Hybrid Hydrogel with Photothermal Stimulation Elicits Immunomodulation‐Mediated Wound Healing

Abstract It is of paramount importance to maintain the thermal environment of wounds in order to facilitate optimal tissue repair and regeneration. Nevertheless, their potential as a hyperthermia regenerative therapy remains to be fully elucidated. In this study, a photothermal hybrid hydrogel constructed through a simple “one‐step” activation process that elicits mild thermal stimulation is presented, thereby providing a stable photothermal cycling capability activating the immune response, and accelerating the restoration of tissue redox and immune homeostasis, ultimately promoting wound healing. The results demonstrate the application of the photothermal HGBM hydrogel in an impaired wound healing model, which exhibited elevated the levels of reactive oxygen species, enhanced immune responses, and the promotion of macrophage polarization M2/M1, thereby inducing a pro‐regenerative response. The RNA‐sequencing data demonstrate that mild hyperthermia therapy at 45 °C enhances the immune response and the respiratory burst process, thereby regulating the immune microenvironment in injured tissues. Furthermore, this process results in a transition from an inflammatory state to an anti‐inflammatory and pro‐healing state, which is promoted by the production of factors such as interleukin‐10 and interleukin‐4. This work therefore provides an effective strategy for hyperthermia regenerative therapy in the context of skin wound repair and tissue regeneration.