A Hybrid Hydrogel with Intrinsic Immunomodulatory Functionality for Treating Multidrug-Resistant <i>Pseudomonas aeruginosa</i> Infected Diabetic Foot Ulcers

Abstract

Contemporary options for multidrug-resistant bacteria infected diabetic foot ulcers (IDFUs) are predominantly nonspecific. These IDFU injuries often display prolonged inflammation and delayed tissue repair, mainly attributed to an overabundance of M1 macrophages in the hostile diabetic microenvironment. Although immunomodulatory hydrogels show promise for IDFU-focused care, a targeted, safe transition from M1 to M2 macrophages using simplified techniques remains a significant obstacle. Here, we introduce a hybrid hydrogel (GGG) with inherent immunomodulatory capabilities for IDFUs. GGG is composed of interpenetrating polymer networks featuring gallium-induced self-assembling glycyrrhizic acid and a photo-cross-linked gelatin methacryloyl matrix. Importantly, GGG effectively decreases the ratio of M1 to M2 macrophages in conditions infected with drug-resistant bacteria by disrupting iron metabolism and scavenging reactive oxygen species, which contributes to enhanced treatment results for diabetic wounds. To sum up, the immunomodulatory strategy we present provides a straightforward, safe, and highly effective therapeutic avenue for managing IDFUs.