Injectable glycyrrhizic acid-based hydrogel with Immunoregulatory and angiogenic properties for diabetic wound healing

Abstract

Diabetic wound healing (DWH) demands multifunctional dressings capable of delivering therapeutic agents to counteract the impaired repair microenvironment. Elevated oxidative stress and chronic inflammation not only suppress regenerative cell viability but also exacerbate apoptosis and vascular dysfunction, collectively hindering wound healing. To address these challenges, we developed an injectable dual-network hydrogel dressing based on immunomodulatory and pro-angiogenic glycyrrhizic acid (GA). This hydrogel combines alkylated glycyrrhizinic acid (AGA) and methacrylated sericin (SFMA) to form a natural extracellular matrix (ECM)-mimetic dual network, achieving both excellent injectability and enhanced mechanical properties. Furthermore, the hydrogel incorporates the pro-angiogenic agent desferrioxamine (DFO) through dynamic covalent bonding, enabling sustained drug release. The resulting AGA/SFMA@DFO hydrogel effectively modulates macrophage polarization and enhances vascular regeneration under inflammatory conditions. Additionally, the residual aldehyde groups in the AGA/SFMA@DFO gel form Schiff base linkages with amino groups on the skin surface, ensuring strong tissue adhesion. Consequently, this multifunctional hydrogel dressing demonstrates significant potential in accelerating diabetic wound repair.