Hypoxic diabetic foot ulcers (HDFUs) pose a challenging chronic condition characterized by oxidative stress damage, bacterial infection, and persistent inflammation. This study introduces a novel therapeutic approach combining ergothioneine (EGT), luteolin (LUT), and quaternized chitosan oxidized dextran (QCOD) to address these challenges and facilitate wound healing in hypoxic DFUs. In vitro, assessments have validated the biosafety, antioxidant, and antimicrobial properties of the ergothioneine-luteolin-chitin (QCOD@EGT-LUT) hydrogel. Furthermore, near-infrared II (NIR-II) fluorescence image-guided the application of QCOD@EGT-LUT hydrogel in simulated HDFUs. Mechanistically, QCOD@EGT-LUT hydrogel modulates the diabetic wound microenvironment by reducing reactive oxygen species (ROS). In vivo studies demonstrated increased expression of angiogenic factors mannose receptor (CD206) and latelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), coupled with decreased inflammatory factors tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6), thereby promoting diabetic wound healing through up-regulation of transforming growth factor β-1 (TGF-β1).
Keywords: ergothioneine; hypoxic diabetic foot ulcers; imaging in the second near‐infrared window (NIR‐II); luteolin; the quaternized chitosan oxidizes dextran (QCOD) hydrogel; therapy.
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