Recombinant Human Bone Morphogenetic Protein-2 as an Osteoinductive Biomaterial and a Biodegradable Carrier in a Rabbit Ulnar Defect Model

摘要

We investigated early local changes induced by recombinant human bone morphogenetic protein(rhBMP)-2 and a novel carrier,poly[L-lactide-co-glycolide]copolymer-coated gelatin sponge(PGS).A 1.5 cm segmental bone defect was created in the diaphysis of the right ulna of male Japanese white rabbit.Defects received PGS with or without rhBMP-2(0,0.4,or 1 mg/cm3)and were harvested at 3,7,14,21,or 28 days post implantation for histological examination.Immuno-staining for vascular endothelial growth factor(VEGF)was also performed.Spindle-shaped cells were observed in the rhBMP-2-treated groups 3 and 7 days after implantation.Bone regeneration was detected after 14 days in the rhBMP-2-treated groups and the bone area increased with time and dose.Expression of VEGF was observed in all groups at 3 days and was maintained by 14 days only in the defects treated with rhBMP-2 at a dose of 1 mg.These results indicate that rhBMP-2 exert its osteo-inductive activities via the promotion of osteogenic cell mobilization,and possibly via angiogenesis based on VEGF induction.Foreign-body reactions to the implanted PGS were similar to those observed when either poly[L-lactide-co-glycolide]copolymer or gelatin was individually implanted.These results indicate that the PGS is a useful and safe carrier for rhBMP-2.