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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Aberrant mechanosensing in injured intervertebral discs as a result of boundary-constraint disruption and residual-strain loss
Nature biomedical engineering, v 3(12), pp 998-1008
Dec 2019
PMID: 31611678
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- Aberrant mechanosensing in injured intervertebral discs as a result of boundary-constraint disruption and residual-strain loss
- Creators
- Edward D Bonnevie - Annenberg Public Policy CenterSarah E Gullbrand - CMC VA Medical Center, Philadelphia, PA, USABeth G Ashinsky - Philadelphia VA Medical CenterTonia K Tsinman - Philadelphia VA Medical CenterDawn M Elliott - University of DelawarePen-Hsiu Grace Chao - National Taiwan UniversityHarvey E Smith - Philadelphia VA Medical CenterRobert L Mauck - Philadelphia VA Medical CenterJason E Cohn
- Publication Details
- Nature biomedical engineering, v 3(12), pp 998-1008
- Publisher
- Springer Nature
- Grant note
- F32 AR072478 / NIAMS NIH HHS P30 AR050950 / NIAMS NIH HHS P30 AR069619 / NIAMS NIH HHS I01 RX002274 / RRD VA R01 EB002425 / NIBIB NIH HHS IK1 RX002445 / RRD VA T32 AR053461 / NIAMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000501592700010
- Scopus ID
- 2-s2.0-85076196993
- Other Identifier
- 991019353627704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Engineering, Biomedical