Effect of recombinant human bone morphogenetic protein-4 with carriers in rat calvarial defects

Background: Bone morphogenetic proteins (BMPs) are being evaluated as candidates for periodontal and bone regenerative therapy. However, the research on recombinant human bone morphogenetic protein-4 (rhBMP-4) has been insufficient to evaluate its capacity to enhance bone formation and its carrier system. The purpose of this study was to evaluate the bone regenerative effect of rhBMP-4 delivered with an absorbable collagen sponge (ACS) or β-tricalcium phosphate (β-TCP). We also compared the potential of β-TCP to that of ACS as a carrier system for rhBMP-4. Methods: Eight-mm calvarial critical-sized defects were created in 100 male Sprague-Dawley rats. The animals were divided into 5 groups of 20 animals each. The defects were treated with rhBMP-4/ACS (rhBMP-4 at 0.05 mg/ml), rhBMP-4/β-TCP (rhBMP-4 at 0.05 mg/ml), ACS alone, β-TCP alone, or left untreated for surgical control. The rats were sacrificed at 2 or 8 weeks postsurgery, and the results were evaluated radiodensitometrically, histologically, and histomorphometrically. Results: The results of radiodensitometric analysis were as follows: the rhBMP-4/ACS and the rhBMP-4/β-TCP groups were more radiopaque than other groups at both 2 and 8 weeks (P <0.01). The histologic observations were as follows: in the rhBMP-4/ACS and the rhBMP-4/β-TCP groups, new bone was evident at the defect sites at 2 weeks and 8 weeks. The results of histomorphometric analysis were as follows: the rhBMP-4/ACS and the rhBMP-4/β-TCP groups had more bone (%) than other groups at both 2 and 8 weeks (P <0.01). Conclusions: Surgical implantation of rhBMP-4/ACS may be used to support bone regeneration in the rat calvarial critical-sized defect, and rhBMP-4/β-TCP may be able to regenerate bone in the rat calvarial critical-sized defect without complication. In addition, both ACS and β-TCP may be considered as available carriers for rhBMP-4.