Effect of bone morphogenetic protein-2/hydroxyapatite on ankle fusion with bone defect in a rabbit model: A pilot study

Abstract

Background: Revision ankle-fusion surgery after a failure of total ankle arthroplasty has a problem with bone-defect management by implant removal. For the reconstruction of bone defects, autogenous bone often causes minor and major complications. Recombinant human-bone morphogenetic protein-2 (rhBMP-2) plays essential roles in bone regeneration strategies, and hydroxyapatite (HA) is beneficial as the rhBMP-2 carrier. In this study, we evaluate whether rhBMP-2/HA can replace autogenous bone in a rabbit ankle-fusion model with distal tibia bone defect. Methods: The bone defect was created in the distal tibia. The ankle fusion was performed by a cannulated screw from lateral malleolus and various treatments on bone defect. Thirty male white New Zealand rabbits were divided into three groups of 10 animals on each group dependent on treatment methods as control group (no treatment into defect), auto-bone group (autogenous bone treatment), and rhBMP-2/HA group (40 μL of 1 μg/mL rhBMP-2/100 μL HA). Bone formation on defect and the union of the ankle joint were evaluated by X-ray, micro-CT, and histological analysis at 8 weeks and 12 weeks, postoperatively. Results: Radiographic assessment found the control and auto-bone groups still had the bone defect present, but rhBMP-2/HA group showed complete replacement of the defect with newly formed bone at 12 weeks. Micro-CT showed significantly higher new bone formation within the defect in the rhBMP-2/HA group than in the auto-bone and control groups at 8 weeks (p > 0.05 and p < 0.01, respectively) and 12 weeks (p < 0.05, p < 0.001, respectively). Fusion rate (%) analysis of micro-CT showed a higher percentage of union in the rhBMP-2/HA group than in the auto bone and control groups at 8 weeks (p > 0.05, p < 0.001, respectively) and 12 weeks (p < 0.001 and p < 0.001, respectively). The histological showed the highest osteointegration between distal tibia and talus in the rhBMP-2/HA group at 12 weeks. Conclusions: This study indicated that rhBMP-2/HA showed much better bone fusion than did the autogenous bone graft and was effective in promoting fusion rate and improving the quality of the ankle joint fusion.