Siverino Claudia, Freitag Linda, Arens Daniel, Styger Ursula, Richards R Geoff, Moriarty T Fintan, Stadelmann Vincent A, Thompson Keith
AO Research Institute Davos, 7270 Davos-Platz, Switzerland.
Department of Teaching, Research and Development, Schulthess Clinic, 8008 Zürich, Switzerland.
Microorganisms. 2021 Sep 13;9(9):1945. doi: 10.3390/microorganisms9091945.
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 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 and WPs, and myeloperoxidase (MPO) and cytokine release were analyzed, respectively. In the ODRI rodent model, rats ( = 36) had a sterile or -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 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 -induced osteolysis.
全关节置换术（TJA）是常见的骨科手术，但细菌感染仍是一个令人担忧的问题。本研究的目的是在体外评估磨损颗粒（WPs）与免疫细胞之间的相互作用，并研究WPs是否会影响啮齿动物模型中骨科器械相关感染（ODRI）的严重程度或对抗生素治疗的反应。用利福平头孢唑林（100μg/mL）对在WPs上生长的生物膜进行攻击，以确定抗生素疗效。将中性粒细胞或外周血单核细胞（PBMCs）与有或无WPs一起孵育，分别分析髓过氧化物酶（MPO）和细胞因子释放情况。在ODRI啮齿动物模型中，36只大鼠在有或无WPs的情况下植入无菌或接种细菌的螺钉，其中一个亚组接受抗生素治疗。使用微型计算机断层扫描（microCT）监测骨骼变化。WPs的存在降低了对生物膜驻留细菌的抗生素疗效，并在体外促进了MPO和促炎细胞因子的产生。WPs加剧了对感染的溶骨反应，并在体内显著降低了抗生素疗效。总体而言，这项研究表明，钛磨损颗粒的存在会降低体外和体内的抗生素疗效，诱导促炎细胞因子释放，并加剧感染诱导的骨溶解。
