The C-glycosyl flavonoid swertisin delivered from a composite hydrogel accelerates skin wound repair.

Achieving coordinated inflammation resolution, oxidative stress control, and angiogenesis remains a key goal for skin wound repair. The plant-derived C-glycosyl flavonoid swertisin has known anti-inflammatory and antioxidant effects, but its role in skin wound repair remains untested. Herein, we loaded swertisin into a sodium alginate/silk sericin composite hydrogel and tested it in a mouse full-thickness skin wound model. The hydrogel released swertisin steadily over 7 days without burst release and maintained a moist, cytocompatible wound environment. In vitro, it promoted fibroblast migration and proliferation. In vivo, it accelerated wound closure and achieved near-complete re-epithelialization by day 10, with improved collagen deposition and extracellular matrix organization. Specifically, the treatment reduced NF-κB p65 nuclear translocation, lowered pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), and increased angiogenic markers CD31 and VEGF. It also upregulated Nrf2 and CD206, reduced iNOS, and moderately modulated TGF-β1, indicating coordinated regulation of antioxidant defense, macrophage polarization, and matrix remodeling. No adverse effects were detected in major organs. Notably, this study provides the first evidence that locally delivered swertisin, released from a natural polymer-based hydrogel, can promote full-thickness skin wound repair by dampening inflammation, restoring redox balance, and boosting angiogenesis, offering a promising approach for wound management.