Near-infrared stimuli-responsive hydrogel mechanically and biologically promote cell migration for accelerating diabetic wound healing

Diabetic wound healing including diabetic foot ulcers is a major clinical challenge, which could bring increased level of mortality and morbidity. However, conventional wound dressings exhibit limited healing efficacy due to their lack of active modulation for healing process. Here, a near-infrared (NIR) stimuli-responsive composite hydrogel dressing with the synergistic effect of both mechanical contraction and epithelial-mesenchymal transition (EMT) was developed to facilitate the cell migration and vascularization for diabetic wound healing. In the methacrylated gelatin (GelMA)-based composite hydrogel, N-isopropylacrylamide (NIPAM) and polydopamine nanoparticles (PDA NPs) were incorporated to endowed the composite hydrogel with thermosensitive and photothermal properties. Linagliptin (LIN) was loaded into the composite hydrogel and the drug release rate could be controlled by NIR laser irradiation. NIR triggered on-demand active contraction of wound area and LIN release for biological stimulation were potentially realized in this responsive system due to the thermally induced sol-gel transition of composite hydrogel. The release of loaded LIN could effectively promote the cell migration by activating EMT and enhance the angiogenesis. In the full-thickness skin defect model, the LIN-loaded composite hydrogel with NIR laser irradiation had the highest wound close rate as compared with pure hydrogel and LIN-loaded hydrogel groups. Therefore, this composite hydrogel can be served as an excellent platform for promoting wound healing and will find more practical value in clinical treatment.