Abstract / Summary
The treatment of corrosive esophageal injury (CEI) remains challenging due to recurrent courses, frequent complications, and severe tissue damage. Enhancing the therapeutic potential of mesenchymal stem cell-derived small extracellular vesicles (sEVs) through cytokine preconditioning has emerged as a promising strategy. In this study, functionally enhanced sEVs (E-sEVs) were generated by pretreating umbilical cord-derived mesenchymal stem cells with interleukin-6 (IL-6). E-sEVs exhibited superior capabilities in promoting fibroblast migration and suppressing macrophage-mediated inflammation compared to naïve sEVs. To improve local retention and therapeutic efficacy, E-sEVs were integrated into a cationic hyaluronic acid (CHA) hydrogel with strong bioadhesive properties, forming a composite system termed E-sEVs@CHA. In vitro assays demonstrated that E-sEVs@CHA effectively promoted endothelial cell invasion, exhibited antioxidant activity, and modulated macrophage polarization toward an anti-inflammatory phenotype. In a rat model of CEI, E-sEVs@CHA significantly reduced esophageal inflammation, oxidative stress, and fibrotic remodeling, leading to improved tissue repair and reduced stricture formation. This study presents a novel cell-free therapeutic strategy with translational potential for the management of corrosive esophageal injury.