Synergistic modulation of inflammation and angiogenesis by a polyphenol-functionalized MOF nanozyme for enhancing wound closure

Persistent inflammation, excessive oxidative stress, and impaired angiogenesis are persistent challenges that adversely affect skin wound healing, which are particularly prominent in diabetic wounds and often lead to hindered repair processes. Bioactive materials with integrated anti-inflammatory, reactive oxygen species (ROS) scavenging, and angiogenesis-promoting functions are emerging as novel therapeutic strategies for enhancing wound healing. Therefore, we pioneered the development of a tannic acid -functionalized cerium-based metal-organic framework (CeMT) with multi-enzyme mimetic activities. Experiments in vitro and in vivo confirm CeMT's good biocompatibility. By mimicking the activities of superoxide dismutase and catalase, CeMT efficiently catalyzes the decomposition of ROS through a cascade reaction to generate oxygen, thereby eliminating excess ROS, alleviating hypoxia in the wound area, and reducing inflammatory responses. Furthermore, CeMT promotes macrophage polarization, angiogenesis, and collagen deposition, which accelerates the skin wound healing process. Proteomic analysis further indicated that CeMT inhibits the formation of neutrophil extracellular traps and remodels the inflammatory microenvironment of the wound. The proposed CeMT-based approach represents a safe, efficient, and clinically promising nanotherapeutic strategy for the treatment of large-scale acute and healing-impaired wounds, such as diabetic wounds.