Biomimetic multilayer nanofiber membranes with sequential drug release–coupled angiogenesis and osteogenesis for guided bone regeneration

Abstract The repair of critical-sized bone defects remains a significant challenge in regenerative medicine. Using guided bone regeneration (GBR) membranes has emerged as a promising treatment strategy. In this study, we fabricate a novel multilayer density-gradient electrospun nanofiber membrane comprising bone morphogenetic protein-2 (BMP-2) combined with nano-hydroxyapatite (nHA) and vascular endothelial growth factor (VEGF) embedded in a polylactic acid (PLA) and type I collagen (COL) nanofiber matrix, denoted as BMP-2@nHA/VEGF@(PLA/COL). The gradient density structure of membranes is engineered to mimic the periosteum tissue, thereby creating an optimal microenvironment for bone regeneration while preventing soft tissue invasion. The membrane exhibits commendable mechanical properties and favorable degradation characteristics. Drug release experiments reveal that the membrane enables an early-phase release of VEGF, coupled with a prolonged release of BMP-2, advantageous for fostering early vascularization and long-term osteogenesis. In vitro studies confirm that the membrane effectively maintains barrier function while enhancing the coordinated advancement of both vascularization and osteogenesis. Furthermore, experiments with a rat cranial bone defect model demonstrate that the membrane substantially accelerates bone regeneration. Consequently, the bionic membrane developed in this research shows considerable potential for clinical applications in GBR therapies.