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PubMed2005

[Segmental mandibular reconstruction by elasticity distraction osteogenesis associated with guided bone regeneration].

OBJECTIVE: To accelerate distraction osteogenesis by utilizing guided bone regeneration technique, and to improve the automatic process of canine segmental mandibular reconstruction by elasticity distraction osteogenesis using shape memory metal alloy distractor. METHODS: Adult hybrid canines were used. Osteotomy was performed to remove a bone segment of 2.5-4.0 cm in one side of the mandible. Mandibular fixation devices and shape memory metal alloy distractor were secured according to the principles of bi-focal distraction technique. A piece of ePTFE membrane was sutured to cover the buccal side of bone defect and osteotomy gap of transport disc, where the periosteum was peeled for exposing mandible in operation. Then the incisions were totally closed. The canines were sacrificed 3 months later to harvest the mandibles for morphological observation and measurement of bone density and intensity. RESULTS: The shape memory metal alloy distractor performed distraction osteogenesis automatically and reconstructed the mandibles with bone defect. A regenerated bone segment of 1.5-2.0 cm was formed in the compression region between transport disc and contralateral mandibular end. The new bone in both of distraction and compression regions had similar height and thickness with normal mandible. Moreover the new bone density and intensity were rather satisfied. CONCLUSIONS: Membrane guided bone regeneration can avoid bone synthesis commonly caused by cicatrization of soft tissue in the bone defect, and accelerate ossification and maturation of new generated bone.

Animals↗
PubMed1996

[Use of densitometric measurements for evaluation of bone regeneration in lengthening of the long bone shaft].

A series of 18 long bone lengthenings in 16 children has been analyzed. To assess new bone formation sonography, DEXA and computerized tomography have been employed. Sonography proved to be most useful for elongation monitoring, but densitometry delivered most data concerning quantity and distribution of the new bone formation especially during stabilization stage. DEXA combined with CT allowed for making decision of the removal of ilizarov apparatus.

Bone Density↗
PubMed1997

Preimplant guided bone regeneration in the anterior maxilla.

Guided bone regeneration is a clinical procedure aimed at promoting bone formation at sites where there is severe bone loss. The purpose of this article was to demonstrate reconstruction of deformations of the alveolar process resulting from traumatic injuries to maxillary incisor teeth by guided bone regeneration procedures followed by insertion of dental implants. In both cases, submembranous space-making was stabilized by human demineralized freeze-dried bone. Implant insertion at the sites of bone augmentation resulted in successful restorations. Histologic examination of biopsy samples from the submembranous hard tissue revealed particles of demineralized freeze-dried bone allografts partially surrounded by uninflamed connective tissue and by vital bone adjacent and adhered to the demineralized freeze-dried bone allograft particles.

Adolescent↗
PubMed1992

Initiation of bone regeneration in adult baboons by osteogenin, a bone morphogenetic protein.

Osteogenin, and related bone morphogenetic proteins, induce endochondral bone differentiation through a cascade of events which include formation of cartilage, hypertrophy and calcification of the cartilage, vascular invasion, differentiation of osteoblasts, and formation of bone. These events have been studied in a postnatal model of bone development in rodents. Information concerning the morphogenetic potential of osteogenin in primates is a prerequisite for potential clinical application in man. The efficacy of allogeneic osteogenin in primates was investigated in both extraskeletal and skeletal sites in 19-Chacma baboons (Papio ursinus). Osteogenin was isolated from demineralized baboon bone matrix and purified by chromatography on heparin-Sepharose, hydroxyapatite, and Sephacryl S-200. Protein fractions with a molecular mass range of 26-42 kDa induced cartilage and bone differentiation in the subcutaneous space of rats. Final purification to homogeneity was obtained by electroendosmotic elution from a preparative sodium dodecyl sulphate (SDS) polyacrylamide gel, resulting in a single band on a SDS-polyacrylamide gel with an apparent molecular mass of 30-34 kDa, with biological activity in rats. The osteoinductive potential of osteogenin in primates was tested first in intramuscular sites in baboons and found to be active. The bone regeneration potential was investigated in nonhealing calvarial defects surgically prepared in adult male baboons. Baboon osteogenin induced complete regeneration of the cranial wound. These findings in adult primates establish a primary role for osteogenin in initiation and promotion of osteogenesis, and imply a potential therapeutic application based on cell biology of extracellular matrix-cell interactions.

Animals↗
PubMed2005

[Clinical implication of bone regeneration in oral surgery].

Bone augmentation or the alveolar ridge augmentation procedure is inevitable for functional and esthetic prosthetic oral rehabilitation. In this article, conventional alveolar ridge augmentation methods are clinically demonstrated and are reviewed with reference to literature. In addition, distraction osteogenesis (DO), which has drawn considerable attention as a regenerative medicine, was clinically demonstrated. Then, the conventional augmentation methods and distraction are compared. Indications, advantages, and disadvantages of conventional augmentation methods including bone grafts, guided bone regeneration (GBR) and GBR with titanium micromesh (TIME technique) are demonstrated. Next, the mechanisms, indications, and advantages of DO are demonstrated and compared with conventional methods. Although conventional augmentation methods are well established, there are some problems including donor site morbidity and risks of wound dehiscence and infection. DO seems to have advantages compared to conventional augmentation methods. However, there still have some clinical problems such as difficulty in vector control and technique sensitivity. For less morbidity and better efficacy in alveolar ridge bone augmentation, tissue engineering offers potential in the future. However, further basic and clinical study will be necessary for clinical application.

Alveolar Ridge Augmentation↗
PubMed1999

[Expression of BMP-2, TGF-beta, bFGF in guided bone regeneration].

OBJECTIVE: To study the mechanism of guided bone regeneration combined with osteoinduction by observation of expression of BMP-2, TGF-beta, bFGF. METHODS: 42 adult, male, New Zealand rabbits were randomly divided into 6 groups, each group being 7 rabbits. 10mm standard bone defect model was produced bilaterally in the middle radial shaft of each rabbit. Randomly, one defect enveloped with silicon membrane was tested, and the other served as control, sacrificed at 3 days, 1, 2, 3, 4, 5 weeks after surgery for histological observation, immunohistochemical staining of BMP-2, TGF-beta, bFGF and in situ hybridization of their cDNA probes. RESULTS: Histologically bone defects was sealed by silicon membrane, in which inflammation tissue and callus were formed from cells in bone ends. Similar expression of BMP-2, TGF-beta, bFGF between the test groups and control groups was noted. Inflammatory cells in the hematoma expressed bFGF and proliferating periosteal cells, endosteal cells, medullary mesenchymal cells expressed TGF-beta at 3 days postoperatively. Osteocytes in the bone ends and osteoblasts lining callus surface started to express BMP-2, TGF-beta at first week after surgery. Following the formation of inflammation tissue, in which giant cells, macrophages, mesenchymal cells expressed TGF-beta, bFGF respectively. Although the expression of three osteoinductors was the same between the test and control sides, their content was very different in both sides. The whole content in all test sides was much more than all control sides (P < 0.01), the content of test side was also much more than control side in each group. CONCLUSIONS: It is a key reason for successful guided bone regeneration that membrane tube formed a relatively independent bone regenerative situation to prevent around tissue from interruption, and to prevent osteoinductors from diffusion, so that enhanced osteoinductors induced bone regeneration to repair bone defects.

Animals↗
PubMed2003

Ex vivo gene therapy in autologous critical-size craniofacial bone regeneration.

In therapeutic bone repairs, autologous bone grafts, conventional or vascularized allografts, and biocompatible artificial bone substitutes all have their shortcomings. The bone formed from peptides [recombinant human bone morphogenetic proteins (BMPs)], demineralized bone powder, or a combination of both is small in size. Tissue engineering may be an alternative for cranial bone repair. In this study, the authors developed an animal model to test the hypothesis that replication-defective, adenovirus-mediated human BMP-2 gene transfer to bone marrow stromal cells enhances the autologous bone formation for repairing a critical-size craniofacial defect. The mesenchymal stromal cells of miniature swine were separated from the iliac crest aspirate and expanded in monolayer culture 1 month before implantation. The cultured mesenchymal stromal cells were infected with recombinant, replication-defective human adenovirus BMP-2, 7 days before implantation. Bilateral 2 x 5-cm2 cranial defects were created, leaving no osteogenic periosteum and dura behind. Mesenchymal stromal cells at 5 x 10(7)/ml were mixed with collagen type I to form mesenchymal stromal cell/polymer constructs. Mesenchymal stromal cells used for the control site were infected with adenovirus beta-Gal under the same conditions. After 6 weeks and 3 months, 10 miniature swine were euthanized and the cranium repair was examined. Near-complete repair of the critical-size cranial defect by tissue-engineered mesenchymal stromal cell/collagen type I construct was observed. The new bone formation area (in square centimeters) measured by three-dimensional computed tomography demonstrated that the improvement from 6 weeks to 3 months was significantly greater on the experimental side than on the control side (2.15 cm2 versus 0.54 cm2, p < 0.001) and significantly greater at 3 months than at 6 weeks (2.13 cm2 versus 0.52 cm2, p < 0.001). The difference between the experimental and control groups was significant at 3 months (mean difference, 2.13 cm2; p < 0.001). The maximal compressive strength of the new bone was similar to that of the normal cranial bone when evaluated by biomechanical testing (cranium bone versus tissue-engineered bone, 88.646 +/- 5.121 MPa versus 80.536 +/- 19.302 MPa; p = 0.227). Adenovirus was absent from all constructs by immunochemical staining at 6 weeks and 3 months after implantation. The successful repair of cranial defects in this experiment demonstrates the efficacy of the integration of the autologous stem cell concept, gene medicine, and polymers in producing tissue-engineered bone.

Animals↗
PubMed2004

Partial spontaneous bone regeneration subsequent to mandibulectomy.

A case of spontaneous bone regeneration after mandibulectomy is presented. The patient was young and had a mandibular resection performed for a large fibroma. Only one of the condyles was preserved. Partial preservation of the periosteum may play an important role in rapid bone regeneration. In this case bone regeneration occurred only in mandibular regions where the periosteum could be preserved.

Adolescent↗
PubMedDate not supplied

Effect of allogeneic, freeze-dried, demineralized bone matrix on guided bone regeneration in supra-alveolar peri-implant defects in dogs.

This randomized, split-mouth design study evaluated the adjunctive effect of allogeneic, freeze-dried, demineralized bone matrix on guided bone regeneration in a critical-size, supra-alveolar, peri-implant defect model. Contralateral supra-alveolar peri-implant defects, 5 mm in height, each including two titanium implants, were surgically created in five beagle dogs. Demineralized bone matrix in autologous blood was placed over the implants in one randomly selected mandibular jaw quadrant. A space-making expanded-polytetrafluoroethylene membrane was used to provide guided bone regeneration bilaterally. Following a 16-week healing interval, tissue blocks were harvested and prepared for histometric analysis. Differences between experimental conditions (guided bone regeneration sites with and without demineralized bone) were evaluated using paired t tests (n = 4). Demineralized bone particles were discernible, with limited signs of resorption. The bone matrix particles appeared to be solidified within a dense connective tissue matrix and in close contact with the implants. Limited matrix remineralization was apparent adjacent to the alveolar crest. No statistically significant differences were found between experimental conditions for any parameter examined. Peri-implant defect height averaged 5.0 +/- 0.2 mm and 4.9 +/- 0.4 mm, vertical bone regeneration 1.5 +/- 0.9 mm and 1.1 +/- 0.4 mm, osseointegration within the extent of the defect 10.0 +/- 3.9% and 15.3 +/- 5.3%, osseointegration within the extent of regenerated bone 30.4 +/- 13.7% and 52.1 +/- 17.9%, and osseointegration within the alveolar base 68.8 +/- 13.1% and 74.4 +/- 7.1% for guided bone sites with and without demineralized bone, respectively (P > .05). The results suggest that freeze-dried demineralized bone has no adjunctive effect on guided bone regeneration in supra-alveolar peri-implant defects, that guided bone regeneration has a limited potential to enhance alveolar regeneration in this defect model, and that a 16-week healing interval appears insufficient for turnover and maturation of demineralized bone under provisions for guided bone regeneration.

Alveolar Bone Loss↗
PubMed1999

Bone regeneration produced in rat femur defects by polymer capsules containing recombinant human bone morphogenetic protein-2.

PURPOSE: This study examines the effect of polymer capsules containing recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone regeneration in a large segmental bone defect in the rat. MATERIALS AND METHODS: Poly(DL-lactide-co-glycolide) (PLGA) capsules containing 3 microg of rhBMP-2 were implanted in a 5-mm segmental femoral defect in rats, and the femurs were harvested at 4 and 8 weeks after implantation and observed by radiographically and microscopically. RESULTS: At 8 weeks after implantation, union of bone was found radiographically and histologically in the femoral defects implanted with the rhBMP-2/PLGA capsules. In contrast, the control animals did not show bridging of the defect. CONCLUSIONS: This study provides evidence that use of rhBMP-2/PLGA capsules is a promising delivery system to regenerate bone.

Animals↗
PubMedDate not supplied

Treatment of peri-implant defects with guided bone regeneration: a comparative clinical study with various membranes and bone grafts.

In this clinical study, a bioabsorbable membrane (Biofix) and two augmentation membranes made of expanded polytetrafluoroethylene (Gore-Tex) were tested for their osteopromotive potential. Forty-six implants were augmented with Gore-Tex membranes, 45 implants with titanium-reinforced Gore-Tex membranes, and 38 peri-implant defects with a resorbable polyglycolid membrane (Biofix). Autogenous bone (n = 85) and bovine bone matrix (Bio-Oss, n = 16) were used as filling materials beneath membranes. The results showed that bone repair is significantly improved by the use of membrane techniques. The average rate of bone regeneration with non-resorbable membranes was 84% (GTAM) and 81% (TR-GTAM). The use of Biofix membranes resulted in an average bone gain of 60%. The differences in efficacy established for the three types of membranes were found to be statistically significant (P < .001). Barrier membranes represent a valid technique for the treatment of peri-implant defects. Clinical and histologic results showed that Bio-Oss is an osteoconductive scaffold that promotes new bone formation.

Absorbable Implants↗
PubMed1994

Experimental investigation of bone regeneration using Pyrost in animals.

A study was undertaken to investigate bone regeneration in guinea pig mandibles implanted with Pyrost in comparison with artificial bone defects as controls. Bone defects were prepared in the angles of mandibles of 30 guinea pigs. The findings demonstrated that this bone substitute material stimulated bone healing, i.e. bone regeneration, in comparison with empty control cavities. Bone regeneration and new bone formation were found to be more extensive in Pyrost-implanted areas than in controls.

Animals↗
PubMed2000

Bone morphogenetic proteins in human bone regeneration.

Recently, the first clinical reports on bone regeneration by two recombinant human bone morphogenetic proteins (rhBMPs), BMP-2 and BMP-7 (also named osteogenic protein-1, OP-1) have been published (1-4). Although both BMPs were able to support bone regeneration, a significant variation in individual response was observed with both proteins. Animal studies and laboratory experiments reveal a number of conditions that influence the osteoinductivity of BMP, such as BMP concentration, carrier properties and influence of local and systemic growth factors and hormones. In this paper, these studies and the clinical reports are reviewed, and the conditions that modulate the BMP-dependent osteoinduction are discussed. The information may provide clues as to how the performance of recombinant human BMP as bone-graft substitute in humans can be improved.

Animals↗
PubMed2003

Aging does not lessen the effectiveness of TGFbeta2-enhanced bone regeneration.

Controversy exists over the potency of bone healing in the aged skeleton, and there is concern that enhancement of bone regeneration after use of bone-stimulating growth factors may not be effective in the aged. In this study, 30 skeletally mature beagles (1-2 or 10-12 years old) had titanium implants placed bilaterally in the proximal humerus for a period of 4 weeks in a model of intramembranous bone regeneration. A bony defect made at the time of surgery created a 3-mm gap between the implant surface and the host bone. Some of the implants were treated with recombinant human TGFbeta2 (rhTGFbeta2) at various does (0.32-35 microg per implant), and some served as paired controls. The dose response was similar in young and old animals. The most effective dose, 35 microg, led to a 3-fold increase in the volume fraction of new bone within the gap in both the young (p = 0.001) and old (p = 0.002) animals. At this dose, there was a 5-fold increase in osteoblast surface. While age did not significantly affect the quantity of new bone formed as assessed by backscatter scanning electron microscopy, the older animals had thinner regenerated trabeculae that tended to be spaced more closely than the younger animals. Coupled with the finding that the increase in osteoid was greater in the old animals compared with the young animals, these qualitative differences suggest that there may have been a slight delay in the rate or a defect of mineralization in the old animals.

Aging↗
PubMed1982

Enhanced acceptance of regenerating bone marrow of random bred newborn mice by random bred adult mice.

Regenerating bone marrow of newborn random bred Sabra mice (9-13 days old) was obtained by the administration of two consecutive i.p. injections of hydroxyurea (HU) (2 x 100 mg/kg body wt), three days prior to collection of the marrow cells. The bone marrow of HU-treated newborn mice was assayed for CFU-S, CFU-C and plasma-clot-diffusion-chamber (PCDC) progenitor cells. A fourfold content of CFU-S was found in the regenerating bone marrow compared with that of the control marrow, while the level of CFU-C and PCDC progenitor cells was the same in treated and untreated newborn mice. In lethally irradiated adult, random bred Sabra recipient mice, transfused with regenerating bone marrow from newborn mice, the initial survival rate was greater than in irradiated animals receiving normal newborn marrow (75% as against 50%); marrow repopulation, 10-14 days after transfusion, was also greater in the former than in the latter group of animals (1.5-2x10(6) nucleated cells per femur as compared with 08.-2x10(5)). The bone marrow of these groups of mice was assayed for CFU-S, CFU-C and PCDC progenitor cells; with a cell inoculum of 5 x 10(4) i.v., 10(5) in vitro and 5 x 10(4) per DC, respectively, pluripotent and committed stem cells were detected in the experimental group and were lacking in control recipients. Regenerating bone marrow of newborn mice was also transfused into lethally irradiated splenectomized recipients. In this experimental group there was high mortality, low marrow repopulation and lack of CFU-S (5-10 x 10(4) cell inoculum). The results of this study indicate that, despite genetic differences among random bred Sabra mice, regenerating bone marrow of newborn mice "takes better" than normal marrow in lethally irradiated recipients. Improved marrow acceptance is possibly due to the increased content of activated CFU-S and/or pre-CFU-S in the regenerating bone marrow

Age Factors↗
PubMed1980

Unusually rapid bone regeneration following mandibular resection.

Two cases of unusually rapid and extensive bone regeneration are presented. Heterotopic bone formation in small deposits has often been reported in the literature, but bone regeneration extending over a distance of one half of the mandible in a period of six months is extremely rare. Both patients were young and had had a resection performed for benign lesions which were infected at the time of operation. Preservation of periosteum, coupled with the age of the patients, possible genetic factors and infection may play important roles in rapid bone regeneration.

Adolescent↗