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.

The escalating prevalence of bacterial infections has intensified the search for innovative antimicrobial strategies, particularly for infected wound management. Chondroitin sulfate (CS), a naturally occurring glycosaminoglycan with established biocompatibility, presents an attractive scaffold for developing metal ion-functionalized biomaterials. This study reports the fabrication of chondroitin sulfate–copper complex (CSCu) and chondroitin sulfate–zinc complex (CSZn) through an ion exchange method, wherein Cu²⁺ and Zn²⁺ ions bind to the groups of carboxylate, sulfate, or N-acetyl from the CS backbone. The resulting complexes exhibited copper or zinc loading capacities of about 6.6% and demonstrated potent antibacterial activity against E. coli and S. aureus. The integration of CSCu or CSZn with sodium alginate yielded a hydrogel system with a higher apparent viscosity, possessing injectability and spreadability on the skin surface and a porous three-dimensional internal structure conducive to wound healing applications. In a murine model of S. aureus-infected full-thickness wounds, topical application of CSCu and CSZn hydrogels substantially accelerated wound closure, achieving 97.46% and 98.11% healing, respectively, by day 10. Additionally, treatment with CSCu or CSZn hydrogels significantly attenuated systemic inflammatory responses, as reflected in lowered serum TNF-α, IL-1β, and IL-6 alongside increased IL-10. Histological evaluation confirmed enhanced re-epithelialization and stratum spinosum formation in treated wounds. These findings establish CSCu and CSZn as a promising bioactive agent for addressing bacterial wound infections through a dual mechanism of direct antibacterial action and immunomodulatory effects, offering a valuable alternative to conventional antibiotic therapies.