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 f...

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Main Authors: Hyun Seung Ryu, Hyun Jung Park, Mi Young Ryu, Young-Hoon Kim, Sang-Il Kim, Hyung-Youl Park
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Orthopaedic Surgery and Research
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Online Access:https://doi.org/10.1186/s13018-025-05966-y
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Summary: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 (μCT), 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 μCT 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 weeks (p < 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.
ISSN:1749-799X