Hydrogel-integrated near-infrared-controlled cascade reaction accelerates healing of MRSA-infected wounds through hypoxia-alleviation-enhanced NO/phototherapy synergistic antibacterial and microenvironment remodeling

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 O 2 supplied by hemin-mediated decomposition of endogenous excess H 2 O 2 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 O 2 supply. Upon NIR turn-off, the CLIHO hydrogel could remodel the microenvironment of chronic wounds by scavenging excessive ROS, reducing local H 2 O 2 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.