Osteogenic evaluation of calcium/magnesium-doped mesoporous silica scaffold with incorporation of rhBMP-2 by synchrotron radiation-based μCT

Abstract

The regenerative treatment of large osseous defects remains a formidable challenge in orthopedic surgery today. In the present study, we have synthesized biodegradable calcium/magnesium-doped silica-based scaffolds with hierarchically macro/mesoporous structure (CMMS), and incorporated recombinant human bone morphogenetic protein-2 (rhBMP-2) into the scaffolds to obtain a hybrid system for osteogenic factor delivery in the functional repair of bone defects. The developed CMMS/rhBMP-2 scaffolds presented interconnected porous network, macropores (200–500 μm) and mesopores (5.7 nm), as well as good bioactivity and biocompatibility and proper degradation rate. Combined with the capacity to deliver ions and growth factors, the CMMS/rhBMP-2 scaffolds significantly promoted the in vitro osteogenic differentiation of bone marrow stromal cells (bMSCs), as evidenced by the enhanced expression of Runx-2, osteopontin, osteocalcin and bone sialoprotein, and induced the ectopic bone formation in the thigh muscle pouches of mice. We further assessed the in vivo effects of CMMS/rhBMP-2 scaffolds in a rabbit femur cavity defect model by using synchrotron radiation-based μCT (SRμCT) imaging and histological analysis, indicating that the CMMS/rhBMP-2 scaffolds resulted in more bone regeneration compared to that observed with the CMMS scaffolds without rhBMP-2. Moreover, scaffolds with or without rhBMP-2 underwent gradual resorption and replacement with bone and almost disappeared at 12 weeks, while the dense CMMS/rhBMP-2 material showed slower degradation rate and promoted the least extensive neo-bone formation. This study suggested that the hybrid CMMS/rhBMP-2 scaffolds system demonstrates promise for bone regeneration in clinical case of large bone defects.