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

Mengting Yin, Yu Zhang, Xinyu Qu, Jiayi Liu, Zhongyi Sun, Haibo Liu, Ziyan Chen, Jing Ru, Jingwen Han, Bingqiang Lu, Yan Lu, Yan Wang, Xinyu Zhao, Feng Chen

Journal:Advanced Science

IF:14.1

DOI:10.1002/advs.202600076

PMID:42524713

Published:2026-07-29

research field:神经科学分子生物学干细胞生物学遗传学疾病动物模型

Abstract

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.

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