Bone regenerative efficacy of limited-dose Escherichia coli-derived rhBMP-2 with biphasic calcium phosphate carrier in rabbit calvarial defect model

Purpose: The aim of this study was to characterize the healing in rabbit calvarial bone defects after delivery of limited-dose (1.5 g) Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2), and evaluate biphasic calcium phosphate (BCP) as a carrier. Materials and Methods: Four 8-mm diameter circular calvarial bone defects were made in 16 rabbits and filled with one of the following: (1) nothing, (2) BCP alone, (3) ErhBMP-2-loaded absorbable collagen sponge (ACS), or (4) ErhBMP-2-loaded BCP. The animals were allowed to heal for either 2 or 8 weeks and were evaluated in clinical, microcomputed tomographic, histological, and histomorphometric analyses. Results: Microcomputed tomography revealed extensive new bone formation in both of the limited-dose ErhBMP-2-loaded groups. However, bony collapse of the upper defect borders was found in the ErhBMP-2-loaded ACS group. Histomorphometric examination revealed significantly greater new bone formation at 8 weeks than at 2 weeks in all 4 groups (P < 0.05). Both new bone formation and the size of the augmented area differed significantly between the ErhBMP-2-loaded BCP group (6.88 ± 0.74 and 19.62 ± 0.77) and the ErhBMP-2-loaded ACS group (3.04 ± 0.27 and 5.41 ± 0.43) at 8 weeks of healing. Conclusion: ErhBMP-2 promotes bone regeneration in rabbit calvarial defects, even at a limited dose (1.5 g). The results of this study suggest that BCP is the more efficient carrier for this protein than ACS.