Bone regeneration using moldable calcium phosphate with and without recombinant human BMP-2 in a rabbit critical-sized metaphyseal core defect model.

Abstract

BACKGROUND: Moldable calcium phosphate (MCaP) biomaterials have been studied as osteoconductive scaffolds for bone regeneration. However, their potential as carriers for recombinant human bone morphogenetic protein-2 (rhBMP-2) and the biological impact of varying rhBMP-2 doses remain to be fully validated. This study aimed to evaluate the efficacy and safety of MCaP alone and in combination with rhBMP-2 in a rabbit metaphyseal bone defect model. METHODS: Bilateral critical-sized metaphyseal core defects were created in the distal femurs of 73 skeletally mature female New Zealand White rabbits. Animals were assigned to six groups: sham, autograft, MCaP alone, or MCaP combined with low (0.04 mg/cc), mid (0.16 mg/cc), or high (0.6 mg/cc) doses of rhBMP-2. Bone formation and healing were assessed at 3 days and 3, 6, and 12 weeks using radiography, microcomputed tomography (&#x3bc;CT), histomorphometry, and histopathology. Local tissue reactions were evaluated according to ISO 10993-6 standards, and systemic toxicity was assessed through distant organ examinations. RESULTS: Radiographic and &#x3bc;CT analyses showed progressive bone formation in all treatment groups. Compared with autografts, both the MCaP and rhBMP-2-treated groups exhibited significantly higher bone in the region of interest at 6 and 12&#xa0;weeks (p&#x2009;<&#x2009;0.05), with no significant differences between the MCaP-only and rhBMP-2 groups. Histological evaluation revealed earlier and more active bone regeneration in rhBMP-2-treated groups, particularly at higher doses. Minimal inflammatory responses were observed across all groups, and no systemic toxicity was detected, supporting the biocompatibility and safety of MCaP-based constructs. CONCLUSIONS: The MCaP carrier demonstrated strong osteoconductive potential and was sufficient to support bone healing compared to autograft in a metaphyseal defect model. The addition of rhBMP-2 promoted earlier bone formation. However, long-term studies in more challenging bone healing environments are warranted to further assess the clinical utility of rhBMP-2 in bone regeneration.