Enhancing bone defect repair by core-shell nanofibrous scaffolds through phase separation-activated autophagy process along with neurogenesis

Bone defects caused by aging or trauma often involve sensory loss, highlighting the need for scaffolds that support both bone regeneration and sensory recovery. This study reports an amino-modified mesoporous bioactive glass (MBG-NH 2 )/K63@silk fibroin (SF)/nerve growth factor (NGF) nanofiber scaffold. The scaffold showed nanoscale porosity, favorable mechanical properties, and calcium deposition in R-simulated body fluid (R-SBF). It promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) through Erk1/2-Runx2 signaling and induced autophagy via K63/p62/LC3-mediated separation, accompanied by increased expression of osteogenesis- and neurogenesis-specific genes. The scaffold supported neural differentiation, as indicated by increased expression of neurogenesis-related genes. The MBG-NH 2 /K63@SF/NGF scaffold significantly improved skull bone repair and the formation of new neurons within Haversian canals in the defect area of mice. The MBG-NH 2 /K63@SF/NGF scaffold promotes autophagy through phase separation and facilitates bone regeneration and neuron formation, indicating its potential as a multifunctional biomaterial for bone defect repair with neuron formation.