Beagan Michael L C, Dreyer Chris H, Jensen Louise K, Jensen Henrik E, Andersen Thomas E, Overgaard Soeren, Ding Ming
Odense University Hospital & University of Southern Denmark, Odense, Denmark.
Odense University Hospital & University of Southern Denmark, Odense, & Slagelse Hospital, Slagelse, Denmark.
J Orthop Translat. 2024 Mar 19;45:120-131. doi: 10.1016/j.jot.2024.02.002. eCollection 2024 Mar.
Reliable animal models are critical for preclinical research and should closely mimic the disease. With respect to route of infection, pathogenic agent, disease progression, clinical signs, and histopathological changes. Sheep have similar bone micro- and macrostructure as well as comparable biomechanical characteristics to humans. Their use in bone research is established, however their use in bone infection research is limited. This systematic review will summarise the key features of the available bone infection models using sheep, providing a reference for further development, validation, and application.
This systematic review was designed according to the PRISMA guidelines and registered with PROSPERO. Quality was assessed using SYRICLE's risk of bias tool adapted for animal studies. PubMed, MEDLINE, Web of Science and EMBASE were searched until March 2022.1921 articles were screened by two independent reviewers, and 25 were included for analysis.
Models have been developed in nine different breeds. was used in the majority of models, typically inoculating 10 colony forming units in tibial or femoral cortical defects. Infection was established with either planktonic or biofilm adherent bacteria, with or without foreign material implanted. Most studies used both radiological and microbiological analyses to confirm osteomyelitis.
There is convincing evidence supporting the use of sheep in bone infection models of clinical disease. The majority of sheep studied demonstrated convincing osteomyelitis and tolerated the infection with minimal complications. Furthermore, the advantages of comparable biology and biomechanics may increase the success for translating results to successful therapies.
In the realm of preclinical research, the translation to viable clinical therapies is often perilous, and the quest for reliable and representative animal models remains paramount. This systematic review accentuates the largely untapped potential of sheep as large animal models, especially in bone infection research. The anatomical and biomechanical parallels between sheep and human bone structures position sheep as an invaluable asset for studying osteomyelitis and periprosthetic joint infection. This comprehensive exploration of the literature demonstrates the robustness and translational promise of these models. Furthermore, this article underscores the potential applicability for sheep in developing effective therapeutic strategies for human bone infections.
可靠的动物模型对临床前研究至关重要，应紧密模拟疾病情况，包括感染途径、病原体、疾病进展、临床症状和组织病理学变化。绵羊的骨骼微观和宏观结构以及生物力学特性与人类相似。它们在骨骼研究中的应用已得到确立，但其在骨感染研究中的应用有限。本系统评价将总结现有绵羊骨感染模型的关键特征，为进一步开发、验证和应用提供参考。
本系统评价根据PRISMA指南设计，并在PROSPERO注册。使用适用于动物研究的SYRICLE偏倚风险工具评估质量。检索了PubMed、MEDLINE、Web of Science和EMBASE数据库，直至2022年3月。由两名独立评审员筛选了1921篇文章，其中25篇纳入分析。
已在9个不同品种的绵羊中建立了模型。大多数模型使用金黄色葡萄球菌，通常在胫骨或股骨皮质缺损处接种10个菌落形成单位。通过浮游菌或生物膜附着菌建立感染，有无植入异物。大多数研究使用放射学和微生物学分析来确诊骨髓炎。
有令人信服的证据支持在临床疾病的骨感染模型中使用绵羊。大多数研究的绵羊表现出令人信服的骨髓炎，且感染耐受性良好，并发症极少。此外，生物学和生物力学相似的优势可能会增加将研究结果转化为成功治疗方法的成功率。
在临床前研究领域，转化为可行临床治疗方法往往充满风险，寻求可靠且具代表性的动物模型仍然至关重要。本系统评价强调了绵羊作为大型动物模型的巨大未开发潜力，尤其是在骨感染研究中。绵羊与人类骨骼结构在解剖学和生物力学上的相似性使绵羊成为研究骨髓炎和假体周围关节感染的宝贵资源。对文献的全面探索证明了这些模型的稳健性和转化前景。此外，本文强调了绵羊在开发人类骨感染有效治疗策略方面的潜在适用性。
