Engineered probiotics biofilm enhances osseointegration via immunoregulation and anti-infection

Abstract

Preventing multidrug-resistant bacteria–related infection and simultaneously improving osseointegration are in great demand for orthopedic implants. However, current strategies are still limited to a combination of non–U.S. Food and Drug Administration–approved antibacterial and osteogenic agents. Here, we develop a food-grade probiotic–modified implant to prevent methicillin-resistant Staphylococcus aureus (MRSA) infection and accelerate bone integration. Lactobacillus casei is cultured on the surface of alkali heat–treated titanium (Ti) substrates and inactivated by ultraviolet irradiation to avoid sepsis induced by viable bacteria. This inactivated L. casei biofilm shows excellent 99.98% antibacterial effectiveness against MRSA due to the production of lactic acid and bacteriocin. In addition, the polysaccharides in the L. casei biofilm stimulate macrophages to secrete abundant osteogenic cytokines such as oncostatin M and improve osseointegration of the Ti implant. Inactivated probiotics modification can be a promising strategy to endow implants with both excellent self-antibacterial activity and osteointegration ability.