[Show abstract][Hide abstract] ABSTRACT: An experimental model for the prefabrication of a vascularized bone flap was developed in this study. To form vascularized bone in the desired configuration and to increase the survival rate of the grafted bone, a muscle vascularized pedicle (MVP) was transformed into vascularized bone by the inducer recombinant human bone morphogenetic protein 2 (rhBMP-2). The muscle flap (8 x 8 mm) raised on saphenous vessels in the rat thigh was sandwiched between same-size collagen (Terudermis) sheets in the presence or absence of impregnated 25 microg of rhBMP-2 for the experimental group and the control group, respectively. The flaps were harvested 1, 2 and 3 weeks postoperatively. Bone transformation was detected by gross examination, radiology, and histologic testing. No evidence of muscle tissue transformation was found in control flaps, whereas all of the experimental flaps produced new bone. Saphenous vessels were observed to supply the new bone upon harvesting, and the newly formed vascularized bone showed good configuration with shape of the Terudermis sheet. This study indicates that this model of effective bone reconstruction could be potentially applied in a therapeutic setting.
International Journal of Oral and Maxillofacial Surgery 11/2003; 32(5):508-14. DOI:10.1016/S0901-5027(03)90409-1 · 1.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Here we report that successful bone formation with a vascular flap inside a cylindrical mold was induced from fat tissue with the use of recombinant human bone morphogenetic protein-2 in rats. Fat tissue connected to blood vessels was prepared to fit into the mold and implanted intramuscularly into the hind leg in Wistar rats. RhBMP-2 (20 micro g) was applied in a collagen sheet previously placed on the inside surface of the mold. Bone formation was confirmed radiologically and morphologically at 2, 4, and 8 weeks after the surgery. In the control group without rhBMP-2 or the group with ligation of the blood vessels before the implantation, bone formation was not observed. Our success in bone formation having a definite size, shape, and blood supply may lead to a therapeutic approach to effective bone reconstitution. The present study is the first report on bone induction from fat tissue by rhBMP-2 in vivo.
Journal of Dental Research 09/2003; 82(8):581-4. DOI:10.1177/154405910308200802 · 4.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the long-term functional properties of regenerated bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) in segmental bone defects of primate mandibles. The 30-mm defects were created in the mandibles of six young monkeys and the mandibles were fixed with titanium plates. Then 9 mg of rhBMP-2 permeating a poly-D, L-lactic-co-glycolic acid-coated gelatin sponge (PGS) was implanted into the bone defect. Dental implants were placed into the regenerated mandible 20 weeks after surgery, then suprastructures were placed and masticatory force loading was begun 8 weeks after the insertion of the dental implants. Bone formation and the quality of new bone were evaluated radiologically and histologically at 15 and 30 weeks after surgery, and 4 and 24 weeks after masticatory force loading. The resected mandibles were completely regenerated with the rhBMP-2-induced bone. Excellent remodelling and consolidation of new bone were observed after loading. This study demonstrated that the new bone induced by rhBMP-2 in large segmental defects was maintained and functional for at least 1 year. Bone regeneration induced by rhBMP-2 holds promise as a future therapy and may be an effective alternative to autogenous bone grafts for implant dentistry and reconstructive surgery.
International Journal of Oral and Maxillofacial Surgery 07/2002; 31(3):287-95. DOI:10.1054/ijom.2001.0207 · 1.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was designed to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with poly D, L lactic-co-glycolic acid (PLGA)/gelatin sponge complex (PGS) on the formation of bone in critically sized marginal defects of the mandible in dogs. Three months after extraction of the pre-molar teeth, rectangular bone defects (10 x 8 x 7 mm) were made in both sides of the mandible. A PGS block soaked in rhBMP-2 (400 microgram/ml) was implanted into one defect (BMP (+) group). As control, an untreated PGS block was implanted into the contralateral defect (BMP (-) group). 2, 4, 8, and 12 weeks after implantation, the defects were examined. In the BMP (+) group, newly formed bone was found in all defects from 4 weeks onward and was marked at 12 weeks. In contrast, the BMP (-) group showed no appreciable new bone formation, even at 12 weeks. Moreover, density of newly formed bone in the BMP (+) group was similar to that of the surrounding cortical bone at 12 weeks. These findings suggest that rhBMP-2/PGS is an effective bone substitute for reconstructive surgery of the dog mandible.
International Journal of Oral and Maxillofacial Surgery 03/2002; 31(1):66-72. DOI:10.1054/ijom.2001.0133 · 1.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
British Journal of Oral and Maxillofacial Surgery 01/2002; 39(6):452-9. DOI:10.1054/bjom.2001.0673 · 1.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, an attempt was made to transform a muscle vascularized pedicle raised on host vessels into a vascularized bone flap, using recombinant human bone morphogenetic protein 2 (rhBMP-2). The purpose of this study was to produce new bone vascularized in nature to increase the survival rate of the subsequently grafted bone and to fabricate the newly formed bone into the desired shape. Silicone molds in the shape of a rat mandible were used to deliver rat bone matrix impregnated with or without rhBMP-2. A muscle pedicle the same size as the mold was raised on the saphenous vessels in the rat thigh and then sandwiched in the center of the silicone molds. The molds were sliced in half and each section was filled with rat bone matrix that was impregnated either with 25 microg of rhBMP-2 for the experimental group or with diluting material alone for the control group. The sandwiched flaps were then secured by tying them to the adjacent muscles and were harvested at 2 and 4 weeks after surgery. Three and six rats were used in the control and experimental groups at each time point, respectively. Bone formation was assessed in the ex vivo specimens by macroscopic, radiologic, and histologic evaluation. Macroscopically, the continuation of the vascular pedicle was clearly visible for both the control and experimental muscle flaps. However, no evidence of muscle-tissue transformation was observed in the control flaps, whereas all the flaps treated with rhBMP-2 produced new bone that replicated the shape of the mold exactly and had saphenous vessels supplying the newly formed bone. This study demonstrates that this experimental model has the potential to be therapeutically applied for effective bone reconstruction.
[Show abstract][Hide abstract] ABSTRACT: A new type of cultured mucosa was developed as a mucosal substitute. This composite cultured oral mucosa (CCOM) was composed of (1) a lamina propria in which fibroblasts were embedded in contacted collagen gel and honeycomb structured collagen sponge and (2) stratified epithelial cell layers on the surface of the cultured lamina propria. CCOM had a well-stratified and differentiated epithelial cell layer, and its involucrin and laminin expression resembled that of normal oral mucosa. Desmosomes were recognizable with transmission electron microscopic examination. In the lamina propria, contracted collagen gel had pooled away from the sponge wall, leaving a sparse structure inside the collagen sponge. Transplantation of CCOM to nude mice was performed by creating full-thickness wound and then applying CCOM (n = 12). Murine skin allograft (n = 4) and no-graft conditions (n = 5) served as controls. The mice were sacrificed for histological evaluation and assessed for wound contraction 28 days after transplantation. The epithelium of the CCOM-treated group had five to 10 cell layers, and the dermis contained many fibroblasts and a large amount of collagen bundles. The wound contraction of the CCOM-treated group was statistically less than that of the no-graft group. These results indicate that CCOM has barrier functions against various stresses and can induce a fibrovascular ingrowth from the surrounding wound bed, and that CCOM could be applied in a clinical setting.
[Show abstract][Hide abstract] ABSTRACT: This study evaluated whether recombinant human bone morphogenetic protein-2 (rhBMP-2) can be used to regenerate a resected part of the mandible in a primate model.
Segmental bone defects were created surgically in the mandible of Japanese monkeys. rhBMP-2 was suspended in a solution of polyglycolic co-lactic acid (PGLA) and lyophilized to make a BMP/PGLA complex. The rhBMP-2/PGLA complex and autogenous bone marrow in ratios of 3:0, 2.5:0.5, or 2:1 (vol:vol) were each implanted into the bone defects in 3 monkeys. Bone marrow or P(GLA alone were each implanted in 1 monkey as a control. The animals were killed 16 weeks after surgery, followed by radiologic and histologic evaluation.
The implantation of bone marrow alone succeeded in reconstruction of the mandible, but the implantation of the rhBMP-2/PGLA complex showed only a small amount of bone formation. The combination graft of rhBMP-2/PGLA and bone marrow resulted in a greater degree of bone formation; especially the 2:1 combination showed the same result as only bone marrow implantation.
The combination graft of rhBMP-2 and bone marrow, which requires only a small amount of bone marrow, was a reliable method for reconstruction of mandibular segmental defects in this animal model.
Journal of Oral and Maxillofacial Surgery 02/2001; 59(1):53-61; discussion 62-3. DOI:10.1053/joms.2001.19286 · 1.43 Impact Factor