Biomimetic Nanozyme-Decorated\nSmart Hydrogel for Promoting\nChronic Refractory Wound Healing

Chronic refractory wounds have become a serious threat\nto human\nhealth and are characterized by prolonged inflammation, recurrent\nbacterial infections, and elevated ROS levels. However, current therapeutic\nstrategies usually target a unilateral healing function and are unable\nto tackle the complexity and sensitivity of chronic refractory wound\nhealing. This study fabricated a biomimetic nanozyme based on rhein\n(Cu-rhein NSs), which effectively mimics the activity of superoxide\ndismutase (SOD) for scavenging various free radicals. Additionally,\nzinc oxide microspheres (ZnO MSs) were prepared to enhance the antibacterial\nactivity and mechanical properties of the modified hydrogel. Cu-rhein\nNSs and ZnO MSs were comodified onto an extracellular matrix-mimetic\ndual-network smart hydrogel constructed from oxidized sodium alginate,\ngelatin, and borax via dynamic borate and Schiff base bonds. The smart\nhydrogel presented the good biocompatibility and targeted the unique\nacidic microenvironment with high oxidative stress of chronic refractory\nwounds, intelligently releasing bionic nanozymes to effectively eliminate\nbacteria, reduce inflammatory responses, and scavenge multiple free\nradicals for reducing ROS. In vivo experiments on the rat model based\non diabetic infection showed that the smart hydrogel could effectively\neliminate bacteria, promote vascular regeneration and collagen deposition,\n reduce inflammatory response, and accelerate the healing of diabetic-infected\nwounds (almost complete healing within 14 days). The advantages of\nan intelligent, biomimetic tissue regeneration cascade management\nstrategy against diabetic infected wound healing are highlighted.