title: Numerical exploration of the combined effect of nutrient supply, tissue condition and deformation in the intervertebral disc.
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.
authors.affiliation: Biomechanics and Mechanobiology, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Malandrino
authors.affiliation: Biomechanics and Mechanobiology, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain; BIOMEC, Department of Mechanical Engineering, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Noailly
authors.affiliation: INSIGNEO Institute for in silico medicine, Department of Mechanical Engineering, University of Sheffield, Sir Frederick Mappin Building, Mappin Street, Sheffield S1 3JD UK. Electronic address: D.Lacroix@sheffield.ac.uk.
authors.forename: Damien
authors.initials: D
authors.lastname: Lacroix
mesh_terms: D001692:Biological Transport; D001696:Biomechanical Phenomena; D016923:Cell Death; D002470:Cell Survival; D019245:Compressive Strength; D020342:Finite Element Analysis; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007403:Intervertebral Disc / Q000378:metabolism / Q000502:physiology*; D055959:Intervertebral Disc Degeneration; D008962:Models, Theoretical; D013314:Stress, Mechanical
chemical_list: D005947:Glucose
keywords: Boundary conditions; Cell nutrition; Cell viability; Computational analysis; Intervertebraldisc; Softtissuebiomechanics