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PubMedDate not supplied

[Repair of cranial defects with regenerating bone during transplantation of gamma-irradiated bone filings].

The authors studied in dog experiments the possibility of repairing cranial defects with allografts of bone filings obtained under unsterile conditions, frozen at -70 degrees C, and sterilized by gamma-irradiation in a dose of 3.5 mrad. It was found that though gamma-irradiation reduced the osteogenic inducing property of the bone filings allografts, they nevertheless were capable of inducing bone regeneration in the region of the bone defect. Frozen and gamma-irradiated bone filings can be recommended for cranioplasty.

Adolescent↗
PubMed1999

Bone regeneration by recombinant human bone morphogenetic protein-2 in rat mandibular defects. An experimental model of defect filling.

BACKGROUND: Bone defects and irregularities are major problems for dental implant and periodontal therapies. METHODS: We investigated whether the application of recombinant human bone morphogenetic protein-2 (rhBMP-2) induces bone formation in through-and-through bone defects in the rat mandible. A round through-and-through bone defect (5 mm in diameter) was created in the angle of the mandible on both sides of the jaw using a steel round bur in each of 8 Long-Evans rats. In the experimental group, polylactic acid-polyglycolic acid copolymer/gelatin sponge (PGS) containing rhBMP-2 (6 microg/60 microl) was inserted in the bone defect. In the control group, the same carrier without rhBMP-2 was applied in the bone defect on the opposite side. Four weeks after application, the rats were sacrificed. Step serial sections stained with hematoxylin and eosin at intervals of 200 microm were prepared in a bucco-lingual direction. The size of the bone defects and new bone formation were evaluated histometrically. RESULTS: In all cases in the experimental group, a large quantity of newly formed bone was observed. The bone defects were completely filled with new bone in 4 of 8 rats in the experimental group. In the control group, small amounts of new bone formation were observed along the border of the original mandibular bone. Histometrical analysis revealed that the amount of new bone was significantly larger in the rhBMP-2 treated sites than in the control sites (P <0.0001; paired t-test). CONCLUSIONS: These results indicate that the rhBMP-2/PGS system induced effective bone regeneration on mandibular defects in rats. This procedure may be suitable as an experimental model for bone regeneration using various growth factors and effective for alveolar ridge augmentation followed by dental implant surgery.

Animals↗
PubMed2004

Combined angiogenic and osteogenic factor delivery enhances bone marrow stromal cell-driven bone regeneration.

UNLABELLED: Bone formation is a coordinated process involving various biological factors. We have developed a scaffold system capable of sustained and localized presentation of osteogenic (BMP-4) and angiogenic (VEGF) growth factors and human bone marrow stromal cells to promote bone formation at an ectopic site. Combined delivery of these factors significantly enhanced bone formation compared with other conditions. INTRODUCTION: Tissue regeneration entails complex interactions between multiple signals and materials platforms. Orchestrating the presentation of these signals may greatly enhance the regeneration of lost tissue mass. Bone formation, for example, is dependent on the signaling of BMPs, molecules initiating vascularization (e.g., vascular endothelial growth factor [VEGF]), and osteogenic precursor cells capable of responding to these cues and forming bone tissue. It was hypothesized that combined and concerted delivery of these factors from biodegradable scaffolds would lead to enhanced bone formation. MATERIALS AND METHODS: Poly(lactic-co-glycolic acid) scaffolds containing combinations of condensed plasmid DNA encoding for BMP-4, VEGF, and human bone marrow stromal cells (hBMSCs) were implanted into the subcutaneous tissue of SCID mice. Implants (n = 6) were retrieved at 3, 8, and 15 weeks after implantation. Bone and blood vessel formation was determined qualitatively and quantitatively by methods including histology, immmunostaining, and muCT. RESULTS: Scaffolds delivering VEGF resulted in a prominent increase in blood vessel formation relative to the conditions without VEGF. BMP-4 expression in scaffolds encapsulating condensed DNA was also confirmed at the 15-week time-point, showing the characteristic of long-term delivery in this system. Combined delivery of all three types of factors resulted in a significant increase in the quantity of regenerated bone compared with any factor alone or any two factors combined, as measured with DXA, X-ray, and histomorphometric analysis. Furthermore, bone formed with all three factors had elastic moduli significantly higher than any other condition. CONCLUSIONS: Concerted delivery of BMP-4, VEGF, and hBMSCs promoted greater bone formation relative to any single factor or combination of two factors. Materials systems that allows multifactorial presentation more closely mimic natural developmental processes, and these results may have important implications for bone regeneration therapeutics.

Animals↗
PubMed2001

Bone regeneration using recombinant human bone morphogenetic protein-2 (rhBMP-2) in alveolar defects of primate mandibles.

The efficacy of bone morphogenetic protein (BMP) for bone reconstruction has been widely studied in numerous animal experiments, but insufficient information exists about its ability to regenerate bone in primates. The purpose of this study was to evaluate the effects of recombinant human BMP-2 (rhBMP-2) on bone formation in alveolar bone defects in the mandibles of young primates. Marginal bone defects were created in the mandibles of nine 5-year-old rhesus monkeys and rhBMP-2 permeated in a polylactic-co-glycolic acid-coated gelatin sponge (PGS) was implanted into the bone defects. The resected bone treated with rhBMP-2 regenerated completely at 12 weeks postoperatively, and remodelling and consolidation of new bone were seen histologically. This study provides evidence of considerable bone regeneration in alveolar defects after surgical implantation of rhBMP-2 in non-human primates. This technique may be an effective alternative to autogenous bone grafts for reconstructive surgery in clinical practice.

Absorbable Implants↗
PubMed2005

Neovascularization and bone regeneration by implantation of autologous bone marrow mononuclear cells.

We examined whether transplantation of autologous bone marrow mononuclear cells (BM-MNCs) can augment neovascularization and bone regeneration of bone marrow in femoral bone defects of rabbits. Gelatin microspheres containing basic fibroblast growth factor (bFGF) were prepared for the controlled release of bFGF. To evaluate the in vivo effect of implanted BM-MNCs, we created bone defects in the rabbit medial femoral condyle, and implanted into them 5 x 10(6) fluorescent-labeled autologous BM-MNCs together with gelatin microspheres containing 10 microg bFGF on an atelocollagen gel scaffold. The four experimental groups, which were Atelocollagen gel (Col), Col + 5 x 10(6) BM-MNCs, Col + 10 microg bFGF, and Col + 5 x 10(6) BM-MNCs + 10 microg bFGF, were implanted into the sites of the prepared defects using Atelocollagen gel as a scaffold. The autologous BM-MNCs expressed CD31, an endothelial lineage cell marker, and induced efficient neovascularization at the implanted site 2 weeks after implantation. Capillary density in Col + BM-MNCs + bFGF was significantly large compared with other groups. This combination also enhanced regeneration of the bone defect after 8 weeks to a significantly greater extent than either BM-MNCs or bFGF on their own. In summary, these findings demonstrate that a combination of BM-MNCs and bFGF gelatin hydrogel enhance the neovascularization and the osteoinductive ability, resulting in bone regeneration.

Animals↗
PubMed2006

Immobilization of bone morphogenetic protein-2 on a nanofibrous chitosan membrane for enhanced guided bone regeneration.

BMP-2 (bone morphogenetic protein-2) has been used in promoting bone formation and, in combination with various delivery carriers, in bone regeneration or bone tissue-engineering practice. In the present study, BMP-2 was immobilized directly on a GBR (guided bone-regenerative) membrane surface made of chitosan nanofibres, providing a bioactive surface that can enhance bone-regeneration capacity. The BMP-2-conjugated membrane surface retained bioactivity for up to 4 weeks of incubation, as well as holding over 50% of the initial BMP-2 attached. The BMP-2-conjugated surface increased osteoblastic cell attachment in accordance with the amount of BMP-2 conjugated. In addition, the BMP-2-conjugated chitosan membrane significantly promoted cell proliferation, alkaline phosphatase activity, as well as calcium deposition when compared with BMP-2-adsorbed membrane, indicating a stable localization of BMP-2 at the surface of the chitosan membrane. Taking these findings together, the conjugation of BMP-2 on a chitosan nanofibrous membrane would seen to be applicable for inducing significant and localized bone formation in future GBR procedures.

Animals↗
PubMed2000

Comparison of pericranium and eggshell as space fillers used in combination with guided bone regeneration: an experimental study.

PURPOSE: The purpose of the study was to determine the potential adjunctive role of 2 space fillers, used in combination with guided tissue regeneration, on bone regeneration in rat skull defects. MATERIALS AND METHODS: The study was conducted on 45 adult Wistar rats. A bilateral 6-mm-wide full-thickness skull defect was created in the parietal region of each animal. The right defect was chosen as the experiment site, and the left defect was left empty as a control. Each experiment site was covered by an inner and outer polytetrafluoroethylene membrane. The 45 rats were divided into 3 groups; no space filler between the 2 membranes was used in group I (n = 15), a free pericranial autograft was used as a space filler between the 2 membranes in group II (n = 15), and purified eggshell powder was used as space filler between the 2 membranes in group III (n = 15). Five animals in each group were killed at 15, 30, and 90 days. The harvested specimens were subjected to contact radiography and standard microscopic examination, and the rates of osteogenesis were assessed by a semiquantitative method. RESULTS: No evidence of bone regeneration was seen in any animals of the three groups at 15 days. At 30 days, bone regeneration only appeared in group I (P > .05). At 90 days, complete bone regeneration was observed in the group I in 3 of 5 animals (P < .05). In group II, the pericranial graft showed no osteogenic properties. In group III, the eggshell powder showed no resorption, but no osteoconduction was noticed. CONCLUSIONS: Although the osteogenic mechanism of guided tissue regeneration is not clear, this study suggests that the physical properties of the membrane are more important than the use of an adjunctive space filler.

Animals↗
PubMed2006

Framework for optimal design of porous scaffold microstructure by computational simulation of bone regeneration.

In bone tissue engineering using a biodegradable scaffold, geometry of the porous scaffold microstructure is a key factor for controlling mechanical function of the bone-scaffold system in the regeneration process as well as after the regeneration. In this study, we propose a framework for the optimal design of the porous scaffold microstructure by three-dimensional computational simulation of bone tissue regeneration that consists of scaffold degradation and new bone formation. The rate of scaffold degradation due to hydrolysis, that leads to decrease in mechanical properties, was simply assumed to relate to the water content diffused from the surface to the bulk material. For the new bone formation on both bone and scaffold surfaces, the rate equation of trabecular surface remodeling driven by mechanical stimulation was applied. Solving these two phenomena in the same time frame, the bone regeneration process in the bone-scaffold system was predicted by computational simulation using a voxel finite element method. The change in the mechanical function of the bone-scaffold system during the regeneration process was quantitatively evaluated by measuring the change in total strain energy, and this was used for the evaluation function to optimize the scaffold microstructure that provides the desired mechanical function during and after the bone regeneration process. A case study conducted for the scaffold with a simple microstructure demonstrated that the proposed simulation method could be applied to the design of a porous scaffold microstructure. In addition, the regeneration process was found to be very complex even though the simple rate equations for scaffold regeneration and new bone formation were used because of the coupling effects of these phenomena.

Animals↗
PubMed2004

Guided bone regeneration (GBR) on healing bone defects: a histological study in rabbits.

In this study, the effects of guided bone regeneration (GBR) on the healing of bone defects were evaluated. Resorbable membranes were placed in experimentally formed cavities in the right posterior tibia of 30 rabbits. Decalcified histological sections were evaluated using optical microscopy at 10, 20, and 30 days after GBR. Osteocondrial bone union, active bone formation and spongiosal bone formation values of the GBR group are higher than the control group. It was found that GBR technique had a positive and accelerating influence in all phases of bone healing.

Absorbable Implants↗
PubMed2004

Intermittent parathyroid hormone treatment enhances guided bone regeneration in rat calvarial bone defects.

This study investigates the effects of intermittent parathyroid hormone (PTH(1-34)) treatment on bone regeneration and mechanical strength of critically sized rat calvarial bone defects covered with expanded membranes. A full-thickness bone defect (diameter 5 mm) was trephined in the central part of the parietal bones in 20-month-old female Wistar rats. The bone defects were covered with an exocranial and an endocranial expanded polytetrafluoroethylene membrane. The animals were killed 35 days after operation. 60 microg PTH(1-34)/kg was administered daily during the healing period, and control animals with calvarial bone defects were given vehicle. Mechanical testing was performed by a punch out testing procedure by placing a steel punch (diameter 3.5 mm) in the center of the healed defect. After mechanical testing, the newly formed tissue inside the defect was removed and the dry weight and ash weight were measured. PTH(1-34) increased dry weight by 48%, ash weight by 51%, and ash concentration by 26%. PTH(1-34) also augmented the mechanical strength of the new bone formed inside the defect by increasing ultimate stiffness by 87%. No differences in body weight were found between the vehicle-injected and the PTH-treated animals during the experiment. The experiment demonstrates that intermittent PTH(1-34) treatment increases bone deposition and enhances mechanical strength of healing rat calvarial defects covered with expanded polytetrafluoroethylene membranes.

Animals↗
PubMed2004

Histomorphometric evaluation of bone regeneration using allogeneic and alloplastic bone substitutes.

PURPOSE: The purpose of this investigation was to assess bone regeneration in critical sized defects in the rabbit calvarium using allogeneic and alloplastic bone substitutes. MATERIALS AND METHODS: Thirty New Zealand White rabbits were divided into 3 groups of 10 animals each. Bilateral 15 mm x 17 mm calvarial defects were made in the parietal bones of each animal. Group 1 had demineralized bone matrix (DBM) gel placed in one defect, while the other defect was left unfilled and served as the control. Group 2 had one defect filled with calcium hydroxide (CaOH)-treated DBM gel and the other defect filled with DBM gel. Group 3, the calcium-phosphate cement group, had Norian CRS (Norian Corp, Cupertino, CA) placed on one side and Bone Source (Howmedica Leibinger, Dallas, TX) placed on the contralateral side. Five animals in each group were killed at 6 and 12 weeks. Data analysis included qualitative assessment of the calvarial specimens and radiographic evaluation. Histomorphometric analysis was used to quantify the amount of new bone within the defects. RESULTS: Histomorphometric analysis showed that DBM gel-treated defects had significantly more new bone at 12 weeks compared with all other groups. There was no significant difference between defects filled with CaOH-treated DBM gel and those filled with DBM gel at 12 weeks. In group 3, Norian CRS- and Bone Source-treated defects were not statistically different from the unfilled controls. CONCLUSION: DBM gel was an effective allogeneic bone substitute that showed reliable osseous healing of critical size defects in the rabbit calvarium. The addition of CaOH to DBM gel did not significantly improve the bone regenerative capacity of the DBM gel. Both Norian CRS and Bone Source did not promote bone regeneration in this animal model.

Animals↗
PubMed2006

Platelet-rich plasma does not improve bone regeneration around peri-implant bone defects--a pilot study in dogs.

The purpose of the present study was to evaluate the influence of platelet-rich plasma (PRP) on bone regeneration in dehiscence-type bone defects around dental implants. Ten male adult mongrel dogs were used. Three months after teeth extractions, an osteotomie for implantation and a buccal dehiscence defect were prepared on both sides of the jaws. Two dental implants with machined surfaces were placed on each implant site of the mandible. Dehiscences were randomly assigned to the following groups: (1) test (PRP) and (2) control. After 3 months animals were sacrificed; implants and adjacent hard tissues were processed for undecalcified sections. Bone-to-implant contact (BIC), bone density (BD) within the limits of implant threads, bone density (BO) and new bone area (NB) in a zone lateral to the implant, corresponding to bone defects, were obtained and measured. Inter group analysis (paired Student's t-test, alpha = 5%) demonstrated no statistically significant differences for any of the parameters when PRP was used (P > 0.05). Within the limits of the present study, it was concluded that platelet-rich plasma alone did not enhance bone regeneration for peri-implant defects.

Animals↗
PubMedDate not supplied

Bone regeneration by grafting of cultured human bone.

A 3-mL sample of bone marrow was collected from the iliac bones of 27 orthopedic patients (8 men and 19 women with a mean age of 56.1 years [range, 17 to 76 years]), followed by culture in standard culture medium (minimal essential medium containing 15% fetal bovine serum). In all 7 patients randomly selected from these 27 patients, significant in vitro osteogenic ability of marrow mesenchymal cells was demonstrated by scanning electron microscopy and biochemical analyses. In all 27 cases, to investigate the in vivo osteogenic potential of this human cultured bone, porous ceramics were impregnated with marrow cells and subcultured in osteogenic culture medium (standard medium supplemented with sodium beta-glycerophosphate, vitamin C phosphate, and dexamethasone). After 3 weeks of subculture, the cultured artificial bones of the cultured bone/porous ceramics were grafted into the abdominal cavity of nude mice. Histological and biochemical (alkaline phosphatase activity and human osteocalcin) examinations indicated that the cultured artificial bone possessed significant ability to regenerate bone. This result suggests that the bone-regenerating ability of human marrow cells may not depend on age, and that cultured artificial bone may be useful for bone regeneration treatment if appropriate cultured marrow cells can be successfully prepared.

Adolescent↗
PubMed2004

Prognostic factors for alveolar regeneration: effect of tissue occlusion on alveolar bone regeneration with guided tissue regeneration.

OBJECTIVES: Design criteria for guided tissue regeneration (GTR) devices include biocompatibility, cell occlusion, space-provision, tissue integration, and ease of use. The objective of this study was to evaluate the effect of cell occlusion and space-provision on alveolar bone regeneration in conjunction with GTR. METHODS: Routine, critical-size, 6 mm, supra-alveolar, periodontal defects were created in 6 young adult Beagle dogs. Space-providing ePTFE devices, with or without 300-microm laser-drilled pores were implanted to provide for GTR. Treatments were alternated between left and right jaw quadrants in subsequent animals. The gingival flaps were advanced for primary intention healing. The animals were euthanized at week 8 post surgery. The histometric analysis assessed regeneration of alveolar bone relative to space-provision by the ePTFE device. RESULTS: A significant relationship was observed between bone regeneration and space-provision for defect sites receiving the occlusive (beta = 0.194; p < 0.02) and porous (beta = 0.229; p < 0.0004) GTR devices irrespective of treatment (p = 0.14). The bivariate analysis showed that both space-provision and device occlusivity significantly enhanced bone regeneration. Hence, sites receiving the occlusive GTR device and sites with enhanced space-provision showed significantly greater bone regeneration compared to sites receiving the porous GTR device (p = 0.03) or more limited space-provision (p = 0.0002). CONCLUSIONS: Cell occlusion and space-provision may significantly influence the magnitude of alveolar bone regeneration in conjunction with guided tissue regeneration.

Alveolar Bone Loss↗
PubMed2000

[Healing behavior and bone regeneration of maxillary osteotomies in the experimental rabbit model. Effect of osteosynthesis and guided bone regeneration].

PURPOSE: The development of fibrous nonunions following orthognathic surgery is thought to result from an interaction of biomechanical stress and the differential and more rapid migration of fibroblasts compared to osteoblasts into the wound site during healing. The present study was designed to test this hypothesis through the manipulation of guided tissue regeneration and osteotomy fixation techniques in an experimental rabbit model. MATERIALS AND METHODS: Bilateral critical size (4 mm) defects (n = 24) were produced in the maxillae of 12 adult New Zealand White rabbits. The maxillary segments were rigidly or nonrigidly fixed using bone microplates and screws or osteosynthetic wires. The defects were then covered with a resorbable collagen membrane or left uncovered. The rabbits were followed for 4 weeks with serial dorsoventral and lateral oblique cephalographs and the maxillae were then harvested for histological analysis. RESULTS: Radiographic and histomorphometric analysis revealed that rigidly fixed defects, covered with membrane, showed the most rapid and organized new bone formation. The rigidly fixed defects with membrane averaged approximately 40% more new bone in the osteotomy site than the rigidly fixed defects with no membrane. Nonrigidly fixed defects with no membrane also showed an ingrowth of fibroblasts and fibrous nonunions. CONCLUSION: These results suggest that an interaction between the decreased fibrous tissue ingrowth through guided tissue regeneration and osteotomy segment stability from rigid fixation prevented postoperative fibrous nonunions and facilitated new bone regeneration and osteotomy site healing in this rabbit model.

Animals↗
PubMed1996

[An experiment study of the guided bone regeneration].

During the process of wound healing, different cellular components have varied speeds of migrating. By implanting a membrane, a space was created for selected cells, that is so called guided tissue regeneration. Since bone had the potential of regeneration, the concept of guided tissue regeneration was used in the process of bone regeneration in the present study, namely, guided bone regeneration. Defects of 10 mm-long were produced on bilateral radii of 10 adult New Zealand rabbits by surgery. The defects on experimental sides were bridged with silicone tube. The opposite side served as the control. Radiography of forearms of rabbits was taken weekly. Samples were treated with 3-point bending test and histology respectively. On experimental sides, by 3-4 weeks, new bone from the fractured ends grew into bone defect, seven of ten healed within 6-8 weeks. The other 2 only had a gap less than 1 mm left. No one healed on the control sides. The maximum value of 3-point bending test on experimental sides was 11.7 times greater than that of the control sides. It was shown that bone regenerated in the tube, and no callus formed out the tube by both gross samples and histologic examinations. On histology, the gap less than 1 mm on X-ray films was fibrocartilage zone, which connected regenerated bone from both distal and proximal bone ends. The defects on the control were occupied by connective tissue. In conclusion, guided bone regeneration also presents in long bone, that may provide a new method in the treatment of bone defect and promote fracture healing.

Animals↗