An icariin-loaded Polycaprolactone (PCL) electrospun scaffold for enhanced tendon-bone healing in rotator cuff repair

BACKGROUND: 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 lipopolysaccharide-induced rat bone marrow mesenchymal stem cells and brain microvascular endothelial cells to assess anti-inflammatory, antioxidant, and proangiogenic effects. In vivo evaluations were conducted in a rat rotator cuff injury model using histological staining, immunofluorescence, western blot, and Enzyme-Linked Immunosorbent Assay to analyze tissue regeneration, macrophage polarization, and safety profiles at 4 and 8 weeks postimplantation. RESULTS: The ICA-PCL scaffold displayed a biphasic release pattern with initial burst release followed by sustained ICA delivery. In vitro, it significantly enhanced rat bone marrow mesenchymal stem cell 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 multimechanistic actions, including immunomodulation, angiogenesis promotion, and structured interface regeneration, demonstrating significant potential as a comprehensive therapeutic strategy for rotator cuff repair.