Titanium Wear Particles Exacerbate S. epidermidis-Induced Implant-Related Osteolysis and Decrease Efficacy of...

Area of Science:

• Orthopedic Surgery
• Biomaterials Science
• Infectious Diseases

Background:

• Bacterial infection is a significant complication following total joint arthroplasty (TJA).
• Wear particles (WPs) generated during TJA may influence infection pathogenesis and treatment.
• Staphylococcus epidermidis is a common cause of orthopedic device-related infections (ODRIs).

Purpose of the Study:

• To investigate the in vitro interactions between WPs and immune cells.
• To determine the effect of WPs on the severity of S. epidermidis ODRIs in a rodent model.
• To assess if WPs impact antibiotic therapy response in ODRIs.

Main Methods:

• In vitro assessment of antibiotic efficacy against S. epidermidis biofilms on WPs.
• Analysis of neutrophil myeloperoxidase (MPO) and peripheral blood mononuclear cell (PBMC) cytokine release upon WP and S. epidermidis exposure.
• Establishment of an S. epidermidis ODRI rodent model with and without WPs, including antibiotic treatment groups.
• Microcomputed tomography (microCT) scanning for monitoring bone changes in vivo.

Main Results:

• WPs reduced the efficacy of rifampin and cefazolin against biofilm-resident bacteria in vitro.
• WPs increased MPO and pro-inflammatory cytokine production by immune cells in vitro.
• In vivo, WPs exacerbated S. epidermidis-induced osteolysis and significantly diminished antibiotic effectiveness.
• Titanium WPs were shown to reduce antibiotic efficacy, promote inflammation, and worsen osteolysis.

Conclusions:

• Titanium wear particles impair antibiotic efficacy against Staphylococcus epidermidis biofilms both in vitro and in vivo.
• Wear particles promote pro-inflammatory responses and exacerbate osteolysis in orthopedic device-related infections.
• The findings highlight the detrimental role of wear particles in TJA infections and suggest potential therapeutic targets.