A comprehensive tool box for large animal studies of intervertebral disc degeneration.

Preclinical studies involving large animal models aim to recapitulate the clinical situation as much as possible and bridge the gap from benchtop to bedside. To date, studies investigating intervertebral disc (IVD) degeneration and regeneration in large animal models have utilized a wide spectrum of methodologies for outcome evaluation. This paper aims to consolidate available knowledge, expertise, and experience in large animal preclinical models of IVD degeneration to create a comprehensive tool box of anatomical and functional outcomes. Herein, we present a Large Animal IVD Scoring Algorithm based on three scales: macroscopic (gross morphology, imaging, and biomechanics), microscopic (histological, biochemical, and biomolecular analyses), and clinical (neurologic state, mobility, and pain). The proposed algorithm encompasses a stepwise evaluation on all three scales, including spinal pain assessment, and relevant structural and functional components of IVD health and disease. This comprehensive tool box was designed for four commonly used preclinical large animal models (dog, pig, goat, and sheep) in order to facilitate standardization and applicability. Furthermore, it is intended to facilitate comparison across studies while discerning relevant differences between species within the context of outcomes with the goal to enhance veterinary clinical relevance as well. Current major challenges in pre-clinical large animal models for IVD regeneration are highlighted and insights into future directions that may improve the understanding of the underlying pathologies are discussed. As such, the IVD research community can deepen its exploration of the molecular, cellular, structural, and biomechanical changes that occur with IVD degeneration and regeneration, paving the path for clinically relevant therapeutic strategies.

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© 2021 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.

Déclaration de conflit d'intérêts

The authors have the following declarations: Naomi N. Lee; Elias Salzer; Andres F. Bonilla; Frances C. Bach; Julie B. Engiles; Andrea Vernengo: No conflicts to declare. James L. Cook: Artelon: Paid consultant Arthrex, Inc: IP royalties; Paid consultant; Paid presenter or speaker; Research support AthleteIQ: IP royalties ConforMIS: Research support CONMED Linvatec: Paid consultant Coulter Foundation: Research support DePuy Synthes, A Johnson & Johnson Company: Research support Eli Lilly: Paid consultant; Research support Journal of Knee Surgery: Editorial or governing board Merial: Research support Midwest Transplant Network: Board or committee member Musculoskeletal Transplant Foundation: Board or committee member; IP royalties; Research support National Institutes of Health (NIAMS & NICHD): Research support Purina: Research support Schwartz Biomedical: Paid consultant Thieme: Publishing royalties, financial or material support Trupanion: Paid consultant U.S. Department of Defense: Research support Zimmer‐Biomet: Research support. Sibylle Grad; Zulma Gazit: JOR Spine—scientific advisory board. Keita Ito: NC Biomatrix: Paid consultant and shareholder; Global Spine Journal: Deputy editor: Biomechanics and Modeling in Mechanobiology: Editorial board. Lachlan J. Smith: JOR Spine—scientific advisory board; PLOS One—academic editorial board member; Connective Tissue Research—Associate Editor; National MPS Society—Scientific Advisory Board; ORS Spine Section—committee member. Hans‐Joachim Wilke: Grammer AG: Paid consultant; European Spine Journal: Deputy Editor. German Spine Foundation: Vice President. Marianna A. Tryfonidou: JOR Spine—scientific advisory board; SentryX—scientific advisor.