Recommendations for design and conduct of preclinical in vivo studies of orthopedic device‐related infection

作者：T. Fintan Moriarty, Llinos G. Harris, Robert A. Mooney, Joseph C. Wenke, Martijn Riool, Sebastian A. J. Zaat, Annette Moter, Thomas P. Schaer, Nina Khanna, Richard Küehl, Volker Alt, Andrea Montali, Jianfeng Liu, Stephan Zeiter, Henk J. Busscher, David W. Grainger, R. Geoff Richards · 发表于：Journal of Orthopaedic Research® · 年份：2019 · DOI：10.1002/jor.24230 · 被引用次数：68 · 研究领域：Orthopedic Infections and Treatments、Orthopaedic implants and arthroplasty、Surgical site infection prevention

Orthopedic device-related infection (ODRI), including both fracture-related infection (FRI) and periprosthetic joint infection (PJI), remain among the most challenging complications in orthopedic and musculoskeletal trauma surgery. ODRI has been convincingly shown to delay healing, worsen functional outcome and incur significant socio-economic costs. To address this clinical problem, ever more sophisticated technologies targeting the prevention and/or treatment of ODRI are being developed and tested in vitro and in vivo. Among the most commonly described innovations are antimicrobial-coated orthopedic devices, antimicrobial-loaded bone cements and void fillers, and dual osteo-inductive/antimicrobial biomaterials. Unfortunately, translation of these technologies to the clinic has been limited, at least partially due to the challenging and still evolving regulatory environment for antimicrobial drug-device combination products, and a lack of clarity in the burden of proof required in preclinical studies. Preclinical in vivo testing (i.e. animal studies) represents a critical phase of the multidisciplinary effort to design, produce and reliably test both safety and efficacy of any new antimicrobial device. Nonetheless, current in vivo testing protocols, procedures, models, and assessments are highly disparate, irregularly conducted and reported, and without standardization and validation. The purpose of the present opinion piece is to discuss best practices in preclinical in viv...