Resveratrol-liposomes loaded polyvinyl alcohol-chitosan fiber scaffolds mediate bone regeneration via autophagy: synergizing angiogenesis and immunomodulation

The core difficulty in bone defect repair lies in the simultaneous regulation of immunity, angiogenesis and osteogenesis. In this study, hydrophobic resveratrol (Res) was encapsulated in liposomes (LP), and then co -spun with polyvinyl alcohol-chitosan (PVA-CS) to construct a “drug-liposome-fiber” multi-level drug-controlled-release scaffold (RL/PVA-CS). Physicochemical characterization confirmed that this scaffold could sustain the release of Res, and CS incorporation significantly enhanced mechanical properties of the PVA-based fiber scaffold. In vitro studies confirmed that the RL/PVA-CS scaffold not only efficiently scavenged free radicals, regulated macrophage polarization to M2 type to improve the immune microenvironment, but also demonstrated a significant potential for promoting angiogenesis. Moreover, this scaffold could effectively recruit bone marrow mesenchymal stem cells (BMSCs) and drove their osteogenic differentiation and matrix mineralization by activating the autophagy pathway. In a rat cranial defect model, the implantation of the RL/PVA-CS scaffold demonstrated excellent angiogenic ability and osteogenic performance, significantly accelerating bone defect repair. The main innovation of this study is the development of a dual-release and multi-functional synergistic RL/PVA-CS fiber scaffold. This system effectively protects drug activity, overcomes single-function limits of traditional materials, coordinates immunity, angiogenesis and osteogenesis via autophagy, offering an integrated solution for complex bone defects.