Microenvironment-Driven Closed-Loop Wound Management Based on Glycyrrhizic Acid/Gelatin/Zinc Sulfide Hydrogel

Wound healing is a complex physiological process with different demands at different stages. In this work, a pH-responsive GA/Gelatin/ZnS (Glycyrrhizic Acid/Gelatin/Zinc Sulfide) hydrogel that can automatically release drugs was constructed in a facile way. It was fabricated by amide bonds, hydrogen bonds, and metal ion coordination among ZnS nanoparticles, glycyrrhizic acid (GA), and gelatin, which was confirmed by the molecular dynamics (MD) simulations and characterization results. Taking advantage of the pathological microenvironments at the wound site, it can synergize with multi-substance therapies at different stages, thus promoting wound healing. The as-prepared hydrogel can not only exhibit excellent coagulation ability in the hemostatic phase, but also release zinc ion (Zn²⁺) and hydrogen sulfide (H₂S) due to the weak acid microenvironment at the wound site, thus boosting inflammatory stage to proliferative phase. Meanwhile, benefit from its good re-epithelialization and angiogenesis properties in proliferative phase, the as-prepared hydrogel can increase collagen deposition during the remodeling phase, thereby accelerating wound healing. It would open a new perspective for effective wound management.