Blood-Glucose-Depleting Hydrogel Dressing as an Activatable Photothermal/Chemodynamic Antibacterial Agent for Healing Diabetic Wounds

Poorly healing and nonhealing diabetic wounds are challenging to treat as the rapid growth of bacteria due to the high local glucose content can lead to persistent inflammation and poor angiogenesis. Herein, a smart hydrogel dressing composed of 3,3′,5,5′-tetramethylbenzidine/ferrous ion/Pluronic F-127/glucose oxidase (TMB/Fe²⁺/PF127/GOx) is designed and demonstrated to consume blood glucose while accelerating wound healing by generating antibacterial agents in situ. The loaded GOx degrades blood glucose to provide hydrogen peroxide (H₂O₂) and gluconic acid to support the Fe²⁺-based Fenton reaction, and the generated hydroxyl radical (·OH) facilitates the oxidation of TMB. The color change from colorless to green caused by the oxidation of TMB in the blood glucose range between 1 and 10 mM can be monitored visually. Simultaneously, this process induced chemodynamic therapy (CDT) by the specific generation of hydroxyl radical (·OH) for killing bacteria. Moreover, the oxidized TMB shows strong absorption in the near infrared (NIR) region so that NIR light can be converted into heat efficiently for photothermal therapy (PTT). As a result, nearly 100% of Staphylococcus aureus and Escherichia coli are killed by synergistic PTT/CDT, and the infected skin wounds undergo complete repair along with downregulation of interleukin-6 (IL-6) and upregulation of the vascular endothelial growth factor (VEGF) and matrix metallopeptidase-2 (MMP-2). Different from traditional wound dressings that can give rise to secondary injury, the excellent thermosensitive properties arising from the sol/gel phase transition render the hydrogel dressing materials injectable, self-reparable, and removable on demand. The multifunctional hydrogel with hypoglycemic, chemodynamic, photothermal, antibacterial, and on-demand thermosensitive properties has immense potential in the treatment of diabetic wounds. © 2023 American Chemical Society.