pH/photothermal-responsive hydrogel with on-demand detachability for diabetic wound healing via macrophage reprogramming

Impaired wound healing in diabetic patients, driven by oxidative stress, bacterial infection, and inflammatory imbalance, poses a significant clinical challenge. Traditional dressings often cause secondary injury and pain during replacement, exacerbating patient distress. Herein, we developed an intelligent, on-demand detachable hydrogel dressing (CFTF) via dynamic crosslinking among carboxymethyl chitosan (CMCS), 2-formylphenylboronic acid (2-FPBA), and tannic acid-Fe3+ nanoparticles (TAFe NPs). Synergistic borate ester and metal-phenolic coordination bonds endowed the hydrogel with superior mechanical strength, self-healing capability, injectability, and tissue adhesiveness. Critically, the dressing enables citric acid-triggered on-demand dissolution for atraumatic removal without damaging fragile regenerating tissue. Its pH- and near-infrared (NIR)-responsive TA release enables efficient reactive oxygen species (ROS) scavenging. Leveraging the photothermal effect of TAFe under NIR irradiation, the hydrogel effectively eradicated pathogenic bacteria and suppressed biofilm formation. Concurrently, the released TA induces macrophage polarization towards the anti-inflammatory M2 phenotype. It rectifies the inflammatory imbalance, downregulates pro-inflammatory cytokines, and thus remodels the wound microenvironment. In diabetic rat models, the CFTF hydrogel significantly accelerated wound closure by promoting granulation tissue formation, angiogenesis, and ordered collagen deposition. This multifunctional hydrogel, integrating on-demand removal with multi-modal therapeutic actions, presents a comprehensive and promising strategy for the management of diabetic wounds.