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Basic Science of Cartilage Collagen Damage and Fatigue Wear Resistance, and Clinical Strategies for Repair /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Basic Science of Cartilage Collagen Damage and Fatigue Wear Resistance, and Clinical Strategies for Repair // Kimberly R Kroupa.
Author:	Kroupa, Kimberly R.,
Description:	1 electronic resource (195 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-11, Section: B.
Contained By:	Dissertations Abstracts International86-11B.
Subject:	Biomechanics. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31940214
ISBN:	9798314884508

Basic Science of Cartilage Collagen Damage and Fatigue Wear Resistance, and Clinical Strategies for Repair /
Kroupa, Kimberly R.,

Basic Science of Cartilage Collagen Damage and Fatigue Wear Resistance, and Clinical Strategies for Repair /Kimberly R Kroupa. - 1 electronic resource (195 pages)

Source: Dissertations Abstracts International, Volume: 86-11, Section: B.

Articular cartilage is a specialized tissue lining diarthrodial joints in the body, where it serves to reduce friction and wear, and sustains contact forces for over 100 million loading cycles in a 60+ year lifespan. Over time cartilage may degrade resulting in osteoarthritis (OA), a painful, debilitating condition. Despite being the leading cause of disability in the U.S. and affecting 52 million Americans, limited early-stage interventions exist, largely due to the complex multifactorial progression of the disease. A clear understanding of the structural contributions of healthy cartilage to its function, as well as the structural changes mediating OA progression are essential precursors to the development of early-stage diagnostic and treatment strategies. As such, the work of this dissertation seeks to improve understanding of the articular cartilage structure-function relationships through (1) investigating the contributions of the collagen to the mechanical function of cartilage (2) probing the intrinsic mechanisms by which cartilage health is maintained, and which may be disrupted in OA.To isolate the functional significance of the type-II dominant collagen extracellular matrix (ECM) of articular cartilage, Chapters 2 and 3 utilized an enzymatic treatment to achieve near-complete (>97%) removal of proteoglycans (PGs) from the tissue. Experimental data was used to develop and validate a reactive viscoelastic model of intrinsic collagen viscoelasticity. Applying this model to rapid loading configurations, it was discovered that intrinsic viscoelasticity of type-II dominant collagen in immature bovine articular cartilage contributes non-negligibly to viscoelastic response of the intact tissue, but that other sources of flow-independent viscoelasticity (such as the contribution of PGs) are likely also needed to account for the enhanced tissue modulus under rapid loading. In Chapter 3 the curling of mature bovine cartilage strips at various ionic concentrations was measured, before and after enzymatic removal of PGs. Results showed some curvature of the sample after PGD, implying that residual stress does arise within the type II matrix of the tissue, not only due to the presence of PGs imparting a Donnan osmotic pressure. When cartilage damages under reciprocal loading, as is seen physiologically, it does so via fatigue failure or breakage of the collagen crosslinks. Fatigue failure refers to a mechanism by which a material subjected to cyclical mechanical loading weakens over time, eventually failing at a threshold of loading significantly below the failure load under a single cycle of loading. This breakage occurs below the surface of the tissue, destabilizing the ECM and causing the tissue to swell, blister, and rupture, through a process termed delamination. However, cartilage normally withstands loading without damage, suggesting the presence of a protective in vivo mechanism preventing fatigue. Studies from Petersen et al. and Sise et al. indicated that synovial fluid (SF) plays a key role in preventing delamination during sliding, which is not tied to lowering of the friction coefficient, with its effectiveness diminishing when diluted below 50%. These findings suggest that SF constituents degrade under loading if not replenished, weakening this protective mechanism and enabling fatigue failure.To this end, Chapter 4 investigates the hypothesis that synovial fluid breaks down duration daily reciprocating sliding frictional contact if not replenished, degrading a protective mechanism and enabling the onset of fatigue failure. Immature bovine tibial strips were subject to reciprocal compressive loading in a bath of either fresh or used SF. Results illustrated that wear testing cartilage strips in reused synovial fluid caused more wear via delamination than testing in fresh synovial fluid. A small increase in shear rate, or equivalently a reduction in shear thinning was seen at shear rates above 103 s-1 , accompanied with an apparent increase in the concentration of high molecular weight (>2000 kDa) SF constituents in used SF. This could suggest entanglement or aggregation of SF components, which may have deleterious effects on the ECM-protective role of SF. The necessitation of SF replenishment in vivo to maintain function is consistent with the 2-4 day complete turnover cycle of SF documented in animal joints9 . This notion also suggests the existence of a critical cellular repair mechanism by which cells address daily damage and maintain the composition of the SF. Proximity and phenotype would indicate this cell population is likely either superficial zone (SZ) chondrocytes or synoviocytes. Interestingly SZ-resident chondrocytes have been shown to die even under normal physiologic loading conditions. However, the mechanism by which these SZ cells preferentially die has not yet been explained. The SZ is known to exhibit lower compressive and shear moduli compared to deeper zones, resulting in excessive SZ compaction under physiological loading. Evidence is limited by experimental constraints that cannot examine field variables throughout the in situ cellular environment. As such, to provide access to data experiments cannot obtain, in Chapter 5, we performed multiscale finite element analysis of articular contact to understand the fate of a chondrocyte embedded in the SZ, by tracking the temporal evolution of its interstitial fluid pressure, hydraulic permeability, and volume change under physiologic loading conditions. Results showed that SZ chondrocytes can lose ninety percent of their intracellular fluid after several hours of intermittent or continuous contact loading, resulting in a reduction of intracellular hydraulic permeability by more than three orders of magnitude. These findings are consistent with loss of cell viability due to the impediment of cellular metabolic pathways induced by the loss of fluid. They suggest that there is a simple mechanical explanation for the vulnerability of SZ chondrocytes to sustained physiological loading conditions. This also begs the question of how these cells are replaced, with some evidence suggesting the most likely supply to be synoviocytes.After much discussion of the importance of collagen crosslinks to the health and function of articular cartilage, particularly in the SZ, the final study of this dissertation, presented in Chapter 6, presents a clinically translation component of this dissertation, investigating the use of a femtosecond laser to (1) prophylactically strengthen the collagen to prevent the onset of damage in cartilage, and (2) repair damaged collagen at an collagenous interface (cartilage implantation, meniscal, ligament and other common musculoskeletal tears), to encourage adhesion and prevent worsening of the tear or swelling of the tissue. Results indicated the induction of additional crosslinks in the superficial zone of cartilage can help to prevent delamination wear in the tissue. Similarly, laser treatment successfully increased the interface strength by an average of 157.0% (n=6).

English

ISBN: 9798314884508Subjects--Topical Terms:

548685
Biomechanics.
Subjects--Index Terms:

Articular cartilage

Basic Science of Cartilage Collagen Damage and Fatigue Wear Resistance, and Clinical Strategies for Repair /
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520 $a Articular cartilage is a specialized tissue lining diarthrodial joints in the body, where it serves to reduce friction and wear, and sustains contact forces for over 100 million loading cycles in a 60+ year lifespan. Over time cartilage may degrade resulting in osteoarthritis (OA), a painful, debilitating condition. Despite being the leading cause of disability in the U.S. and affecting 52 million Americans, limited early-stage interventions exist, largely due to the complex multifactorial progression of the disease. A clear understanding of the structural contributions of healthy cartilage to its function, as well as the structural changes mediating OA progression are essential precursors to the development of early-stage diagnostic and treatment strategies. As such, the work of this dissertation seeks to improve understanding of the articular cartilage structure-function relationships through (1) investigating the contributions of the collagen to the mechanical function of cartilage (2) probing the intrinsic mechanisms by which cartilage health is maintained, and which may be disrupted in OA.To isolate the functional significance of the type-II dominant collagen extracellular matrix (ECM) of articular cartilage, Chapters 2 and 3 utilized an enzymatic treatment to achieve near-complete (>97%) removal of proteoglycans (PGs) from the tissue. Experimental data was used to develop and validate a reactive viscoelastic model of intrinsic collagen viscoelasticity. Applying this model to rapid loading configurations, it was discovered that intrinsic viscoelasticity of type-II dominant collagen in immature bovine articular cartilage contributes non-negligibly to viscoelastic response of the intact tissue, but that other sources of flow-independent viscoelasticity (such as the contribution of PGs) are likely also needed to account for the enhanced tissue modulus under rapid loading. In Chapter 3 the curling of mature bovine cartilage strips at various ionic concentrations was measured, before and after enzymatic removal of PGs. Results showed some curvature of the sample after PGD, implying that residual stress does arise within the type II matrix of the tissue, not only due to the presence of PGs imparting a Donnan osmotic pressure. When cartilage damages under reciprocal loading, as is seen physiologically, it does so via fatigue failure or breakage of the collagen crosslinks. Fatigue failure refers to a mechanism by which a material subjected to cyclical mechanical loading weakens over time, eventually failing at a threshold of loading significantly below the failure load under a single cycle of loading. This breakage occurs below the surface of the tissue, destabilizing the ECM and causing the tissue to swell, blister, and rupture, through a process termed delamination. However, cartilage normally withstands loading without damage, suggesting the presence of a protective in vivo mechanism preventing fatigue. Studies from Petersen et al. and Sise et al. indicated that synovial fluid (SF) plays a key role in preventing delamination during sliding, which is not tied to lowering of the friction coefficient, with its effectiveness diminishing when diluted below 50%. These findings suggest that SF constituents degrade under loading if not replenished, weakening this protective mechanism and enabling fatigue failure.To this end, Chapter 4 investigates the hypothesis that synovial fluid breaks down duration daily reciprocating sliding frictional contact if not replenished, degrading a protective mechanism and enabling the onset of fatigue failure. Immature bovine tibial strips were subject to reciprocal compressive loading in a bath of either fresh or used SF. Results illustrated that wear testing cartilage strips in reused synovial fluid caused more wear via delamination than testing in fresh synovial fluid. A small increase in shear rate, or equivalently a reduction in shear thinning was seen at shear rates above 103 s-1 , accompanied with an apparent increase in the concentration of high molecular weight (>2000 kDa) SF constituents in used SF. This could suggest entanglement or aggregation of SF components, which may have deleterious effects on the ECM-protective role of SF. The necessitation of SF replenishment in vivo to maintain function is consistent with the 2-4 day complete turnover cycle of SF documented in animal joints9 . This notion also suggests the existence of a critical cellular repair mechanism by which cells address daily damage and maintain the composition of the SF. Proximity and phenotype would indicate this cell population is likely either superficial zone (SZ) chondrocytes or synoviocytes. Interestingly SZ-resident chondrocytes have been shown to die even under normal physiologic loading conditions. However, the mechanism by which these SZ cells preferentially die has not yet been explained. The SZ is known to exhibit lower compressive and shear moduli compared to deeper zones, resulting in excessive SZ compaction under physiological loading. Evidence is limited by experimental constraints that cannot examine field variables throughout the in situ cellular environment. As such, to provide access to data experiments cannot obtain, in Chapter 5, we performed multiscale finite element analysis of articular contact to understand the fate of a chondrocyte embedded in the SZ, by tracking the temporal evolution of its interstitial fluid pressure, hydraulic permeability, and volume change under physiologic loading conditions. Results showed that SZ chondrocytes can lose ninety percent of their intracellular fluid after several hours of intermittent or continuous contact loading, resulting in a reduction of intracellular hydraulic permeability by more than three orders of magnitude. These findings are consistent with loss of cell viability due to the impediment of cellular metabolic pathways induced by the loss of fluid. They suggest that there is a simple mechanical explanation for the vulnerability of SZ chondrocytes to sustained physiological loading conditions. This also begs the question of how these cells are replaced, with some evidence suggesting the most likely supply to be synoviocytes.After much discussion of the importance of collagen crosslinks to the health and function of articular cartilage, particularly in the SZ, the final study of this dissertation, presented in Chapter 6, presents a clinically translation component of this dissertation, investigating the use of a femtosecond laser to (1) prophylactically strengthen the collagen to prevent the onset of damage in cartilage, and (2) repair damaged collagen at an collagenous interface (cartilage implantation, meniscal, ligament and other common musculoskeletal tears), to encourage adhesion and prevent worsening of the tear or swelling of the tissue. Results indicated the induction of additional crosslinks in the superficial zone of cartilage can help to prevent delamination wear in the tissue. Similarly, laser treatment successfully increased the interface strength by an average of 157.0% (n=6).
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650 4 $a Physiology. $3 518431
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653 $a Collagen
653 $a Fatigue failure
653 $a Osteoarthritis
653 $a Viscoelasticity
653 $a Wear
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