightly, in layers. The second group of the experiment was staffed with 16 animals (main group); the similar bone defect of the size 2 x 2mm was created on the rat's jaw's body. After washing of modeled defect we inserted osteopathic materials PORESORB-TCP crystals with the size of 0,6-1.0 mm the wound was sutured tightly, in layers. After the 3-rd, 15-th, 30-th and 90-th days from the date of operation there was performed X-ray and morphological examination over the animals in the control as well as the main group. The analysis of the examination performed over the experimental materials showed that in the control group in samples taken at 90th day the defects were not completely restored. In the test group in samples taken at 90th day reparative regeneration is confirmed. This is stimulated by the factor that within the main group's animals the defect regeneration process is supported with the osteoplastic material PORESORB-TCP. PMID:22306506

  17. Induction of fully stabilized cortical bone defects to study intramembranous bone regeneration

    PubMed Central

    McGee-Lawrence, Meghan E.; Razidlo, David F.

    2015-01-01

    Summary Bone is a regenerative tissue with an innate ability to self-remodel in response to environmental stimuli and the need to repair damage. Rodent models of fracture healing, and in particular genetic mouse models, can be used to study the contributions of specific molecular switches to skeletal repair, as well as to recreate and exacerbate biological development and repair mechanisms in postnatal skeletons. Here, we describe methodology for producing fully stabilized, single-cortex defects in mouse femurs to study mechanisms of intramembranous bone regeneration. PMID:25331051

  18. Double-layered cell transfer technology for bone regeneration.

    PubMed

    Akazawa, Keiko; Iwasaki, Kengo; Nagata, Mizuki; Yokoyama, Naoki; Ayame, Hirohito; Yamaki, Kazumasa; Tanaka, Yuichi; Honda, Izumi; Morioka, Chikako; Kimura, Tsuyoshi; Komaki, Motohiro; Kishida, Akio; Izumi, Yuichi; Morita, Ikuo

    2016-01-01

    For cell-based medicine, to mimic in vivo cellular localization, various tissue engineering approaches have been studied to obtain a desirable arrangement of cells on scaffold materials. We have developed a novel method of cell manipulation called "cell transfer technology", enabling the transfer of cultured cells onto scaffold materials, and controlling cell topology. Here we show that using this technique, two different cell types can be transferred onto a scaffold surface as stable double layers or in patterned arrangements. Various combinations of adherent cells were transferred to a scaffold, amniotic membrane, in overlapping bilayers (double-layered cell transfer), and transferred cells showed stability upon deformations of the material including folding and trimming. Transplantation of mesenchymal stem cells from periodontal ligaments (PDLSC) and osteoblasts, using double-layered cell transfer significantly enhanced bone formation, when compared to single cell type transplantation. Our findings suggest that this double-layer cell transfer is useful to produce a cell transplantation material that can bear two cell layers. Moreover, the transplantation of an amniotic membrane with PDLSCs/osteoblasts by cell transfer technology has therapeutic potential for bone defects. We conclude that cell transfer technology provides a novel and unique cell transplantation method for bone regeneration. PMID:27624174

  19. Synthetic Bone Substitute Engineered with Amniotic Epithelial Cells Enhances Bone Regeneration after Maxillary Sinus Augmentation

    PubMed Central

    Barboni, Barbara; Mangano, Carlo; Valbonetti, Luca; Marruchella, Giuseppe; Berardinelli, Paolo; Martelli, Alessandra; Muttini, Aurelio; Mauro, Annunziata; Bedini, Rossella; Turriani, Maura; Pecci, Raffaella; Nardinocchi, Delia; Zizzari, Vincenzo Luca; Tetè, Stefano; Piattelli, Adriano; Mattioli, Mauro

    2013-01-01

    Background Evidence has been provided that a cell-based therapy combined with the use of bioactive materials may significantly improve bone regeneration prior to dental implant, although the identification of an ideal source of progenitor/stem cells remains to be determined. Aim In the present research, the bone regenerative property of an emerging source of progenitor cells, the amniotic epithelial cells (AEC), loaded on a calcium-phosphate synthetic bone substitute, made by direct rapid prototyping (rPT) technique, was evaluated in an animal study. Material And Methods Two blocks of synthetic bone substitute (∼0.14 cm3), alone or engineered with 1×106 ovine AEC (oAEC), were grafted bilaterally into maxillary sinuses of six adult sheep, an animal model chosen for its high translational value in dentistry. The sheep were then randomly divided into two groups and sacrificed at 45 and 90 days post implantation (p.i.). Tissue regeneration was evaluated in the sinus explants by micro-computer tomography (micro-CT), morphological, morphometric and biochemical analyses. Results And Conclusions The obtained data suggest that scaffold integration and bone deposition are positively influenced by allotransplantated oAEC. Sinus explants derived from sheep grafted with oAEC engineered scaffolds displayed a reduced fibrotic reaction, a limited inflammatory response and an accelerated process of angiogenesis. In addition, the presence of oAEC significantly stimulated osteogenesis either by enhancing bone deposition or making more extent the foci of bone nucleation. Besides the modulatory role played by oAEC in the crucial events successfully guiding tissue regeneration (angiogenesis, vascular endothelial growth factor expression and inflammation), data provided herein show that oAEC were also able to directly participate in the process of bone deposition, as suggested by the presence of oAEC entrapped within the newly deposited osteoid matrix and by their ability to switch

  20. Guided bone regeneration in the treatment of fenestration osseous defect.

    PubMed

    Mahesh, H V; Ramya, K S

    2013-01-01

    This article presents a case with a fenestration defect which was treated by placing a resorbable barrier alone. In the case presented, the osseous defect was a natural space maker with the wall of the defect providing sufficient support to prevent collapse of the membrane into the space. So the use of membrane alone is the preferred treatment. Resorbable collagen membrane was placed in order to avoid a second surgical procedure to remove the nonresorbable membrane. The membrane was positioned by placing a resorbable sling suture such that it covered the defective site adequately. Postsurgical healing of the defect was evaluated 1 month after the surgery and it was satisfactory. Thus guided bone regeneration of the fenestration defect is a reliable treatment procedure. PMID:23965465

  1. Bioactive glasses: Importance of structure and properties in bone regeneration

    NASA Astrophysics Data System (ADS)

    Hench, Larry L.; Roki, Niksa; Fenn, Michael B.

    2014-09-01

    This review provides a brief background on the applications, mechanisms and genetics involved with use of bioactive glass to stimulate regeneration of bone. The emphasis is on the role of structural changes of the bioactive glasses, in particular Bioglass, which result in controlled release of osteostimulative ions. The review also summarizes the use of Raman spectroscopy, referred to hereto forward as bio-Raman spectroscopy, to obtain rapid, real time in vitro analysis of human cells in contact with bioactive glasses, and the osteostimulative dissolution ions that lead to osteogenesis. The bio-Raman studies support the results obtained from in vivo studies of bioactive glasses, as well as extensive cell and molecular biology studies, and thus offers an innovative means for rapid screening of new bioactive materials while reducing the need for animal testing.

  2. Engineering Pre-vascularized Scaffolds for Bone Regeneration.

    PubMed

    Barabaschi, Giada D G; Manoharan, Vijayan; Li, Qing; Bertassoni, Luiz E

    2015-01-01

    Survival of functional tissue constructs of clinically relevant size depends on the formation of an organized and uniformly distributed network of blood vessels and capillaries. The lack of such vasculature leads to spatio-temporal gradients in oxygen, nutrients and accumulation of waste products inside engineered tissue constructs resulting in negative biological events at the core of the scaffold. Unavailability of a well-defined vasculature also results in ineffective integration of scaffolds to the host vasculature upon implantation. Arguably, one of the greatest challenges in engineering clinically relevant bone substitutes, therefore, has been the development of vascularized bone scaffolds. Various approaches ranging from peptide and growth factor functionalized biomaterials to hyper-porous scaffolds have been proposed to address this problem with reasonable success. An emerging alternative to address this challenge has been the fabrication of pre-vascularized scaffolds by taking advantage of biomanufacturing techniques, such as soft- and photo-lithography or 3D bioprinting, and cell-based approaches, where functional capillaries are engineered in cell-laden scaffolds prior to implantation. These strategies seek to engineer pre-vascularized tissues in vitro, allowing for improved anastomosis with the host vasculature upon implantation, while also improving cell viability and tissue development in vitro. This book chapter provides an overview of recent methods to engineer pre-vascularized scaffolds for bone regeneration. We first review the development of functional blood capillaries in bony structures and discuss controlled delivery of growth factors, co-culture systems, and on-chip studies to engineer vascularized cell-laden biomaterials. Lastly, we review recent studies using microfabrication techniques and 3D printing to engineer pre-vascularized scaffolds for bone tissue engineering. PMID:26545745

  3. Effects of bovine lactoferrin in surgically created bone defects on bone regeneration around implants.

    PubMed

    Görmez, Ulaş; Kürkcü, Mehmet; E Benlidayi, Mehmet; Ulubayram, Kezban; Sertdemir, Yaşar; Dağlioğlu, Kenan

    2015-03-01

    The aim of this experimental study was to evaluate the effect of bovine lactoferrin (bLF)-loaded gelatin microspheres (GM) used in combination with anorganic bovine bone on bone regeneration in surgically created bone defects around tooth implants. Twenty-four uniform bone defects were created in the frontal bone via an extraoral approach in 12 domestic pigs. Twenty-four implants were placed at the center of the defects. In eight animals one of these defects was filled with 0.3 mL anorganic bovine bone while the other was left empty. In four animals, all defects were filled with 3 mg/defect bLF-loaded GM and anorganic bovine bone. All the defects were covered with collagen membranes. All animals were sacrificed after 10 weeks of healing, and the implants with the surrounding bone defects were removed en bloc. Undecalcified sections were prepared for histomorphometric analysis. The mean total area of hard tissue was 26.9 ± 6.0% in the empty defect group, 31.8 ± 8.4% in the graft group, and 47.6 ± 5.0% in the lactoferrin group (P < 0.001). The mean area of newly formed bone was 26.9 ± 6.0% in the empty defect group, 22.4 ± 8.2% in the graft group, and 46.1 ± 5.1% in the lactoferrin group (P < 0.001). The mean residual graft area was 9.4 ± 3.2% in the graft group and 1.5 ± 0.6% in the lactoferrin group (P < 0.001). The mean proportion of bone-implant contact in the defect region was 21.9 ± 8.4% in the empty defect group, 26.9 ± 10.1% in the graft group and 29.9 ± 10.3% in the lactoferrin group (P = 0.143). These data indicate that a combination of 3 mg bLF-loaded GM and bovine-derived HA promotes bone regeneration in defects around implants. PMID:25807903

  4. VEGF and BMP-2 promote bone regeneration by facilitating bone marrow stem cell homing and differentiation.

    PubMed

    Zhang, W; Zhu, C; Wu, Y; Ye, D; Wang, S; Zou, D; Zhang, X; Kaplan, D L; Jiang, X

    2014-01-01

    Vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) have been widely used in the fields of tissue engineering and regenerative medicine to stimulate angiogenesis and bone formation. The goal of this study was to determine whether VEGF and BMP-2 are involved in the homing of bone marrow stem cells (BMSCs) for bone regeneration and to provide insights into their mechanism of action. The chemoattraction of BMSCs to VEGF and BMP-2 was analysed in vitro using a checkerboard assay. VEGF and BMP-2 stimulated the chemotaxis of BMSCs but not chemokinesis. In vivo, both VEGF and BMP-2 also have been confirmed to induce the homing of tail vein injected BMSCs to the site of silk scaffold subcutaneous implantation in nude mice. When the scaffolds were implanted in the rabbit skull defects, more SSEA+ mesenchymal stem cells were mobilised and homed to silk scaffolds containing VEGF and/or BMP-2. More importantly, autogenic BMSCs were reinjected via the ear vein after labelling with lenti-GFP, and the cells were detected to home to the defects and differentiate into endothelial cells and osteogenic cells induced by VEGF and BMP-2. Finally, perfusion with Microfil showed that initial angiogenesis was enhanced in tissue-engineered complexes containing VEGF. Observations based on µCT assay and histological study revealed that bone formation was accelerated on BMP-2-containing scaffolds. These findings support our hypothesis that the localised release of VEGF and BMP-2 promote bone regeneration, in part by facilitating the mobilisation of endogenous stem cells and directing the differentiation of these cells into endothelial and osteogenic lineages. PMID:24425156

  5. Chitosan and alginate scaffolds for bone tissue regeneration.

    PubMed

    Olmez, S S; Korkusuz, P; Bilgili, H; Senel, S

    2007-06-01

    Polymeric scaffold for tissue regeneration was developed for veterinary applications. Oxytetracycline hydrochloride (OTC), which is a widely used antibiotic in veterinary medicine was chosen as the model compound. Gel formulations using chitosan and alginate were prepared in distilled water or in 1% (v/v) acetic acid solution. Sponges were also prepared by a freeze-drying process. Tripolyphosphate was used for cross-linking. Viscosity was decreased in the presence of OTC in chitosan gels whereas no difference was found with alginate gels. All gels showed pseudoplastic behaviour. Water absorption capacity was highest with chitosan/alginate sponges. The solvent used for preparation of the chitosan gels was found to affect the release of OTC. The release of OTC from the sponges was increased by cross-linking. Chitosan/alginate sponges showed the slowest and lowest drug release among the developed sponge formulations in this study. The formulations were found to be biocompatible, inducing no adverse reaction in vivo on surgically formed bone defects of radius of rabbits. The level of organization of the remodelled new bone in the treatment groups was better than that of control. Incorporation of OTC into formulations did not show any considerable enhancing effect. PMID:17663189

  6. Bioabsorbable bone plates enabled with local, sustained delivery of alendronate for bone regeneration.

    PubMed

    Hur, Woojune; Park, Min; Lee, Jae Yeon; Kim, Myung Hun; Lee, Seung Ho; Park, Chun Gwon; Kim, Se-Na; Min, Hye Sook; Min, Hye Jeong; Chai, Jin Ho; Lee, Sang Jeong; Kim, Sukwha; Choi, Tae Hyun; Choy, Young Bin

    2016-01-28

    We prepared a bone plate enabled with the local, sustained release of alendronate, which is a drug known to inhibit osteoclast-mediated bone resorption and also expedite the bone-remodeling activity of osteoblasts. For this, we coated a bone plate already in clinical use (PLT-1031, Inion, Finland) with a blend of alendronate and a biocompatible polymer, azidobenzoic acid-modified chitosan (i.e., Az-CH) photo-crosslinked by UV irradiation. As we performed the in vitro drug release study, the drug was released from the coating at an average rate of 4.03μg/day for 63days in a sustained manner. To examine the effect on bone regeneration, the plate was fixed on an 8mm cranial critical size defect in living rats and the newly formed bone volume was quantitatively evaluated by micro-computed tomography (micro-CT) at scheduled times over 8weeks. At week 8, the group implanted with the plate enabled with sustained delivery of alendronate showed a significantly higher volume of newly formed bone (52.78±6.84%) than the groups implanted with the plates without drug (23.6±3.81%) (p<0.05). The plate enabled with alendronate delivery also exhibited good biocompatibility on H&E staining, which was comparable to the Inion plate already in clinical use. Therefore, we suggest that a bone plate enabled with local, sustained delivery of alendronate can be a promising system with the combined functionality of bone fixation and its expedited repair. PMID:26682503

  7. Strontium-rich injectable hybrid system for bone regeneration.

    PubMed

    Neves, Nuno; Campos, Bruno B; Almeida, Isabel F; Costa, Paulo C; Cabral, Abel Trigo; Barbosa, Mário A; Ribeiro, Cristina C

    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 over the viscous one and that the higher storage modulus was obtained for the 3.5%Alg–35%Sr-HAp-Sr formulation. PMID:26652437

  8. Macroporous hydrogels upregulate osteogenic signal expression and promote bone regeneration.

    PubMed

    Betz, Martha W; Yeatts, Andrew B; Richbourg, William J; Caccamese, John F; Coletti, Domenick P; Falco, Erin E; Fisher, John P

    2010-05-10

    The objective of this work was to investigate the effects of macroporous hydrogel architecture on the osteogenic signal expression and differentiation of human mesenchymal stem cells (hMSCs). In particular, we have proposed a tissue engineering approach for orbital bone repair based on a cyclic acetal biomaterial formed from 5-ethyl-5-(hydroxymethyl)-beta,beta-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA). The EHD monomer and PEGDA polymer may be fabricated into macroporous EH-PEG hydrogels by radical polymerization and subsequent porogen leaching, a novel technique for hydrophilic gels. We hypothesized that EH-PEG hydrogel macroporosity facilitates intercellular signaling among hMSCs. To investigate this phenomenon, hMSCs were loaded into EH-PEG hydrogels with varying pore size and porosity. The viability of hMSCs, the expression of bone morphogenetic protein-2 (BMP-2), BMP receptor type 1A, and BMP receptor type 2 by hMSCs, and the differentiation of hMSCs were then assessed. Results demonstrate that macroporous EH-PEG hydrogels support hMSCs and that this macroporous environment promotes a dramatic increase in BMP-2 expression by hMSCs. This upregulation of BMP-2 expression is associated by a more rapid hMSC differentiation, as measured by alkaline phosphatase expression. Altering hMSC interactions with the EH-PEG hydrogel surface, by the addition of fibronectin, did not appear to augment BMP-2 expression. We therefore speculate that EH-PEG hydrogel macroporosity facilitates autocrine and paracrine signaling by localizing endogenously expressed factors within the hydrogel's pores and thus promotes hMSC osteoblastic differentiation and bone regeneration. PMID:20345129

  9. Imaging regenerating bone tissue based on neural networks applied to micro-diffraction measurements

    SciTech Connect

    Campi, G.; Pezzotti, G.; Fratini, M.; Ricci, A.; Burghammer, M.; Cancedda, R.; Mastrogiacomo, M.; Bukreeva, I.; Cedola, A.

    2013-12-16

    We monitored bone regeneration in a tissue engineering approach. To visualize and understand the structural evolution, the samples have been measured by X-ray micro-diffraction. We find that bone tissue regeneration proceeds through a multi-step mechanism, each step providing a specific diffraction signal. The large amount of data have been classified according to their structure and associated to the process they came from combining Neural Networks algorithms with least square pattern analysis. In this way, we obtain spatial maps of the different components of the tissues visualizing the complex kinetic at the base of the bone regeneration.

  10. A novel in vivo platform for studying alveolar bone regeneration in rat

    PubMed Central

    Kim, Joong-Hyun; Moon, Ho-Jin; Kim, Tae-Hyun; Jo, Jong-Min; Yang, Sung Hee; Naskar, Deboki; Kundu, Subhas C; Chrzanowski, Wojciech

    2013-01-01

    Alveolar bone regeneration is a significant challenge in dental implantation. Novel biomaterials and tissue-engineered constructs are under extensive development and awaiting in vivo animal tests to find clinical endpoint. Here, we establish a novel in vivo model, modifying gingivoperiosteoplasty in rat for the alveolar bone regeneration. Rat premaxillary bone defects were filled with silk scaffold or remained empty during the implantation period (up to 6 weeks), and harvested samples were analyzed by micro-computed tomography and histopathology. Empty defects showed increased but limited new bone formation with increasing implantation period. In defects implanted with silk sponge, the bone formation was significantly greater than that of empty defect, indicating an effective role of silk scaffold in the defect model. The modified premaxillary defect model in rat is simple to perform, while mimicking the clinical conditions, finding usefulness for the development of biomaterials and tissue-engineered constructs targeting alveolar bone regeneration in dental implantation. PMID:24555013

  11. A novel in vivo platform for studying alveolar bone regeneration in rat.

    PubMed

    Kim, Joong-Hyun; Moon, Ho-Jin; Kim, Tae-Hyun; Jo, Jong-Min; Yang, Sung Hee; Naskar, Deboki; Kundu, Subhas C; Chrzanowski, Wojciech; Kim, Hae-Won

    2013-01-01

    Alveolar bone regeneration is a significant challenge in dental implantation. Novel biomaterials and tissue-engineered constructs are under extensive development and awaiting in vivo animal tests to find clinical endpoint. Here, we establish a novel in vivo model, modifying gingivoperiosteoplasty in rat for the alveolar bone regeneration. Rat premaxillary bone defects were filled with silk scaffold or remained empty during the implantation period (up to 6 weeks), and harvested samples were analyzed by micro-computed tomography and histopathology. Empty defects showed increased but limited new bone formation with increasing implantation period. In defects implanted with silk sponge, the bone formation was significantly greater than that of empty defect, indicating an effective role of silk scaffold in the defect model. The modified premaxillary defect model in rat is simple to perform, while mimicking the clinical conditions, finding usefulness for the development of biomaterials and tissue-engineered constructs targeting alveolar bone regeneration in dental implantation. PMID:24555013

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

    PubMed

    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. PMID:27316294

  13. Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects.

    PubMed

    García, José R; Clark, Amy Y; García, Andrés J

    2016-04-01

    Vascularization of bone defects is considered a crucial component to the successful regeneration of large bone defects. Although vascular endothelial growth factor (VEGF) has been delivered to critical-size bone defect models to augment blood vessel infiltration into the defect area, its potential to increase bone repair remains ambiguous. In this study, we investigated whether integrin-specific biomaterials modulate the effects of VEGF on bone regeneration. We engineered protease-degradable, VEGF-loaded poly(ethylene glycol) (PEG) hydrogels functionalized with either a triple-helical, α2 β1 integrin-specific peptide GGYGGGP(GPP)5 GFOGER(GPP)5 GPC (GFOGER) or an αv β3 integrin-targeting peptide GRGDSPC (RGD). Covalent incorporation of VEGF into the PEG hydrogel allowed for protease degradation-dependent release of the protein while maintaining VEGF bioactivity. When applied to critical-size segmental defects in the murine radius, GFOGER-functionalized VEGF-free hydrogels exhibited significantly increased vascular volume and density and resulted in a larger number of thicker blood vessels compared to RGD-functionalized VEGF-free hydrogels. VEGF-loaded RGD hydrogels increased vascularization compared to VEGF-free RGD hydrogels, but the levels of vascularization for these VEGF-containing RGD hydrogels were similar to those of VEGF-free GFOGER hydrogels. VEGF transiently increased bone regeneration in RGD hydrogels but had no effect at later time points. In GFOGER hydrogels, VEGF did not show an effect on bone regeneration. However, VEGF-free GFOGER hydrogels resulted in increased bone regeneration compared to VEGF-free RGD hydrogels. These findings demonstrate the importance of integrin-specificity in engineering constructs for vascularization and associated bone regeneration. PMID:26662727

  14. N-methyl pyrrolidone as a potent bone morphogenetic protein enhancer for bone tissue regeneration.

    PubMed

    Miguel, Blanca San; Ghayor, Chafik; Ehrbar, Martin; Jung, Ronald E; Zwahlen, Roger A; Hortschansky, Peter; Schmoekel, Hugo G; Weber, Franz E

    2009-10-01

    In medicine, N-methyl pyrrolidone (NMP) has a long track record as a constituent in medical devices approved by the Food and Drug Administration and thus can be considered as a safe and biologically inactive small chemical. In the present study, we report on the newly discovered pharmaceutical property of NMP in enhancing bone regeneration in a rabbit calvarial defect model in vivo. At the cellular level, the pharmaceutical effect of NMP was confirmed, in particular, in combination with bone morphogenetic protein (BMP)-2, because NMP increased early and late markers for maturation of preosteoblasts and human bone marrow-derived stem cells in vitro. When we used the multipotent cell line C2C12 without autologous BMP expression, NMP alone had no effect on alkaline phosphatase activity, a marker for osteogenic transdifferentiation. Nevertheless, in combination with low BMP-2 doses, alkaline phosphatase activity was more than eight times as great. Thus, the pharmaceutical NMP mode of action is that of an enhancer of BMP activity. The dependency of the effects of NMP on BMP was confirmed in preosteoblasts because noggin, an extracellular BMP inhibitor, suppressed NMP-induced increases in early markers for osteoblast maturation in vitro. At the molecular level, NMP was shown to have no effect on the binding of BMP-2 to the ectodomain of the high-affinity BMP receptor IA. However, NMP further increased the phosphorylation of p38 and Smad1,5,8 induced by BMP-2. Thus, the small chemical NMP enhances BMP activity by increasing the kinase activity of the BMP receptor complex for Smad1,5,8 and p38 and could be employed as a potent drug for bone tissue regeneration and engineering. PMID:19320543

  15. Influence of structural load-bearing scaffolds on mechanical load- and BMP-2-mediated bone regeneration.

    PubMed

    McDermott, Anna M; Mason, Devon E; Lin, Angela S P; Guldberg, Robert E; Boerckel, Joel D

    2016-09-01

    A common design constraint in functional tissue engineering is that scaffolds intended for use in load-bearing sites possess similar mechanical properties to the replaced tissue. Here, we tested the hypothesis that in vivo loading would enhance bone morphogenetic protein-2 (BMP-2)-mediated bone regeneration in the presence of a load-bearing PLDL scaffold, whose pores and central core were filled with BMP-2-releasing alginate hydrogel. First, we evaluated the effects of in vivo mechanical loading on bone regeneration in the structural scaffolds. Second, we compared scaffold-mediated bone regeneration, independent of mechanical loading, with alginate hydrogel constructs, without the structural scaffold, that have been shown previously to facilitate in vivo mechanical stimulation of bone formation. Contrary to our hypothesis, mechanical loading had no effect on bone formation, distribution, or biomechanical properties in structural scaffolds. Independent of loading, the structural scaffolds reduced bone formation compared to non-structural alginate, particularly in regions in which the scaffold was concentrated, resulting in impaired functional regeneration. This is attributable to a combination of stress shielding by the scaffold and inhibition of cellular infiltration and tissue ingrowth. Collectively, these data question the necessity of scaffold similarity to mature tissue at the time of implantation and emphasize development of an environment conducive to cellular activation of matrix production and ultimate functional regeneration. PMID:27208510

  16. A novel peptide-modified and gene-activated biomimetic bone matrix accelerating bone regeneration.

    PubMed

    Pan, Haitao; Zheng, Qixin; Yang, Shuhua; Guo, Xiaodong; Wu, Bin; Zou, Zhenwei; Duan, Zhixia

    2014-08-01

    The osteogenic differentiation of bone marrow stromal cells (BMSCs) can be regulated by systemic or local growth factor, especially by transforming growth factor beta 1 (TGF-β1). However, how to maintain the bioactivity of exogenous TGF-β1 is a great challenge due to its short half-life time. The most promising solution is to transfer TGF-β1 gene into seed cells through transgenic technology and then transgenic cells to continuously secret endogenous TGF-β1 protein via gene expression. In this study, a novel non-viral vector (K)16GRGDSPC was chemically linked to bioactive bone matrices PLGA-[ASP-PEG]n using cross-linker to construct a novel non-viral gene transfer system. TGF-β1 gene was incubated with this system and subsequently rabbit-derived BMSCs were co-cultured with this gene-activated PLGA-[ASP-PEG]n, while co-cultured with PLGA-[ASP-PEG]n modified with (K)16GRGDSPC only and original PLGA-[ASP-PEG]n as control. Thus we fabricated three kinds of composites: Group A (BMSCs-TGF-β1DNA-(K)16GRGDSPC-PLGA-[ASP-PEG]n composite); Group B (BMSCs-(K)16GRGDSPC-PLGA-[ASP-PEG]n composite); and Group C (BMSCs-PLGA-[ASP-PEG]n composite). TGF-β1 and other osteogenic phenotype markers of alkaline phosphatase, osteocalcin, osteopontin and type I collagen in Group A were all significantly higher than the other two groups ex vivo. In vivo, 15-mm long segmental rabbit bone defects were created and randomly implanted the aforementioned composites separately, and then fixed with plate-screws. The results demonstrated that the implants in Group A significantly accelerated bone regeneration compared with the other implants based on X-rays, histological and biomechanical examinations. Therefore, we conclude this novel peptide-modified and gene-activated biomimetic bone matrix of TGF-β1DNA-(K)16GRGDSPC-PLGA-[ASP-PEG]n is a very promising scaffold biomaterial for accelerating bone regeneration. PMID:24115366

  17. Hollow hydroxyapatite microspheres: a novel bioactive and osteoconductive carrier for controlled release of bone morphogenetic protein-2 in bone regeneration

    PubMed Central

    Xiao, Wei; Fu, Hailuo; Rahaman, Mohamed N.; Liu, Yonxing; Bal, B. Sonny

    2013-01-01

    The regeneration of large bone defects is a common and significant clinical problem. Limitations associated with existing treatments such as autologous bone grafts and allografts have increased the need for synthetic bone graft substitutes. The objective of this study was to evaluate the capacity of novel hollow hydroxyapatite (HA) microspheres to serve as a carrier for controlled release of bone morphogenetic-2 (BMP2) in bone regeneration. Hollow HA microspheres (106–150 μm) with a high surface area (>100 m2/g) and a mesoporous shell wall (pore size 10–20 nm) were created using a glass conversion technique. The release of BMP2 from the microspheres into a medium composed of diluted fetal bovine serum in vitro was slow, but it occurred continuously for over 2 weeks. When implanted in rat calvarial defects for 3 or 6 weeks, the microspheres loaded with BMP2 (1 μg/defect) showed a significantly better capacity to regenerate bone than those without BMP2. The amount of new bone in the defects implanted with the BMP2-loaded microspheres was 40% and 43%, respectively, at 3 and 6 weeks, compared to 13% and 17%, respectively, for the microspheres without BMP2. Coating the BMP2-loaded microspheres with a biodegradable polymer, poly(lactic-co-glycolic acid), reduced the amount of BMP2 released in vitro and, above a certain coating thickness, significantly reduced bone regeneration in vivo. The results indicate that these hollow HA microspheres could provide a bioactive and osteoconductive carrier for growth factors in bone regeneration. PMID:23747325

  18. Alveolar bone regeneration for immediate implant placement using an injectable bone substitute: an experimental study in dogs

    PubMed Central

    Boix, Damien; Gauthier, Olivier; Guicheux, Jérôme; Pilet, Paul; Weiss, Pierre; Grimandi, Gaël; Daculsi, Guy

    2004-01-01

    Background The aim of the present study was to assess the efficacy of a ready-to-use injectable bone substitute for bone regeneration around dental implants placed into fresh extraction sockets. Methods Third and fourth mandibular premolars were extracted from 3 Beagle dogs and the interradicular septa were surgically reduced to induce a mesial bone defect. Thereafter, immediate placements of titanium implants were performed. On the left side of the jaw, mesial bone defects were filled with an injectable bone substitute (IBS), obtained by combining a polymer and a biphasic calcium phosphate ceramic. As a control, the right defects were left unfilled. After 3 months of healing, specimens were prepared for histological and histomorphometric evaluations. Results No post surgical complication was observed during the healing period. In all experimental conditions, histological observations revealed a lamellar bone formation in contact with the implant. Histomorphometric analysis showed that IBS triggers a significant (p<0.05) increase in term of thread numbers in contact with bone (TN), bone-to-implant contact (BIC) and peri-implant bone density (PBD), of about 8.6%, 11.0% and 14.7%, respectively. In addition, no significant difference was observed when TN, BIC and PBD in filled defects were compared to no-defect sites. Conclusion It is concluded that an injectable bone substitute composed of a polymeric carrier and calcium phosphate significantly increase bone regeneration around immediate implants. PMID:15212348

  19. From bench to clinic and back: skeletal stem cells and impaction bone grafting for regeneration of bone defects.

    PubMed

    Aarvold, A; Smith, J O; Tayton, E R; Jones, A M H; Dawson, J I; Lanham, S; Briscoe, A; Dunlop, D G; Oreffo, R O C

    2014-10-01

    Tissue engineering offers enormous potential for bone regeneration. Despite extensive in vitro and in vivo work, few strategies translate into clinical practice. This paper describes the combination of skeletal stem cells (SSCs) and impaction bone grafting (IBG) for the treatment of patients with bone defects associated with avascular necrosis of the femoral head. SSCs and milled allograft were impacted into necrotic bone in the femoral heads of four patients. Three patients remained asymptomatic at 22-44 month follow-up, but one patient has required total hip replacement (both hips). This has allowed retrieval of the femoral heads, which were analysed structurally and functionally by μCT, histology and mechanical testing. A central channel of impacted bone was found in the femoral heads, which displayed a mature trabecular micro-architecture. The impacted bone was denser than the surrounding trabecular bone, as strong in compression and with histological micro-architecture comparable to that of trabecular bone. Analysis of the retrieved femoral head samples has demonstrated that this tissue-engineering strategy regenerates bone that is both structurally and functionally analogous to normal trabecular bone. SSCs, together with IBG, have proved an effective treatment for avascular necrosis of the femoral head and offer significant potential for the broader spectrum of bone defects. PMID:23038218

  20. Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones

    PubMed Central

    Ignjatović, Nenad; Ajduković, Zorica; Savić, Vojin; Najman, Stevo; Mihailović, Dragan; Vasiljević, Perica; Stojanović, Zoran; Uskoković, Vuk; Uskoković, Dragan

    2012-01-01

    Indications exist that paramagnetic calcium phosphates may be able to promote regeneration of bone faster than their regular, diamagnetic counterparts. In this study, analyzed was the influence of paramagnetic cobalt-substituted hydroxyapatite nanoparticles on osteoporotic alveolar bone regeneration in rats. Simultaneously, biocompatibility of the material was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. The material was shown to be biocompatible and nontoxic when added to epithelial monolayers in vitro, while it caused a substantial decrease in the cell viability as well as deformation of the cytoskeleton and cell morphology when incubated with the osteoblastic cells. In the course of six months after the implantation of the material containing different amounts of cobalt, ranging from 5 – 12 wt%, in the osteoporotic alveolar bone of the lower jaw, the following parameters were investigated: histopathological parameters, alkaline phosphatase and alveolar bone density. The best result in terms of osteoporotic bone tissue regeneration was observed for hydroxyapatite nanoparticles with the largest content of cobalt ions. The histological analysis showed a high level of reparatory ability of the nanoparticulate material implanted in the bone defect, paralleled by a corresponding increase in the alveolar bone density. The combined effect of growth factors from autologous plasma admixed to cobalt-substituted hydroxyapatite was furthermore shown to have a crucial effect on the augmented osteoporotic bone regeneration upon the implantation of the biomaterial investigated in this study. PMID:23090835

  1. Evaluation of nanostructure and microstructure of bone regenerated by BMP-2-porous scaffolds.

    PubMed

    Del Rosario, Carlos; Rodríguez-Evora, Maria; Reyes, Ricardo; González-Orive, Alejandro; Hernández-Creus, Alberto; Shakesheff, Kevin M; White, Lisa J; Delgado, Araceli; Evora, Carmen

    2015-09-01

    In this study, three systems containing BMP-2 were fabricated, including two electrospun sandwich-like-systems of PLGA 75:25 and PLGA 50:50 and a microsphere system of PLGA 50:50 to be implanted in a critical size defect in rat calvaria. The in vivo BMP-2 release profiles of the three systems were similar. The total dose was released during the first two weeks. To evaluate the nano and microstructure of the regenerated bone a multi-technique analysis was used, including stereo microscope, X-Ray; AFM, micro-CT, and histological analyses. The progression of bone regeneration was followed at 4, 8, and 12 weeks after the microsphere system implantation whereas the two electrospun systems were evaluated at fixed 12 weeks. All the techniques applied showed high bone regeneration. The average values of bone volume density, bone mineral density, Young's modulus, and the percent of bone repair were ∼70% of the values of the native bone. Besides, SEM-EDX analysis indicated that the main chemical elements in the new bone were oxygen, calcium, and phosphorus in a ratio similar to that of native bone. In comparison, the micro-CT may provide an alternative to histology for the evaluation of bone formation at the defect size. PMID:25689580

  2. The roles of vascular endothelial growth factor in bone repair and regeneration.

    PubMed

    Hu, Kai; Olsen, Bjorn R

    2016-10-01

    Vascular endothelial growth factor-A (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. Since bone is a highly vascularized organ and angiogenesis plays an important role in osteogenesis, VEGF also influences skeletal development and postnatal bone repair. Compromised bone repair and regeneration in many patients can be attributed to impaired blood supply; thus, modulation of VEGF levels in bones represents a potential strategy for treating compromised bone repair and improving bone regeneration. This review (i) summarizes the roles of VEGF at different stages of bone repair, including the phases of inflammation, endochondral ossification, intramembranous ossification during callus formation and bone remodeling; (ii) discusses different mechanisms underlying the effects of VEGF on osteoblast function, including paracrine, autocrine and intracrine signaling during bone repair; (iii) summarizes the role of VEGF in the bone regenerative procedure, distraction osteogenesis; and (iv) reviews evidence for the effects of VEGF in the context of repair and regeneration techniques involving the use of scaffolds, skeletal stem cells and growth factors. PMID:27353702

  3. Immediate placement and provisionalization of maxillary anterior single implant with guided bone regeneration, connective tissue graft, and coronally positioned flap procedures.

    PubMed

    Waki, Tomonori; Kan, Joseph Y K

    2016-01-01

    Immediate implant placement and provisionalization in the esthetic zone have been documented with success. The benefit of immediate implant placement and provisionalization is the preservation of papillary mucosa. However, in cases with osseous defects presenting on the facial bony plate, immediate implant placement procedures have resulted in facial gingival recession. Subepithelial connective tissue grafts for immediate implant placement and provisionalization procedures have been reported with a good esthetic outcome. Biotype conversion around implants with subepithelial connective tissue grafts have been advocated, and the resulting tissues appear to be more resistant to recession. The dimensions of peri-implant mucosa in a thick biotype were significantly greater than in a thin biotype. Connective tissue graft with coronally positioned flap procedures on natural teeth has also been documented with success. This article describes a technique combining immediate implant placement, provisionalization, guided bone regeneration (GBR), connective tissue graft, and a coronally positioned flap in order to achieve more stable peri-implant tissue in facial osseous defect situations. PMID:27092345

  4. Cotton-wool-like bioactive glasses for bone regeneration.

    PubMed

    Poologasundarampillai, G; Wang, D; Li, S; Nakamura, J; Bradley, R; Lee, P D; Stevens, M M; McPhail, D S; Kasuga, T; Jones, J R

    2014-08-01

    Inorganic sol-gel solutions were electrospun to produce the first bioactive three-dimensional (3-D) scaffolds for bone tissue regeneration with a structure like cotton-wool (or cotton candy). This flexible 3-D fibrous structure is ideal for packing into complex defects. It also has large inter-fiber spaces to promote vascularization, penetration of cells and transport of nutrients throughout the scaffold. The 3-D fibrous structure was obtained by electrospinning, where the applied electric field and the instabilities exert tremendous force on the spinning jet, which is required to be viscoelastic to prevent jet break up. Previously, polymer binding agents were used with inorganic solutions to produce electrospun composite two-dimensional fibermats, requiring calcination to remove the polymer. This study presents novel reaction and processing conditions for producing a viscoelastic inorganic sol-gel solution that results in fibers by the entanglement of the intermolecularly overlapped nanosilica species in the solution, eliminating the need for a binder. Three-dimensional cotton-wool-like structures were only produced when solutions containing calcium nitrate were used, suggesting that the charge of the Ca(2+) ions had a significant effect. The resulting bioactive silica fibers had a narrow diameter range of 0.5-2μm and were nanoporous. A hydroxycarbonate apatite layer was formed on the fibers within the first 12h of soaking in simulated body fluid. MC3T3-E1 preosteoblast cells cultured on the fibers showed no adverse cytotoxic effect and they were observed to attach to and spread in the material. PMID:24874652

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

    PubMed Central

    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

  6. Effect of autologous bone marrow-derived cells associated with guided bone regeneration or not in the treatment of peri-implant defects.

    PubMed

    Ribeiro, F V; Suaid, F F; Ruiz, K G S; Rodrigues, T L; Carvalho, M D; Nociti, F H; Sallum, E A; Casati, M Z

    2012-01-01

    This study investigated the effect of bone marrow-derived cells associated with guided bone regeneration in the treatment of dehiscence bone defects around dental implants. Iliac-derived bone marrow cells were harvested from dogs and phenotypically characterized with regard to their osteogenic properties. After teeth extraction, three implant sites were drilled, dehiscences created and implants placed. Dehiscences were randomly assigned to: bone marrow-derived cells, bone marrow-derived cells+guided bone regeneration, and control (no treatment). After 3 months, implants with adjacent tissues were processed histologically, bone-to-implant contact, bone fill within the threads, new bone area in a zone lateral to the implant, new bone height, and new bone weight at the bottom of the defect were determined. Phenotypic characterization demonstrated that bone marrow-derived cells presented osteogenic potential. Statistically higher bone fill within the threads was observed in both bone marrow-derived cells+guided bone regeneration bone marrow-derived cell groups compared with the control group (P<0.05), with no difference between the groups treated with cells (P>0.05). For the other parameters (new bone area, bone-to-implant contact, new bone height and new bone weight), only the bone marrow-derived cells+guided bone regeneration group presented higher values compared with the non-treated control (P<0.05). Bone marrow-derived cells provided promising results for peri-implantar bone regeneration, although the combined approach seems to be relevant, especially to bone formation out of the implant threads. PMID:21924867

  7. Graded Porous β-Tricalcium Phosphate Scaffolds Enhance Bone Regeneration in Mandible Augmentation

    PubMed Central

    Yang, Jingwen; Kang, Yunqing; Browne, Christopher; Jiang, Ting; Yang, Yunzhi

    2015-01-01

    Abstract Bone augmentation requires scaffold to promote forming of natural bone structure. Currently, most of the reported bone scaffolds are porous solids with uniform pores. The aim of the currentstudy is to evaluate the effect of a graded porous β-tricalcium phosphate scaffolds on alveolar bone augmentation. Three groups of scaffolds were fabricated by a template-casting method: (1) graded porous scaffolds with large pores in the center and small pores at theperiphery, (2) scaffolds with large uniform pores, and (3) scaffolds with small uniform pores. Bone augmentation on rabbit mandible wasinvestigated by microcomputed tomography, sequential fluorescentlabeling, and histologic examination 3 months after implantation.The result presents that all the scaffold groups maintain their augmented bone height after 3-month observation, whereas the autograftinggroup presents an obvious bone resorption. Microcomputed tomography reveals that the graded porous group has significantly greater volume of new bone (P < 0.05) and similar bone density compared with the uniform pores groups. Bone substance distributes unevenly in all the 3 experimental groups. Greater bone volume can be observed in the area closer to the bone bed. The sequential fluorescentlabeling observation reveals robust bone regeneration in the first month and faster bone growth in the graded porous scaffold group than that in the large porous scaffold group. Histologic examinationsconfirm bone structure in the aspect of distribution, activity, and maturity. We conclude that graded porous designed biodegradableβ-tricalcium phosphate scaffolds are beneficial to promote bone augmentation in the aspect of bone volume. PMID:25675019

  8. Hydroxyapatite-calcium sulfate-hyaluronic acid composite encapsulated with collagenase as bone substitute for alveolar bone regeneration.

    PubMed

    Subramaniam, Sadhasivam; Fang, Yen-Hsin; Sivasubramanian, Savitha; Lin, Feng-Huei; Lin, Chun-pin

    2016-01-01

    Periodontitis is a very severe inflammatory condition of the periodontium that progressively damages the soft tissue and destroys the alveolar bone that supports the teeth. The bone loss is naturally irreversible because of limited reparability of the teeth. Advancement in tissue engineering provides an effective regeneration of osseous defects with suitable dental implants or tissue-engineered constructs. This study reports a hydroxyapatite, calcium sulfate hemihydrate and hyaluronic acid laden collagenase (HAP/CS/HA-Col) as a bone substitute for the alveolar bone regeneration. The composite material was mechanically tested and the biocompatibility was evaluated by WST-1 assay. The in vivo bone formation was assessed in rat with alveolar bone defects and the bone augmentation by the HAP/CS/HA-Col composite was confirmed by micro-CT images and histological examination. The mechanical strength of 6.69 MPa with excellent biocompatibility was obtained for the HAP/CS/HA-Col composite. The collagenase release profile had facilitated the acceleration of bone remodeling process and it was confirmed by the findings of micro-CT and H&E staining. The bone defects implanted with HAP/CS/HA composite containing 2 mg/mL type I collagenase have shown improved new bone formation with matured bone morphology in comparison with the HAP/CS/HA composite that lacks the collagenase and the porous hydroxyapatite (p-HAP) granules. The said findings demonstrated that the collagenase inclusion in HAP/CS/HA composite is a feasible approach for the alveolar bone regeneration and the same design can also be applied to other defective tissues. PMID:26454048

  9. Exosome: A Novel Approach to Stimulate Bone Regeneration through Regulation of Osteogenesis and Angiogenesis

    PubMed Central

    Qin, Yunhao; Sun, Ruixin; Wu, Chuanlong; Wang, Lian; Zhang, Changqing

    2016-01-01

    The clinical need for effective bone regeneration therapy remains in huge demands. However, the current “gold standard” treatments of autologous and allogeneic bone grafts may result in various complications. Furthermore, safety considerations of biomaterials and cell-based treatment require further clarification. Therefore, developing new therapies with stronger osteogenic potential and a lower incidence of complications is worthwhile. Recently, exosomes, small vesicles of endocytic origin, have attracted attention in bone regeneration field. The vesicles travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating targeted cells differentiation, commitment, function, and proliferation. Much evidence has demonstrated the important roles of exosomes in osteogenesis both in vitro and in vivo. In this review, we summarize the properties, origins and biogenesis of exosomes, and the recent reports using exosomes to regulate osteogenesis and promote bone regeneration. PMID:27213355

  10. Exosome: A Novel Approach to Stimulate Bone Regeneration through Regulation of Osteogenesis and Angiogenesis.

    PubMed

    Qin, Yunhao; Sun, Ruixin; Wu, Chuanlong; Wang, Lian; Zhang, Changqing

    2016-01-01

    The clinical need for effective bone regeneration therapy remains in huge demands. However, the current "gold standard" treatments of autologous and allogeneic bone grafts may result in various complications. Furthermore, safety considerations of biomaterials and cell-based treatment require further clarification. Therefore, developing new therapies with stronger osteogenic potential and a lower incidence of complications is worthwhile. Recently, exosomes, small vesicles of endocytic origin, have attracted attention in bone regeneration field. The vesicles travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating targeted cells differentiation, commitment, function, and proliferation. Much evidence has demonstrated the important roles of exosomes in osteogenesis both in vitro and in vivo. In this review, we summarize the properties, origins and biogenesis of exosomes, and the recent reports using exosomes to regulate osteogenesis and promote bone regeneration. PMID:27213355

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

    PubMed Central

    Sarkar, Swapan Kumar

    2015-01-01

    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. PMID:25995658

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

    PubMed

    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. PMID:25995658

  13. Targeting the hypoxic response in bone tissue engineering: A balance between supply and consumption to improve bone regeneration.

    PubMed

    Stiers, Pieter-Jan; van Gastel, Nick; Carmeliet, Geert

    2016-09-01

    Bone tissue engineering is a promising therapeutic alternative for bone grafting of large skeletal defects. It generally comprises an ex vivo engineered combination of a carrier structure, stem/progenitor cells and growth factors. However, the success of these regenerative implants largely depends on how well implanted cells will adapt to the hostile and hypoxic host environment they encounter after implantation. In this review, we will discuss how hypoxia signalling may be used to improve bone regeneration in a tissue-engineered construct. First, hypoxia signalling induces angiogenesis which increases the survival of the implanted cells as well as stimulates bone formation. Second, hypoxia signalling has also angiogenesis-independent effects on mesenchymal cells in vitro, offering exciting new possibilities to improve tissue-engineered bone regeneration in vivo. In addition, studies in other fields have shown that benefits of modulating hypoxia signalling include enhanced cell survival, proliferation and differentiation, culminating in a more potent regenerative implant. Finally, the stimulation of endochondral bone formation as a physiological pathway to circumvent the harmful effects of hypoxia will be briefly touched upon. Thus, angiogenic dependent and independent processes may counteract the deleterious hypoxic effects and we will discuss several therapeutic strategies that may be combined to withstand the hypoxia upon implantation and improve bone regeneration. PMID:26768117

  14. Silica-based mesoporous nanobiomaterials as promoter of bone regeneration process.

    PubMed

    Shadjou, Nasrin; Hasanzadeh, Mohammad

    2015-11-01

    Silica-based mesostructured nanomaterials have emerged as a full family of biomaterials with tremendous potential to address the requirements for the bone regeneration process. This review focuses on more recent advances in bone regeneration process based on silica-based mesoporous biomaterials during 2012 to January 2015. In this review, we describe application of silica-based mesoporous mesostructured nanomaterials (possessing pore sizes in the range 2-50 nm) for the bone regeneration process. We summarize the preparation methods, the effect of mesopore templates and composition on the mesopore-structure characteristics, and different forms of these materials, including particles, fibers, spheres, scaffolds, and composites. The effect of structural and textural properties of mesoporous materials on the development of new biomaterials for treatment of different bone pathologies such as infection, osteoporosis, cancer, and so forth is discussed. In addition, silica-based mesoporous bioactive glass, as a potential drug/growth factor carrier, is reviewed, which includes the composition-structure-drug delivery relationship and the functional effect on the antibacteria and tissue-stimulation properties. Also, application of different mesoporous materials on construction of 3D macroporous scaffolds for bone tissue engineering was disused. Finally, this review discusses the possibility of covalently grafting different osteoinductive agents to the silica-based mesoporous scaffold surface that act as attracting signals for bone cells to promote the bone regeneration process. PMID:26011776

  15. Osteogenic Potential of Multipotent Adult Progenitor Cells for Calvaria Bone Regeneration

    PubMed Central

    Lee, Dong Joon; Park, Yonsil; Hu, Wei-Shou; Ko, Ching-Chang

    2016-01-01

    Osteogenic cells derived from rat multipotent adult progenitor cells (rMAPCs) were investigated for their potential use in bone regeneration. rMAPCs are adult stem cells derived from bone marrow that have a high proliferation capacity and the differentiation potential to multiple lineages. They may also offer immunomodulatory properties favorable for applications for regenerative medicine. rMAPCs were cultivated as single cells or as 3D aggregates in osteogenic media for up to 38 days, and their differentiation to bone lineage was then assessed by immunostaining of osteocalcin and collagen type I and by mineralization assays. The capability of rMAPCs in facilitating bone regeneration was evaluated in vivo by the direct implantation of multipotent adult progenitor cell (MAPC) aggregates in rat calvarial defects. Bone regeneration was examined radiographically, histologically, and histomorphometrically. Results showed that rMAPCs successfully differentiated into osteogenic lineage by demonstrating mineralized extracellular matrix formation in vitro and induced new bone formation by the effect of rMAPC aggregates in vivo. These outcomes confirm that rMAPCs have a good osteogenic potential and provide insights into rMAPCs as a novel adult stem cell source for bone regeneration. PMID:27239552

  16. The axolotl limb: a model for bone development, regeneration and fracture healing.

    PubMed

    Hutchison, Cara; Pilote, Mireille; Roy, Stéphane

    2007-01-01

    Among vertebrates, urodele amphibians (e.g., axolotls) have the unique ability to perfectly regenerate complex body parts after amputation. The limb has been the most widely studied due to the presence of three defined axes and its ease of manipulation. Hence, the limb has been chosen as a model to study the process of skeletogenesis during axolotl development, regeneration and to analyze this animal's ability to heal bone fractures. Extensive studies have allowed researchers to gain some knowledge of the mechanisms controlling growth and pattern formation in regenerating and developing limbs, offering an insight into how vertebrates are able to regenerate tissues. In this study, we report the cloning and characterization of two axolotl genes; Cbfa-1, a transcription factor that controls the remodeling of cartilage into bone and PTHrP, known for its involvement in the differentiation and maturation of chondrocytes. Whole-mount in situ hybridization and immunohistochemistry results show that Cbfa-1, PTHrP and type II collagen are expressed during limb development and regeneration. These genes are expressed during specific stages of limb development and regeneration which are consistent with the appearance of skeletal elements. The expression pattern for Cbfa-1 in late limb development was similar to the expression pattern found in the late stages of limb regeneration (i.e. re-development phase) and it did not overlap with the expression of type II collagen. It has been reported that the molecular mechanisms involved in the re-development phase of limb regeneration are a recapitulation of those used in developing limbs; therefore the detection of Cbfa-1 expression during regeneration supports this assertion. Conversely, PTHrP expression pattern was different during limb development and regeneration, by its intensity and by the localization of the signal. Finally, despite its unsurpassed abilities to regenerate, we tested whether the axolotl was able to regenerate non

  17. Bone regeneration associated with nontherapeutic and therapeutic surface coatings for dental implants in osteoporosis.

    PubMed

    Alghamdi, Hamdan S; Jansen, John A

    2013-06-01

    Oral implantology is considered as the treatment of choice for replacing missing teeth in elderly people. However, implant complications may occur in patients with osteoporosis. The pathogenesis underlying osteoporosis is due to an alteration in bone cell response to hormonal, nutritional, and aging factors. For such challenging situations, improved bone regeneration has been shown around dental implants for certain surface modifications. These modifications include coatings of titanium implants with calcium phosphate (CaP) ceramics. Surface coating developments also allow for the addition of organic biomolecules, like growth factors, into the inorganic coatings that increase the bone formation process at the bone-implant interface. The application of therapeutic-based coatings is becoming a rapidly growing research field of interest. CaP-coated implants have the ability to incorporate anti-osteoporotic drugs, which then can be locally released over time from an implant surface in a controlled manner. Thus, it can be anticipated that nontherapeutic and/or therapeutic coated implants can significantly increase low bone density as well as improve impaired bone regeneration in osteoporosis. This review aims to provide a thorough understanding of the underlying mechanisms for impaired bone regeneration around dental implants in osteoporosis. Secondly, the review will focus on biological interactions and beneficial role of the surface-coated (i.e., nontherapeutics and therapeutics) bone implants in osteoporotic bone tissue. PMID:23088597

  18. BMP2 Genetically Engineered MSCs and EPCs Promote Vascularized Bone Regeneration in Rat Critical-Sized Calvarial Bone Defects

    PubMed Central

    He, Xiaoning; Dziak, Rosemary; Yuan, Xue; Mao, Keya; Genco, Robert; Swihart, Mark; Sarkar, Debanjan; Li, Chunyi; Wang, Changdong; Lu, Li; Andreadis, Stelios; Yang, Shuying

    2013-01-01

    Current clinical therapies for critical-sized bone defects (CSBDs) remain far from ideal. Previous studies have demonstrated that engineering bone tissue using mesenchymal stem cells (MSCs) is feasible. However, this approach is not effective for CSBDs due to inadequate vascularization. In our previous study, we have developed an injectable and porous nano calcium sulfate/alginate (nCS/A) scaffold and demonstrated that nCS/A composition is biocompatible and has proper biodegradability for bone regeneration. Here, we hypothesized that the combination of an injectable and porous nCS/A with bone morphogenetic protein 2 (BMP2) gene-modified MSCs and endothelial progenitor cells (EPCs) could significantly enhance vascularized bone regeneration. Our results demonstrated that delivery of MSCs and EPCs with the injectable nCS/A scaffold did not affect cell viability. Moreover, co-culture of BMP2 gene-modified MSCs and EPCs dramatically increased osteoblast differentiation of MSCs and endothelial differentiation of EPCs in vitro. We further tested the multifunctional bone reconstruction system consisting of an injectable and porous nCS/A scaffold (mimicking the nano-calcium matrix of bone) and BMP2 genetically-engineered MSCs and EPCs in a rat critical-sized (8 mm) caviarial bone defect model. Our in vivo results showed that, compared to the groups of nCS/A, nCS/A+MSCs, nCS/A+MSCs+EPCs and nCS/A+BMP2 gene-modified MSCs, the combination of BMP2 gene -modified MSCs and EPCs in nCS/A dramatically increased the new bone and vascular formation. These results demonstrated that EPCs increase new vascular growth, and that BMP2 gene modification for MSCs and EPCs dramatically promotes bone regeneration. This system could ultimately enable clinicians to better reconstruct the craniofacial bone and avoid donor site morbidity for CSBDs. PMID:23565253

  19. Physiological bases of bone regeneration II. The remodeling process.

    PubMed

    Fernández-Tresguerres-Hernández-Gil, Isabel; Alobera-Gracia, Miguel Angel; del-Canto-Pingarrón, Mariano; Blanco-Jerez, Luis

    2006-03-01

    Bone remodeling is the restructuring process of existing bone, which is in constant resorption and formation. Under normal conditions, this balanced process allows the renewal of 5-10% of bone volume per year. At the microscopic level, bone remodeling is produced in basic multicellular units, where osteoclasts resorb a certain quantity of bone and osteoblasts form the osteoid matrix and mineralize it to fill the previously created cavity. These units contain osteoclasts, macrophages, preosteoblasts and osteoblasts, and are controlled by a series of factors, both general and local, allowing normal bone function and maintaining the bone mass. When this process becomes unbalanced then bone pathology appears, either in excess (osteopetrosis) or deficit (osteoporosis). The purpose of this study is to undertake a revision of current knowledge on the physiological and biological mechanisms of the bone remodeling process; highlighting the role played by the regulating factors, in particular that of the growth factors. PMID:16505794

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

    PubMed

    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. PMID:26758898

  1. Biodegradable composite scaffolds of bioactive glass/chitosan/carboxymethyl cellulose for hemostatic and bone regeneration.

    PubMed

    Chen, Chen; Li, Hong; Pan, Jianfeng; Yan, Zuoqin; Yao, Zhenjun; Fan, Wenshuai; Guo, Changan

    2015-02-01

    Hemostasis in orthopedic osteotomy or bone cutting requires different methods and materials. The bleeding of bone marrow can be mostly stopped by bone wax. However, the wax cannot be absorbed, which leads to artificial prosthesis loosening, foreign matter reaction, and infection. Here, a bioactive glass/chitosan/carboxymethyl cellulose (BG/CS/CMC) composite scaffold was designed to replace traditional wax. WST-1 assay indicated the BG/CS/CMC composite resulted in excellent biocompatibility with no cytotoxicity. In vivo osteogenesis assessment revealed that the BG/CS/CMC composite played a dominant role in bone regeneration and hemostasis. The BG/CS/CMC composite had the same hemostasis effect as bone wax; in addition its biodegradation also led to the functional reconstruction of bone defects. Thus, BG/CS/CMC scaffolds can serve as a potential material for bone repair and hemostasis in critical-sized bone defects. PMID:25326173

  2. Effect of simvastatin versus low level laser therapy (LLLT) on bone regeneration in rabbit's tibia

    NASA Astrophysics Data System (ADS)

    Gheith, Mostafa E.; Khairy, Maggie A.

    2014-02-01

    Simvastatin is a cholesterol lowering drug which proved effective on promoting bone healing. Recently low level laser therapy (LLLT) proved its effect as a biostimulator promoting bone regeneration. This study aims to compare the effect of both Simvastatin versus low level laser on bone healing in surgically created bone defects in rabbit's tibia. Material and methods: The study included 12 New Zealand white rabbits. Three successive 3mm defects were created in rabbits tibia first defect was left as control, second defect was filled with Simvastatin while the third defect was acted on with Low Level Laser (optical fiber 320micrometer). Rabbits were sacrificed after 48 hours, 1 week and 2 weeks intervals. Histopathology was conducted on the three defects Results: The histopathologic studies showed that the bony defects treated with the Low Level Laser showed superior healing patterns and bone regeneration than those treated with Simvastatin. While the control defect showed the least healing pattern.

  3. Sustained, localized salicylic acid delivery enhances diabetic bone regeneration via prolonged mitigation of inflammation.

    PubMed

    Yu, Weiling; Bien-Aime, Stephan; Mattos, Marcelo; Alsadun, Sarah; Wada, Keisuke; Rogado, Sarah; Fiorellini, Joseph; Graves, Dana; Uhrich, Kathryn

    2016-10-01

    Diabetes is a metabolic disorder caused by insulin resistance and/or deficiency and impairs bone quality and bone healing due to altered gene expression, reduced vascularization, and prolonged inflammation. No effective treatments for diabetic bone healing are currently available, and most existing treatments do not directly address the diabetic complications that impair bone healing. We recently demonstrated that sustained and localized delivery of salicylic acid (SA) via an SA-based polymer provides a low-cost approach to enhance diabetic bone regeneration. Herein, we report mechanistic studies that delve into the biological action and local pharmacokinetics of SA-releasing polymers shown to enhance diabetic bone regeneration. The results suggest that low SA concentrations were locally maintained at the bone defect site for more than 1 month. As a result of the sustained SA release, a significantly reduced inflammation was observed in diabetic animals, which in turn, yielded reduced osteoclast density and activity, as well as increased osteoblastogenesis. Based upon these results, localized and sustained SA delivery from the SA-based polymer effectively improved bone regeneration in diabetic animals by affecting both osteoclasts and osteoblasts, thereby providing a positive basis for clinical treatments. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2595-2603, 2016. PMID:27194511

  4. Bone Regeneration Using Dentin Matrix Depends on the Degree of Demineralization and Particle Size

    PubMed Central

    Koga, Takamitsu; Minamizato, Tokutaro; Kawai, Yosuke; Miura, Kei-ichiro; I, Takashi; Nakatani, Yuya; Sumita, Yoshinori; Asahina, Izumi

    2016-01-01

    Objectives This study aimed to examine the influence of particle size and extent of demineralization of dentin matrix on bone regeneration. Materials and Methods Extracted human teeth were pulverized and divided into 3 groups according to particle size; 200, 500, and 1000 μm. Each group was divided into 3 groups depending on the extent of demineralization; undemineralized dentin (UDD), partially demineralized dentin matrix (PDDM), and completely demineralized dentin matrix (CDDM). The dentin sample was implanted into rat calvarial bone defects. After 4 and 8 weeks, the bone regeneration was evaluated with micro-CT images, histomorphometric and immunohistochemical analyses. Osteoblasts were cultured on UDD and DDM to evaluate the cell attachment using electron microscope. Results Micro-CT images and histological observation revealed that CDDM had largely resorbed but UDD had not, and both of them induced little bone formation, whereas all particle sizes of PDDM induced more new bone, especially the 1000 μm. Electron microscopic observation showed osteoblasts attached to DDM but not to UDD. Conclusions PDDM with larger particle size induced prominent bone regeneration, probably because PDDM possessed a suitable surface for cell attachment. There might be an exquisite balance between its resorption and bone formation on it. PDDM could be considered as a potential bone substitute. PMID:26795024

  5. Bone regeneration assessment by optical coherence tomography and MicroCT synchrotron radiation

    NASA Astrophysics Data System (ADS)

    Negrutiu, Meda L.; Sinescu, Cosmin; Canjau, Silvana; Manescu, Adrian; Topalá, Florin I.; Hoinoiu, Bogdan; Romînu, Mihai; Márcáuteanu, Corina; Duma, Virgil; Bradu, Adrian; Podoleanu, Adrian G.

    2013-06-01

    Bone grafting is a commonly performed surgical procedure to augment bone regeneration in a variety of orthopaedic and maxillofacial procedures, with autologous bone being considered as the "gold standard" bone-grafting material, as it combines all properties required in a bone-graft material: osteoinduction (bone morphogenetic proteins - BMPs - and other growth factors), osteogenesis (osteoprogenitor cells) and osteoconduction (scaffold). The problematic elements of bone regenerative materials are represented by their quality control methods, the adjustment of the initial bone regenerative material, the monitoring (noninvasive, if possible) during their osteoconduction and osteointegration period and biomedical evaluation of the new regenerated bone. One of the research directions was the interface investigation of the regenerative bone materials and their behavior at different time periods on the normal femoral rat bone. 12 rat femurs were used for this investigation. In each ones a 1 mm diameter hole were drilled and a bone grafting material was inserted in the artificial defect. The femurs were removed after one, three and six months. The defects repaired by bone grafting material were evaluated by optical coherence tomography working in Time Domain Mode at 1300 nm. Three dimensional reconstructions of the interfaces were generated. The validations of the results were evaluated by microCT. Synchrotron Radiation allows achieving high spatial resolution images to be generated with high signal-to-noise ratio. In addition, Synchrotron Radiation allows acquisition of volumes at different energies and volume subtraction to enhance contrast. Evaluation of the bone grafting material/bone interface with noninvasive methods such as optical coherence tomography could act as a valuable procedure that can be use in the future in the usual clinical techniques. The results were confirmed by microCT. Optical coherence tomography can be performed in vivo and can provide a

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

    PubMed Central

    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

  7. Maintenance of regenerated bone beneath pontics: preliminary clinical report of 43 sites.

    PubMed

    Fugazzotto, P A; De Paoli, S

    1999-01-01

    Ridge augmentation was achieved through the use of guided bone regeneration procedures in pontic areas of 43 planned fixed prostheses. Measurements taken through templates, which fit over the final fixed prostheses, at the time of prosthetic placement and a mean of 123 weeks after prosthesis placement demonstrated a change of less than 0.1 mm in buccopalatal dimensions of the regenerated hard tissues. PMID:10379113

  8. Circulating Progenitor Cells in Regenerative Technologies: A Realistic Strategy in Bone Regeneration?

    PubMed Central

    Chang, Jessica B.; Lee, Justine C.

    2016-01-01

    Strategies in skeletal regeneration research have been primarily focused on optimization of three components: cellular progenitors, biomaterials, and growth factors. With the increased understanding that circulating progenitor cells exist in peripheral blood, the question arises whether such cell types would allow for adequate osteogenesis and mineralization. In this review, we discuss the current literature on circulating progenitor cells in in vitro and in vivo studies on bone regeneration. PMID:27331195

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

    PubMed Central

    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

  10. Efficacy of Mucograft vs Conventional Resorbable Collagen Membranes in Guided Bone Regeneration Around Standardized Calvarial Defects in Rats: An In Vivo Microcomputed Tomographic Analysis.

    PubMed

    Babay, Nadir; Ramalingam, Sundar; Basudan, Amani; Nooh, Nasser; AlKindi, Mohammed; Al-Rasheed, Abdulaziz; Al-Hezaimi, Khalid

    2016-01-01

    The aim of this in vivo microcomputed tomographic (μCT) study was to compare the efficacy of Mucograft (MG) vs resorbable collagen membranes (RCMs) in facilitating guided bone regeneration (GBR) around standardized calvarial defects in rats. Forty female Wistar albino rats with a mean age and weight of 6 to 9 weeks and 250 to 300 g, respectively, were used. With the rats under general anesthesia, the skin over the calvaria was exposed using a full-thickness flap. A standardized calvarial defect with a 4.6-mm diameter was created in the left parietal bone. For treatment, the rats were randomly divided into four groups (n = 10 per group): (1) defects covered with MG (MG group); (2) defects covered with an RCM (RCM group); (3) defects filled with xenograft bone particles and covered by MG (MG + bone group); and (4) defects filled with xenograft bone particles and covered by an RCM (RCM + bone group). Primary closure was achieved using interrupted resorbable sutures. The animals underwent high-resolution, three-dimensional μCT scans at baseline and at 2, 4, 6, and 8 weeks after the surgical procedures. Data regarding volume and bone mineral density (BMD) of newly formed bone (NFB) and bone particles revealed an increase in the volume of NFB in all the groups from baseline to 8 weeks. The MG group had the lowest volume of NFB (mean ± standard deviation [SD], 1.32 ± 0.22 mm(3)). No significant differences in mean ± SD values for volume of NFB were observed between the RCM (3.50 ± 0.24 mm(3)) and MG + bone (3.87 ± 0.36 mm(3)) groups, but their values were significantly lower than that of the RCM + bone group (2.95 ± 0.15 mm(3), F = 131.91, dfN = 2, dfD = 27, P < .001). Significant differences in BMD of NFB between the groups (F = 332.46, dfN = 3, dfD = 36, P < .001) and during different data collection periods (F = 97.04, dfN = 3, dfD = 36, P < .01) were observed, with the RCM group having the highest mean ± SD BMD of NFB (0.42 ± 0.05 g/mm(3)). Significant

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

    PubMed

    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 colonyforming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls. PMID:124758

  12. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    PubMed Central

    Anbari, Fatemeh; Khalili, Mohammad Ali; Bahrami, Ahmad Reza; Khoradmehr, Arezoo; Sadeghian, Fatemeh; Fesahat, Farzaneh; Nabi, Ali

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significantly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells. PMID:25206912

  13. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopic analysis of regenerated bone

    NASA Astrophysics Data System (ADS)

    Benetti, Carolina; Kazarain, Sergei G.; Alves, Marco A. V.; Blay, Alberto; Correa, Luciana; Zezell, Denise M.

    2014-03-01

    The cutting of bone is routinely required in medical procedures, especially in dental applications. In such cases, bone regeneration and new bone quality can determine the success of the treatment. This study investigated the main spectral differences of undamaged and healed bone using the ATR-FTIR spectroscopy technique. Three rabbits were submitted to a surgical procedure; a small piece of bone (3x3 mm2) was removed from both sides of their jaws using a high speed drill. After 15 days, the rabbits were euthanized and the jaws were removed. A bone slice was cut from each side of the jaw containing regions of undamaged and newly formed bone, resulting in six samples which were polished for spectroscopic comparison. The samples were analyzed by FTIR spectroscopy using a diamond ATR accessory. Spectral characteristics were compared and particular attention was paid to the proportion of phosphate to amide I bands and the width of the phosphate band. The results show that the ratio of phosphate to amide I is smaller in new bone tissue than in the undamaged bone, indicating a higher organic content in the newly formed bone. The analysis of the width of the phosphate band suggests a crystallinity difference between both tissues, since the width was higher in the new bone than in the natural bone. These results suggest that the differences observed in bone aging processes by FTIR spectroscopic can be applied to the study of healing processes.

  14. Small Players Ruling the Hard Game: siRNA in Bone Regeneration.

    PubMed

    Ghadakzadeh, Saber; Mekhail, Mina; Aoude, Ahmed; Hamdy, Reggie; Tabrizian, Maryam

    2016-03-01

    Silencing gene expression through a sequence-specific manner can be achieved by small interfering RNAs (siRNAs). The discovery of this process has opened the doors to the development of siRNA therapeutics. Although several preclinical and clinical studies have shown great promise in the treatment of neurological disorders, cancers, dominant disorders, and viral infections with siRNA, siRNA therapy is still gaining ground in musculoskeletal tissue repair and bone regeneration. Here we present a comprehensive review of the literature to summarize different siRNA delivery strategies utilized to enhance bone regeneration. With advancement in understanding the targetable biological pathways involved in bone regeneration and also the rapid progress in siRNA technologies, application of siRNA for bone regeneration has great therapeutic potential. High rates of musculoskeletal injuries and diseases, and their inevitable consequences, impose a huge financial burden on individuals and healthcare systems worldwide. © 2016 American Society for Bone and Mineral Research. PMID:26890411

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

    NASA Astrophysics Data System (ADS)

    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.

  16. Bone regeneration: molecular and cellular interactions with calcium phosphate ceramics

    PubMed Central

    Barrère, Florence; van Blitterswijk, Clemens A; de Groot, Klaas

    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 interactions of their surface with the extracellular fluids and cells, ie, ionic exchanges, superficial molecular rearrangement and cellular activity. PMID:17717972

  17. Focused low-intensity pulsed ultrasound enhances bone regeneration in rat calvarial bone defect through enhancement of cell proliferation.

    PubMed

    Jung, Yu Jin; Kim, Ran; Ham, Hyun-Joo; Park, Sang In; Lee, Min Young; Kim, Jongmin; Hwang, Jihwan; Park, Moon-Seo; Yoo, Seung-Schik; Maeng, Lee-So; Chang, Woochul; Chung, Yong-An

    2015-04-01

    A number of studies have reported the therapeutic potential of low-intensity pulsed ultrasound (LIPUS) for induction of bone repair. This study investigated whether bone regeneration might be enhanced by application of focused LIPUS to selectively stimulate fractured calvarial bone. To accomplish this, bone defects were surgically created in the middle of the skull of rats that were subsequently exposed to focused LIPUS. Bone regeneration was assessed by repeated computed tomography imaging after the operation, as well as histologic analysis with calcein, hematoxylin and eosin and proliferating cell nuclear antigen assay. At 6 wk after surgery, bone formation in the focused LIPUS-treated group improved significantly relative to the control. Interestingly, new bone tissue sprouted from focused LIPUS target points. Histologic analysis after exposure to focused LIPUS revealed that proliferating cells were significantly increased relative to the control. Taken together, these results suggest that focused LIPUS can improve re-ossification through enhancement of cell proliferation in calvarial defect sites. PMID:25701528

  18. Ultrastructure of regenerated bone mineral surrounding hydroxyapatite-alginate composite and sintered hydroxyapatite.

    PubMed

    Rossi, Andre L; Barreto, Isabela C; Maciel, William Q; Rosa, Fabiana P; Rocha-Leão, Maria H; Werckmann, Jacques; Rossi, Alexandre M; Borojevic, Radovan; Farina, Marcos

    2012-01-01

    We report the ultrastructure of regenerated bone surrounding two types of biomaterials: hydroxyapatite-alginate composite and sintered hydroxyapatite. Critical defects in the calvaria of Wistar rats were filled with micrometer-sized spherical biomaterials and analyzed after 90 and 120 days of implantation by high-resolution transmission electron microscopy and Fourier transform infrared attenuated total reflectance microscopy, respectively. Infrared spectroscopy showed that hydroxyapatite of both biomaterials became more disordered after implantation in the rat calvaria, indicating that the biological environment induced modifications in biomaterials structure. We observed that the regenerated bone surrounding both biomaterials had a lamellar structure with type I collagen fibers alternating in adjacent lamella with angles of approximately 90°. In each lamella, plate-like apatite crystals were aligned in the c-axis direction, although a rotation around the c-axis could be present. Bone plate-like crystal dimensions were similar in regenerated bone around biomaterials and pre-existing bone in the rat calvaria. No epitaxial growth was observed around any of the biomaterials. A distinct mineralized layer was observed between new bone and hydroxyapatite-alginate biomaterial. This region presented a particular ultrastructure with crystallites smaller than those of the bulk of the biomaterial, and was possibly formed during the synthesis of alginate-containing composite or in the biological environment after implantation. Round nanoparticles were observed in regions of newly formed bone. The findings of this work contribute to a better understanding of the role of hydroxyapatite based biomaterials in bone regeneration processes at the nanoscale. PMID:22057083

  19. Cellular therapy in bone-tendon interface regeneration

    PubMed Central

    Rothrauff, Benjamin B; Tuan, Rocky S

    2014-01-01

    The intrasynovial bone-tendon interface is a gradual transition from soft tissue to bone, with two intervening zones of uncalcified and calcified fibrocartilage. Following injury, the native anatomy is not restored, resulting in inferior mechanical properties and an increased risk of re-injury. Recent in vivo studies provide evidence of improved healing when surgical repair of the bone-tendon interface is augmented with cells capable of undergoing chondrogenesis. In particular, cellular therapy in bone-tendon healing can promote fibrocartilage formation and associated improvements in mechanical properties. Despite these promising results in animal models, cellular therapy in human patients remains largely unexplored. This review highlights the development and structure-function relationship of normal bone-tendon insertions. The natural healing response to injury is discussed, with subsequent review of recent research on cellular approaches for improved healing. Finally, opportunities for translating in vivo findings into clinical practice are identified. PMID:24326955

  20. Sulfated hyaluronan improves bone regeneration of diabetic rats by binding sclerostin and enhancing osteoblast function.

    PubMed

    Picke, Ann-Kristin; Salbach-Hirsch, Juliane; Hintze, Vera; Rother, Sandra; Rauner, Martina; Kascholke, Christian; Möller, Stephanie; Bernhardt, Ricardo; Rammelt, Stefan; Pisabarro, M Teresa; Ruiz-Gómez, Gloria; Schnabelrauch, Matthias; Schulz-Siegmund, Michaela; Hacker, Michael C; Scharnweber, Dieter; Hofbauer, Christine; Hofbauer, Lorenz C

    2016-07-01

    Bone fractures in patients with diabetes mellitus heal poorly and require innovative therapies to support bone regeneration. Here, we assessed whether sulfated hyaluronan included in collagen-based scaffold coatings can improve fracture healing in diabetic rats. Macroporous thermopolymerized lactide-based scaffolds were coated with collagen including non-sulfated or sulfated hyaluronan (HA/sHA3) and inserted into 3 mm femoral defects of non-diabetic and diabetic ZDF rats. After 12 weeks, scaffolds coated with collagen/HA or collagen/sHA3 accelerated bone defect regeneration in diabetic, but not in non-diabetic rats as compared to their non-coated controls. At the tissue level, collagen/sHA3 promoted bone mineralization and decreased the amount of non-mineralized bone matrix. Moreover, collagen/sHA3-coated scaffolds from diabetic rats bound more sclerostin in vivo than the respective controls. Binding assays confirmed a high binding affinity of sHA3 to sclerostin. In vitro, sHA3 induced BMP-2 and lowered the RANKL/OPG expression ratio, regardless of the glucose concentration in osteoblastic cells. Both sHA3 and high glucose concentrations decreased the differentiation of osteoclastic cells. In summary, scaffolds coated with collagen/sHA3 represent a potentially suitable biomaterial to improve bone defect regeneration in diabetic conditions. The underlying mechanism involves improved osteoblast function and binding sclerostin, a potent inhibitor of Wnt signaling and osteoblast function. PMID:27131598

  1. Pilot in vivo animal study of bone regeneration by fractional Er: YAG-laser

    NASA Astrophysics Data System (ADS)

    Altshuler, Gregory B.; Belikov, Andrey V.; Shatilova, Ksenia V.; Yaremenko, Andrey I.; Zernitskiy, Alexander Y.; Zernitckaia, Ekaterina A.

    2016-04-01

    The histological structure of the rabbit parietal bone during its regeneration after fractional Er: YAG-laser (λ=2.94μm) treatment was investigated by hematoxylin and eosin (H&E) stain. In 48 days after fractional laser treatment, bone samples contained micro-cavities and fragments of necrotic tissue with empty cellular lacuna and coagulated protein of bone matrix. In this case, necrotic lesions appeared around the periphery of micro-cavities created by laser radiation. Fragmentation of detrital mass and partial substitution of micro-cavities with fatty bone marrow were observed in bone samples in 100 days after fractional laser treatment, in contrast to the earlier period. Partial filling of micro-cavities edges by fibrous tissue with presence of osteoblasts on their inner surface was observed in 100 days also, that indicates regenerative processes in the bone.

  2. Mesoporous bioactive glasses: structure characteristics, drug/growth factor delivery and bone regeneration application

    PubMed Central

    Wu, Chengtie; Chang, Jiang

    2012-01-01

    The impact of bone diseases and trauma in the whole world has increased significantly in the past decades. Bioactive glasses are regarded as an important bone regeneration material owing to their generally excellent osteoconductivity and osteostimulativity. A new class of bioactive glass, referred to as mesoporous bioglass (MBG), was developed 7 years ago, which possess a highly ordered mesoporous channel structure and a highly specific surface area. The study of MBG for drug/growth factor delivery and bone tissue engineering has grown significantly in the past several years. In this article, we review the recent advances of MBG materials, including the preparation of different forms of MBG, composition–structure relationship, efficient drug/growth factor delivery and bone tissue engineering application. By summarizing our recent research, the interaction of MBG scaffolds with bone-forming cells, the effect of drug/growth factor delivery on proliferation and differentiation of tissue cells and the in vivo osteogenesis of MBG scaffolds are highlighted. The advantages and limitations of MBG for drug delivery and bone tissue engineering have been compared with microsize bioactive glasses and nanosize bioactive glasses. The future perspective of MBG is discussed for bone regeneration application by combining drug delivery with bone tissue engineering and investigating the in vivo osteogenesis mechanism in large animal models. PMID:23741607

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

    SciTech Connect

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

    2013-02-05

    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{sub 2} 70 mol%, CaO 26 mol % and P{sub 2}O{sub 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.

  4. Preparation and Characterization of Chemically Synthesized Hybrid Composites for Bone Tissue Regeneration

    NASA Astrophysics Data System (ADS)

    Raucci, M. G.; Guarino, V.; Ambrosio, L.

    2008-08-01

    The aim of this study concerns the development of bioresorbable composite materials for bone repair and regeneration. Hydroxyapatite loaded composites were synthesized by a colloidal non-aqueous chemical precipitation technique at room temperature. This study describes the synthesis and characterization of HA/PCL composite material, in order to verify the interaction between the ceramic and the polymer phases by a morphological investigation.

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

    PubMed

    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. PMID:27597965

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

    PubMed Central

    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

  7. Controlling Stem Cell-mediated Bone Regeneration through Tailored Mechanical Properties of Collagen Scaffolds

    PubMed Central

    Sun, Hongli; Zhu, Feng; Hu, Qingang; Krebsbach, Paul H.

    2014-01-01

    Mechanical properties of the extracellular matrix (ECM) play an essential role in cell fate determination. To study the role of mechanical properties of ECM in stem cell-mediated bone regeneration, we used a 3D in vivo ossicle model that recapitulates endochondral bone formation. Three-dimensional gelatin scaffolds with distinct stiffness were developed using 1-Ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) mediated zero-length crosslinking. The mechanical strength of the scaffolds was significantly increased by EDC treatment, while the microstructure of the scaffold was preserved. Cell behavior on the scaffolds with different mechanical properties was evaluated in vitro and in vivo. EDC-treated scaffolds promoted early chondrogenic differentiation, while it promoted both chondrogenic and osteogenic differentiation at later time points. Both micro-computed tomography and histologic data demonstrated that EDC-treatment significantly increased trabecular bone formation by transplanted cells transduced with AdBMP. Moreover, significantly increased chondrogenesis was observed in the EDC-treated scaffolds. Based on both in vitro and in vivo data, we conclude that the high mechanical strength of 3D scaffolds promoted stem cell mediated bone regeneration by promoting endochondral ossification. These data suggest a new method for harnessing stem cells for bone regeneration in vivo by tailoring the mechanical properties of 3D scaffolds. PMID:24211076

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

    PubMed

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

    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. PMID:26117793

  9. Bioactive polymeric-ceramic hybrid 3D scaffold for application in bone tissue regeneration.

    PubMed

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

    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. PMID:23910366

  10. Surface Functionalization of Titanium Alloy with miR-29b Nanocapsules To Enhance Bone Regeneration.

    PubMed

    Meng, Yubin; Li, Xue; Li, Zhaoyang; Liu, Chaoyong; Zhao, Jin; Wang, Jianwei; Liu, Yunde; Yuan, Xubo; Cui, Zhenduo; Yang, Xianjin

    2016-03-01

    Titanium and its alloys have been widely used over the past 3 decades as implants for healing bone defects. Nevertheless, the bioinert property of titanium alloy limits its clinical application and surface modification method is frequently performed to improve the biological and chemical properties. Recently, the delivery of microRNA with osteogenesis capability has been recognized as a promising tool to enhance bone regeneration of implants. Here, we developed a biodegradable coating to modify the titanium surface in order to enhance osteogenic bioactivity. The previous developed nanocapsules were used as the building blocks, and then a bioactive titanium coating was designed to entrap the miR-29b nanocapsules. This coating was not only favorable for cell adhesion and growth but also provided sufficient microRNA transfection efficacy and osteoinductive potential, resulting in a significant enhancement of bone regeneration on the surface of bioinert titanium alloy. PMID:26887789

  11. The scope and sequence of growth factor delivery for vascularized bone tissue regeneration.

    PubMed

    Bayer, E A; Gottardi, R; Fedorchak, M V; Little, S R

    2015-12-10

    Bone regeneration is a complex process, that in vivo, requires the highly coordinated presentation of biochemical cues to promote the various stages of angiogenesis and osteogenesis. Taking inspiration from the natural healing process, a wide variety of growth factors are currently being released within next generation tissue engineered scaffolds (in a variety of ways) in order to heal non-union fractures and bone defects. This review will focus on the delivery of multiple growth factors to the bone regeneration niche, specifically 1) dual growth factor delivery signaling and crosstalk, 2) the importance of growth factor timing and temporal separation, and 3) the engineering of delivery systems that allow for temporal control over presentation of soluble growth factors. Alternative methods for growth factor presentation, including the use of gene therapy and platelet-rich plasma scaffolds, are also discussed. PMID:26264834

  12. COMPOSITE POLYMER-COATED MINERAL SCAFFOLDS FOR BONE REGENERATION: FROM MATERIAL CHARACTERIZATION TO HUMAN STUDIES.

    PubMed

    Pertici, G; Carinci, F; Carusi, G; Epistatus, D; Villa, T; Crivelli, F; Rossi, F; Perale, G

    2015-01-01

    Bovine bone xenografts, made of hydroxyapatite (HA), were coated with poly(L-lactide-co-ε- caprolactone) (PLCL) and RGD-containing collagen fragments in order to increase mechanical properties, hydrophilicity, cell adhesion and osteogenicity. In vitro the scaffold microstructure was investigated with Environmental Scanning Electronic Microscopy (ESEM) analysis and micro tomography, while mechanical properties were investigated by means compression tests. In addition, cell attachment and growth within the three-dimensional scaffold inner structure were validated using human osteosarcoma cell lines (SAOS-2 and MG-63). Standard ISO in vivo biocompatibility studies were carried out on model animals, while bone regenerations in humans were performed to assess the efficacy of the product. All results from in vitro to in vivo investigations are here reported, underlining that this scaffold promotes bone regeneration and has good clinical outcome. PMID:26511194

  13. Stem Cells for Bone Regeneration: From Cell-Based Therapies to Decellularised Engineered Extracellular Matrices

    PubMed Central

    Fisher, James N.; Peretti, Giuseppe M.; Scotti, Celeste

    2016-01-01

    Currently, autologous bone grafting represents the clinical gold standard in orthopaedic surgery. In certain cases, however, alternative techniques are required. The clinical utility of stem and stromal cells has been demonstrated for the repair and regeneration of craniomaxillofacial and long bone defects although clinical adoption of bone tissue engineering protocols has been very limited. Initial tissue engineering studies focused on the bone marrow as a source of cells for bone regeneration, and while a number of promising results continue to emerge, limitations to this technique have prompted the exploration of alternative cell sources, including adipose and muscle tissue. In this review paper we discuss the advantages and disadvantages of cell sources with a focus on adipose tissue and the bone marrow. Additionally, we highlight the relatively recent paradigm of developmental engineering, which promotes the recapitulation of naturally occurring developmental processes to allow the implant to optimally respond to endogenous cues. Finally we examine efforts to apply lessons from studies into different cell sources and developmental approaches to stimulate bone growth by use of decellularised hypertrophic cartilage templates. PMID:26997959

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

    PubMed

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

    2012-04-01

    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 standardized 5.0mm circular defect was created in the left mandibular angle. New bone formation was demonstrated by post mortem micro-radiography, micro-computed tomography imaging and histological analysis. Four groups (control, PTMC, collagen, e-PTFE) were evaluated at three time intervals (2, 4 and 12 weeks). In the membrane groups the defects were covered; in the control group the defects were left uncovered. Data were analysed using a multiple regression model. In contrast to uncovered mandibular defects, substantial bone healing was observed in defects covered with a barrier membrane. In the latter case, the formation of bone was progressive over 12 weeks. No statistically significant differences between the amount of new bone formed under the PTMC membranes and the amount of bone formed under the collagen and e-PTFE membranes were observed. Therefore, it can be concluded that PTMC membranes are well suited for use in guided bone regeneration. PMID:22186161

  15. Experimental model for bone regeneration in oral and cranio-maxillo-facial surgery.

    PubMed

    Mardas, Nikos; Dereka, Xanthippi; Donos, Nikolaos; Dard, Michel

    2014-02-01

    Bone and tooth loss, as a result of trauma, anatomical or congenital reasons, cancer, and periodontal disease, is a common therapeutic problem in the fields of cranio-maxillo-facial surgery and periodontics. The proposed techniques for the treatment of various bone defects encountered include bone grafts, bone substitutes, guided tissue regeneration, and distraction osteogenesis as well as their combinations. In addition, dental implants have been successfully utilized for the restoration of full or partial edentulism. The introduction and development of new therapeutic approaches and devices demand the use of appropriate animal models that present bone anatomy and healing comparable to human. Among other animal models, the pig is extensively documented in several biomedical areas and has been largely used in maxillo-facial surgery and implants dentistry-related research. Anatomical and physiological similarities with human in size, physiology, and bone biology contribute to a successful involvement of this animal to understand and treat various osseous lesions. However, improvements and standardization are requested with respect to consistency and discrimination abilities. The aim of this review is to provide a critical appraisal of the literature related to swine models for the evaluation of cranio-maxillo-facial osseous defect healing, regeneration, and bone-implant interface. This review should assist researchers in the field to select the most appropriate model for each dedicated purpose and also contribute to stimulate an innovative thinking on the use of porcine models. PMID:23957784

  16. Stem Cells for Bone Regeneration: From Cell-Based Therapies to Decellularised Engineered Extracellular Matrices.

    PubMed

    Fisher, James N; Peretti, Giuseppe M; Scotti, Celeste

    2016-01-01

    Currently, autologous bone grafting represents the clinical gold standard in orthopaedic surgery. In certain cases, however, alternative techniques are required. The clinical utility of stem and stromal cells has been demonstrated for the repair and regeneration of craniomaxillofacial and long bone defects although clinical adoption of bone tissue engineering protocols has been very limited. Initial tissue engineering studies focused on the bone marrow as a source of cells for bone regeneration, and while a number of promising results continue to emerge, limitations to this technique have prompted the exploration of alternative cell sources, including adipose and muscle tissue. In this review paper we discuss the advantages and disadvantages of cell sources with a focus on adipose tissue and the bone marrow. Additionally, we highlight the relatively recent paradigm of developmental engineering, which promotes the recapitulation of naturally occurring developmental processes to allow the implant to optimally respond to endogenous cues. Finally we examine efforts to apply lessons from studies into different cell sources and developmental approaches to stimulate bone growth by use of decellularised hypertrophic cartilage templates. PMID:26997959

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

    PubMed Central

    Altaie, Ala; Owston, Heather; Jones, Elena

    2016-01-01

    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. PMID:26981170

  18. Bone regeneration following the in vivo bioreactor principle: is in vitro manipulation of exogenous elements still needed?

    PubMed

    Huang, Ru-Lin; Liu, Kai; Li, Qingfeng

    2016-07-01

    Large bone defect treatment is a key challenge due to the difficulty of functional and aesthetic reconstruction. A promising approach for bone regeneration is bone tissue engineering which is based on in vitro manipulation of seed cells, growth factors and bioscaffolds. However, many formidable conceptual and technical challenges impede clinical translation of experimental successes into clinical practices. An emerging strategy for bone regeneration is using the body as a bioreactor to cultivate the traditional triad and leveraging the body's own regenerative capacity to create new bone tissue. Based on the understanding of bone regeneration and in vivo bioreactor principle, we hypothesize that functional bone tissue may be eventually generated in vivo only using autologous costal periosteum, without participation of any exogenous elements. PMID:27357365

  19. Optimization of tyrosine-derived polycarbonate terpolymers for bone regeneration scaffolds

    NASA Astrophysics Data System (ADS)

    Resurreccion-Magno, Maria Hanshella C.

    Tyrosine-derived polycarbonates (TyrPC) are a versatile class of polymers highly suitable for bone tissue engineering. Among the tyrosine-derived polycarbonates, poly(DTE carbonate) has an FDA masterfile that documents its biocompatibility and non-toxicity and has shown potential utility in orthopedics due to its osteoconductive properties and strength. DTE stands for desaminotyrosyl-tyrosine ethyl ester and is the most commonly used tyrosine-derived monomer. However, in vitro degradation studies showed that poly(DTE carbonate) did not completely resorb even after four years of incubation in phosphate buffered saline. Thus for bone regeneration, which only requires a temporary implant until the bone heals, poly(DTE carbonate) would not be the best choice. The goal of the present research was to optimize a scaffold composition for bone regeneration that is based on desaminotyrosyl-tyrosine alkyl ester (DTR), desaminotyrosyl-tyrosine (DT) and poly(ethylene glycol) (PEG). Five areas of research were presented: (1) synthesis and characterization of a focused library of TyrPC terpolymers; (2) evaluation of the effects of how small changes on the composition affected the mechanism and kinetics of polymer degradation and erosion; (3) fabrication of bioactive three-dimensional porous scaffold constructs for bone regeneration; (4) assessment of osteogenic properties in vitro using pre-osteoblasts; and (5) evaluation of bone regeneration potential, with or without recombinant human bone morphogenetic protein-2 (rhBMP-2), in vivo using a critical sized defect (CSD) rabbit calvaria (cranium) model. Small changes in the composition, such as changing the R group of DTR from ethyl to methyl, varying the mole percentages of DT and PEG, and using a different PEG block length, affected the overall properties of these polymers. Porous scaffolds were prepared by a combination of solvent casting, porogen leaching and phase separation techniques. Calcium phosphate was coated on the

  20. Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo

    PubMed Central

    Dennis, S. Connor; Berkland, Cory J.; Bonewald, Lynda F.

    2015-01-01

    Autologous bone grafting (ABG) remains entrenched as the gold standard of treatment in bone regenerative surgery. Consequently, many marginally successful bone tissue engineering strategies have focused on mimicking portions of ABG's “ideal” osteoconductive, osteoinductive, and osteogenic composition resembling the late reparative stage extracellular matrix (ECM) in bone fracture repair, also known as the “hard” or “bony” callus. An alternative, less common approach that has emerged in the last decade harnesses endochondral (EC) ossification through developmental engineering principles, which acknowledges that the molecular and cellular mechanisms involved in developmental skeletogenesis, specifically EC ossification, are closely paralleled during native bone healing. EC ossification naturally occurs during the majority of bone fractures and, thus, can potentially be utilized to enhance bone regeneration for nearly any orthopedic indication, especially in avascular critical-sized defects where hypoxic conditions favor initial chondrogenesis instead of direct intramembranous ossification. The body's native EC ossification response, however, is not capable of regenerating critical-sized defects without intervention. We propose that an underexplored potential exists to regenerate bone through the native EC ossification response by utilizing strategies which mimic the initial inflammatory or fibrocartilaginous ECM (i.e., “pro-” or “soft” callus) observed in the early reparative stage of bone fracture repair. To date, the majority of strategies utilizing this approach rely on clinically burdensome in vitro cell expansion protocols. This review will focus on the confluence of two evolving areas, (1) native ECM biomaterials and (2) developmental engineering, which will attempt to overcome the technical, business, and regulatory challenges that persist in the area of bone regeneration. Significant attention will be given to native “raw” materials

  1. Bone Defect Regeneration by a Combination of a β-Tricalcium Phosphate Scaffold and Bone Marrow Stromal Cells in a Non-Human Primate Model

    PubMed Central

    Masaoka, Tomokazu; Yoshii, Toshitaka; Yuasa, Masato; Yamada, Tsuyoshi; Taniyama, Takashi; Torigoe, Ichiro; Shinomiya, Kenichi; Okawa, Atsushi; Morita, Sadao; Sotome, Shinichi

    2016-01-01

    Background: Reconstruction of large bone defects is a great challenge in orthopedic research. In the present study, we prepared composites of bone marrow-derived stromal cells (BMSCs) and β-tricalcium phosphate (β-TCP) with three novel aspects: proliferation of BMSCs with continuous dexamethasone treatment, cell loading under low pressure, and use of autologous plasma as the cell loading medium. The effectiveness of the resulting composite for large bone-defect reconstruction was tested in a non-human primate model, and the bone union capability of the regenerated bones was examined. Materials and Methods: Primary surgery: Bone defects (5 cm long) were created in the left femurs of nine cynomolgus monkeys with resection of the periosteum (five cases) or without resection (four cases), and porous β-TCP blocks were transplanted into the defects. Secondary surgery: Bone marrow aspirates harvested from seven of the nine monkeys were cultured with dexamethasone, and BMSCs were obtained. BMSCs were suspended in autologous plasma and introduced into a porous β-TCP block under low-pressure conditions. The BMSC/β-TCP composites were transplanted into bone defects created at the same sites as the primary surgery. Bone union evaluation: Five regenerated femurs were shortened by osteotomy surgery 8 to 15 months after transplantation of the β-TCP/BMSC composites, and bone union was evaluated radiographically. Results: After the primary surgery and treatment with β-TCP alone, one of the five periosteum-resected monkeys and two of the four periosteum-preserved monkeys exhibited successful bone reconstruction. In contrast, five of the seven cases treated with the β-TCP/MSC composite showed successful bone regeneration. In four of the five osteotomy cases, bone union was confirmed. Conclusion: We validated the effectiveness of a novel β-TCP/BMSC composite for large bone defect regeneration and confirmed the bone union capability of the regenerated bone. PMID:27073583

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    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.

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

    PubMed Central

    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

  4. IL-17-producing γδ T cells enhance bone regeneration

    PubMed Central

    Ono, Takehito; Okamoto, Kazuo; Nakashima, Tomoki; Nitta, Takeshi; Hori, Shohei; Iwakura, Yoichiro; Takayanagi, Hiroshi

    2016-01-01

    Immune responses are crucial not only for host defence against pathogens but also for tissue maintenance and repair after injury. Lymphocytes are involved in the healing process after tissue injury, including bone fracture and muscle damage. However, the specific immune cell subsets and mediators of healing are not entirely clear. Here we show that γδ T cells produce IL-17A, which promotes bone formation and facilitates bone fracture healing. Repair is impaired in IL-17A-deficient mice due to a defect in osteoblastic bone formation. IL-17A accelerates bone formation by stimulating the proliferation and osteoblastic differentiation of mesenchymal progenitor cells. This study identifies a novel role for IL-17-producing γδ T cells in skeletal tissue regeneration. PMID:26965320

  5. IL-17-producing γδ T cells enhance bone regeneration.

    PubMed

    Ono, Takehito; Okamoto, Kazuo; Nakashima, Tomoki; Nitta, Takeshi; Hori, Shohei; Iwakura, Yoichiro; Takayanagi, Hiroshi

    2016-01-01

    Immune responses are crucial not only for host defence against pathogens but also for tissue maintenance and repair after injury. Lymphocytes are involved in the healing process after tissue injury, including bone fracture and muscle damage. However, the specific immune cell subsets and mediators of healing are not entirely clear. Here we show that γδ T cells produce IL-17A, which promotes bone formation and facilitates bone fracture healing. Repair is impaired in IL-17A-deficient mice due to a defect in osteoblastic bone formation. IL-17A accelerates bone formation by stimulating the proliferation and osteoblastic differentiation of mesenchymal progenitor cells. This study identifies a novel role for IL-17-producing γδ T cells in skeletal tissue regeneration. PMID:26965320

  6. Electrospun poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/hydroxyapatite scaffold with unrestricted somatic stem cells for bone regeneration.

    PubMed

    Biazar, Esmaeil; Heidari Keshel, Saeed

    2015-01-01

    The combination of scaffolds and cells can be useful in tissue reconstruction. In this study, nanofibrous poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/nanohydroxyapatite (nano-HAp) scaffolds, filled with unrestricted somatic stem cells (USSCs), were used for healing calvarial bone in rat model. The healing effects of these scaffolds, with and without stem cells, in bone regeneration were investigated by computed tomography (CT) analysis and pathology assays after 28 days of grafting. The results of CT analysis showed that bone regeneration on the scaffolds, and the amounts of regenerated new bone for polymer/nano-HAp scaffold with USSC, was significantly greater than the scaffold without cell and untreated control samples. Therefore, the combination of scaffold especially with USSC could be considered as a useful method for bone regeneration. PMID:25710767

  7. Expression of osteoblastic and osteoclastic genes during spontaneous regeneration and autotransplantation of goldfish scale: a new tool to study intramembranous bone regeneration.

    PubMed

    Thamamongood, Thiparpa Aime; Furuya, Ryo; Fukuba, Shunsuke; Nakamura, Masahisa; Suzuki, Nobuo; Hattori, Atsuhiko

    2012-06-01

    Complementary DNA of osteoblast-specific genes (dlx5, runx2a, runx2b, osterix, RANKL, type I collagen, ALP, and osteocalcin) was cloned from goldfish (Carassius auratus) scale. Messenger RNA expressions were analyzed during spontaneous scale regeneration. Dlx5 had an early peak of expression on day 7, whereas osterix was constantly expressed during days 7-21. Runx2, a major osteoblastic transcription factor in mammalian bone, did not show any significant expression. The expressions of two functional genes, type I collagen and ALP, continually increased after day 7, while that of osteocalcin increased on day 14. As for osteoclastic markers, in addition to the cloning of two functional genes, TRAP and cathepsin K, in our previous study, we here cloned the transcription factor NFATc1 to use as an early osteoclastic marker. Using these bone markers, we investigate the signal key that controls the onset of scale resorption and regeneration by performing intra-scale-pocket autotransplantation of five groups of modified scales, namely, 1) methanol-fixed scale, 2) proteinase K-treated cell-free scale, 3) polarity reversal (upside-down) scale, 4) U-shape trimmed scale, and 5) circular-hole perforated scale. In this autotransplantation, each ontogenic scale was pulled out, modified, and then re-inserted into the same scale pocket. At post-transplant, inside the pockets of all modified transplant groups, new regenerating scales formed, attaching to the ongoing resorbed transplants. Autotransplantation of methanol-fixed scale, proteinase K-treated cell-free scale, and polarity reversal (upside-down) scale triggered scale resorption and scale regeneration. These two processes of scale resorption and regeneration occurred in accordance with osteoclastic and osteoblastic marker gene expressions. These results were microscopically confirmed using TRAP and ALP staining. Regarding the autotransplantation of U-shape trimmed and circular-hole perforated scales, new scales regenerated

  8. The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence

    PubMed Central

    2012-01-01

    Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a sinlge-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness. PMID:22834465

  9. Functionalized d-form self-assembling peptide hydrogels for bone regeneration

    PubMed Central

    He, Bin; Ou, Yunsheng; Zhou, Ao; Chen, Shuo; Zhao, Weikang; Zhao, Jinqiu; Li, Hong; Zhu, Yong; Zhao, Zenghui; Jiang, Dianming

    2016-01-01

    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. PMID:27114701

  10. Role of mesenchymal stem cells in bone regeneration and fracture repair: a review.

    PubMed

    Wang, Xin; Wang, Yu; Gou, Wenlong; Lu, Qiang; Peng, Jiang; Lu, Shibi

    2013-12-01

    Mesenchymal stem cells (MSCs) are non-haematopoietic stromal stem cells that have many sources, such as bone marrow, periosteum, vessel walls, adipose, muscle, tendon, peripheral circulation, umbilical cord blood, skin and dental tissues. They are capable of self-replication and of differentiating into, and contributing to the regeneration of, mesenchymal tissues, such as bone, cartilage, ligament, tendon, muscle and adipose tissue. The homing of MSCs may play an important role in the repair of bone fractures. As a composite material, the formation and growth of bone tissue is a complex process, including molecular, cell and biochemical metabolic changes. The recruitment of factors with an adequate number of MSCs and the micro-environment around the fracture are effective for fracture repair. Several studies have investigated the functional expression of various chemokine receptors, trophic factors and adhesion molecules in human MSCs. Many external factors affect MSC homing. MSCs have been used as seed cells in building tissue-engineered bone grafts. Scaffolds seeded with MSCs are most often used in tissue engineering and include biotic and abiotic materials. This knowledge provides a platform for the development of novel therapies for bone regeneration with endogenous MSCs. PMID:23948983

  11. Paracrine Effect of Mesenchymal Stem Cells Derived from Human Adipose Tissue in Bone Regeneration

    PubMed Central

    Linero, Itali; Chaparro, Orlando

    2014-01-01

    Mesenchymal stem cell (MSC) transplantation has proved to be a promising strategy in cell therapy and regenerative medicine. Although their mechanism of action is not completely clear, it has been suggested that their therapeutic activity may be mediated by a paracrine effect. The main goal of this study was to evaluate by radiographic, morphometric and histological analysis the ability of mesenchymal stem cells derived from human adipose tissue (Ad-MSC) and their conditioned medium (CM), to repair surgical bone lesions using an in vivo model (rabbit mandibles). The results demonstrated that both, Ad-MSC and CM, induce bone regeneration in surgically created lesions in rabbit's jaws, suggesting that Ad-MSC improve the process of bone regeneration mainly by releasing paracrine factors. The evidence of the paracrine effect of MSC on bone regeneration has a major impact on regenerative medicine, and the use of their CM can address some issues and difficulties related to cell transplants. In particular, CM can be easily stored and transported, and is easier to handle by medical personnel during clinical procedures. PMID:25198551

  12. [Mandibular bone tissue regeneration after the introduction of the implantation system performed on the basis of carbon composite material].

    PubMed

    Chetvertnykh, V A; Loginova, N P; Astashina, N B; Rogozhnikov, G I; Rapekta, S I

    2013-01-01

    The purpose of this study was to investigate the processes of regeneration of bone tissue after the introduction of new implant systems. In the experiment, performed on 10 male pigs of Landras breed aged 50-55 days and weighing 17-18.5 kg, the time course of histological changes was studied in the area of mandibular regeneration after the formation of tissue defect and the introduction of the implant of a proposed construction. Morphological analysis of the experimental results 90, 180 and 270 days after the operation demonstrated the process of reparative regeneration of damaged bone along implant-bone block boundaries. Bone repair proceeded through the stage of formation of the woven bone with its progressive substitution by the lamellar bone, with the maintenance of the shape, size and symmetry of the damaged organ. PMID:23805619

  13. Mandibular Jaw Bone Regeneration Using Human Dental Cell-Seeded Tyrosine-Derived Polycarbonate Scaffolds.

    PubMed

    Zhang, Weibo; Zhang, Zheng; Chen, Shuang; Macri, Lauren; Kohn, Joachim; Yelick, Pamela C

    2016-07-01

    Here we present a new model for alveolar jaw bone regeneration, which uses human dental pulp cells (hDPCs) combined with tyrosine-derived polycarbonate polymer scaffolds [E1001(1k)] containing beta-tricalcium phosphate (β-TCP) [E1001(1k)/β-TCP]. E1001(1k)/β-TCP scaffolds (5 mm diameter × 1 mm thickness) were fabricated to fit a 5 mm rat mandibular ramus critical bone defect. Five experimental groups were examined in this study: (1) E1001(1k)/β-TCP scaffolds seeded with a high density of hDPCs, 5.0 × 10(5) hDPCs/scaffold (CH); (2) E1001(1k)/β-TCP scaffolds seeded with a lower density of hDPCs, 2.5 × 10(5) hDPCs/scaffold (CL); (3) acellular E1001(1k)/β-TCP scaffolds (SA); (4) acellular E1001(1k)/β-TCP scaffolds supplemented with 4 μg recombinant human bone morphogenetic protein-2 (BMP); and (5) empty defects (EDs). Replicate hDPC-seeded and acellular E1001(1k)/β-TCP scaffolds were cultured in vitro in osteogenic media for 1 week before implantation for 3 and 6 weeks. Live microcomputed tomography (μCT) imaging at 3 and 6 weeks postimplantation revealed robust bone regeneration in the BMP implant group. CH and CL groups exhibited similar uniformly distributed mineralized tissue coverage throughout the defects, but less than the BMP implants. In contrast, SA-treated defects exhibited sparse areas of mineralized tissue regeneration. The ED group exhibited slightly reduced defect size. Histological analyses revealed no indication of an immune response. In addition, robust expression of dentin and bone differentiation marker expression was observed in hDPC-seeded scaffolds, whereas, in contrast, BMP and SA implants exhibited only bone and not dentin differentiation marker expression. hDPCs were detected in 3-week but not in 6-week hDPC-seeded scaffold groups, indicating their survival for at least 3 weeks. Together, these results show that hDPC-seeded E1001(1k)/β-TCP scaffolds support the rapid regeneration of osteo

  14. [Hydroxyapatite bone substitute (Ostim) in sinus floor elevation. Maxillary sinus floor augmentation: bone regeneration by means of a nanocrystalline in-phase hydroxyapatite (Ostim)].

    PubMed

    Smeets, Ralf; Grosjean, Maurice B; Jelitte, Gerd; Heiland, Max; Kasaj, Adrian; Riediger, Dieter; Yildirim, Murat; Spiekermann, Hubertus; Maciejewski, Oliver

    2008-01-01

    The range of bone regeneration materials suitable for maxillar bone augmentation has increased steadily in the past few years and there is now a wide variety of materials being used. In the present case report, we analyzed the state of bone regeneration after sinus floor augmentation using a nanocrystalline in-phase synthetic anorganic hydroxyapatite bone grafting material (Ostim). A 60-year-old female patient underwent maxillary sinus floor elevation and the cavity was filled with Ostim three years before. Actually, she presented herself with loosening of the dental implant at position 17, as a result of parafunction. At the time of the insertion of a second implant at position 17, bone samples were taken by using a trepan drilling device from the previously augmented area. These samples were analyzed histologically to determine the extent of bone remodeling around the deposits of Ostim. We found that the Ostim deposits were surrounded largely by woven bone and, in parts, by lamellar bone and had facilitated osteoconductive bone regeneration. The adjacent implant, at position 16, which beared a crown exposed to proper biting forces without parafunction, showed proper clinical and radiological characteristics of complete and firm integration into the area which was also filled with Ostim three years ago. We conclude that the use of the nanocrystalline hydroxyapatite Ostim with its stable volume properties appears to be suitable for maxillary sinus floor augmentation. Furthermore, we even found osteoconductive bone regeneration under Ostim near the site of the loosened implant. PMID:18422056

  15. Aged Male Rats Regenerate Cortical Bone with Reduced Osteocyte Density and Reduced Secretion of Nitric Oxide After Mechanical Stimulation

    PubMed Central

    Tayim, Riyad J.; McElderry, John-David; Morris, Michael D.; Goldstein, Steven A.

    2016-01-01

    Mechanical loading is integral to the repair of bone damage. Osteocytes are mechanosensors in bone and participate in signaling through gap junction channels, which are primarily comprised of connexin 43 (Cx43). Nitric oxide (NO) and prostaglandin E2 (PGE2) have anabolic and catabolic effects on bone, and the secretion of these molecules occurs after mechanical stimulation. The effect of age on the repair of bone tissue after damage and on the ability of regenerated bone to transduce mechanical stimulation into a cellular response is unexplored. The goal of this study was to examine (1) osteocytes and their mineralized matrix within regenerated bone from aged and mature animals and (2) the ability of regenerated bone explants from aged and mature animals to transduce cyclic mechanical loading into a cellular response through NO and PGE2 secretion. Bilateral cortical defects were created in the diaphysis of aged (21-month-old) or mature (6-month-old) male rats, and new bone tissue was allowed to grow into a custom implant of controlled geometry. Mineralization and mineral-to-matrix ratio were significantly higher in regenerated bone from aged animals, while lacunar and osteocyte density and phosphorylated (pCx43) and total Cx43 protein were significantly lower, relative to mature animals. Regenerated bone from mature rats had increased pCx43 protein and PGE2 secretion with loading and greater NO secretion relative to aged animals. Reduced osteocyte density and Cx43 in regenerated bone in aged animals could limit the establishment of gap junctions as well as NO and PGE2 secretion after loading, thereby altering bone formation and resorption in vivo. PMID:24370615

  16. Potential of Magnetic Nanofiber Scaffolds with Mechanical and Biological Properties Applicable for Bone Regeneration

    PubMed Central

    Singh, Rajendra K.; Patel, Kapil D.; Lee, Jae Ho; Lee, Eun-Jung; Kim, Joong-Hyun; Kim, Tae-Hyun; Kim, Hae-Won

    2014-01-01

    Magnetic nanofibrous scaffolds of poly(caprolactone) (PCL) incorporating magnetic nanoparticles (MNP) were produced, and their effects on physico-chemical, mechanical and biological properties were extensively addressed to find efficacy for bone regeneration purpose. MNPs 12 nm in diameter were citrated and evenly distributed in PCL solutions up to 20% and then were electrospun into nonwoven nanofibrous webs. Incorporation of MNPs greatly improved the hydrophilicity of the nanofibers. Tensile mechanical properties of the nanofibers (tensile strength, yield strength, elastic modulus and elongation) were significantly enhanced with the addition of MNPs up to 15%. In particular, the tensile strength increase was as high as ∼25 MPa at 15% MNPs vs. ∼10 MPa in pure PCL. PCL-MNP nanofibers exhibited magnetic behaviors, with a high saturation point and hysteresis loop area, which increased gradually with MNP content. The incorporation of MNPs substantially increased the degradation of the nanofibers, with a weight loss of ∼20% in pure PCL, ∼45% in 10% MNPs and ∼60% in 20% MNPs. Apatite forming ability of the nanofibers tested in vitro in simulated body fluid confirmed the substantial improvement gained by the addition of MNPs. Osteoblastic cells favored the MNPs-incorporated nanofibers with significantly improved initial cell adhesion and subsequent penetration through the nanofibers, compared to pure PCL. Alkaline phosphatase activity and expression of genes associated with bone (collagen I, osteopontin and bone sialoprotein) were significantly up-regulated in cells cultured on PCL-MNP nanofibers than those on pure PCL. PCL-MNP nanofibers subcutaneously implanted in rats exhibited minimal adverse tissue reactions, while inducing substantial neoblood vessel formation, which however, greatly limited in pure PCL. In vivo study in radial segmental defects also signified the bone regeneration ability of the PCL-MNP nanofibrous scaffolds. The magnetic, bone

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

    PubMed Central

    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

  18. Guided bone regeneration in the treatment of periimplantitis.

    PubMed

    Persson, L G; Ericsson, I; Berglundh, T; Lindhe, J

    1996-12-01

    The objective of the present experiment was to study the soft and hard tissue healing following treatment of experimentally induced periimplantitis. 5 labrador dogs about 1-year old were used. The mandibular right and left 1st molars, 4th and 3rd premolars were removed, titanium fixtures (Brånemark System) were installed, and standard abutments were connected in a 2nd stage procedure. After 3 months experimental periimplantitis was induced by the placement of cotton floss ligatures in a submarginal position. 6 weeks later the ligatures were removed. 1 month after ligature removal, an antibiotic regimen was initiated. During a 3-week period, each dog was given tablets of amoxicillin and metronidazole. In the left side of the mandible, buccal and lingual mucoperiosteal flaps were elevated and granulation tissue within the bone craters curetted. The abutments were removed. The exposed outer surfaces and the internal part of the fixtures were carefully cleaned with a detergent (delmopinol HC1). An e-PTFE membrane was placed over each fixture and adjusted to cover the bone crater. New cover screws were fitted through the membranes to the cleaned fixtures. The implants were submerged and the flaps sutured. In the right side of the mandible no local treatment was performed. The dogs were sacrificed after 4 months and biopsies prepared for histological examination. The findings indicated that treatment of a periimplantitis lesion, including comprehensive systemic antimicrobial therapy and cleaning of submerged implants resulted in (i) the elimination of the inflammatory process in the periimplant tissues and (ii) the establishment of a dense connective tissue capsule in direct contact with the previously exposed surface of the implant system. It was also observed that (iii) new bone was frequently laid down on the pristine cover screws. PMID:9151604

  19. Allogeneic adipose-derived stem cells regenerate bone in a critical-sized ulna segmental defect.

    PubMed

    Wen, Congji; Yan, Hai; Fu, Shibo; Qian, Yunliang; Wang, Danru; Wang, Chen

    2016-07-01

    Adipose-derived stem cells (ASCs) with multilineage potential can be induced into osteoblasts, adipocytes and chondrocytes. ASCs as seed cell are widely used in the field of tissue engineering, but most studies either use autologous cells as the source or an immunodeficient animal as the host. In our present study, we explored the feasibility of applying allogeneic ASCs and demineralized bone matrix (DBM) scaffolds for repairing tubular bone defects without using immunosuppressive therapy. Allogeneic ASCs were expanded and seeded on DBM scaffolds and induced to differentiate along the osteogenic lineage. Eight Sprague-Dawley (SD) rats were used in this study and bilateral critical-sized defects (8 mm) of the ulna were created and divided into two groups: with ASC-DBM constructs or DBM alone. The systemic immune response and the extent of bone healing were evaluated post-operatively. Twenty-four weeks after implantation, digital radiography (DR) testing showed that new bones had formed in the experimental group. By contrast, no bone tissue formation was observed in the control group. This study demonstrated that allogeneic ASCs could promote bone regeneration and repair tubular bone defects combined with DBM by histologically typical bone without systemic immune response. PMID:25819682

  20. Physicochemical Properties and Applications of Poly(lactic-co-glycolic acid) for Use in Bone Regeneration

    PubMed Central

    Félix Lanao, Rosa P.; Jonker, Anika M.; Wolke, Joop G.C.; Jansen, John A.; van Hest, Jan C.M.

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) is the most often used synthetic polymer within the field of bone regeneration owing to its biocompatibility and biodegradability. As a consequence, a large number of medical devices comprising PLGA have been approved for clinical use in humans by the American Food and Drug Administration. As compared with the homopolymers of lactic acid poly(lactic acid) and poly(glycolic acid), the co-polymer PLGA is much more versatile with regard to the control over degradation rate. As a material for bone regeneration, the use of PLGA has been extensively studied for application and is included as either scaffolds, coatings, fibers, or micro- and nanospheres to meet various clinical requirements. PMID:23350707

  1. Extracellular matrix-inspired growth factor delivery systems for bone regeneration

    SciTech Connect

    Martino, Mikaël M.; Briquez, Priscilla S.; Maruyama, Kenta; Hubbell, Jeffrey A.

    2015-04-17

    Growth factors are very promising molecules to enhance bone regeneration. However, their translation to clinical use has been seriously limited, facing issues related to safety and cost-effectiveness. These problems derive from the vastly supra-physiological doses of growth factor used without optimized delivery systems. Therefore, these issues have motivated the development of new delivery systems allowing better control of the spatio-temporal release and signaling of growth factors. Because the extracellular matrix (ECM) naturally plays a fundamental role in coordinating growth factor activity in vivo, a number of novel delivery systems have been inspired by the growth factor regulatory function of the ECM. After introducing the role of growth factors during the bone regeneration process, this review exposes different issues that growth factor-based therapies have encountered in the clinic and highlights recent delivery approaches based on the natural interaction between growth factor and the ECM.

  2. Development and performance analysis of PCL/silica nanocomposites for bone regeneration.

    PubMed

    Calandrelli, Luigi; Annunziata, Marco; Della Ragione, Fulvio; Laurienzo, Paola; Malinconico, Mario; Oliva, Adriana

    2010-11-01

    In the present article, several developments of biocomposites containing silica nanoparticles intended for bone regeneration are reported. Nanocomposites of poly(ε-caprolactone) (PCL) and silica, in which either the silica nanoparticles or the PCL have been modified in order to improve interfacial adhesion through chemical graft between the phases are hereafter described. The composites are characterized with respect to their chemical-physical and mechanical properties. Their biocompatibility and capacity to induce the osteoblastic phenotype in human bone marrow mesenchymal stem cells have been assessed. PMID:20976531

  3. Electrospun silk fibroin/poly(lactide-co-ε-caprolactone) nanofibrous scaffolds for bone regeneration

    PubMed Central

    Wang, Zi; Lin, Ming; Xie, Qing; Sun, Hao; Huang, Yazhuo; Zhang, DanDan; Yu, Zhang; Bi, Xiaoping; Chen, Junzhao; Wang, Jing; Shi, Wodong; Gu, Ping; Fan, Xianqun

    2016-01-01

    Background Tissue engineering has become a promising therapeutic approach for bone regeneration. Nanofibrous scaffolds have attracted great interest mainly due to their structural similarity to natural extracellular matrix (ECM). Poly(lactide-co-ε-caprolactone) (PLCL) has been successfully used in bone regeneration, but PLCL polymers are inert and lack natural cell recognition sites, and the surface of PLCL scaffold is hydrophobic. Silk fibroin (SF) is a kind of natural polymer with inherent bioactivity, and supports mesenchymal stem cell attachment, osteogenesis, and ECM deposition. Therefore, we fabricated hybrid nanofibrous scaffolds by adding different weight ratios of SF to PLCL in order to find a scaffold with improved properties for bone regeneration. Methods Hybrid nanofibrous scaffolds were fabricated by blending different weight ratios of SF with PLCL. Human adipose-derived stem cells (hADSCs) were seeded on SF/PLCL nanofibrous scaffolds of various ratios for a systematic evaluation of cell adhesion, proliferation, cytotoxicity, and osteogenic differentiation; the efficacy of the composite of hADSCs and scaffolds in repairing critical-sized calvarial defects in rats was investigated. Results The SF/PLCL (50/50) scaffold exhibited favorable tensile strength, surface roughness, and hydrophilicity, which facilitated cell adhesion and proliferation. Moreover, the SF/PLCL (50/50) scaffold promoted the osteogenic differentiation of hADSCs by elevating the expression levels of osteogenic marker genes such as BSP, Ocn, Col1A1, and OPN and enhanced ECM mineralization. In vivo assays showed that SF/PLCL (50/50) scaffold improved the repair of the critical-sized calvarial defect in rats, resulting in increased bone volume, higher trabecular number, enhanced bone mineral density, and increased new bone areas, compared with the pure PLCL scaffold. Conclusion The SF/PLCL (50/50) nanofibrous scaffold facilitated hADSC proliferation and osteogenic differentiation in

  4. In vitro response of macrophages to ceramic scaffolds used for bone regeneration.

    PubMed

    Graney, Pamela L; Roohani-Esfahani, Seyed-Iman; Zreiqat, Hala; Spiller, Kara L

    2016-07-01

    Macrophages, the primary cells of the inflammatory response, are major regulators of healing, and mediate both bone fracture healing and the inflammatory response to implanted biomaterials. However, their phenotypic contributions to biomaterial-mediated bone repair are incompletely understood. Therefore, we used gene expression and protein secretion analysis to investigate the interactions in vitro between primary human monocyte-derived macrophages and ceramic scaffolds that have been shown to have varying degrees of success in promoting bone regeneration in vivo Specifically, baghdadite (Ca3ZrSi2O9) and strontium-hardystonite-gahnite (Sr-Ca2ZnSi2O7-ZnAl2O4) scaffolds were chosen as two materials that enhanced bone regeneration in vivo in large defects under load compared with clinically used tricalcium phosphate-hydroxyapatite (TCP-HA). Principal component analysis revealed that the scaffolds differentially regulated macrophage phenotype. Temporal changes in gene expression included shifts in markers of pro-inflammatory M1, anti-inflammatory M2a and pro-remodelling M2c macrophage phenotypes. Of note, TCP-HA scaffolds promoted upregulation of many M1-related genes and downregulation of many M2a- and M2c-related genes. Effects of the scaffolds on macrophages were attributed primarily to direct cell-scaffold interactions because of only minor changes observed in transwell culture. Ultimately, elucidating macrophage-biomaterial interactions will facilitate the design of immunomodulatory biomaterials for bone repair. PMID:27466438

  5. Stem cell technology for bone regeneration: current status and potential applications.

    PubMed

    Asatrian, Greg; Pham, Dalton; Hardy, Winters R; James, Aaron W; Peault, Bruno

    2015-01-01

    Continued improvements in the understanding and application of mesenchymal stem cells (MSC) have revolutionized tissue engineering. This is particularly true within the field of skeletal regenerative medicine. However, much remains unknown regarding the native origins of MSC, the relative advantages of different MSC populations for bone regeneration, and even the biologic safety of such unpurified, grossly characterized cells. This review will first summarize the initial discovery of MSC, as well as the current and future applications of MSC in bone tissue engineering. Next, the relative advantages and disadvantages of MSC isolated from distinct tissue origins are debated, including the MSC from adipose, bone marrow, and dental pulp, among others. The perivascular origin of MSC is next discussed. Finally, we briefly comment on pluripotent stem cell populations and their possible application in bone tissue engineering. While continually expanding, the field of MSC-based bone tissue engineering and regeneration shows potential to become a clinical reality in the not-so-distant future. PMID:25709479

  6. PDGF in bone formation and regeneration: new insights into a novel mechanism involving MSCs.

    PubMed

    Caplan, Arnold I; Correa, Diego

    2011-12-01

    With the identification of mesenchymal stem cells (MSCs) as pericytes, the details of bone formation, regeneration, and repair take on new meaning. Growth factors and other signaling molecules together with MSCs play important roles in these bone fabrication processes. However, the interaction of these cellular healing components is not completely understood. The formation of new vasculature is critical to regeneration and repair as both the driver and orientor of new bone formation. In this context, MSCs are proposed to be largely derived from pericytes associated with the vasculature. A comprehensive perspective is presented in which signaling molecules such as PDGF take on new significance in the vasculature-pericyte-MSC-osteoblast dynamics. Current data suggest that PDGF could function as a central connector between the cellular components and contributors of the osteoblast differentiation program. The inference is that PDGF could function at sites of injury to mobilize the pericytes from their abluminal location, stimulate mitotic expansion of these cells and help organize them. In this way, PDGF both contributes to the osteogenic lineage and helps to stabilize newly forming vessels that act to drive the multistep, multicomponent cascade of new bone formation. This thesis explains how PDGF functions as a powerful therapeutic agent for bone formation and repair. PMID:21618276

  7. Nanostructured Tendon-Derived Scaffolds for Enhanced Bone Regeneration by Human Adipose-Derived Stem Cells.

    PubMed

    Ko, Eunkyung; Alberti, Kyle; Lee, Jong Seung; Yang, Kisuk; Jin, Yoonhee; Shin, Jisoo; Yang, Hee Seok; Xu, Qiaobing; Cho, Seung-Woo

    2016-09-01

    Decellularized matrix-based scaffolds can induce enhanced tissue regeneration due to their biochemical, biophysical, and mechanical similarity to native tissues. In this study, we report a nanostructured decellularized tendon scaffold with aligned, nanofibrous structures to enhance osteogenic differentiation and in vivo bone formation of human adipose-derived stem cells (hADSCs). Using a bioskiving method, we prepared decellularized tendon scaffolds from tissue slices of bovine Achilles and neck tendons with or without fixation, and investigated the effects on physical and mechanical properties of decellularized tendon scaffolds, based on the types and concentrations of cross-linking agents. In general, we found that decellularized tendon scaffolds without fixative treatments were more effective in inducing osteogenic differentiation and mineralization of hADSCs in vitro. When non-cross-linked decellularized tendon scaffolds were applied together with hydroxyapatite for hADSC transplantation in critical-sized bone defects, they promoted bone-specific collagen deposition and mineralized bone formation 4 and 8 weeks after hADSC transplantation, compared to conventional collagen type I scaffolds. Interestingly, stacking of decellularized tendon scaffolds cultured with osteogenically committed hADSCs and those containing human cord blood-derived endothelial progenitor cells (hEPCs) induced vascularized bone regeneration in the defects 8 weeks after transplantation. Our study suggests that biomimetic nanostructured scaffolds made of decellularized tissue matrices can serve as functional tissue-engineering scaffolds for enhanced osteogenesis of stem cells. PMID:27502160

  8. Hybrid Matrix Grafts to Favor Tissue Regeneration in Rabbit Femur Bone Lesions

    PubMed Central

    Goy, Dante Pascual; Gorosito, Emmanuel; Costa, Hermes S; Mortarino, Pablo; Pedemonte, Noelia Acosta; Toledo, Javier; Mansur, Herman S; Pereira, Marivalda M; Battaglino, Ricardo; Feldman, Sara

    2012-01-01

    At present, typical approaches employed to repair fractures and other bone lesions tend to use matrix grafts to promote tissue regeneration. These grafts act as templates, which promote cellular adhesion, growth and proliferation, osteoconduction, and even osteoinduction, which commonly results in de novo osteogenesis. The present work aimed to study the bone-repairing ability of hybrid matrixes (HM) prepared with polyvinyl alcohol (PVA) and bioactive glass in an experimental rabbit model. The HM were prepared by combining 30% bioactive glass (nominal composition of 58% SiO2 -33 % CaO - 9% P2O5) and 70% PVA. New Zealand rabbits were randomly divided into the control group (C group) and two groups with bone lesions, in which one received a matrix implant HM (Implant group), while the other did not (no Implant group). Clinical monitoring showed no altered parameters from either the Implant or the no Implant groups as compared to the control group, for the variables of diet grades, day and night temperatures and hemograms. In the Implant group, radiologic and tomographic studies showed implanted areas with clean edges in femoral non-articular direction, and radio-dense images that suggest incipient integration. Minimum signs of phlogosis could be observed, whereas no signs of rejection at this imaging level could be identified. Histological analysis showed evidence of osteo-integration, with the formation of a trabecular bone within the implant. Together, these results show that implants of hybrid matrixes of bioactive glass are capable of promoting bone regeneration. PMID:22848334

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

    SciTech Connect

    Gotman, Irena Gutmanas, Elazar Y.; Zaretzky, Asaph; Psakhie, Sergey G.

    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.

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

    NASA Astrophysics Data System (ADS)

    Gotman, Irena; Zaretzky, Asaph; Psakhie, Sergey G.; Gutmanas, Elazar Y.

    2015-10-01

    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.