ROS-responsive GelMA/L-Arginine hydrogel with locally sustained NO release for accelerated skin wound healing

Nitric oxide (NO) plays crucial regulatory roles in accelerating cutaneous wound repair via modulating angiogenesis and macrophage polarization. Herein, a reactive oxygen species (ROS)-responsive GelMA/L-arginine (L-Arg) composite hydrogel was fabricated through 405-nm photocrosslinking for localized NO delivery and high-efficiency wound treatment. Physicochemical characterizations verified that L-Arg incorporation maintained the favorable moldability and interconnected porous microstructure of pristine GelMA hydrogel, and enabled sustained ROS-triggered NO release under oxidative microenvironment. In vivo full-thickness skin defect rat models demonstrated that the GelMA/L-Arg hydrogel markedly expedited wound closure, achieving a healing rate of 93.7% at day 14, and facilitated ordered re-epithelialization with a collagen area fraction of 64.6%. Further immunofluorescence results confirmed that the hydrogel improved regenerative quality by promoting mature angiogenesis with a vessel density of 116/mm 2 and switching macrophages toward anti-inflammatory M2 phenotype. Systemic biosafety evaluation via major organ histological staining validated favorable biocompatibility without obvious organ toxicity. In conclusion, this multifunctional NO-releasing GelMA/L-Arg hydrogel represents a promising candidate for clinical wound dressing applications.