Carli Alberto V, Bhimani Samrath, Yang Xu, Shirley Matthew B, de Mesy Bentley Karen L, Ross F Patrick, Bostrom Mathias P G
1Hospital for Special Surgery, New York, NY 2University of Rochester, Rochester, New York.
J Bone Joint Surg Am. 2017 Mar 15;99(6):e25. doi: 10.2106/JBJS.16.00815.
Periprosthetic joint infection (PJI) is a devastating complication following total joint arthroplasty. Current animal models of PJI are limited because of a lack of quantitative methods and failure to effectively recreate the periprosthetic space. We therefore developed a murine PJI model involving a 3-dimensionally printed Ti-6Al-4V implant capable of bearing weight and permitting quantitative analysis of periprosthetic bacterial load and evaluation of biofilm.
Twenty-five 12-week-old C57BL/6 mice received a unilateral proximal tibial implant and intra-articular injection of either 3 × 10 colony forming units (CFUs) of Staphylococcus aureus Xen 36 or saline solution. Postoperatively, mice underwent gait analysis, knee radiographs, and serum inflammatory marker measurements. Following euthanasia at 2 or 6 weeks, bone and soft tissues were homogenized to quantify bacteria within periprosthetic tissues. Implants were either sonicated to quantify adherent bacteria or examined under scanning electron microscopy (SEM) to characterize biofilm.
All mice survived surgery and were not systemically septic. The control mice immediately tolerated weight-bearing and had normal inflammatory markers and radiographic signs of osseointegration. Infected mice had difficulty walking over time, exhibited radiographic findings of septic implant loosening, and had significantly elevated inflammatory markers. Periprosthetic tissues of the infected animals displayed a mean of 4.46 × 10 CFUs of S. aureus at 2 weeks and 2.53 × 10 CFUs at 6 weeks. Viable S. aureus was quantified on retrieved implant surfaces. SEM demonstrated S. aureus cocci in clusters encased within biofilm.
This animal model is, to our knowledge, the most clinically representative PJI replication to date. It is the first that we know of to produce infection through the same method hypothesized to occur clinically, utilize a weight-bearing implant that can osseointegrate, and provide quantitative data on 8 aspects of PJI, including radiographic features, inflammatory markers, and bacterial loads.
This novel animal model is, to our knowledge, the first to provide a load-bearing translational representation of clinical PJI that effectively recreates the periprosthetic space.
人工关节周围感染（PJI）是全关节置换术后一种严重的并发症。目前的PJI动物模型存在局限性，因为缺乏定量方法且未能有效重建假体周围空间。因此，我们开发了一种小鼠PJI模型，该模型使用三维打印的Ti-6Al-4V植入物，能够承重并允许对假体周围细菌载量进行定量分析以及对生物膜进行评估。
25只12周龄的C57BL/6小鼠接受单侧胫骨近端植入物，并关节内注射3×10个金黄色葡萄球菌Xen 36菌落形成单位（CFUs）或盐溶液。术后，小鼠接受步态分析、膝关节X线片检查和血清炎症标志物测量。在2周或6周实施安乐死后，将骨骼和软组织匀浆以量化假体周围组织内的细菌。对植入物进行超声处理以量化附着细菌，或在扫描电子显微镜（SEM）下检查以表征生物膜。
所有小鼠均存活至手术结束，且无全身感染。对照小鼠立即耐受负重，具有正常的炎症标志物和骨整合的影像学表现。随着时间的推移，感染小鼠行走困难，表现出感染性植入物松动的影像学表现，且炎症标志物显著升高。感染动物的假体周围组织在2周时平均显示4.46×10个金黄色葡萄球菌CFUs，在6周时为2.53×10个CFUs。在取出的植入物表面对存活的金黄色葡萄球菌进行了定量。SEM显示生物膜内包裹着成簇的金黄色葡萄球菌球菌。
据我们所知，该动物模型是迄今为止最具临床代表性的PJI复制模型。它是我们所知的第一个通过假设在临床上发生的相同方法产生感染、使用能够骨整合的负重植入物并提供关于PJI的8个方面的定量数据的模型，包括影像学特征、炎症标志物和细菌载量。
据我们所知，这种新型动物模型是第一个提供临床PJI的负重转化模型，能够有效重建假体周围空间。
