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Recommendations for design and conduct of preclinical in vivo studies of orthopedic device‐related infection
Author(s) -
Moriarty T Fintan,
Harris Llinos G.,
Mooney Robert A.,
Wenke Joseph C.,
Riool Martijn,
Zaat Sebastian A. J.,
Moter Annette,
Schaer Thomas P.,
Khanina,
Kuehl Richard,
Alt Volker,
Montali Andrea,
Liu Jianfeng,
Zeiter Stephan,
Busscher Henk J.,
Grainger David W.,
Richards R. Geoff
Publication year - 2019
Publication title -
journal of orthopaedic research®
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.24230
Subject(s) - medicine , preclinical testing , orthopedic surgery , intensive care medicine , antimicrobial , periprosthetic , medical physics , surgery , arthroplasty , biology , microbiology and biotechnology
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 vivo testing of antimicrobial interventions targeting ODRI. By sharing these experience‐driven views, we aim to aid others in conducting such studies both for fundamental biomedical research, but also for regulatory and clinical evaluation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:271–287, 2019.