Abstract

Total joint arthroplasty (TJA) surgeries are common orthopedic procedures, but bacterial infection remains a concern. The aim of this study was to assess interactions between wear particles (WPs) and immune cells in vitro and to investigate if WPs affect the severity, or response to antibiotic therapy, of a Staphylococcus epidermidis orthopedic device-related infection (ODRI) in a rodent model. Biofilms grown on WPs were challenged with rifampin and cefazolin (100 µg/mL) to determine antibiotic efficacy. Neutrophils or peripheral blood mononuclear cells (PBMCs) were incubated with or without S. epidermidis and WPs, and myeloperoxidase (MPO) and cytokine release were analyzed, respectively. In the ODRI rodent model, rats (n = 36) had a sterile or S. epidermidis-inoculated screw implanted in the presence or absence of WPs, and a subgroup was treated with antibiotics. Bone changes were monitored using microCT scanning. The presence of WPs decreased antibiotic efficacy against biofilm-resident bacteria and promoted MPO and pro-inflammatory cytokine production in vitro. WPs exacerbated osteolytic responses to S. epidermidis infection and markedly reduced antibiotic efficacy in vivo. Overall, this work shows that the presence of titanium WPs reduces antibiotic efficacy in vitro and in vivo, induces proinflammatory cytokine release, and exacerbates S. epidermidis-induced osteolysis.

Highlights

  • Total joint arthroplasty (TJA) is one of the most successful surgical procedures offering improved quality of life for patients with pain or functional limitations due to conditions such as osteoarthritis [1]

  • Our findings show that the presence of wear particles (WPs) diminishes antibiotic efficacy in vitro and promotes pro-inflammatory cytokine production by immune cells

  • The bacteria grown for 24 h in the presence of 1 mg/mL of WPs were imaged by SEM to assess morphological changes in response to antibiotic exposure (Figure 1B)

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Summary

Introduction

Total joint arthroplasty (TJA) is one of the most successful surgical procedures offering improved quality of life for patients with pain or functional limitations due to conditions such as osteoarthritis [1]. There are more than 1 million TJAs performed in the United States annually, and this number is expected to increase to nearly 4 million by 2030 [2]. Complication rates following primary hip replacement, for example, range between 2 and. Treatment of PJI often involves revision surgery, which has an even higher postoperative complication rate and increased duration of hospital stays [5]. The incidence of PJIs in primary total hip arthroplasties is 0.2–2%, while for revision surgeries it may reach 5% [6]

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