Zhongjie Ji, Dong Yang, Hongru Wang, Zhenqian Sun, Li Song, Xin Liu, Hongliang Wang, Yunzhen Chen, Hongxin Cao, Yunhao You, Guangjun Jiao
Abstract Skin wound infection represents one of the most frequent complications in the management of surgical diseases, significantly delaying healing processes and potentially leading to life‐threatening conditions. Bacterial invasion promotes biofilm formation, which increases local reactive oxygen species (ROS) levels, disrupts the wound microenvironment, and compromises regenerative capacity. Conventional treatments often fail to effectively eradicate deep biofilm‐associated infections, while prolonged antibiotic use fosters multidrug‐resistant bacteria and biofilm persistence, underscoring the urgent need for novel antibacterial approaches. In this study, a multifunctional hydrogel dressing is developed that integrates MXene nanosheets with a metal‐phenolic network (EGCG‐Cu) and the nitric oxide (NO) donor BNN6. This composite hydrogel enables near‐infrared (NIR)‐triggered photothermal therapy and simultaneous NO release, resulting in synergistic antibacterial activity against Staphylococcus aureus and Escherichia coli , along with effective biofilm eradication. The EGCG‐Cu coating further confers remarkable antioxidant and anti‐inflammatory properties by scavenging ROS and modulating cytokine expression. In a murine model of infected wound healing, the hydrogel accelerated tissue repair through enhanced collagen deposition, angiogenesis, and regulation of the immune microenvironment. This non‐antibiotic strategy provides spatiotemporal control over antibacterial and healing‐promoting functions, demonstrating considerable promise for the treatment of complex wound infections.