@article{Shao2025, 
author = {Shuai Shao and Anni Zhu and Yi Chai and Zheming Song and Yutong Chen and Yi Xie and Yicheng Lv and Xiaoxun Huang and Wenjun Wang and Jingchao Li and Qin Zhang and Deping Kong and Qian Tan},
title = {Sequentially triggered triple-responsive hydrogels for targeted regulation of inflammation and angiogenesis in diabetic-infected wound healing},
year = {2025},
journal = {Nano Research},
volume = {18},
number = {11},
pages = {94907883},
keywords = {diabetic-infected wounds, sequentially triggered, triple-responsive hydrogels, antibacterial, anti-inflammatory, pro-angiogenesis},
url = {https://www.sciopen.com/article/10.26599/NR.2025.94907883},
doi = {10.26599/NR.2025.94907883},
abstract = {Bacterial infection, excessive inflammatory response, and impaired angiogenesis caused by the hyperglycemic microenvironment of diabetic wounds are the primary factors of non-healing wounds. Most contemporary wound repair materials passively release loaded drugs, resulting in poor therapeutic outcomes. In this study, we designed sequentially triggered triple-responsive hydrogels containing alginate (ALG)-phenylboronic acid (PBA), copper polydopamine (Cu-PDA), metformin (MET), and deferoxamine mesylate (DFO) to cover the continuous process of diabetic-infected wound healing and improve the wound microenvironment through warming in the infectious phase and on-demand drug release in the inflammatory and proliferative phase. The hydrogels exhibited good adhesivity, injectability, self-healing ability, and biocompatibility. The hydrogels show remarkable photothermal responsiveness due to the presence of PDA. Studies showed that appropriate high temperatures and the release of Cu2+ resulted in the hydrogels displaying excellent bactericidal properties in the infectious phase. Furthermore, the instability of the phenyl borate bond in a hyperglycemic and acidic microenvironment enables the glucose/pH responsiveness of the release of MET and DFO from the hydrogels. Mechanistic studies have shown that the hydrogels could suppress the activity of the NOD-, LRR-, and pyrin structural domain-containing protein 3 (NLRP3)/caspase-1/GasderminD (GSDMD)/IL-1β pathway and activate the hypoxia-inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. These effects enabled the hydrogels to promote the healing of diabetic-infected wounds.}
}