Development of Silk Fibroin-Based Sponges Loaded with LL-37-Derived Peptides for the Control of Orthopedic Infections

Staphylococcus species are often the cause of implant-related infections, posing a significant clinical challenge in orthopedics. Antimicrobial peptides (AMPs) like LL-37-derived FK-16 and GF-17 offer promising alternatives to conventional antibiotics; however, they require suitable delivery systems to overcome rapid degradation. The aim of this study was to develop and evaluate silk fibroin (SF) and osteoinductive peptide-enriched silk fibroin (PSF) sponges that can be used locally for FK-16 and GF-17 delivery. Two concentrations of FK-16 or GF-17 were loaded into SF and PSF sponges. Swelling behavior and AMP release profiles were analyzed for 72 h. Time-kill assays were conducted on MRSE and MRSA clinical strains to assess antimicrobial activity. FK-16 released quickly (>90% within 24 h) and then maintained a stable plateau from both SF and PSF matrices, which was associated with bactericidal activity against MRSE strains. In contrast, the release efficiency of GF-17 was lower and did not achieve significant antimicrobial effects. Neither peptide exhibited effective activity against MRSA under the tested conditions. PSF sponges showed higher swelling and enhanced FK-16-mediated antibacterial performance compared to SF counterparts. FK-16-loaded PSF sponges are a promising biomaterial for treating local orthopedic infections related to MRSE. The findings underscore the significance of peptide–matrix interactions in determining therapeutic outcomes and suggest the need for more in vivo evaluation of AMP-functionalized PSF scaffolds.