Photothermal-responsive MXene/curcumin-copper composite hydrogel with antioxidant, immunoregulatory, and angiogenic functions for diabetic wound healing

Diabetic wounds are a critical clinical challenge due to chronic inflammation, impaired tissue regeneration, and bacterial infection. The absence of multifunctional therapeutic systems that can address these pathological barriers simultaneously is a major obstacle in managing diabetic wounds. In this study, we developed a versatile photothermal-responsive hydrogel (HPCT) by incorporating Ti3C2 MXene nanosheets and Cur-Cu nanoparticles (NPs) into a dual-network polymer matrix. This hydrogel exhibits robust physicochemical stability, efficient photothermal conversion, and on-demand release properties. Due to the synergistic effects of its components, HPCT effectively scavenges ROS/RNS, reprograms macrophages, and promotes fibroblast and endothelial proliferation and migration. Additionally, it exhibits potent antibacterial activity. Transcriptomic analysis reveals that the bioactive material activates the PI3K-AKT and Wnt signaling pathways, providing a mechanistic basis for its regenerative potential. In vivo, HPCT significantly accelerates wound closure in diabetic mice by reducing inflammation and oxidative stress, enhancing angiogenesis, and improving collagen deposition while maintaining good biocompatibility. Overall, this multifunctional hydrogel is a promising therapeutic strategy for treating diabetic and other chronic wounds.