Thesis (Ph.D.)--University of Delaware, 2006. / Principal faculty advisor: Andras Z. Szeri, Dept. of Mechanical Engineering. Includes bibliographical references.

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Abstract Osteoarthritis (OA) is the most common degenerative joint disease and a growing health problem affecting more than half of the population over the age of 65. It is characterized by inflammation in the cartilage and synovium, resulting in the loss of joint structure and progressive damage to the cartilage. Many pro-inflammatory mediators are elevated in OA, including reactive oxygen species (ROS) such as nitric oxide (NO) and hydrogen peroxide (H2O2). Damaged articular cartilage remains a challenge to treat due to the limited self-healing capacity of the tissue and unsuccessful biological interventions. This highlights the need for better therapeutic strategies to heal damaged articular cartilage. Ozone (O3) therapy has been shown to have positive results in the treatment of OA; however the use of O3 therapy as a therapeutic agent is controversial. There is a perception that O3 is always toxic, whereas evidence indicates that when it is applied following a specified method, O3 can be effective in the treatment of degenerative diseases. The mechanism of action of O3 therapy in OA is not fully understood and this review summarizes the use of O3 therapy in the treatment of damaged articular cartilage in OA.

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In this study an <i>in vitro</i> model was used to simulate joint trauma by subjecting explants of articular cartilage to a single impact load using a specially designed drop-tower loading machine for which two different loading attachments were developed. The aim was to compare the biophysical effects of impact loading on bovine and human cartilage. The proteolytic lysomal enzyme, cathepsin B and the proinflammatory mediators, prostaglandin E₂ (PGE₂) and nitric oxide (NO) have been implicated in the degradation of cartilage following trauma. This study aimed to investigate the role of these degradatory mediators. Human cartilage was found to be less damaged than bovine after impact and the type of loading attachment affected the nature of the damage observed. Following an impact load on human cartilage explants, the levels of glycosaminoglycans (GAGs), a measure of cartilage breakdown, in the culture medium and the percentage of apoptotic chondrocytes were significantly increased. The levels of pro-cathepsin B were significantly increased in the culture medium compared to unloaded controls. Addition of human cystatin C and the synthetic cathepsin B inhibitor, CA-074Me, reduced this release. However these inhibitors had no effect on the release of GAGs or the levels of apoptosis following impact. A marked increase in PGE₂ and NO was measured in the medium following an impact load, which was reduced by the selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, and the non-selective inhibitor, indomethacin. These inhibitors reduced chondrocyte apoptosis but no change was observed in the release of GAGs from the explants. This <i>in vitro</i> study indicates that cell viability and matrix degeneration are separately regulated and that it is unlikely that cathepsin B or COX-2 inhibition alone would slow down or prevent the development of secondary osteoarthritis.

Articular cartilage is a tough and resilient tissue lining the ends of articulating bones. It provides a smooth surface for joint locomotion as well as transmitting the force between bones. The main components of articular cartilage are collagen (20% w/w), proteoglycans (10% w/w) and water (70% w/w). The interactions between these three give the tissue its special characteristics. Water as a molecule is often forgotten when considering the mechanical properties of articular cartilage. This thesis aims to increase our knowledge of the role of water molecules in the load bearing mechanisms of the tissue. It will also investigate the material properties of cartilage as hydrogel. Different rates of loading (impact and slow compression) were used on partially dehydrated articular cartilage (bovine and human). The impact was also recorded using high-speed video cameras. Values of modulus of elasticity, Poisson's ratio, energetic coefficient of restitution were measured together with viscoelastic spectra, by Fourier transformation, and Dynamic Mechanical Analysis. Differential scanning calorimetry (DSC) was also performed on bovine and human articular cartilage, as well as transmission electron microscopy where different freeze substitution solvents were used. The stiffness of the tissue increased and the energetic coefficient of restitution decreased with decreasing water content. Cartilage explants had a smaller volume at the point of full strain than at the start of the impact and this volume loss was associated with the level of hydration of the tissue. Poisson's ratio was not associated with the water content of the tissue. The DSC showed that the water existed in the tissue in different environments, as the exothermic traces showed melting patterns with multiple peaks. Transmission electron micrographs revealed an area surrounding the collagen molecules that could be associated water. These results indicate that water might exist in a structured way in the tissue, and that it is important for the mechanical capabilities of the tissue.

Thesis (Ph. D.)--Ohio State University, 2006. / Full text release at OhioLINK's ETD Center delayed at author's request

Thesis (Ph. D.)--University of Rhode Island, 2005. / Typescript. Includes bibliographical references (leaves 189-201).

Osteoarthritis (OA) is one of the most concerned diseases in the field of orthopaedics. During the process of this disease, articular cartilages are degenerated and worn out at the end stage, which create pain and disabilities to the patients. Although multiple mechanical and biochemical factors may initiate and/or enhance the progression of OA, alternation of biomechanical properties of articular cartilage is one of the products. There are several major components in articular cartilage; it is believed that each of their contribution cannot be entirely neglected. Superficial zone is mainly consisted with collagen and it was found that the biomechanical properties of this part of cartilage are also alternated significantly as a result of OA. Hence, degeneration of collagen network also occurs. Alternatively, osteoporosis (OP) is another common disease, which is associated to the decrease of bone mineral density; the effect of OP on articular cartilage is limited. In reverse, increasing bone mineral density in subchondral plate alters the loads distribution on articular cartilage and possibly leads to OA. This current study investigated the morphological and biomechanical properties of individual collagen fibrils extracted from OA, OP and healthy cartilages. A total of ten joint specimens were recruited, 3 OA joints were from 3 OA patients, 3 OP joints were from 3 OP patients, and 4 joints were from 2 healthy individuals. All cartilages were harvested from non weight-bearing zone, and average diameters were calculated from 350 fibrils’ measurements. In addition, 50 fibrils were randomly selected for nano-indentation under ambient condition. However, the representation of biomechanical properties tested at low humidity may be questionable. This current study also investigated the stiffness of hydrated fibrils. The results showed that the collagen fibrils extracted from OA cartilages were thinner than the ones extracted from OP and healthy cartilages. It was believe that the fibrillation and derangement of collagen network spread from superficial zone towards deeper zones. However, the number of thinner collagen fibrils increased in OA specimens could be the reason of the loss of larger fibrils and/or fragmentation occurred in the superficial zone, where contains thinner fibrils. The biomechanical tests showed that fibrils extracted from OA cartilages owned the highest elastic modulus, while the ones from OP had the lowest; significant differences were found between all groups when tested under ambient condition. Alternatively, the same pattern of results could also be found when hydrated fibrils were tested; however, due to the limited amount of samples, only the difference between OA and OP were considered significant. In addition, no individual difference was found; no significant difference between samples within each group could be observed. Since nano-indentations were performed at the center of each fibril, the elastic moduli measured represented the stiffness of the crosslinks and molecules within fibrils. Assuming the triple helix structure of collagen is relatively tough, the decrease of tensile modulus of superficial zone in OA cartilages could due to the changes of the crosslinks between fibrils in collagen network. / published_or_final_version / Orthopaedics and Traumatology / Master / Master of Philosophy