Ultrasmall Prussian blue-integrated cryogel for enhanced ROS scavenging and immunomodulation via cGAS-STING inhibition in wound healing

Intractable wounds remain a major clinical challenge due to persistent oxidative stress, dysregulated inflammation, and impaired macrophage polarization. Here, we develop a therapeutic cryogel by integrating ultrasmall Prussian blue (USPB) nanozymes into a GelMA-quaternary ammonium chitosan methacryloyl matrix via cryogelation. The resulting Cryogel@USPB features high porosity, large interconnected pores, and strong swelling capacity, supporting its application in wound environments. Cryogel@USPB exhibits potent catalase-, peroxidase-, and superoxide dismutase-like activities, enabling efficient ROS scavenging. In vitro, it promotes macrophage polarization toward a regenerative phenotype and suppresses pro-inflammatory cytokines. In vivo, Cryogel@USPB significantly accelerates the healing of deep second-degree burn and diabetic wound models, achieving wound closure rates of 94.07 ± 1.94% and 98.69 ± 1.02%, respectively, with improved skin structure and Collagen deposition. Mechanistically, Cryogel@USPB modulates the wound microenvironment by inhibiting cGAS-STING signaling. These findings identify Cryogel@USPB as a promising immuno-regulatory nanozyme platform for treating complex wounds.