Diabetic pressure injuries represent a significant clinical challenge, characterized by impaired mechanotransduction and excessive oxidative stress. To address these issues, we developed a double-network hydrogel composed of poly (acrylic acid-co-hydroxyethyl methacrylate-co-N-hydroxysuccinimide ester) (PAHN) and methacrylated silk fibroin (SilMA). This hydrogel featured a unique glucose-responsive secondary polymerization following initial photocuring, enabling autonomous matrix reinforcement in the hyperglycemic wound environment. The material demonstrated a 45-fold increase in storage modulus under high-glucose conditions, providing adaptive mechanical support. Incorporated cyanidin chloride (CC) conferred potent reactive oxygen species (ROS) scavenging capacity. In a hyperglycemic pressure injury model, the hydrogel significantly accelerated wound closure and enhanced neovascularization. Mechanistic studies revealed that these therapeutic benefits were mediated through synergistic activation of the TRPV4-CaMKII mechanotransduction axis and effective mitigation of oxidative stress. This work presented a promising strategy for treating complex chronic wounds by integrating dynamic mechanical reinforcement with targeted biochemical regulation. • SilMA/PAHN@CC@GOx hydrogel achieved glucose-responsive mechanical reinforcement in diabetic wounds. • SilMA/PAHN@CC@GOx restored mechanotransduction via activating early calcium signaling and the TRPV4-CaMKII pathway. • Mechanoadaptation combined with ROS scavenging accelerated healing and enhanced tissue regeneration.
Wang et al. (Sun,) studied this question.