An injectable self-healing hydrogel with cytokine-regulating and antioxidant activities for accelerating diabetic wound repair.

Abstract

Diabetic wounds remain a formidable clinical challenge owing to persistent hyperglycemia, excessive oxidative stress, bacterial infection, and protracted inflammation. Herein, we developed a multifunctional hydrogel, designated QCS/4-FPBA/BC, integrating anti-inflammatory, antibacterial, injectable, and self-healing properties. The hydrogel was constructed using a quaternized chitosan (QCS) crosslinked with 4-formylphenylboronic acid (4-FPBA) via dynamic Schiff base and borate ester bonds, conferring favorable injectability and self-healing capacity, while the intrinsic quaternary ammonium cations of QCS endowed it with inherent antibacterial activity. Baicalein-cerium nanoparticles (BC NPs) were further loaded in situ into the hydrogel network to enable efficient and sustained scavenging of excessive reactive oxygen species (ROS). As a multifunctional platform, the QCS/4-FPBA/BC hydrogel exhibited robust anti-inflammatory activity in LPS-stimulated macrophages, as shown by decreased TNF-α and IL-6 levels and increased IL-10 expression. It also influenced macrophage phenotype, reducing the M1-associated iNOS signal while augmenting the M2-associated CD206 signal. In addition, treatment with the hydrogel upregulated VEGF in HUVECs and elevated collagen I in L929 cells, indicating pro-angiogenic and pro-matrix-synthesis capabilities. With these combined attributes, including ROS scavenging, antimicrobial action, inflammatory cytokine rebalancing, and promotion of vascular and fibroblast functions, the QCS/4-FPBA/BC hydrogel offers a comprehensive strategy for diabetic wound management and holds great promise for improving healing outcomes.