國立虎尾科技大學 |

Imaging the Spatiotemporal Evolution of Injuryinduced Dysfunction in Articular Cartilage.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Imaging the Spatiotemporal Evolution of Injuryinduced Dysfunction in Articular Cartilage./
Author:	Bartell, Lena Renee.
Description:	1 online resource (166 pages)
Notes:	Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Contained By:	Dissertation Abstracts International79-10B(E).
Subject:	Applied physics. -
Online resource:	click for full text (PQDT)
ISBN:	9780438026995

Imaging the Spatiotemporal Evolution of Injuryinduced Dysfunction in Articular Cartilage.
Bartell, Lena Renee.

Imaging the Spatiotemporal Evolution of Injuryinduced Dysfunction in Articular Cartilage. - 1 online resource (166 pages)

Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.

Thesis (Ph.D.)--Cornell University, 2018.

Includes bibliographical references

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.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

ISBN: 9780438026995Subjects--Topical Terms:

1181953
Applied physics.
Index Terms--Genre/Form:

554714
Electronic books.

Imaging the Spatiotemporal Evolution of Injuryinduced Dysfunction in Articular Cartilage.
LDR:04532ntm a2200349Ki 4500 001 918893
005 20181106104114.5
006 m o u
007 cr mn||||a|a||
008 190606s2018 xx obm 000 0 eng d
020 $a 9780438026995
035 $a (MiAaPQ)AAI10816449
035 $a (MiAaPQ)cornellgrad:10836
035 $a AAI10816449
040 $a MiAaPQ $b eng $c MiAaPQ $d NTU
100 1 $a Bartell, Lena Renee. $3 1193335
245 1 0 $a Imaging the Spatiotemporal Evolution of Injuryinduced Dysfunction in Articular Cartilage.
264 0 $c 2018
300 $a 1 online resource (166 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
500 $a Adviser: Itai Cohen.
502 $a Thesis (Ph.D.)--Cornell University, 2018.
504 $a Includes bibliographical references
520 $a 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.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2018
538 $a Mode of access: World Wide Web
650 4 $a Applied physics. $3 1181953
650 4 $a Biomedical engineering. $3 588770
650 4 $a Biomechanics. $3 565307
655 7 $a Electronic books. $2 local $3 554714
690 $a 0215
690 $a 0541
690 $a 0648
710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a Cornell University. $b Applied Physics. $3 1181952
773 0 $t Dissertation Abstracts International $g 79-10B(E).
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10816449 $z click for full text (PQDT)