Polyphenol-hyaluronic acid-based hydrogel remodels the wound microenvironment and eliminates bacterial infection for accelerating wound healing

The wound microenvironment, often characterized by alkaline pH and severe hypoxia, presents significant challenges to the healing of bacterial-infected wounds. While considerable research has focused on improving wound healing through effective bacterial elimination using advanced therapeutic approaches, the importance of regulating the wound microenvironment has received less emphasis. In this work, we developed a biocompatible hydrogel, HTFC, by incorporating CaO 2 nanoparticles (CaO 2 NPs) into a gel formed by tannic acid (TA), hyaluronic acid (HA), and Fe 3+ . The HA and TA in HTFC hydrogel help to create a slightly acidic microenvironment, facilitating the decomposition of CaO 2 NPs to release H 2 O 2 for chemodynamic therapy (CDT). The reduction properties of TA promote the recycling of Fe 3+ /Fe 2+ , enhancing CDT efficacy and partially converting H 2 O 2 to O 2 , thereby alleviating hypoxia. Additionally, Fe III TA complexes in HTFC enhance CDT through photothermal therapy (PTT)-induced improvement of the Fenton reaction. This multifunctional hydrogel, with its synergistic effects of PTT and CDT, along with its ability to remodel the wound microenvironment from hypoxic and alkaline to normoxic and acidic, accelerates the bacterial-infected wound healing process.