Preparation of DFO/HACC/PCL-gel coaxial electrospun nanofibrous membranes and their effect on bone defect repair

• Fabricates HACC/DFO-loaded coaxial electrospun nanofibrous membranes. • Achieves sustained DFO release and good degradability via core–shell structure. • Shows high antibacterial activity and good biocompatibility in vitro. • Upregulates VEGF in vitro and enhances angiogenesis and osteogenesis in vivo. Persistent risks of infection, insufficient angiogenesis, and weak osteogenic function hinder bone defect repair. This study designed a coaxial electrospun nanofibrous membrane loaded with HACC and DFO (DHPG) to address these challenges by simulating the periosteal structure. Experiments confirmed that the optimal loading concentrations of HACC and DFO were 3% and 10 μmol/mL, respectively. Material characterization showed DHPG had a nanoscale fiber diameter, good hydrophilicity, appropriate degradability and sustained release ability. In vitro, HACC inhibited Staphylococcus aureus and Escherichia coli , reducing the risk of infection; DFO promoted cell migration, angiogenesis, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by upregulating Vascular Endothelial Growth Factor (VEGF) expression. In vivo experiments using a mouse calvarial defect model confirmed that DHPG accelerated vascular regeneration and new bone formation in the defect area without obvious toxic side effects. By mimicking the structure and function of the periosteum, this material balances anti-infection effects with a favorable bone regeneration microenvironment. It provides a novel approach to addressing the challenge of inefficient bone defect repair under infection interference, offers robust evidence for multifunctional tissue-engineered scaffold design, and bridges basic research and clinical applications.