Near-Infrared Stimuli-Responsive\nHydrogel Promotes\nCell Migration for Accelerated Diabetic Wound Healing

Diabetic wound healing including diabetic foot ulcers\nis a major\nclinical challenge, which could bring an increased level of mortality\nand morbidity. However, conventional wound dressings exhibit limited\nhealing efficacy due to their lack of active modulation for the healing\nprocess. Here, a near-infrared (NIR) stimuli-responsive composite\nhydrogel dressing with the synergistic effect of both mechanical contraction\nand epithelial-mesenchymal transition (EMT) was developed to facilitate\ncell migration and vascularization for diabetic wound healing. In\nthe methacrylated gelatin-based composite hydrogel, <i>N</i>-isopropylacrylamide and polydopamine nanoparticles were incorporated\nto endow the composite hydrogel with thermosensitive and photothermal\nproperties. Linagliptin (LIN) was loaded into the composite hydrogel,\nand the drug release rate could be controlled by NIR laser irradiation.\nNIR-triggered on-demand active contraction of wound area and LIN release\nfor biological stimulation were potentially realized in this responsive\nsystem due to the thermally induced sol–gel transition of the\ncomposite hydrogel. The release of loaded LIN could effectively promote\ncell migration by activating EMT and enhancing angiogenesis. In the\nfull-thickness skin defect model, the LIN-loaded composite hydrogel\nwith NIR laser irradiation had the highest wound closure rate as compared\nwith the pure hydrogel and LIN-loaded hydrogel groups. Therefore,\nthis composite hydrogel can serve as an excellent platform for promoting\nwound healing and will find more practical value in clinical treatment.