Repair of 20-mm long rabbit radial bone defects using BMP-derived peptide combined with an alpha-tricalcium phosphate...

In previous studies, we have reported that the BMP-2-derived peptide KIPKASSVPTELSAISTLYL, corresponding to BMP-2 residues 73-92, binds to a BMP-2-specific receptor, and elevates both alkaline phosphatase activity and osteocalcin mRNA in the murine mesenchymal cell line, C3H10T1/2. This 73-92 peptide conjugated to a covalently crosslinked alginate gel induced ectopic bone formation in rat calf muscle, and activated osteoblasts to promote the repair of rat tibial bone defects. Here, we report repair of 20-mm long rabbit radial bone defects using the 73-92 peptide combined with a porous alpha-tricalcium phosphate (TCP) scaffold. In vitro, the 73-92 peptide was released from the porous alpha-TCP scaffold over more than one week. In vivo, radiomorphometric analysis showed that the 73-92 peptide combined with the porous alpha-TCP scaffold promoted calcification in the implanted area in a dose-dependent manner, and that 5 mg of the 73-92 peptide induced connection of 20-mm long defects, defects of critical size, 12 weeks after implantation. Histological examination revealed newly formed bone and a marrow cavity in the implanted area. The area of bone denser than 690 mg/cm(3) induced by the 73-92 peptide was nearly equal to that of the contralateral radius.