Ultrasound-activated UiO-66 enables ROS-mediated antibacterial therapy and accelerates diabetic wound healing

Abstract The development of noninvasive and dual-functional therapeutic strategies is of critical importance for the treatment of infected diabetic wounds, which require both effective bacterial eradication and enhanced tissue regeneration. Conventional approaches are frequently constrained by single-function modalities or adverse side effects, emphasizing the demand for safer and more versatile alternatives. In this study, we demonstrate for the first time that pristine UiO-66, a metal–organic framework without surface modification, can serve as a novel nanoplatform for sonodynamic therapy (SDT), simultaneously achieving antibacterial and pro-regenerative effects. Comprehensive structural and photochemical analyses reveal that UiO-66 efficiently generates reactive oxygen species (ROS) under ultrasound irradiation, which endow it with broad-spectrum antibacterial capacity. These effects are validated by in vitro plate-count assays and RNA sequencing analysis. In parallel, UiO-66 exhibits excellent biocompatibility and significantly promotes the proliferation and migration of HUVECs and L929 fibroblasts, underscoring its potential to facilitate tissue repair. Importantly, in a diabetic mouse model of Staphylococcus aureus-infected wounds, UiO-66-mediated SDT markedly reduces bacterial burden and accelerates wound closure. Collectively, this work establishes pristine UiO-66 as a sonodynamically activated dual-functional therapeutic platform, offering a promising paradigm for integrated infection control and tissue regeneration in chronic wound management, and highlighting its translational potential in clinical wound care.