David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Orthopedic Surgery, University of California, Los Angeles, Santa Monica, CA, USA.
Department of Orthopedic Surgery, University of California, Los Angeles, Santa Monica, CA, USA.
J Shoulder Elbow Surg. 2020 Jul;29(7):1412-1424. doi: 10.1016/j.jse.2019.10.032. Epub 2020 Jan 31.
Animal models are used to guide management of periprosthetic implant infections. No adequate model exists for periprosthetic shoulder infections, and clinicians thus have no preclinical tools to assess potential therapeutics. We hypothesize that it is possible to establish a mouse model of shoulder implant infection (SII) that allows noninvasive, longitudinal tracking of biofilm and host response through in vivo optical imaging. The model may then be employed to validate a targeting probe (1D9-680) with clinical translation potential for diagnosing infection and image-guided débridement.
A surgical implant was press-fit into the proximal humerus of c57BL/6J mice and inoculated with 2 μL of 1 × 10 (e3), or 1 × 10 (e4), colony-forming units (CFUs) of bioluminescent Staphylococcus aureus Xen-36. The control group received 2 μL sterile saline. Bacterial activity was monitored in vivo over 42 days, directly (bioluminescence) and indirectly (targeting probe). Weekly radiographs assessed implant loosening. CFU harvests, confocal microscopy, and histology were performed.
Both inoculated groups established chronic infections. CFUs on postoperative day (POD) 42 were increased in the infected groups compared with the sterile group (P < .001). By POD 14, osteolysis was visualized in both infected groups. The e4 group developed catastrophic bone destruction by POD 42. The e3 group maintained a congruent shoulder joint. Targeting probes helped to visualize low-grade infections via fluorescence.
Given bone destruction in the e4 group, a longitudinal, noninvasive mouse model of SII and chronic osteolysis was produced using e3 of S aureus Xen-36, mimicking clinical presentations of chronic SII.
The development of this model provides a foundation to study new therapeutics, interventions, and host modifications.
动物模型被用于指导假体周围植入物感染的管理。目前尚不存在假体肩关节感染的合适模型，因此临床医生没有用于评估潜在治疗方法的临床前工具。我们假设可以建立一种小鼠肩部植入物感染（SII）模型，该模型可以通过体内光学成像对生物膜和宿主反应进行非侵入性、纵向跟踪。然后可以使用该模型来验证具有临床转化潜力的靶向探针（1D9-680），用于诊断感染和图像引导清创。
将手术植入物压入 c57BL/6J 小鼠的肱骨近端，并接种 2 μL 浓度为 1×10（e3）或 1×10（e4）的生物发光金黄色葡萄球菌 Xen-36 集落形成单位（CFU）。对照组接受 2 μL 无菌生理盐水。在 42 天内直接（生物发光）和间接（靶向探针）监测体内细菌活性。每周进行 X 光检查以评估植入物松动情况。进行 CFU 收获、共聚焦显微镜和组织学检查。
两组接种动物均建立了慢性感染。与无菌组相比，感染组在术后第 42 天的 CFU 增加（P <.001）。在感染组中，在术后第 14 天就可以观察到骨溶解。在感染组中，e4 组在术后第 42 天发生灾难性骨破坏。e3 组保持了一致的肩关节。靶向探针通过荧光有助于可视化低级别感染。
鉴于 e4 组的骨破坏，使用 Xen-36 金黄色葡萄球菌的 e3 建立了 SII 和慢性骨溶解的纵向、非侵入性小鼠模型，模拟了慢性 SII 的临床表现。
该模型的开发为研究新的治疗方法、干预措施和宿主修饰提供了基础。
