Induction of bone formation by Escherichia coli-expressed recombinant human bone morphogenetic protein-2 using block-type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models

Objective: The potential of the Escherichia coli-expressed recombinant human bone morphogenetic protein-2 (ErhBMP-2) to support new bone formation/maturation using a block-type of macroporous biphasic calcium phosphate (bMBCP) carrier was evaluated in an orthotopic and ectopic rat model. Material and Methods: Critical-size (Φ8mm) calvarial defects and subcutaneous pockets in 32 Sprague-Dawley rats received implants of rhBMP-2 (2.5μg) in a bMBCP carrier or bMBCP alone (control). Implant sites were evaluated using histological and histometric analysis following 2- and 8-wk healing intervals (eight animals/group/interval). Results: ErhBMP-2/bMBCP supported significantly greater bone formation at 2 and 8wk (10.8% and 25.4%, respectively) than the control at 2 and 8wk (5.3% and 14.0%, respectively) in calvarial defects (p<0.01). Bone formation was only observed for the ErhBMP-2/bMBCP ectopic sites and was significantly greater at 8wk (7.5%) than at 2wk (4.5%) (p<0.01). Appositional and endochondral bone formation was usually associated with a significant increase in fatty marrow at 8wk. The bMBCP carrier showed no evidence of bioresorption. Conclusion: ErhBMP-2/bMBCP induced significant bone formation in both calvarial and ectopic sites. Further study appears to be required to evaluate the relevance of the bMBCP carrier.