Synergistic mechanochemical regulation in PNIPAM/tannic acid hydrogels for enhanced diabetic wound healing

Skin, the body's primary protective barrier, faces formidable repair hurdles in chronic wounds like diabetic ulcers. Hyperglycemia-induced oxidative stress accumulates reactive oxygen species (ROS), inhibiting keratinocyte and fibroblast migration to delay re-epithelialization and granulation tissue formation; impaired myofibroblast function further weakens skin contraction, collectively hindering wound closure. To address these limitations, a multifunctional hydrogel (PGA-TA) with integrated antioxidant and thermoresponsive contraction properties was developed. In this study, <i>N</i>-isopropylacrylamide (NIPAM) and acrylic acid (AAc) were copolymerized <i>via</i> redox-initiated free radical polymerization in the presence of hydroxyl-rich guar gum (GG) to form a semi-interpenetrating network, followed by tannic acid (TA) incorporation. The GG framework was shown to enhance mechanical strength and tissue adhesion, while TA, <i>via</i> its phenolic hydroxyl groups, effectively scavenged ROS, mitigating oxidative stress. The thermoresponsive PNIPAM network exhibited temperature-dependent shrinkage, mimicking the contractile behavior of myofibroblasts to actively promote wound edge closure. Experimental results demonstrated that the hydrogel possessed excellent biocompatibility, antioxidant capacity, and dynamic mechanical adaptability. The synergistic combination of physical contraction and chemical regulation accelerated diabetic wound healing. This strategy may provide a novel approach for chronic wound therapy by integrating mechanical stimulation with biochemical modulation.