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Aberrant mechanosensing in injured intervertebral discs as a result of boundary-constraint disruption and residual-strain loss
Journal article   Open access   Peer reviewed

Aberrant mechanosensing in injured intervertebral discs as a result of boundary-constraint disruption and residual-strain loss

Edward D Bonnevie, Sarah E Gullbrand, Beth G Ashinsky, Tonia K Tsinman, Dawn M Elliott, Pen-Hsiu Grace Chao, Harvey E Smith, Robert L Mauck and Jason E Cohn
Nature biomedical engineering, v 3(12), pp 998-1008
Dec 2019
DOI: https://doi.org/10.1038/s41551-019-0458-4
PMID: 31611678
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc6899202View
Accepted (AM) Open Open Access (License Unspecified)

Abstract

Animals Annulus Fibrosus - diagnostic imaging Annulus Fibrosus - metabolism Annulus Fibrosus - pathology Apoptosis Biomechanical Phenomena Disease Models, Animal Intervertebral Disc - diagnostic imaging Intervertebral Disc - injuries Intervertebral Disc - metabolism Intervertebral Disc - pathology Intervertebral Disc Degeneration - metabolism Phenotype Rabbits Stress, Mechanical
In fibrous tissues, prestressed boundary constraints at bone interfaces instil residual strain throughout the tissue, even when unloaded. For example, internal swelling pressures in the central nucleus pulposus of the intervertebral disc generate prestrain in the outer annulus fibrosus. With injury and depressurization, these residual strains are lost. Here we show that the loss of residual strains in the intervertebral disc alters the microenvironment and instigates aberrant tissue remodelling and the adoption of atypical cellular phenotypes. By using puncture surgery of the annulus fibrosus in rabbits, ex vivo puncture experiments and electrospun nanofibrous scaffolds recapitulating these evolving boundary constraints, we show that the loss of residual strain promotes short-term apoptosis and the emergence of a fibrotic phenotype. We also show that local fibre organization and cellular contractility mediate this process and that the aberrant cellular changes could be abrogated by targeting the cell-mechanosensing machinery with small molecules. Our findings indicate that injury to dense connective tissues under prestrain alters boundary constraints and residual strain; this leads to aberrant mechanosensing, which in turn promotes disease progression.

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71 citations in Web of Science
66 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Engineering, Biomedical
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