Silver Cross-Linking of Silk Sericin-Based Hydrogels for Improved Stability and Broad-Spectrum Antimicrobial Properties

Silk sericin (SS), a biocompatible protein derived from silkworms, exhibits valuable properties for medicinal applications, including antioxidant activity and cell growth support. However, their rapid degradation limits their practical use. This study introduces silver ions (Ag⁺) as a dual-function cross-linking agent to enhance the structural and functional properties of SS-based hydrogels. The incorporation of Ag⁺ stabilized the hydrogel network through dityrosine cross-links and coordination bonds with SS amino acid side chains, significantly improving hydrolytic and enzymatic resistance. Hydrogels cross-linked with 1 mM Ag⁺ demonstrated optimal performance, retaining excellent structural integrity while preserving the cytocompatibility and antioxidant activity of SS. These hydrogels also exhibited broad-spectrum antimicrobial activity against bacteria (<i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, <i>Staphylococcus aureus</i>, and methicillin-resistant <i>S. aureus</i>), fungus (<i>Aspergillus niger</i>), and yeast (<i>Candida albicans</i>). Higher Ag⁺ concentrations, however, increased the cytotoxicity without enhancing the antimicrobial efficacy. This study highlights the potential of Ag⁺ cross-linked SS-based hydrogels as scalable, multifunctional 3D structures for antimicrobial applications.