Silk fibroin nanofibers for infectious bone defect repair: From structural functionalization to immune-regenerative translation.

Infected bone defects (IBDs) present a major clinical challenge, requiring simultaneous infection clearance, immune modulation, and guided bone regeneration. This complex pathology poses a severe test for existing biomaterials. As a natural protein-based material, silk fibroin nanofibers (SFNs) offer an ideal solution due to their excellent biocompatibility, tunable degradation, and unparalleled structural and functional plasticity. This review systematically describes key engineering strategies-from ion doping and nanocomposite integration to surface modification-that synergistically endow SFNs with potent antibacterial, immunomodulatory, and osteoinductive properties. Furthermore, smart SFN systems responsive to pH, enzymes, or light stimuli enable targeted drug delivery and precise infection control. Mechanistically, we highlight how SFNs orchestrate an ordered transition of the infected microenvironment from a pro-inflammatory to a pro-reparative state by regulating key signaling pathways such as NF-κB, JAK/STAT, and BMP/Smad. Although preclinical results are promising, critical hurdles to clinical translation remain, including batch-to-batch consistency, sterilization compatibility, and scalable manufacturing. Looking ahead, the convergence of SFNs with 4D printing and bioelectronics will undoubtedly usher in a new era of personalized, intelligent scaffolds for precision-guided bone repair.