Combined Mesenchymal Stem Cell Sheets and rhBMP-2-Releasing Calcium Sulfate–rhBMP-2 Scaffolds for Segmental Bone Tissue Engineering

Abstract

Repair of segmental bone defects remains a major challenge for orthopedic surgeons. This study aimed to investigate whether recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium sulfate (CS) combined with mesenchymal stem cell (MSC) sheets could accelerate bone regeneration in ulnar segmental defects of rabbits. In vitro, the osteogenic differentiation of MSCs cultured on rhBMP-2-loaded CS was investigated. Forty complete 1.2-cm bone defects were treated with CS (group A), rhBMP-2-loaded CS (group B), MSC sheet-wrapped CS (group C), and MSC sheet-wrapped rhBMP-2-loaded CS (group D). At 4 and 8 weeks after implantation, the samples were treated by X-ray, microcomputed tomography, and histological observation. The rhBMP-2 could be released from the rhBMP-2-loaded CS scaffolds and maintain its bioactivity. The alkaline phosphatase (ALP) of MSCs cultured on rhBMP-2-loaded CS was significantly higher than that of CS at both 7 and 14 days ( p < 0.05). The defects treated with MSC sheet-wrapped rhBMP-2-loaded CS showed significantly higher scores by X-ray analysis and more bone formation determined by both histology and microcomputed tomography than the other three groups at both 4 and 8 weeks after implantation ( p < 0.05). No significant difference in X-ray score and bone formation was found between groups B and C, both significantly higher than group A ( p < 0.05). The results suggested that MSC sheet-wrapped rhBMP-2-loaded CS may be an effective approach to promote the repair of segmental bone defects and has great potential for repairing large segmental bone defects in clinic.