Bone morphogenetic protein (BMP)-2 plays an important role in bone growth and regeneration; however, BMP-2 is easily lost by diffusion through body fluid and has some inhibitory pathways. To address this problem, we previously immobilized recombinant human BMP-2 (rhBMP-2) on succinylated type I atelocollagen. Here, we examined the effect of immobilized rhBMP-2 in vitro and vivo. In ST2, MC3T3-E1, and C2C12 cells, alkaline phosphatase activity, which is a marker of osteoblast differentiation, was enhanced more by immobilized than nonimmobilized rhBMP-2. In addition, the phosphorylation of receptor-activated Smads, part of the signaling pathway activated by BMP-2, was prolonged by immobilized rhBMP-2 in these cells. Furthermore, implantation of immobilized rhBMP-2 into the backs of rats promoted the formation of mature bone-like structure. These results demonstrate that immobilized rhBMP-2 has higher bioactivity than nonimmobilized rhBMP-2, and, therefore, immobilization of rhBMP-2 can prolong BMP signaling.

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We investigated the osteogenic potential of a combination graft of beta-tricalcium phosphate (TCP) and periosteum in the rat calvarial defect model. The combination beta-TCP and periosteum graft was grafted into rat calvarial defects; the newly formed bone in the defect was studied histologically and radiographically and compared with periosteum grafts and TCP grafts. Ten days after combination grafting, the grafted periosteum showed cell proliferation and Runx2 immunoreaction; 20 days after grafting, new bone formation was seen around the beta-TCP; and 30 days after grafting, new bone developed and actively replaced beta-TCP, while radiography showed calcified areas. Total bone formation of the combination periosteum and beta-TCP graft was significantly increased compared with single grafts of beta-TCP or periosteum (P < 0.01). The combination graft of periosteum and beta-TCP showed marked bone formation in rat calvarial defects. This result suggests that combination grafts may be effective for repairing bone defects.

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