Immunoregulation in Diabetic Wound Repair with a Photoenhanced Glycyrrhizic Acid Hydrogel Scaffold

TLDR

M1 macrophage accumulation and excessive inflammation impede diabetic wound healing, and while immunoregulatory hydrogel dressings hold promise, existing options require costly, complex interventions such as cytokines or cell therapies. This study develops a glycyrrhizic acid–based hybrid hydrogel dressing with intrinsic immunoregulatory properties to accelerate diabetic wound repair. The hydrogel is an interpenetrating network of Zn²⁺‑induced self‑assembled GA and photo‑crosslinked methyl‑acrylated silk fibroin, providing excellent injectability and mechanical strength. The SF/GA/Zn hybrid hydrogel modulates macrophage responses without additives, accelerating all three phases of wound healing and offering a safe, effective dressing for diabetic wounds.

Abstract

M1 macrophage accumulation and excessive inflammation are commonly encountered issues in diabetic wounds and can fail in the healing process. Hence, hydrogel dressings with immunoregulatory capacity have great promise in the clinical practice of diabetic wound healing. However, current immunoregulatory hydrogels are always needed for complex interventions and high-cost treatments, such as cytokines and cell therapies. In this study, a novel glycyrrhizic acid (GA)-based hybrid hydrogel dressing with intrinsic immunoregulatory properties is developed to promote rapid diabetic wound healing. This hybrid hydrogel consists of interpenetrating polymer networks composed of inorganic Zn2+ -induced self-assembled GA and photo-crosslinked methyl acrylated silk fibroin (SF), realizing both excellent injectability and mechanical strength. Notably, the SF/GA/Zn hybrid hydrogel can regulate macrophage responses in the inflammatory microenvironment, circumventing the use of any additives. The immunomodulatory properties of the hydrogel can be harnessed for safe and efficient therapeutics that accelerate the three phases of wound repair and serve as a promising dressing for the management of diabetic wounds.