title: Adherent lipopolysaccharide inhibits the osseointegration of orthopedic implants by impairing osteoblast differentiation.
abstract: Osseointegration is the process by which an orthopedic implant makes direct bone-to-implant contact and is crucial for the long-term function of the implant. Surface contaminants, such as bacterial debris and manufacturing residues, may remain on orthopedic implants after sterilization and impair osseointegration. For example, specific lots of implants that were associated with impaired osseointegration and high failure rates were discovered to have contaminants including bacterial debris. Therefore, the goals of this study were to determine if bacterial debris exists on sterile orthopedic implants and if adherent bacterial debris inhibits the osseointegration of orthopedic implants. We found that debris containing lipopolysaccharide (LPS) from Gram-negative bacteria exists on both sterile craniofacial implants and wrist implants. Levels of bacterial debris vary not only between different lots of implants but within an individual lot. Using our murine model of osseointegration, we found that ultrapure LPS adherent to the implants inhibited bone-to-implant contact and biomechanical pullout measures. Analysis of osseointegration in knock-out mice demonstrated that adherent LPS inhibited osseointegration by signaling through its primary receptor, Toll-like receptor 4, and not by signaling through Toll-like receptor 2. Ultrapure LPS adherent to titanium alloy discs had no detectable effect on early stages of MC3T3-E1 osteogenesis in vitro such as attachment, spreading or growth. However, later stages of osteogenic differentiation and mineralization were inhibited by adherent LPS. Thus, LPS may inhibit osseointegration in part through cell autonomous effects on osteoblasts. These results highlight bacterial debris as a type of surface contaminant that can impair the osseointegration of orthopedic implants.
authors.affiliation: Department of Orthopaedics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Bonsignore
authors.forename: J Robert
authors.initials: JR
authors.lastname: Anderson
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Lee
authors.forename: Victor M
authors.initials: VM
authors.lastname: Goldberg
authors.forename: Edward M
authors.initials: EM
authors.lastname: Greenfield
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D016348:Osseointegration / Q000187:drug effects*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D019736:Prostheses and Implants; D014025:Titanium
chemical_list: D008070:Lipopolysaccharides; D014025:Titanium