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

<i>Staphylococcus</i> 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.