Cell viability in intervertebral disc under various nutritional and dynamic loading conditions: 3d Finite element analysis

Abstract

In this study, a new cell density model was developed and incorporated into the formulation of the mechano-electrochemical mixture theory to investigate the effects of deprivation of nutrition supply at boundary source, degeneration, and dynamic loading on the cell viability of intervertebral disc (IVD) using finite element methods. The deprivation of nutrition supply at boundary source was simulated by reduction in nutrition level at CEP and AF boundaries. Cases with 100%, 75%, 60%, 50% and 30% of normal nutrition level at both CEP and AF boundaries were modeled. Unconfined axial sinusoidal dynamic compressions with different combinations of amplitude (u=10%±2.5%, ±5%) and frequency (f=1, 10, 20 cycle/day) were applied. Degenerated IVD was modeled with altered material properties. Cell density decreased substantially with reduction of nutrition level at boundaries. Cell death was initiated primarily near the NP–AF interface on the mid-plane. Dynamic loading did not result in a change in the cell density in non-degenerated IVD, since glucose levels did not fall below the minimum value for cell survival; in degenerated IVDs, we found that increasing frequency and amplitude both resulted in higher cell density, because dynamic compression facilitates the diffusion of nutrients and thus increases the nutrition level around IVD cells. The novel computational model can be used to quantitatively predict both when and where cells start to die within the IVD under various kinds of nutritional and mechanical conditions.

Simulating the sensitivity of cell nutritive environment to composition changes within the intervertebral disc

“…Supporting to our results, several simulation reports pointed out that the glucose concentration in inner AF is easily affected by any simulated degenerative change (Galbusera et al 2011;Zhu et al 2012;Malandrino et al 2014a). This phenomenon was largely attributed to the strong local consolidation of the TZ regions, due to the lateral pressure exerted on the fibre-reinforced AF by the lateral expansion of the NP under mechanical loads (Ruiz et al 2013).…”

“…Moreover, the calculations of Malandrino et al (2014) suggested that simulating CEP calcification (50%) was necessary in order to predict cell death, the latter occurring because of an increased lack of glucose in the inner AF. These results were qualitatively similar to those achieved by Zhu et al (2012) with a slightly different cell viability function, in which pH was not an explicit trigger of cell death and where cell death rate (i.e. in Eq.…”

“…However, these measurements were performed in agarose gels and not in extracted tissues. Other strain-dependent diffusivity laws have been proposed (Zhu et al 2012), and how they influence predictions in comparison to the Mackie and Meares law would have to be assessed.…”

“…For a given disc geometry, a predominant impact of tissue consolidation on nutrition-related cell death was further reported based on the calculations results obtained by Malandrino et al (2014a). Interestingly, Zhu et al (2012) found that dynamic compression might limit nutrition-related cell death when degenerated disc properties were simulated, whilst earlier reported simulations suggested that dynamic loads limit the mechanically-induced water loss from the disc (Ruiz et al 2013). However, none of the reported mechano-transport models incorporated explicit information about ECM composition, e.g.…”

CK8 phosphorylation induced by compressive loads underlies the downregulation of CK8 in human disc degeneration by activating protein kinase C

“…[26][27][28][29] Until now, several lines of evidence have demonstrated that prolonged exposure to hyper-physiological loads is harmful to the disc and consequently contributes to IDD. 21,30 The structure of NP is unique within the intervertebral disc, which is under tremendous forces and compressive load environment. 31,32 The exact mechanisms of this effect are complicated, including decreased proteoglycan production, increased apoptosis, the accumulation of inflammatory agents and cell volume changes.…”