Enhancement of Recombinant Human BMP-7 Bone Formation with BMP Binding Peptide in a Rodent Femoral Defect Model

Bone morphogenetic binding peptide (BBP) is an 18.5 kDa fragment of a bone matrix protein peptide. A rat femoral defect model was used to test the effect of BBP combined with recombinant human bone morphogenetic protein-7 (rhBMP-7) to induced bone healing. Two doses of BBP (500 and 1000 mu g) were tested with two doses of rhBMP-7 (2 and 5 mu g), and the results were compared with a positive control (10 mu g rhBMP-7). Bone healing was evaluated by radiology, manual palpation, microcomputed tomography, and histology. The high dose of 10 mu g of rhBMP-7 resulted in a consistent 100% bone union rate and a mature histological appearance on histology, and was used as a positive control. When 1000 mu g of BBP was combined with lower doses of BMP-7 (2 mu g rhBMP-7 or 5 mu g rhBMP-7) significant differences were seen in radiographic scores, manual palpation, and bone volume, when compared to 2 mu g rhBMP-7 or 5 mu g rhBMP-7 alone. The combination of 1000 mu g of BBP and 5 mu g rhBMP-7 also achieved 100% fusion rate, induced a larger amount of bone formation, and yielded similar maturity of bone marrow when compared with the high dosage 10 mu g rhBMP-7 group. This study demonstrated that when combined together, BBP can enhance the bone healing of rhBMP-7. Improved healing imparted by the addition of BBP may result in lesser amounts of rhBMP-7 needed to achieve union in the clinical setting. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:753-759, 2011