Photothermal-programmed hydrogel patches for stress-oriented contraction and regeneration of penetrating oral fistulas

Penetrating oral fistulas (POFs) are difficult to close because of high edge tension and often persist to enlarge, inflame, and lesion in complex microenvironments. Here, we engineered a photothermal-programmed contractile hydrogel coupled with multistimulus response behavior via a cascade enzyme-catalyzed polymerization approach to synergistically counteract tension, assist in contraction, and modulate the immune microenvironment. Thermal-mediated stress enhancement (4.04-fold increase) optimized the strong interfacial adhesion (2.53-fold increase), which provided the prerequisite for synchronized contraction. Under near-infrared (NIR) light stimulation, photothermal-programmed mechanical changes increased the expression of mechanosensitive integrin β1 in myoblasts and promoted cell-oriented elongation (orientation factor of up to 0.87) and myotube fusion, which facilitated muscle regeneration. In addition, inflammatory microenvironmental modulation and stress compensation for photothermal-programmed contraction synergistically accelerated the healing of POFs in rabbits and reduced the overdeposition of fibrotic scars. Mechanical assistance and microenvironment modulation strategies provide promising therapeutic options for difficult-to-heal penetrating fistulas (PFs).