Stage-Adaptive Janus Microneedle System for Redox-Immune Regulation and Mitochondrial Protection in Infected Diabetic...

Infected diabetic wounds are sustained by a vicious cycle of hyperglycemia-driven bacterial infection, persistent oxidative stress, and excessive inflammation, which collectively disrupt the ordered progression of tissue repair. Here, we engineered a stage-adaptive Janus microneedle patch (MN-FeSAC-PPE) to enable a staged therapeutic process from early antibacterial intervention to subsequent redox-immune microenvironment remodeling and regenerative tissue repair. This stage-adaptive design integrates Fe single-atom nanozymes (Fe-SACs) into the microneedle base to rapidly kill bacteria using near-infrared light, which activates reactive oxygen species (ROS) production, enabling rapid antibacterial activity against wound pathogens. Meanwhile, propolis extract-loaded (PPE) tips deliver antioxidant bioactive compounds into the wound bed to mitigate oxidative stress, modulate the redox-immune microenvironment, and support the inflammatory-to-regenerative transition. In vitro, MN-FeSAC-PPE enhanced antioxidant defense, suppressed pro-inflammatory factors, and protected fibroblasts from oxidative stress-induced mitochondrial dysfunction. Transcriptomic analysis further supported reduced inflammatory signaling and enhanced metabolism-related programs. In S. aureus-infected diabetic wounds, NIR-activated MN-FeSAC-PPE accelerated wound closure, promoted angiogenesis and collagen remodeling, and alleviated inflammation. These findings establish a stageadaptive redox-immune and bioenergetic regulatory microneedle platform for infected diabetic wound repair.