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      On the Relative Relevance of Subject-Specific Geometries and Degeneration-Specific Mechanical Properties for the Study of Cell Death in Human Intervertebral Disk Models

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          Abstract

          Capturing patient- or condition-specific intervertebral disk (IVD) properties in finite element models is outmost important in order to explore how biomechanical and biophysical processes may interact in spine diseases. However, disk degenerative changes are often modeled through equations similar to those employed for healthy organs, which might not be valid. As for the simulated effects of degenerative changes, they likely depend on specific disk geometries. Accordingly, we explored the ability of continuum tissue models to simulate disk degenerative changes. We further used the results in order to assess the interplay between these simulated changes and particular IVD morphologies, in relation to disk cell nutrition, a potentially important factor in disk tissue regulation. A protocol to derive patient-specific computational models from clinical images was applied to different spine specimens. In vitro, IVD creep tests were used to optimize poro-hyperelastic input material parameters in these models, in function of the IVD degeneration grade. The use of condition-specific tissue model parameters in the specimen-specific geometrical models was validated against independent kinematic measurements in vitro. Then, models were coupled to a transport-cell viability model in order to assess the respective effects of tissue degeneration and disk geometry on cell viability. While classic disk poro-mechanical models failed in representing known degenerative changes, additional simulation of tissue damage allowed model validation and gave degeneration-dependent material properties related to osmotic pressure and water loss, and to increased fibrosis. Surprisingly, nutrition-induced cell death was independent of the grade-dependent material properties, but was favored by increased diffusion distances in large IVDs. Our results suggest that in situ geometrical screening of IVD morphology might help to anticipate particular mechanisms of disk degeneration.

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          Most cited references 60

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            Design and Analysis of Experiments

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              New in vivo measurements of pressures in the intervertebral disc in daily life.

              We conducted intradiscal pressure measurements with one volunteer performing various activities normally found in daily life, sports, and spinal therapy. The goal of this study was to measure intradiscal pressure to complement earlier data from Nachemson with dynamic and long-term measurements over a broad range of activities. Loading of the spine still is not well understood. The most important in vivo data are from pioneering intradiscal pressure measurements recorded by Nachemson during the 1960s. Since that time, there have been few data to corroborate or dispute those findings. Under sterile surgical conditions, a pressure transducer with a diameter of 1.5 mm was implanted in the nucleus pulposus of a nondegenerated L4-L5 disc of a male volunteer 45-years-old and weighing 70 kg. Pressure was recorded with a telemetry system during a period of approximately 24 hours for various lying positions; sitting positions in a chair, in an armchair, and on a pezziball (ergonomic sitting ball); during sneezing, laughing, walking, jogging, stair climbing, load lifting during hydration over 7 hours of sleeping, and others. The following values and more were measured: lying prone, 0.1 MPa; lying laterally, 0.12 MPa; relaxed standing, 0.5 MPa; standing flexed forward, 1.1 MPa; sitting unsupported, 0.46 MPa; sitting with maximum flexion, 0.83 MPa; nonchalant sitting, 0.3 MPa; and lifting a 20-kg weight with round flexed back, 2.3 MPa; with flexed knees, 1.7 MPa; and close to the body, 1.1 MPa. During the night, pressure increased from 0.1 to 0.24 MPa. Good correlation was found with Nachemson's data during many exercises, with the exception of the comparison of standing and sitting or of the various lying positions. Notwithstanding the limitations related to the single-subject design of this study, these differences may be explained by the different transducers used. It can be cautiously concluded that the intradiscal pressure during sitting may in fact be less than that in erect standing, that muscle activity increases pressure, that constantly changing position is important to promote flow of fluid (nutrition) to the disc, and that many of the physiotherapy methods studied are valid, but a number of them should be re-evaluated.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/176104
                URI : http://frontiersin.org/people/u/194820
                URI : http://frontiersin.org/people/u/35327
                URI : http://frontiersin.org/people/u/190041
                URI : http://frontiersin.org/people/u/206390
                URI : http://frontiersin.org/people/u/59318
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                11 February 2015
                2015
                : 3
                Affiliations
                1Biomechanics and Mechanobiology, Institute for Bioengineering of Catalonia , Barcelona, Spain
                2Center for Computational Imaging and Simulation Technologies in Biomedicine (CISTIB), Department of Mechanical Engineering, The University of Sheffield , Sheffield, UK
                3Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology , Eindhoven, Netherlands
                4Center of Musculoskeletal Research Ulm, Institute of Orthopaedic Research and Biomechanics, University of Ulm , Ulm, Germany
                5UTC CNRS UMR 7338, Biomécanique et Biongénierie (BMBI), Université de Technologie de Compiègne , Compiègne, France
                Author notes

                Edited by: Fabio Galbusera, University of Ulm, Germany

                Reviewed by: Henrique De Amorim Almeida, Polytechnic Institute of Leiria, Portugal; Olga Panagiotopoulou, The University of Queensland, Australia

                *Correspondence: Jérôme Noailly, Biomechanics and Mechanobiology, Institute for Bioengineering of Catalonia, C/Baldiri Reixac, 4-8, Torre I, Planta 10, Barcelona 08028, Spain e-mail: jnoailly@ 123456ibecbarcelona.eu

                This article was submitted to Biomechanics, a section of the journal Frontiers in Bioengineering and Biotechnology.

                Article
                10.3389/fbioe.2015.00005
                4324300
                Copyright © 2015 Malandrino, Pozo, Castro-Mateos, Frangi, van Rijsbergen, Ito, Wilke, Dao, Ho Ba Tho and Noailly.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 8, Tables: 5, Equations: 20, References: 75, Pages: 15, Words: 11355
                Categories
                Bioengineering and Biotechnology
                Hypothesis and Theory

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