Electrospun Biomimetic Periosteum Promotes Diabetic Bone Defect Regeneration through Regulating Macrophage Polarization and Sequential Drug Release

The inadequate vascularization and abnormal immune microenvironment in the diabetic bone defect region present a significant challenge to osteogenic regulation. Inspired by the distinctive characteristics of healing staged in diabetic bone defects and the structure-function relationship in the natural periosteum, we fabricated an electrospun bilayer biomimetic periosteum (Bilayer@E) to promote regeneration of diabetic bone defects. Here, the inner layer of biomimetic periosteum was fabricated using coaxial electrospinning fibers, with a shell incorporating zinc oxide nanoparticles (ZnO NPs) and a core containing silicon dioxide nanoparticles (SiO₂ NPs) mimicking the cambium of periosteum; the outer layer consisted of randomly aligned electrospun fibers loaded with deferoxamine (DFO), simulating the fibrous layer of periosteum; finally, epigallocatechin-3-gallate (EGCG) was coated onto the bilayer membrane to obtain Bilayer@E. The presence of EGCG on the Bilayer@E surface efficiently triggers a phenotypic transition in macrophages, shifting them from an M1 proinflammatory state to an M2 anti-inflammatory state. Moreover, the sequential release of ZnO NPs, DFO, and SiO₂ NPs exhibits antimicrobial characteristics while coordinating angiogenesis and promoting osteogenic mineralization in cells. Importantly, the biomimetic periosteum shows strong <i>in vivo</i> bone tissue and periosteal regeneration properties in diabetic rats. The integration of sequential drug release and immunomodulation, tailored to meet the specific healing requirements during bone regeneration, offers new insights for advancing the application of biomaterials in this field.