Multienzyme-mimetic MnO₂ aerogels with NIR-enhanced ROS regulation for treating MRSA-infected diabetic wounds

Diabetes mellitus represents a global health crisis, with an ever-growing population of patients suffering from chronic, non-healing diabetic wounds. These wounds are marked by a hostile microenvironment characterized by hyperglycemia, oxidative stress, inflammation, hypoxia, and bacterial colonization, all of which severely impair tissue regeneration and angiogenesis. Amid these interrelated pathological factors, regulating reactive oxygen species (ROS) dynamics has emerged as a key therapeutic strategy. Appropriate spatiotemporal control of ROS is critical: insufficient ROS in the early stages of infection compromises antimicrobial defense, whereas excessive ROS accumulation during the inflammatory phase induces oxidative damage and sustains chronic inflammation. To simultaneously modulate ROS and address the multifactorial diabetic wound microenvironment, herein we present a multifunctional manganese dioxide (MnO₂) aerogel synthesized via a freeze-thaw method in a water/N,N-dimethylformamide (DMF) mixture, forming a three-dimensional (3D) interconnected network with hierarchical porosity and nanoflower-like morphology. The MnO₂ aerogel mimics five key enzyme-like activities—oxidase, glucose oxidase (GOx), glutathione peroxidase (GPX), catalase (CAT), and superoxide dismutase (SOD)—thereby enabling antibacterial, antioxidant, glucose-regulating, and tissue-regenerative functions. Additionally, near-infrared (NIR) photothermal activation further augments its antimicrobial efficacy by disrupting bacterial biofilms and promoting ROS generation. Taken together, in vitro and in vivo experiments reveal that MnO₂ aerogels significantly attenuate inflammation, re-establish glucose and redox homeostasis, and accelerate wound closure by enhancing angiogenesis and tissue regeneration. This work highlights metallic oxide aerogel as a promising platform for advanced diabetic wound therapy, providing an integrated strategy to address the complex challenges of wound management.