A Chondroitin Sulfate-Iron Complex with Antibacterial Activity and Its Derived Hydrogel for Infected Wound Healing

In this study, a hydrogel was developed based on a chondroitin sulfate-iron complex (CSFe) incorporated into a sodium alginate matrix. The CSFe complex was first prepared through the interaction of chondroitin sulfate (CS) with Fe³⁺ ions, achieving an iron content of 2.06%. Structural characterization confirmed that Fe³⁺ coordinated with the carboxyl, sulfate, and N-acetyl groups of CS, resulting in increased molecular weight and altered physicochemical properties. The CSFe complex exhibited significant antibacterial activity against Escherichia coli and Staphylococcus aureus (S. aureus), and was further incorporated into a sodium alginate matrix to form an injectable hydrogel with favorable physicochemical properties such as spreadability, shear-thinning behavior, and a compact porous microstructure. In a mouse model of S. aureus-infected wounds, the CSFe hydrogel significantly accelerated wound closure, reduced the levels of pro-inflammatory cytokines (TNF-α and IL-6), and increased the anti-inflammatory cytokine IL-10, indicating potent anti-infective and immunomodulatory functions. Overall, this work presents a multifunctional CSFe-incorporated hydrogel system that integrates antibacterial, anti-inflammatory, and tissue-regenerative properties, offering a promising strategy for infected wound healing and highlighting the potential of trivalent iron-polysaccharide coordination complexes in the development of advanced biomedical materials.