Self‐Adaptive Dynamic Hydrogel Disrupts Ironclad Defense to Augment Photothermal‐Catalytic Therapy Against Melanoma Recurrence and Promote Post‐Surgical Wound Healing

Abstract Post‐surgical photothermal therapy for melanoma faces significant challenges including photothermal resistance, tumor recurrence, and wound healing. In response, a self‐adaptive hydrogel (VPHCh) is designed, synthesized from carboxymethyl chitosan, and integrated with a vanadium‐polydopamine (V‐PDA) nanoplatform, which significantly enhances both photothermal and catalytic properties. The advanced hydrogel effectively inhibits tumor recurrence and facilitates wound healing through the precise modulation of V‐PDA release dynamics. In the tumor and infection microenvironment, V‐PDA is rapidly released, delivering outstanding photothermal effects. Furthermore, through the synergistic actions of photothermal and catalytic reactions, V‐PDA induces endoplasmic reticulum stress, disrupting the Wnt/β‐catenin signaling pathway and enhancing V 5+ ‐mediated glutathione depletion, thereby increasing tumor cell sensitivity to ferroptosis. Importantly, lipid peroxidation during ferroptosis further facilitates the degradation of heat shock protein 90, markedly augmenting the synergistic effects of photothermal and catalytic therapies. Additionally, within the wound healing microenvironment, VPHCh enables the controlled and sustained release of V‐PDA, promoting cell proliferation, angiogenesis, and M2 macrophage polarization, thereby accelerating wound healing. The hydrogel also exhibits remarkable antibacterial properties, effectively inhibiting bacterial proliferation, and further facilitating wound healing. Consequently, this dynamically adaptive hydrogel represents a promising adjuvant therapy in post‐surgical treatment, offering substantial potential to inhibit melanoma recurrence and accelerate wound healing.