Abstract
The treatment of diabetic ulcers often becomes complicated because of complex microenvironmental factors such as infection, oxidative stress, and hypoxia. To address these issues, we developed a multifunctional microneedle system IR780-Ce-MOF@MN (ICMN) integrated with nanozymes for synergistic therapy. This system combines photothermal (PTT) and photodynamic (PDT) therapies with metal-organic framework (MOF) based catalysis to enable broad-spectrum antibacterial activity, regulate redox homeostasis, and alleviate hypoxia, collectively accelerating wound healing. The ICMN operates through an auto-circulating "antibacterial, antioxidant, oxygen supplying" mechanism. It physically disrupts biofilms with an efficiency of 80.65 ± 1.29 % and releases nanozymes composed of IR780 and Ce-MOFs, which exhibit potent antibacterial effects against E. coli, S. aureus, P. acnes, and MRSA, achieving antibacterial rates exceeding 60 %. Simultaneously, the nanozymes scavenge reactive oxygen species (ROS) to mitigate oxidative stress and catalyze oxygen generation from ROS, reversing the hypoxic microenvironment. In a diabetic rat model with infected ulcers, ICMN treatment significantly upregulated the expression of EGF, α-SMA, and CD31, promoting epithelialization and angiogenesis, while downregulating MPO and HIF-1α, indicating reduced inflammation and oxidative stress. Complete wound closure was achieved within 14 days. These findings demonstrate that the ICMN offers a novel and effective strategy for diabetic ulcer treatment by simultaneously targeting infection control, redox balance, and tissue regeneration.