An injectable triple-responsive chitosan-based hydrogel encapsulating QCT-Cu self-assembled nanoparticles accelerating diabetic wound healing via remodeling the local microenvironment

The healing process of diabetic wounds is notably impeded due to reduced cellular functions, impaired vascularization, and persistent malignant inflammation, posing a significant obstacle in clinical management. Herein, 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. Furthermore, experimental evidence has demonstrated that the CMCSMF/QCT-Cu composite hydrogel displays superior mechanical properties, with a storage modulus exceeding 700 Pa and an average adhesion strength of approximately 12.5 kPa, thereby enabling the hydrogel to effectively prevent external irritation and exhibit rapid hemostatic effects after injection. Moreover, this composite hydrogel exerted excellent collective functions including remodeling the homeostasis of fibroblast, accelerated angiogenesis and regulating immune microenvironment, ultimately accelerating diabetic wound healing, while the immunoregulatory effect may be attributed to the activation of the PI3K-AKT signaling pathway. Overall, the innovative multifunctional composite hydrogel presents a promising potential clinical therapy for enhancing diabetic wound healing.