GelMA‐Based Hydrogel Encapsulating Astragalus Polysaccharides and Umbilical Cord Mesenchymal Stem Cell Exosomes Promotes Full‐Thickness Skin Wound Healing

Background Wound healing involves excessive oxidative stress and cellular dysfunction, while current single therapies remain inadequate. Astragalus polysaccharides (APS) and exosomes (Exos) possess antioxidative and regenerative properties, and gelatin methacryloyl (GelMA) hydrogel provides a biocompatible platform for localized delivery. Here, we developed an APS–Exos@GelMA hydrogel to promote wound repair. Methods The biological effects of APS and Exos were assessed through in vitro cellular assays, while the physicochemical properties and biocompatibility of APS–Exos@GelMA were characterized. Its therapeutic efficacy was further evaluated in a full‐thickness skin defect model through macroscopic observation and histological analysis. Results APS–Exos treatment showed enhanced effects compared with APS or Exos alone, improving fibroblast (130.90% ± 2.98%, p < 0.05) and keratinocyte (124.50% ± 3.18%, p < 0.01) viability, promoting fibroblast migration (74.15% ± 7.72%), and reducing oxidative damage (72.11% ± 2.13%). APS–Exos@GelMA maintained favorable hydrogel properties and biocompatibility while enabling localized incorporation and application of APS and Exos. In vivo, APS–Exos@GelMA accelerated wound closure, promoted epidermal reconstruction and extracellular matrix deposition, and exhibited good biosafety. Conclusion The combination of APS and Exos within an appropriate concentration range demonstrated improved therapeutic potential compared with individual treatments. The APS–Exos@GelMA hydrogel served as a biocompatible localized delivery platform to facilitate tissue repair, highlighting its potential for wound‐healing applications.