Short communication Numerical exploration of the combined effect of nutrient supply, tissue condition and deformation in the intervertebral disc Andrea Malandrino a , Jérôme Noailly a,b , Damien Lacroix c,n a Biomechanics and Mechanobiology, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain b BIOMEC, Department of Mechanical Engineering, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain c INSIGNEO Institute for in silico medicine, Department of Mechanical Engineering, University of Sheffield, Sir Frederick Mappin Building, Mappin Street, Sheffield S1 3JD UK article info Article history: Accepted 7 February 2014 Keywords: Intervertebraldisc Softtissuebiomechanics Cell viability Boundary conditions Cell nutrition Computational analysis abstract Novel strategies to heal discogenic low back pain could highly benefit from comprehensive biophysical studies that consider both mechanical and biological factors involved in intervertebral disc degeneration. A decrease in nutrient availability at the bone–disc interface has been indicated as a relevant risk factor and as a possible initiator of cell death processes. Mechanical behaviour of both healthy and degenerated discs could highly interact with cell death in these compromised situations. In the present study, a mechano-transport finite element model was used to investigate the nature of mechanical effects on cell death processes via load-induced metabolic transport variations. Cycles of static sustained compression were chosen to simulate daily human activity. Healthy and degenerated cases were simulated as well as a reduced supply of solutes and an increase in solute exchange area at the bone–disc interface. Results showed that a reduction in metabolite concentrations at the bone–disc boundaries induced cell death, even when the increased exchange area was simulated. Slight local mechanical enhancements of glucose in the disc centre were capable of decelerating cell death but occurred only with healthy mechanical properties. However, mechanical deformations were responsible for a worsening in terms of cell death in the inner annulus, a disadvantaged zone far from the boundary supply with both an increased cell demand and a strain-dependent decrease of diffusivity. Such adverse mechanical effects were more accentuated when degenerative properties were simulated. Overall, this study paves the way for the use of biophysical models for a more integrated understanding of intervertebral disc pathophysiology. & 2014 Elsevier Ltd. All rights reserved. 1. Introduction Deciphering the interactions between cell biophysics and tissue condition is fundamental to better understand degeneration of the intervertebral disc (IVD) (Iatridis et al., 2006). Biophysical factors, such as IVD cell viability and catabolic activity, are both largely mediated by nutritional cues (Rinkler et al., 2010), and these are in turn related to mechanical loads (Fernando et al., 2011). In avascular IVDs, cell survival relies on metabolic pathways that mainly involve glucose and oxygen consumption, and lactate accu- mulation (Bibby et al., 2005). These solutes, together with other biochemical factors, are unbalanced in degenerated IVDs, or under compromised nutrient supply (Freemont et al., 2002; Holm and Nachemson, 1988). Although heredity alone could explain more than 50% of the variations in degeneration for the upper spine levels, it would not explain variations at the lower levels (Battié et al., 2009). Complex interactions between anthropometric and environmental factors may thus intervene in the degenerative process (Adams and Dolan, 2012; Battié et al., 2009). Stressful mechanical conditions act daily on the IVD and determine its cellular fate (Iatridis, 2009). Mechanical deforma- tions affect the transport of metabolites and of waste products, both regulating the cell viability. This transport is further affected by the morphology-dependent location and integrity of the boundary vasculature that can be altered by sclerosis and calcifi- cation at the endplates (Lee et al., 2006; Rajasekaran et al., 2010). As a result, it is difficult to address the effective disc cell activity in vivo, solely based on in vitro experiments. Largely focused on the critical influence of nutrition, various in silico models have been developed to simulate the transport of solutes (Malandrino et al., 2011; Mokhbi Soukane et al., 2009), and the cell viability (Shirazi-Adl et al., 2010; Zhu et al., 2012). These approaches Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/jbiomech www.JBiomech.com Journal of Biomechanics http://dx.doi.org/10.1016/j.jbiomech.2014.02.004 0021-9290 & 2014 Elsevier Ltd. All rights reserved. n Corresponding author. Tel.: þ44 114 2220156. E-mail address: D.Lacroix@sheffield.ac.uk (D. Lacroix). Journal of Biomechanics 47 (2014) 1520–1525