Temperature-Triggered Reversible Adhesion Hydrogel with Responsive Drug Release, Mild Photothermal Therapy, and Biofilm Clearance for Skin Infection Healing

Bacterial infection gives rise to a hypoxic, H₂O₂-abundant, and acidic local microenvironment at the site of inflammation, which prevents the healing of skin tissues. In this work, gelatin and oxidized carboxymethyl cellulose were developed as the framework of hydrogels. Tannic acid and 3-formylphenylboronic acid served as small-molecule anchors. Through the introduction of multiple dynamic cross-linkings, the hydrogel was endowed with various functions. These functions encompassed mechanical compatibility with the skin, reversible adhesion characteristics, and rapid self-healing capabilities. In addition, nanoflower-like MnO₂ microparticles loaded with berberine hydrochloride were embedded. MnO₂ has the ability not only to kill bacteria through the photothermal effect (PTT) but also to catalyze the decomposition of H₂O₂ and release oxygen, effectively improving the inflammatory microenvironment. Remarkably, based on the drug/PTT synergistic strategy, the hydrogel exhibited significant antibacterial activity and biofilm removal ability under mild conditions (<50 °C), avoiding thermal damage to healthy tissues. Consequently, the hydrogels demonstrate favorable biocompatibility, significant cell proliferation, migration, angiogenesis, collagen deposition, and tissue regeneration. Therefore, the multifunctional antimicrobial hydrogel is expected to be a skin-friendly medical dressing with enormous potential in the treatment of skin and soft tissue infections.