An Icariin-Loaded PCL Electrospun Scaffold for Enhanced Tendon-Bone Healing in Rotator Cuff Repair

OBJECTIVE: This study aimed to fabricate an icariin (ICA)-loaded polycaprolactone (PCL) electrospun scaffold and systematically evaluate its effects on tendon-bone healing in a rat rotator cuff injury model, with particular focus on its immunomodulatory, angiogenic, and fibrocartilaginous regeneration capabilities. METHODS: ICA-PCL scaffolds were prepared using electrospinning technology and characterized for microstructure, drug release kinetics, and cytocompatibility. In vitro experiments involved LPS-induced rat bone marrow mesenchymal stem cells (rBMSCs) and brain microvascular endothelial cells to assess anti-inflammatory, antioxidant, and pro-angiogenic effects. In vivo evaluations were conducted in a rat rotator cuff injury model using histological staining, immunofluorescence, western blot, and ELISA to analyze tissue regeneration, macrophage polarization, and safety profiles at 4 and 8 weeks post-implantation. RESULTS: The ICA-PCL scaffold displayed a biphasic release pattern with initial burst release followed by sustained ICA delivery. In vitro, it significantly enhanced rBMSC proliferation, reduced apoptosis and oxidative stress, downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and promoted endothelial tube formation. In vivo results demonstrated that the scaffold modulated macrophage polarization toward M2 phenotype, enhanced angiogenesis (increased CD31/EMCN expression), and facilitated fibrocartilaginous interface regeneration with organized collagen architecture and elevated collagen I/II expression. No evident systemic toxicity or organ damage was observed. CONCLUSION: The ICA-PCL electrospun scaffold effectively promotes tendon-bone healing through multi-mechanistic actions, including immunomodulation, angiogenesis promotion, and structured interface regeneration, demonstrating significant potential as a comprehensive therapeutic strategy for rotator cuff repair.