Microenvironment‐Responsive Hydrogels with Detachable Skin Adhesion and Mild‐Temperature Photothermal Property for Chronic Wound Healing

Abstract Chronic wounds have emerged as a global healthcare burden that have inability to heal within an expected time frame owing to the complex pathophysiological microenvironment, bacterial infection, multidrug resistance, and fragile skin tissue. Tailored to the features of chronic wounds, a multifunctional hydrogel (GA) composed of ethylenediamine‐modified gelatin (Gela‐amino) and oxidized sodium alginate (Alg─CHO) is reported. The thermosensitivity of gelatin and Schiff base bonds endow GA hydrogels with physiological temperature‐enhanced nonirritating tissue adhesion and low‐temperature‐triggered nondestructive separation, beneficial for the management of vulnerable and sensitive wounds. In addition, GA hydrogels exhibit pH‐responsive degradation that adapt to the acidic wound microenvironment. Under near‐infrared (NIR) irradiation, DNase I enzyme and indocyanine green‐loaded GA hydrogels (DI@GA) efficiently eradicate drug‐resistant bacteria biofilm and subsequently exert an antibacterial effect attributed to the bioactity of GA hydrogels and mild‐temperature photothermal therapy (≈45 °C). Remarkably, DI@GA/NIR hydrogels accelerate diabetic wound recovery and skin regeneration by dispersing biofilm, killing bacteria, inhibiting inflammation, promoting collagen deposition, and improving angiogenesis. The advanced hydrogels without the addition of antibiotics are promising to act as skin‐friendly wound dressings for rescuing infectious and stalled chronic wounds.