Intervertebral disc degeneration: an experimental and numerical study using a rabbit model

Abstract

Animal models have been extensively used for the study of degenerative diseases and evaluation of new therapies to stop or even reverse the disease progression. The aim of this study is to reproduce lumbar intervertebral disc degeneration in a rabbit model by performing a percutaneous annular puncture at L4L5 level. The effect of this damage on the spine behaviour was analysed combining three different techniques: imaging processing, mechanical testing and computational modelling. Twenty New Zealand white rabbits were divided into control and experimental groups and followed up during 6 months. Intervertebral disc height, as well as nucleus area and signal intensity, decreased with degeneration while storage and loss moduli increased. Both changes may be related to the loss of water and tissue fibrosis. Similar but slighter changes were reported for adjacent discs. A finite element model was built based on MRI and mechanical testing findings to add new biomechanical information that cannot be obtained experimentally. Four stages were computationally simulated representing the different experimental phases. The numerical simulations showed that compressive stresses in the damaged and adjacent discs were modified with the progression of degeneration. Although extrapolation to humans should be carefully made, the use of numerical animal models combined with an experimental one could give a new insight of the overall mechanical behaviour of the spine.

Delamination of the Annulus Fibrosus of the Intervertebral Disc: Using a Bovine Tail Model to Examine Effect of Separation Rate

“…The peel test in the current study aims to quantify the tensile strain in the ILM when resisting delamination (Gregory et al, 2012). A limited number of studies have reported adhesion strength and variability in the AF including in the bovine tail (Harvey-Burgess and Gregory, 2019), rabbit (Gregory et al, 2014), porcine (Snow et al, 2018;Ghelani et al, 2020;McMorran and Gregory, 2021), and human (Calvo-Echenique et al, 2018) IVD. The peel strength values reported in the current study are similar to those reported previously in the bovine tail and porcine; while the reported values in the rabbit and human IVD were much lower (less than 1.0N/mm); however this may be a result of the high degree of degeneration in those experiments.…”

“…Interestingly, defects in adhesion of various non-biological composites have been shown to result in variability in the adhesion strength ( Rodríguez-Ramos et al, 2013 ). Similarly, a weakened and/or compromised AF may also increase the variability of adhesion strength which could in turn increase the possibility of circumferential tearing that can lead to IVD herniation, spinal nerve root compression, and a significant state of degeneration and pain in the spine ( Iyer and Kim, 2016 ; Calvo-Echenique et al, 2018 ).…”

Physalin A alleviates intervertebral disc degeneration via anti-inflammatory and anti-fibrotic effects

“…Various factors such as the inflammatory environment [ 4 , 5 ], autoimmunity [ 6 , 7 ], autophagy [ 8 ], fibrosis [ 9 ], and mechanical load [ 10 ] affect and mediate IVDD progression. Under the persistent influence of pathological mechanisms, NP cell extracellular matrix (ECM) causes degenerative phenotypic changes, including secretion of matrix metalloproteinases (MMPs) [ 11 ], various inflammatory mediators [ 12 ], and degeneration of aggrecan (Acan) and type II collagen (Col2a1) [ 13 ].…”

Development, Pathogenesis, and Regeneration of the Intervertebral Disc: Current and Future Insights Spanning Traditional to Omics Methods

“…Non-rodent animal models for IVD include rabbits, which display a similar disc morphology to humans and have been used to study degeneration as well as potential therapeutics ( Kroeber et al, 2002 ; Liu et al, 2011 ; Calvo-Echenique et al, 2018 ). Multiple larger animal models have also been established including canine, ovine, caprine, camelid, and porcine models ( Reid et al, 2002 ; Yoon et al, 2008 ; Bergknut et al, 2012 ; Stolworthy et al, 2015 ; Gullbrand et al, 2017a ).…”