Guided Bone Regeneration Membrane Materials Loaded with Chimeric Nanovesicles Promote Early Bone Defect Regeneration

Abstract

Early bone defect regeneration remains a major clinical challenge owing to a compromised osteogenic microenvironment characterized by insufficient mineralization and immature collagen deposition, which severely impede mechanical stability. Although conventional guided bone regeneration (GBR) membranes provide passive barrier functions, their lack of dynamic immune response regulation often leads to delayed ossification. To address this critical gap, a plasma-treated polycaprolactone (PT-PCL) electrospun nanofiber membrane functionalized with ultrasound sequentially extruded stromal vascular fraction chimeric vesicles (USE-SCNVs) is developed. The ultrasound-sequential extrusion approach requires less equipment, is faster, and holds greater potential for clinical application than traditional extrusion methods. Compared with nanovesicles formed by simple adipose-derived stem cells, these nanovesicles are more efficiently internalized by macrophages and are enriched with miRNAs, s uch as miR-30b, which promote rapid M2 macrophage polarization. In vivo experiments demonstrated that the nanofiber membranes loaded with USE-SCNVs can promote the rapid formation and maturation of new bone in the bone defect area within 2 weeks, forming primarily mature bone with increased platelet-like bone density.