Finding the Links between Knee Injuries and Osteoarthritis

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dc.contributor.advisor Shim, V en
dc.contributor.advisor Anderson, I en
dc.contributor.advisor Cornish, J en Leung, Sophia en 2017-02-21T21:07:48Z en 2016 en
dc.identifier.uri en
dc.description.abstract The focus of this thesis was to accurately investigate how mechanical loading influences cellular functions of cartilage. The knee joint is one of the most complex organs in our bodies, and is also one the most susceptible to injury. Traumatic injuries to the knee joint can cause pain, instability, and misalignment that alter joint loading patterns. This in turn can cause a cascade of events that leads to the development of osteoarthritis. Therefore, there has been considerable research dedicated to understanding the onset and development of this disease. Research studies have tried to simulate in vivo joint loading in vitro by using mechanical devices to apply various loads on 3D chondrocyte (cartilage cells) seeded in hydrogel culture models, and then using gene expression techniques to identify the biochemical changes that may occur as a response of the loading. However, these in vitro models have often not been validated, and the mechanical devices used to apply mechanical loads do not simulate physiological joint loading. This has therefore led to the development of a precise multiaxial-loading device that can mimic physiological joint loading. In addition, a 3D hydrogel construct was also developed to withstand these mechanical loads. To validate our in vitro model, we first had to validate the hydrogels, which are inherently inhomogeneous. A strain distribution technique was first developed to determine the strain distribution of dynamic compression through different regions or zones of our hydrogel construct. Then, these construct strains were correlated with the cellular-shape change and angle of rotation of the cells subjected to dynamic compression, tension and shear loads in the different zones of the constructs to improve our understanding of how mechanical loads affect chondrocytes. Finally, gene expression techniques were used to determine the effects of applying different loading modes (compression, tension, shear, and a combination of the three) using our device, on chondrocyte mechanobiology. Two loading regimes, physiological and injurious loading were used. Our results showed that more physiological loading regimes promoted cartilage homeostasis, rather than increased anabolic activities, closely imitating the behaviour of in vivo chondrocytes. The system developed in this research has been the closest device capable of fully mimicking in vivo conditions in health and disease. Work here has significantly enhanced knowledge of chondrocyte mechanobiology. Continued work using the device and techniques developed in this work will advance towards clinical understanding of disease progression and treatment. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof PhD Thesis - University of Auckland en
dc.relation.isreferencedby UoA99264934810902091 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.rights.uri en
dc.title Finding the Links between Knee Injuries and Osteoarthritis en
dc.type Thesis en Bioengineering en The University of Auckland en Doctoral en PhD en
dc.rights.holder Copyright: The author en
dc.rights.accessrights en
pubs.elements-id 614278 en Medical and Health Sciences en Medical Sciences en Anatomy and Medical Imaging en
pubs.record-created-at-source-date 2017-02-22 en

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