Bionic strategy-based design of chirality-dependent activity Cu-Trp nanozymes: tight orchestration of the chronic refractory wound healing phase

Chronic refractory wounds have become a serious threat to human health, characterized by persistent inflammation, recurrent bacterial infections, and elevated levels of reactive oxygen species (ROS). Their treatment requires close coordination of each stage of chronic refractory wound healing. Inspired by octopus hemocyanin, a chirality-dependent strategy was designed to modulate the superoxide dismutase (SOD) and catalase (CAT) mimetic activities of metal-organic framework (MOF) nanozymes. Using different chiral tryptophan ligands, Cu-Trp (D/L) MOFs were rationally prepared (where D represents dextrorotatory and L represents levorotatory). With the best one as an example, during the inflammatory stage, Cu-Trp (L) effectively scavenged ROS, alleviated oxidative stress, and exerted antibacterial and immunomodulatory effects. During the proliferation phase, Cu-Trp (L) promoted L929 cell migration and proliferation, as well as the secretion of the endothelial growth factor. During the remodeling phase, Cu-Trp (L) effectively promoted wound closure and collagen deposition. This study demonstrates that antioxidant enzymes designed using a biomimetic chirality-dependent strategy exhibit potential for managing chronic refractory wounds.