TY - JOUR
T1 - Recommendations for design and conduct of preclinical in vivo studies of orthopedic device-related infection
AU - Moriarty, T. Fintan
AU - Harris, Llinos G.
AU - Mooney, Robert A.
AU - Wenke, Joseph C.
AU - Riool, Martijn
AU - Zaat, Sebastian A. J.
AU - Moter, Annette
AU - Schaer, Thomas P.
AU - Khanna, Nina
AU - Kuehl, Richard
AU - Alt, Volker
AU - Montali, Andrea
AU - Liu, Jianfeng
AU - Zeiter, Stephan
AU - Busscher, Henk J.
AU - Grainger, David W.
AU - Richards, R. Geoff
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85062693336&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30667561
U2 - https://doi.org/10.1002/jor.24230
DO - https://doi.org/10.1002/jor.24230
M3 - Review article
C2 - 30667561
SN - 0736-0266
VL - 37
SP - 271
EP - 287
JO - Journal of orthopaedic research
JF - Journal of orthopaedic research
IS - 2
ER -