Adherent lipopolysaccharide inhibits the osseointegration of orthopedic implants by impairing osteoblast differentiation

Abstract

Osseointegration is the process by which an orthopaedic 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 orthopaedic 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 orthopaedic implants and if adherent bacterial debris inhibits the osseointegration of orthopaedic 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 orthopaedic implants.

Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration

“…Bacterial suspensions were centrifuged (1500 g, 5 minutes) and resuspended in 1/30 volume of LB (3 9 10 10 CFUs/mL). Rigorously cleaned implants were incubated with 100 lL of the bacterial suspensions for 20 minutes at room temperature with gentle shaking, rinsed three times in phosphate-buffered saline (PBS), and immediately implanted into pilot holes in the middiaphysis of the femur [4,5] of 6-to 8-week-old female C57BL/6 J or macrophage Fas-induced apoptosis (MAFIA) mice. Macrophage recruitment was measured in the MAFIA mice, in which the monocyte/macrophage-specific colony-stimulating factor receptor promoter drives both expression of enhanced green fluorescent protein and a Fas apoptosis system activated by the dimerization drug, AP20187 [8,10].…”

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

“…A final potential source of PAMPs during aseptic loosening is contamination of the surface of implants during the manufacturing process [2, 11,41,59,93]. Contaminating PAMPs can also impair the initial osseointegration of the implants [2, 11,41,59], which can in turn predispose patients to aseptic loosening [83].…”

Can anodised zirconium implants stimulate bone formation? Preliminary study in rat model

“…It is well known that the clinical success of orthopaedic implants depends on two main factors: initial fixation due to osseointegration in the first few months; and maintenance of the fixation over the long term (Bonsignore et al 2013). Branemark et al (1959, 1983) defined the term osseointegration as the “direct structural and functional connection between ordered, living bone and the surface of a load-carrying implant”.…”