Biomechanical and rheological characterization of mild intervertebral disc degeneration in a large animal model

Abstract

Biomechanical properties of healthy and degenerated nucleus pulposus (NP) are thought to be important for future regenerative strategies for intervertebral disc (IVD) repair. However, which properties are pivotal as design criteria when developing NP replacement materials is ill understood. Therefore, we determined and compared segmental biomechanics and NP viscoelastic properties in normal and mildly degenerated discs. In eight goats, three lumbar IVDs were chemically degenerated using chondroitinase ABC (CABC), confirmed with radiography and MRI after euthanasia 12 weeks post-operative. Neutral zone (NZ) stiffness and range of motion (ROM) were determined sagitally, laterally, and rotationally for each spinal motion segment (SMS) using a mechanical testing device. NPs were isolated for oscillatory shear experiments; elastic and viscous shear moduli followed from the ratio between shear stress and strain. Water content was quantified by weighing before and after freeze-drying. Disc height on radiographs and signal intensity on MRI decreased (6% and 22%, respectively, p < 0.01) after CABC treatment, confirming that chemical degeneration provides a good model of disc degeneration. Furthermore, CABC-injected IVDs had significantly lower NZ stiffness and larger ROM in lateral bending (LB) and axial rotation (AR) than controls. Rheometry consistently revealed significantly lower (10-12%) viscoelastic moduli after mild degeneration within goats, though the inter-animal differences were relatively large (complex modulus $12 to 41 kPa). Relative water content in the NP was unaffected by CABC, remaining at $75%. These observations suggest that viscoelastic properties have a marginal influence on mechanical behavior of the whole SMS. Therefore, when developing replacement materials the focus should be on other design criteria, such as biochemical cues and swelling pressure.

A large animal model that recapitulates the spectrum of human intervertebral disc degeneration

“…18,46 Increases in disc ROM in lateral bending and axial rotation, and reduced stiffness in axial rotation have also been reported in this model, consistent with the alterations in mechanical properties observed in the current study. 47 Increases in catabolic gene expression have also been illustrated in this model with increasing severity of degeneration. 48 Mild to moderate changes to the goat disc have also been reported following surgically induced injury to the annulus, based on histological outcomes.…”

A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for Intervertebral Disc Regeneration

“…A major hindrance to the assessment of the efficacy of such therapeutic strategies has been the inadequacy of the animal models available to examine DDD (reviewed in [68]). Large animal models of DDD have been developed in dogs [76,77,119], sheep [70,71,72], goats [73,74,75] and pigs [79,80,81]. The latter two species suffer from anomalously high spontaneous healing responses and persistence of notochordal cells in the IVD with ageing, compounding unequivocal interpretation of the efficacy of therapeutic repair strategies.…”

“…Large animal models of DDD have been developed in sheep [70,71,72], goats [73,74,75], dogs [76,77,78], and pigs [79,80,81] and, of these, the sheep represents the gold standard large animal model. In 1990, Osti and colleagues developed a model of DDD induced by controlled anterolateral (5 × 5 mm) surgical defects over a 24 months post operative (PO) period [71].…”

Viscoelastic heating of insulated bovine intervertebral disc

“…The IVD consists of 2 distinct parts: the fibrocartilaginous outer annulus fibrosus (AF) and the more viscous inner nucleus pulposus (NP). Collectively, the IVD is a viscoelastic tissue . Viscoelastic materials possess mechanical properties that resemble both viscous fluids and elastic solids .…”