A multifunctional bilayer hydrogel patch with photothermal-driven directional contraction and bioregulation for enhanced wound healing

• A rapid, one-step method creates anisotropic thermo-responsive hydrogels. • Anisotropic tension in thermo-responsive hydrogels is precisely controlled. • Physical and biological stimuli synergize to guide material function. Tension-induced stress concentration, particularly perpendicular to Langer lines, exacerbates wound expansion, inflammation, delayed healing, and scarring. Therefore, directional tension reduction represents a promising strategy to enhance wound repair. We designed a multifunctional bilayer hydrogel patch (DCTH/PH) that integrates directional tension reduction with bioregulatory properties to synergistically enhance wound healing. The inner layer, a photothermal-responsive hydrogel (PH), formed by a dynamic network of oxidized sodium alginate and carboxymethyl chitosan, enabling wound contour adaptation. Photothermal nanozyme (PNZ) consisting of tannic acid and Ce 4+ are embedded within PH to provide bioregulatory and photothermal capabilities. The outer layer, a directional contraction thermo-responsive hydrogel (DCTH), employs an anisotropic poly(N-isopropylacrylamide)/alginate matrix engineered via tunable stretching and fixation to achieve directional temperature-responsive contraction. Under near-infrared irradiation, PNZ trigger a rapid temperature increase, inducing DCTH self-contraction. The released PNZ further exhibit inflammation reducing effects and promotes angiogenesis, enabling multi-regulatory functionality. In an incision model, DCTH/PH induced anisotropic contraction (up to 27.6 kPa), reducing mechanical stress by 90.3 % to maintain a low-tension microenvironment. Simultaneously, it promoted skin regeneration by enhancing angiogenesis and modulating inflammation, thereby accelerating healing with minimal scar formation. In a large acute wound model, DCTH/PH achieved closure approximately 3.4 times faster than conventional methods, accompanied by reduced inflammation and fibrosis through downregulation of genes such as Cxcl17 and Tnfsf11. Collectively, the integration of wound tension reduction and bioregulation in the DCTH/PH presents a significant advancement in wound care. By addressing both the mechanical and biological barriers to healing, this system promotes efficient wound closure and minimizes scarring.