Multimodal antibacterial microneedles with nanozymes mediated ROS-scavenging and oxygen-generation synergistic photothermal/photodynamic therapy to promote diabetic ulcer healing

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 <i>E. coli</i>, <i>S. aureus</i>, <i>P. acnes</i>, and <i>MRSA</i>, 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.