Microenvironment Self-Adaptive Ce-Ag-Doped Mesoporous Silica Nanomaterials (CA@MSNs) for Multidrug-Resistant Bacteria-Infected Diabetic Wound Treatment

Chronic wound healing remains a major challenge in diabetes management due to prolonged inflammation, autonomic neuropathy, and bacterial infections. In particular, multidrug-resistant bacterial infections are important to the development of diabetic wounds, leading to persistent inflammation and delayed healing. To address this issue, we developed a self-adaptive nanozyme designed to modulate infectious and inflammatory microenvironments by doping Ce and Ag into mesoporous silicon nanomaterials (MSNs). The resulting CA@MSNs exhibited strong bacterial capture capabilities via electrostatic attraction. Additionally, the synergistic effects of Ce and Ag endowed CA@MSNs with peroxidase (POD)-like activity, enabling the generation of reactive oxygen species (ROS) to eradicate bacteria in infectious microenvironments. Notably, CA@MSNs also demonstrated the ability to scavenge a broad spectrum of ROS, including hydroxyl free radicals, hydrogen peroxide, and superoxide radicals, in inflammatory microenvironments. This dual functionality helped mitigate inflammation and promote endothelial cell migration. Consequently, treatment with CA@MSNs significantly reduced inflammation, enhanced fibroblast activation, and facilitated collagen deposition, ultimately accelerating the healing of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)-infected wounds in diabetic mice. In conclusion, this study presents a promising therapeutic strategy for chronic diabetic wounds, offering a novel approach to overcoming infection-related healing delays.