Introduction

Due to the avascular nature of the intervertebral (IVD), cell nutritional stress in the organ is believed to be a risk factor of disc degeneration¹. Diffusion is the main mechanism of transporting nutrients to the disc cells. It highly depends on both diffusion distances and tissue material properties², but the coupled effects thereof on solute concentrations in the IVD have not been well explored under mechanical loads. Hence, we explicitly calculated these effects on the transport of oxygen, glucose and lactate, through finite element (FE) simulations, with patient-specific IVD models with varying geometries under normal and degenerate disc material properties.

Method

Poromechanical FE models of three different patient-specific L4/5 lumbar IVDs with mean heights of 8 mm (thin), 12 mm (medium) and 16 mm (tall) were considered (Fig.1A). Mechanical simulations were coupled with a reactive oxygen, glucose and lactate transport model, and a corresponding cell viability model⁴ (Fig.1B, D). Each coupled model simulated three days of physiological compressive loading, including 16 hours of activity and 8 hours of rest under healthy (GR1 - Pfirrmann grade 1) and degenerated (GR3 - Pfirrmann grade 3) tissue conditions⁵ (Fig.1C)

Results

Results after 3 simulated days showed oxygen and glucose concentrations for thin IVD increased by 62% and 40%, respectively, in the NP center under healthy material property compared to that for medium IVD (DE, Fig 2A). In contrast, concentrations of oxygen and glucose in the TR zone decreased by 38% and 48%, respectively, in comparison with the medium concentrations (IE, Fig.2 A). Changing material properties from GR1 to GR3 affected glucose concentration in the TR zone for thin, medium and tall IVDs by -22%, -30% and -50%, respectively (Fig.2B). Cell viability, as the result of glucose drop below a critical value of 0.5 mM⁴, was also affected by coupled variations of disc height and material properties. Cell death was observed only in the TR zone of tall IVD under GR3 tissue.

 Discussion

Time-dependent concentrations of oxygen, glucose and lactate in the NP center and transition zone (TR) for the three morphologies of IVDs under GR1 and GR3 tissue conditions were successfully calculated. As previously reported⁴ oxygen and glucose concentrations were higher in thin IVD compared to medium and tall IVDs, with lactate concentration behaving exactly in a reversed manner due to shorter diffusion distance. Change in material properties also affected meaningfully the metabolite concentrations. Tall IVD with GR3 material properties might favor strong nutritional stress, which might happen as GR3 IVD may have unaltered heights. The TR was particularly affected, while it turns out to be the region where early structural alterations appear in degenerate discs. In conclusion, our mechano-transport FE simulations revealed that inter-individual variations in IVD morphologies in combination with tissue material properties can stand for a risk of disc cell nutritional stress. Nutritional stress might lead to local disc cell death and hampered regulation of IVD extracellular matrix, therein compromising tissue integrity.

Acknowledgments

Catalan Government (AGAUR, Beatriu de Pinós 2020 BP 00282).