Characterization of chondroitinase-induced lumbar intervertebral disc degeneration in a sheep model intended for assessing biomaterials

BioRxiv : the Preprint Server for Biology
R. BoremJeremy Mercuri

Abstract

Intervertebral disc (IVD) degeneration (IVDD) leads to structural and functional changes. Biomaterials for restoring IVD function and promoting regeneration are currently being investigated; however, such approaches require validation using animal models that recapitulate clinical, biochemical, and biomechanical hallmarks of the human pathology. Herein, we comprehensively characterized a sheep model of chondroitinase-ABC (C-ABC) induced IVDD. Briefly, C-ABC (1U) was injected into the L1/2, L2/3, and L3/4 IVDs. Degeneration was assessed via longitudinal magnetic resonance (MR) and radiographic imaging. Additionally, kinematic, biochemical, and histological analyses were performed on explanted functional spinal units (FSUs). At 17-weeks, C-ABC treated IVDs demonstrated significant reductions in MR index (p=0.030) and disc height (p=0.009) compared to pre-operative values. Additionally, C-ABC treated IVDs exhibited significantly increased creep displacement (p=0.004) and axial range of motion (p=0.007) concomitant with significant decreases in tensile (p=0.034) and torsional (p=0.021) stiffnesses and long-term viscoelastic properties (p=0.016). C-ABC treated IVDs also exhibited a significant decrease in NP glycosaminoglycan : hydr...Continue Reading

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