Mimicking bone matrix through coaxial electrospinning of core-shell nanofibrous scaffold for improving neurogenesis bone regeneration

There is a significant clinical demand for bone repair materials with high efficacy. This study was designed to fabricate nanofibrous scaffolds to promote bone defect regeneration using magnesium doped mesoporous bioactive glass (MBG), a fusion protein Osteocalcin-Osteopontin-Biglycan (OOB), silk fibroin (SF) and nerve growth factor (NGF) for facilitating accelerated bone formation. We found that MBG adsorbed with OOB ([email protected]) as core, and SF adsorbed with NGF ([email protected]) as shell to fabricate the nanofibrous scaffolds ([email protected]/[email protected]) through coaxial electrospinning. [email protected]/[email protected] scaffolds could effectively mimic the component and structure of bone matrix. Interestingly, we observed that [email protected]/[email protected] scaffolds could substantially promote bone mesenchymal stem cells (BMSCs) osteogenesis through stimulating Erk1/2 activated Runx2 and mTOR pathway, and it could also activate the expression level of various osteogenic marker genes. Intriguingly, [email protected]/[email protected] scaffolds could also enhance BMSCs induced neural differentiation cells differentiated into neuron, and activate the expression of the different neuron specific marker genes. Moreover, it was found that [email protected]/[email protected] scaffolds accelerated bone regeneration with neurogenesis, and new neurons were formed in Haversian canal in vivo. Consistent with these observations, we found that Erk1/2 and mTOR signaling pathways also regulated osteogenesis with the neurogenesis process from RNA sequencing result. Overall, our findings provided novel evidence suggesting that [email protected]/[email protected] scaffolds could function as a potential biomaterial in accelerating bone defect regeneration with neurogenesis, as well as in recovering the motor ability and improving the quality of life of patients.