Green synthesis-inspired antibacterial, antioxidant and adhesive hydrogels with ultra-fast gelation and hemostasis for promoting infected skin wound healing.

Bacterial infections are a serious threat to wound healing and skin regeneration. In recent years, photothermal therapy (PTT) has become one of the most promising tools in the treatment of infectious diseases. However, wound dressings with photo-responsive properties are currently still limited by the difficulties of biosafety and thermal stability brought by the introduction of photosensitizers or photothermal agents. Therefore, how to improve the therapeutic efficiency and biosafety from material design is still a major challenge at present. In this study, the carboxymethyl chitosan (CMCS) and protocatechuic aldehyde (PA) hydrogels based on horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2 ) enzymatic catalysis was developed. Therein, HRP and H 2 O 2 catalyzed cross-linking while polymerizing PA, which not only endowed the hydrogels with photothermal responsiveness but also with good biosafety through this enzyme-catalyzed green approach. Meanwhile, the hydrogels possessed highly efficient bacteriostatic ability with the assistance of near infrared (NIR). Moreover, the ultra-rapid gelation, strong tissue adhesion, high swelling ability, good antioxidant property and hemostatic property of the CMCS-PA hydrogels based on HRP/H 2 O 2 enzymatic catalysis were suitable for the treatment of skin wounds. Meanwhile, NIR-assistant CMCS-PA hydrogels based on HRP/H 2 O 2 enzymatic catalysis reduced inflammation, decreased bacterial infection, and promoted collagen deposition and angiogenesis, which showed remarkable therapeutic effects in a skin wound infection model. All results indicate that this green approach to introduce photothermal property by HRP-catalyzed PA polymerization endows the hydrogels with efficient photothermal conversion efficiency, suggesting that they are promising to provide new options for replacing photothermal agents and photosensitizers. STATEMENT OF SIGNIFICANCE: In recent years, wound dressings with photo-responsive properties are currently still limited by the difficulties of biosafety and thermal stability brought by the introduction of agent photosensitizers or photothermal agents. In this study, the carboxymethyl chitosan and protocatechuic aldehyde hydrogels based on horseradish peroxidase and hydrogen peroxide enzymatic catalysis was developed. The photothermal properties of hydrogels were transformed from absent to present just by horseradish peroxidase-catalyzed protocatechuic aldehyde polymerization in a green approach. Meanwhile, the hydrogels possessed highly efficient bacteriostatic ability with the assistance of near infrared. The green approach of introducing photothermal properties from material design solves the biosafety challenge. Therefore, this study is expected to provide new options for alternative photothermal agents and photosensitizers.