Silk Fibroin as a Platform for Advanced Antibacterial Biomaterials: Structure, Immune Modulation, and Biomedical Applications

Bacterial infection remains a major challenge in biomedical applications, particularly with the rise of antibiotic-resistant pathogens. Developing antibacterial biomaterials that both prevent infection and support tissue regeneration has become an essential goal in biomedical research. Silk fibroin (SF) is a natural protein derived from <i>Bombyx mori</i> which has been identified as a broad-spectrum, biocompatible, and programmable material in biomedical applications. This review emphasizes SF for antibacterial infection, summarizing its structural features and modulations to immune responses and synergistic combination with multiple antibacterial agents. The unique β-sheet structure of silk fibroin provides resilience and tunable functionality, allowing it to serve as a stable matrix for diverse antibacterial agents. Antibacterial agents enhance antibacterial performance by generating reactive oxygen species, disrupting bacterial membranes, and suppressing biofilm formation. Silk fibroin supports immune modulation by promoting macrophage polarization and reducing inflammation, thereby facilitating tissue repair and wound healing. Overall, SF represents a next-generation antibacterial biomaterial that integrates antimicrobial efficacy with immune modulation, structural tunability, and biocompatibility, having strong potential for infection control and tissue regeneration in clinical applications. Despite advancements in biofunctionality, optimization of controlled release and long-term compatibility challenges still exist for SF's clinical applications, particularly against antibiotic-resistant pathogens.