Wong Ronald M Y, Li Tsz-Kiu, Li Jie, Ho Wing-Tung, Chow Simon K-H, Leung Sharon S Y, Cheung Wing-Hoi, Ip Margaret
Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.
School of Pharmacy, The Chinese University of Hong Kong, Hong Kong.
J Orthop Translat. 2020 Mar 30;23:8-20. doi: 10.1016/j.jot.2020.03.002. eCollection 2020 Jul.
Osteosynthesis-associated infection is a challenging complication post fracture fixation, burdening the patients and the orthopaedic surgeons alike. A clinically relevant animal model is critical in devising new therapeutic strategies. Our aim was to perform a systematic review to evaluate existing preclinical models and identify their applications in aspects of animal selection, bacterial induction, fracture fixation and complications.
A systematic literature research was conducted in PubMed and Embase up to February 2020. A total of 31 studies were included. Information on the animal, bacterial induction, fracture fixation, healing result and complications were extracted.
Animals selected included murine (23), rabbit (6), ewe (1) and goat (1). Larger animals had enabled the use of human-sized implant, however small animals were more economical and easier in handling. was the most frequently chosen bacteria for induction. Bacterial inoculation dose ranged from 10 CFU. Consistent and replicable infections were observed from 10 CFU in general. Methods of inoculation included injections of bacterial suspension (20), placement of foreign objects (8) and pretreatment of implants with established biofilm (3). Intramedullary implants (13), plates and screws (18) were used in most models. Radiological (29) and histological evaluations (24) in osseous healing were performed. Complications such as instability of fracture fixation (7), unexpected surgical death (5), sepsis (1) and persistent lameness (1) were encountered.
The most common animal model is the infected open fracture internally fixated. Replicable infections were mainly from 10 CFU of bacteria. However, with the increase in antibiotic resistance, future directions should explore polymicrobial and antibiotic resistant strains, as these will no doubt play a major role in bone infection. Currently, there is also a lack of osteoporotic bone infection models and the pathophysiology is unexplored, which would be important with our aging population.
This systematic review provides an updated overview and compares the currently available animal models of osteosynthesis-associated infections. A discussion on future research directions and suggestion of animal model settings were made, which is expected to advance the research in this field.
骨合成相关感染是骨折固定术后具有挑战性的并发症，给患者和骨科医生都带来负担。一个具有临床相关性的动物模型对于设计新的治疗策略至关重要。我们的目的是进行一项系统综述，以评估现有的临床前模型，并确定它们在动物选择、细菌诱导、骨折固定和并发症方面的应用。
截至2020年2月，在PubMed和Embase上进行了系统的文献研究。共纳入31项研究。提取了有关动物、细菌诱导、骨折固定、愈合结果和并发症的信息。
所选动物包括小鼠（23只）、兔子（6只）、母羊（1只）和山羊（1只）。较大的动物能够使用人类尺寸的植入物，然而小动物更经济且易于操作。是诱导时最常选择的细菌。细菌接种剂量范围为10CFU。一般从10CFU观察到一致且可重复的感染。接种方法包括注射细菌悬液（20次）、放置异物（8次）和用已建立的生物膜对植入物进行预处理（3次）。大多数模型使用髓内植入物（13个）、钢板和螺钉（18个）。对骨愈合进行了放射学（29次）和组织学评估（24次）。遇到了诸如骨折固定不稳定（7例）、意外手术死亡（5例）、败血症（1例）和持续跛行（1例）等并发症。
最常见的动物模型是感染的开放性骨折内固定模型。可重复的感染主要来自10CFU的细菌。然而，随着抗生素耐药性的增加，未来的方向应该探索多微生物和耐药菌株，因为这些无疑将在骨感染中起主要作用。目前，也缺乏骨质疏松性骨感染模型，其病理生理学尚未得到探索，而随着人口老龄化，这将是很重要的。
本系统综述提供了最新的概述，并比较了目前可用的骨合成相关感染动物模型。对未来的研究方向进行了讨论，并提出了动物模型设置的建议，有望推动该领域的研究。
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