An Injectable Triple-Responsive Hydrogel Accelerates Diabetic Wound Healing

Aim or purpose: In this study, a novel injectable multifunctional composite hydrogel(CMCSMF/QCT-Cu) with photo-/glucose-/ROS-responsivity was fabricated for enhancing diabetic wound healing which could be adapted to the local irregular anatomical shape as well as the microenvironment of high glucose and oxidative stress. Materials and methods: The in vitro characterization of the composite hydrogel systematically evaluated its cellular biocompatibility, chemotactic properties, hemostatic capacity, immune reprogramming effects, and antioxidant efficiency. The hydrogel's therapeutic efficacy was further validated in vivo using a diabetic rat model (8-week-old male Sprague-Dawley rats; all procedures approved by the Institutional Animal Care and Use Committee). A full-thickness cutaneous wound (1 cm diameter) was created on both sides of the spine's centerline. Rats were randomly divided into four groups: control, DM (diabetic model), CMCSMF and CMCSMF/QCT-CuM. Finally, wound measurements were taken on days 0, 3, 7, 11 and 14 post-treatment. Histological analysis included H&E staining, Masson's trichrome staining, and immunohistochemical evaluation of VEGF, iNOS, and Arg-1. Results: Experimental evidence has demonstrated that the hydrogel displays excellent collective functions including fibroblast homeostasis remodeling, accelerated angiogenesis and immune microenvironment regulation, ultimately accelerating diabetic wound healing. These immunomodulatory effects were potentially mediated through PI3K-AKT signaling pathway activation. In vivo experiments also suggested that the CMCSMF/QCT-CuM hydrogel can effectively promote diabetic wound healing. Conclusions: The CMCSMF/QCT-Cu composite hydrogel effectively facilitates diabetic wound healing, paving the way for future chitosan-based multifunctional hydrogel dressings.