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Review

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

1
BCN MedTech, Department of Information and Communication Technologies, Universitat Pompeu Fabra, 08018 Barcelona, Spain
2
Department of Biomedical Engineering, Rochester Institute of Technology (RIT), Rochester, NY 14623, USA
3
Schön Clinic Munich Harlaching, Spine Center, Academic Teaching Hospital and Spine Research Institute of the Paracelsus Medical University Salzburg (Austria), 81547 Munich, Germany
4
Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield S1 1WB, UK
5
Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, Oxford Road, Manchester M13 9PT, UK
6
Catalan Institution for Research and Advanced Studies (ICREA), Pg. Lluis Companys 23, 08010 Barcelona, Spain
7
Department of Mechanical Engineering, National Technical University of Athens, 15780 Athens, Greece
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(2), 703; https://doi.org/10.3390/ijms22020703
Received: 25 November 2020 / Revised: 22 December 2020 / Accepted: 24 December 2020 / Published: 12 January 2021
(This article belongs to the Special Issue Intervertebral Disc Disease: From Pathophysiology to Novel Therapies)
Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations’ processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies. View Full-Text
Keywords: intervertebral disc; extracellular matrix; disc cell molecular biology; multifactorial cell stimulation; intervertebral disc degeneration; regenerative medicine; multiscale modeling; computational multiphysics; computational systems biology intervertebral disc; extracellular matrix; disc cell molecular biology; multifactorial cell stimulation; intervertebral disc degeneration; regenerative medicine; multiscale modeling; computational multiphysics; computational systems biology
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MDPI and ACS Style

Baumgartner, L.; Wuertz-Kozak, K.; Le Maitre, C.L.; Wignall, F.; Richardson, S.M.; Hoyland, J.; Ruiz Wills, C.; González Ballester, M.A.; Neidlin, M.; Alexopoulos, L.G.; Noailly, J. Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research. Int. J. Mol. Sci. 2021, 22, 703. https://doi.org/10.3390/ijms22020703

AMA Style

Baumgartner L, Wuertz-Kozak K, Le Maitre CL, Wignall F, Richardson SM, Hoyland J, Ruiz Wills C, González Ballester MA, Neidlin M, Alexopoulos LG, Noailly J. Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research. International Journal of Molecular Sciences. 2021; 22(2):703. https://doi.org/10.3390/ijms22020703

Chicago/Turabian Style

Baumgartner, Laura, Karin Wuertz-Kozak, Christine L. Le Maitre, Francis Wignall, Stephen M. Richardson, Judith Hoyland, Carlos Ruiz Wills, Miguel A. González Ballester, Michael Neidlin, Leonidas G. Alexopoulos, and Jérôme Noailly. 2021. "Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research" International Journal of Molecular Sciences 22, no. 2: 703. https://doi.org/10.3390/ijms22020703

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