Nanozyme Cryogel Accelerates Diabetic Wound Healing by Targeting Biofilms and Inflammations of the Wound Bed

The repair of diabetic wounds faces significant challenges due to the abnormal accumulation of advanced glycation end products (AGEs) and biofilm infections caused by prolonged hyperglycemia. Here, this study designed and constructed a microenvironment-responsive ZIF-67/GOx nanozyme (ZG) with multienzyme activities, which was integrated into GelMA-based aligned fiber cryogel (ZG@AFC) to achieve efficient repair of infected diabetic wounds through dynamic regulation of the wound microenvironment. Research demonstrated that under the acidic hyperglycemic microenvironment of infected diabetic wounds, the ZG nanozyme activates GOx/POD-mimic enzyme activities to eradicate pathogenic bacteria and their biofilms via chemodynamic therapy while continuously consuming local glucose. Following effective biofilm elimination, in the weakly alkaline microenvironment of chronic wounds, the ZG nanozyme triggers SOD/CAT-mimic cascade catalytic reactions to efficiently scavenge reactive oxygen species (ROS) and supply local oxygen. Combined in vitro/in vivo studies and RNA sequencing analysis revealed that this nanozyme-integrated cryogel inhibits AGE-RAGE signaling pathway-mediated oxidative stress cascades while synergistically promoting angiogenesis, collagen deposition, epithelial regeneration, and inflammation regulation, ultimately accelerating diabetic wound healing. This study proposes a nanozyme-mediated microenvironment regulation strategy, offering a promising strategy for treating infected diabetic wounds.