Exos‐Loaded Gox‐Modified Smart‐Response Self‐Healing Hydrogel Improves the Microenvironment and Promotes Wound Healing in Diabetic Wounds

GOx-modified self-healing hydrogel directs the responsive degradation of the hydrogel by regulating the high glucose microenvironment and pH of diabetic wounds, which in turn releases active ingredients such as Exosomes. These active ingredients further ameliorate the problems of inflammation, infection, and insufficient blood supply that exist in the pathological microenvironment of the wound.

Abstract

Wound management has always been a challenge in the clinical treatment of diabetes. In this study, glucose oxidase (GOx) is grafted onto natural pullulan polysaccharides, and oxidization is carried out to form a self-healing hydrogel using carboxymethyl chitosan by means of reversible Schiff base covalent bonding. The smart-response drug release properties of this natural self-healing hydrogel are demonstrated in diabetic wounds by taking advantage of two key factors, namely the pH-responsive nature of Schiff base bonding and the fact that GOx reduces the pH in diabetic wounds. To further enhance the biological functions of the hydrogel dressing, exosomes (Exos) are introduced into the hydrogel system. The GOx present in the hydrogel system improves the high-glucose microenvironment of diabetic wounds, releasing H₂O₂ to impart antimicrobial effects, and ensuring that the hydrogel realizes a smart-response function. The carboxymethyl chitosan component used to construct the hydrogel plays an effective antibacterial role. Moreover, the Exos loaded into the hydrogel effectively promotes neovascularization of the wound. The Exos also regulates macrophage polarization and reduces the levels of persistent inflammation in diabetic wounds. These results suggest that this smart responsive, multifunctional, and self-healing hydrogel dressing is ideal for the management of diabetic wounds.