Metal polyphenol CA-V nanozymes promote acute wound healing by destroying the ROS-inflammation cascade cycle

Skin ulceration impairs barrier function, and high concentrations of reactive oxygen species (ROS) and inflammatory factors in the wound microenvironment significantly delay the healing process. The effects of current clinical treatment schemes are limited, and a new strategy with both economic benefits and remarkable curative effects is urgently needed. Therefore, we constructed a metal polyphenol nanozyme with multienzyme activity aimed at targeting the key vicious cycle of ROS-induced inflammation and accelerating the early healing of wounds. First, caffeic acid and NH₄VO₃ were synthesized via a simple hydrothermal method, and then, purified CA-V nanoparticles were obtained via dialysis and freeze-drying. <i>In vitro</i> experiments revealed that it has good SOD-like enzyme and CAT-like activities, can eliminate ROS/RNS, and can promote the migration of fibroblasts to complete epithelization. The results of the oxidative stress model and RNA sequencing revealed that it has excellent antioxidant and antiapoptotic abilities and obviously downregulates TNF-α and IL-17, which are typical inflammatory pathways. <i>In vivo</i> experiments and RNA sequencing in mice also verified that CA-V can slow inflammation, promote angiogenesis and collagen arrangement, and accelerate wound healing. Notably, CA-V has good biosafety <i>in vitro</i> and <i>in vivo</i>. The use of the ROS-inflammatory circulation system as a therapeutic target provides a promising therapeutic strategy for promoting early healing of acute wounds.