Lipopeptide 01 from Staphylococcus Epidermidis Resists Pathogenic Bacteria and Promotes Bone Healing in Implant-Associated Infections

Abstract

Implant-associated infections (IAI) present a significant clinical challenge. Effective prevention of and recovery from IAI is complex, involving antibacterial treatment and the promotion of bone integration. However, the current artificial implants used in clinics often lack effective antibacterial properties and have limited functionality. In this study, Lipopeptide 01 (LP01), a lipopeptide derived from the skin commensal Staphylococcus epidermidis is successfully immobilized, onto the porous surface of sulfonated Poly (ether-ether-ketone) (SPEEK) to create a novel artificial implant, LP01-PS. Both in vivo and in vitro experiments demonstrates that LP01-PS displays favorable material properties, biocompatibility, outstanding antibacterial characteristics, and the ability to promote bone formation. Mechanistically, LP01-PS enhances antibacterial activities by triggering TLR2/P65 signaling, upregulating the expression of LL37 and β-defensins in macrophages. Furthermore, it can boost the osteogenic differentiation capability of bone marrow mesenchymal stem cells (BMSCs) through the β-catenin signaling pathway, thereby facilitating bone formation. The discovery of LP01-PS with dual antibacterial and osteogenic effects, coupled with insights into its mode of action, suggests that LP01-PS can serve as a promising implant material to enhance the success rates of total joint replacement surgeries, mitigate the risks of infection and prosthetic loosening, and foster the repair and regeneration of bone tissue.