Large Animal Models of Meniscus Repair and Regeneration: A Systematic Review of the State of the Field.

Abstract Injury to the meniscus is common but few viable strategies exist for its repair or regeneration. To address this, animal models have been developed to translate new treatment strategies towards the clinic. However, there is not yet a regulatory document guiding such studies. The purpose of this study was to carry out a systematic review of the literature on meniscus treatment methods and outcomes to define the state of the field. Public databases were queried using search terms related to animal models and meniscus injury and/or repair over the years 1980-2015. Identified peer reviewed manuscripts were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Nine reviewers read each manuscript and scored based on whether the publication described a series of pre-defined study descriptors and outcome measures. Additional data were extracted to identify common assays used. A total of 128 full-length peer reviewed manuscripts were identified. The number of publications increased over the time frame analyzed, with 48% focused on augmented repair. Rabbit was by far the most prevalent species utilized (46%), with dog (21%) and sheep (20%) being the next most common. Analysis of study descriptors revealed that most studies appropriately documented details of the animal used, the surgical approach, and defect and implant characteristics (e.g., 63% of studies identified clearly the defect size). In terms of outcome parameters, most studies carried out macroscopic (85%), histologic (90%), and healing/integration (83%) analyses of the meniscus. However, many studies did not provide further analysis beyond these fundamental measures, and less than 40% reported on the adjacent cartilage and synovium, and joint function. There is intense interest in the field of meniscus repair. However, given the current lack of guidance documentation in this area, pre-clinical animal models are not performed in a standardized fashion. The development of a 'Best Practices' document would increase reproducibility and external validity of experiments, while accelerating advancements in translational research. Advancement is of paramount importance given the high prevalence of meniscal injuries and the paucity of effective repair or regenerative strategies.