Imaging the spatiotemporal evolution of injury-induced dysfunction in articular cartilage
| dc.contributor.author | Bartell, Lena | |
| dc.contributor.chair | Cohen, Itai | |
| dc.contributor.committeeMember | Zipfel, Warren R. | |
| dc.contributor.committeeMember | Bonassar, Lawrence | |
| dc.date.accessioned | 2018-10-23T13:22:13Z | |
| dc.date.available | 2018-10-23T13:22:13Z | |
| dc.date.issued | 2018-05-30 | |
| dc.description.abstract | Articular cartilage is a fascinating biological material wherein a careful balance of mechanical and biological homeostasis ensures healthy joint function over decades of normal loading. Injurious loading, however, can upset this balance, inducing cartilage’s chondrocyte cells to dysfunction and leading to both the degradation of the tissue and, ultimately, the debilitating joint disease osteoarthritis. Understanding how injury causes dysfunction is important not only for understanding disease pathogenesis, but also for targeting treatments to protect and preserve cartilage. Previous studies have explored both the mechanical and biological deterioration of cartilage after injury, observing cracks in the extracellular matrix and a complex wave of cellular responses, including respiratory dysfunction and death. However, many open questions remain regarding the link between injury mechanics and cartilage dysfunction. In the first part of this thesis, I explore the spatiotemporal evolution of cellular dysfunction after impact injury in order to relate this dysfunction to the mechanics of injury and elucidate promising therapeutic targets. First, I present a custom impact device to injure cartilage explants while interfacing with microscopy. Analyzing such imaging data, I found that injury induces a wave of mitochondrial dysfunction within 15 minutes of impact and cell death within 3 hours. Both measures are highly correlated with the local strain experienced during injury, showing that injury mechanics dictate peracute cellular dysfunction. Consequently, cartilage’s compliant surface layer may serve to protect underlying cells by absorbing excess strain. Remarkably, I also found that treating samples with the mitoprotective peptide SS-31 completely eliminated the strain-dependent mitochondrial dysfunction after impact. These results have important clinical implications for understanding the very first changes in cartilage after injury and targeting these responses with clinically-relevant treatment. In the next part of this thesis, I explore one commonly-observed form of mechanical deterioration induced by cartilage injury: cracks. In particular, I present a method to indent cartilage with a sharp blade while simultaneously tracking bulk and local mechanics. Results showed significant dependence across physiologically relevant rates and were modified by cartilage’s layered structure. Taken together, this study highlights the importance of rate and inhomogeneity in governing cartilage failure and suggests important parallels between failure in cartilage and in high-toughness double-network hydrogels. Finally, I close by exploring spatiotemporal mechanics and indentation failure in an entirely new system: protective glass coatings. Tracking embedded fiducial markers in polymeric coatings with rapid 3D confocal videos, I show that incorporating nanosilica beads in the coatings modulates their adhesion and indentation response, with important implications for their ability to protect the underlying glass. Overall, this thesis champions the utility of imaging in concert with spatiotemporal analysis in order to relate the complex mechanical behavior of a system, such as articular cartilage, to its function and dysfunction. | |
| dc.identifier.doi | https://doi.org/10.7298/X44X561N | |
| dc.identifier.other | Bartell_cornellgrad_0058F_10836 | |
| dc.identifier.other | http://dissertations.umi.com/cornellgrad:10836 | |
| dc.identifier.other | bibid: 10489459 | |
| dc.identifier.uri | https://hdl.handle.net/1813/59374 | |
| dc.language.iso | en_US | |
| dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | * |
| dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
| dc.subject | Applied physics | |
| dc.subject | elastography | |
| dc.subject | mechanobiology | |
| dc.subject | Biomedical engineering | |
| dc.subject | Biomechanics | |
| dc.subject | Microscopy | |
| dc.subject | Cartilage | |
| dc.subject | Mitochondria | |
| dc.title | Imaging the spatiotemporal evolution of injury-induced dysfunction in articular cartilage | |
| dc.type | dissertation or thesis | |
| dcterms.license | https://hdl.handle.net/1813/59810 | |
| thesis.degree.discipline | Applied Physics | |
| thesis.degree.grantor | Cornell University | |
| thesis.degree.level | Doctor of Philosophy | |
| thesis.degree.name | Ph. D., Applied Physics |
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