Abstract: Chronic wound healing remains challenging due to the risk of bacterial infection and the typical microenvironments characterized by oxidative stress, hypoxia, and insufficient angiogenesis. Herein, a hydrogel dressing (CLIHO) has been developed to efficiently promote the healing of methicillin-resistant Staphylococcus aureus (MRSA) infected wounds by integrating near-infrared (NIR)-controlled cascade reactions among hemin, indocyanine green (ICG), and L-arginine (L-Arg). Mild heat (approximately 45 °C) and cascade generation of reactive oxygen species (ROS), nitric oxide (NO), and ONOO− from the CLIHO hydrogel have been demonstrated under NIR irradiation. Benefiting from the O2 supplied by hemin-mediated decomposition of endogenous excess H2O2 in wounds, CLIHO hydrogel demonstrated hypoxia-alleviation-enhanced NO/phototherapy synergistic antibacterial activity, enabling it to effectively inhibit MRSA, Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis) proliferation, as well as eradicate the formed biofilms. The antibacterial performance of the CLIHO hydrogel was significantly superior to that of the CIO hydrogel with phototherapy alone and the CLIO hydrogel without O2 supply. Upon NIR turn-off, the CLIHO hydrogel could remodel the microenvironment of chronic wounds by scavenging excessive ROS, reducing local H2O2 levels, and alleviating hypoxia while promoting angiogenesis by releasing trace amounts of NO under endogenous nitric oxide synthase. Importantly, compared with CLIO hydrogel (without hemin), the CLIHO hydrogel significantly accelerated the high-quality healing of MRSA-infected wounds by efficiently eliminating bacterial infection, balancing inflammatory responses, and promoting angiogenesis and collagen deposition. Hence, the prepared CLIHO hydrogel integrating NIR-controlled cascade reaction provides an efficient and secure dressing for accelerating healing of MRSA-infected wounds via hypoxia-alleviation-enhanced NO/phototherapy synergistic antibacterial and microenvironment remodeling.

水凝胶结合近红外光控级联反应加速耐甲氧西林金黄色葡萄球菌感染伤口的愈合：通过缺氧缓解增强的一氧化氮/光疗协同抗菌作用及微环境重塑

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