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Cascade ROS-modulating Au/Cu nanozyme hydrogel with nitric oxide release ability for accelerated diabetic foot ulcer
Xue Wang1, Yuanyuan Zhang1, Yingying Chen2
1School and Hospital of Stomatology, Liaoning Provincial Key laboratory of Oral Diseases, China Medical University, Shenyang 110101, China.
Colloids and Surfaces. B, Biointerfaces
|December 31, 2025
Summary
This study developed a novel hydrogel embedding nanozymes to treat diabetic foot ulcers by managing reactive oxygen species, killing bacteria, and promoting healing. The innovative therapy significantly accelerated wound closure in diabetic rats.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Regenerative Medicine
Background:
- Diabetic foot ulcers (DFUs) are challenging to heal due to high reactive oxygen species (ROS), infection, and impaired blood vessel formation (angiogenesis).
- Existing treatments often fail to address these multiple barriers simultaneously, leading to chronic wound persistence.
Purpose of the Study:
- To engineer an injectable hydrogel (AuCu-Arg/Gel) incorporating gold/copper nanozymes for synergistic treatment of DFUs.
- To investigate the platform's ability to rebalance ROS, eliminate bacteria, promote nitric oxide (NO) release, and enhance vascularization.
Main Methods:
- Development of a guar gum hydrogel embedding gold/copper nanozymes (Au@Cu₂(OH)₃Cl-L-Arg) with peroxidase, superoxide dismutase, and catalase-like activities.
- Evaluation of nanozyme activity in acidic, bacteria-laden conditions, including ROS modulation and nitric oxide (NO) generation from L-arginine.
- Assessment of mild near-infrared (NIR) photothermal enhancement on nanozyme activity and therapeutic efficacy in a diabetic rat wound model.
Main Results:
- The nanozymes effectively rebalanced ROS and exhibited potent antibacterial activity, reducing bacterial viability to <1% in vitro.
- The hydrogel facilitated nitric oxide (NO) release, upregulating vascular endothelial growth factor (VEGF) and promoting neovascularization.
- In diabetic rats, the AuCu-Arg/Gel combined with NIR treatment significantly accelerated wound closure (2.1% residual area at day 12), reduced inflammation, and increased collagen deposition and vascular density.
Conclusions:
- The engineered AuCu-Arg/Gel platform offers a spatiotemporally programmable approach for DFU management.
- This multi-functional system synergistically addresses key barriers to wound healing: ROS overproduction, infection, and poor angiogenesis, with added photothermal enhancement.
