Post-traumatic osteoarthritis (PTOA) of the knee is a complication resulting from direct injury to the joint, such as anterior cruciate ligament and meniscus tears, and accounts for approximately 12% of all OA cases. The economic and clinical impact of PTOA is also greater than idiopathic OA, as patients are younger and often more active, requiring treatments for symptomatic OA over a greater fraction of their lifetime. A common strategy to manage pain and inflammation associated with PTOA is the intraarticular administration of corticosteroids. However, these injections are limited due to the requirement of high-doses imposed by synovial joint clearance rates and their resulting systemic side effects. In addition, currently used broad-spectrum corticosteroids are palliative and not curative, stemming from incomplete knowledge of specific mechanisms that drive cartilage degeneration and other joint pathologies. Thus, most patients with PTOA eventually undergo surgical procedures such as osteochondral graft transplantation for focal defects and in more severe cases, total knee arthroplasty. As such, the studies presented in this dissertation (i) offer specific insights into mechanisms by which traumatic injury can drive joint degeneration and (ii) present novel strategies to modulate joint responses to pathological factors by leveraging sustained drug-delivery platforms. In Part I, mechanistic assessments of human cartilage and synovium responses to insults are conducted to identify novel pathways that may lead to impaired joint homeostasis. First, a direct consequence of traumatic injury, hemarthrosis, is explored as a potential contributor to the development of PTOA specifically through contributions by red blood cells. We demonstrate for the first time the differential roles of erythrocytes in their intact and lysed states through measures of oxidative stress and changes to metabolomic profiles in the context of ferroptosis. Furthermore, we demonstrate the therapeutic potential of Ferrostatin-1, a lipophilic radical scavenger in inhibiting pathological changes to cartilage and its crosstalk with the neighboring synovium in an in vitro model of hemophilic arthropathy. Second, a strategy to prevent an indirect consequence of traumatic injury, arthrofibrosis, is presented in an in vitro model of joint contraction. Fibrosis and the presence of hyperplastic synovium are implicated in the progression of OA through pathological shifts in tissue composition as well as secreted factors that promote cartilage degeneration and the maintenance of a pro-inflammatory joint environment. A type I transforming growth factor beta-1 receptor inhibitor, SB-431542, is encapsulated in polymeric microspheres for the prophylactic treatment of arthrofibrosis through sustained low-dose drug delivery to circumvent the challenges associated with resident joint clearance rates. Utilizing human-based in vitro models of cartilage and synovium pathology, we present novel mechanisms and therapeutic strategies to prevent pathological changes following traumatic joint injury that may contribute to the development of PTOA. In Part II, the sustained delivery platform introduced in Part I is extended to the treatment of PTOA. Osteochondral graft transplantation is currently the clinical gold standard for large focal cartilage lesions. However, allograft procedures are limited due to the lack of available donor tissues and autografts are associated with complications due to donor-site morbidity. In both cases, grafts are subject to failure, potentially in part due to the continual presence of pro-inflammatory factors following surgical procedure. In this section, we present cellular agarose hydrogels embedded with dexamethasone-releasing microspheres that are integrated with a titanium base as a functional tissue-engineered alternative to native osteochondral allografts. These allogenic tissue-engineered grafts were assessed in an in vivo preclinical canine model in their ability to maintain clinical function and to modulate the inflammatory response over the course of 12 months. We successfully demonstrated the feasibility of using engineered grafts by comparing clinical measures of range of motion, function, lameness, and pain, as well as modified cartilage graft scores, against native osteochondral allograft controls. In addition, improvements in the histopathological scoring of neighboring synovial and meniscal tissues indicate the therapeutic capacity of dexamethasone released from within the joint to modulate the inflammatory response up to one-year post-implantation. Taken together, the studies presented in this dissertation identify novel mechanisms behind pathological changes to the cartilage and synovium that may contribute to the development of PTOA following injury. Potential therapeutic targets, inhibitory compounds, and delivery strategies are also assessed using human-based in vitro models of disease and further validated in an in vivo canine model through a clinically relevant timeframe. Ultimately, we demonstrate for the first time, the use of dual-function tissue-engineered grafts in a weight-bearing region of the knee joint to circumvent limitations associated with the clinical gold standard for the treatment of large focal cartilage defects.

Call number: LD2668 .T4 1931 A91

Call number: LD2668 .T4 1956 M32 / Master of Science

Call number: LD2668 .T4 1959 C47

Call number: LD2668 .T4 1961 S66

Call number: LD2668 .T4 1979 S57 / Master of Science

Call number: LD2668 .T4 1985 A82 / Master of Science

Call number: LD2668 .T4 1955 B66 / Master of Science

Thesis (M.Tech.: Chiropractic)-Dept. of Chiropractic, Durban Institute of Technology, 2004 1 v. (various pagings) / Classical ballet is generally defined as a form of art although it has been found to be more physically demanding than most sports, perhaps due to its very precise technique that differs considerably from normal movement. Epidemiological studies investigating ballet injuries in other countries suggest that the incidence and prevalence of injuries among ballet dancers is high. However, no such studies had been conducted in South Africa. Consequently the purpose of this study was to determine the lifetime incidence and prevalence of ballet injuries in the greater Durban area, and to examine the association between certain individual factors and ballet injuries, in order to identify potential risk factors.

Thesis (M.Tech.: Chiropractic) -Dept. of Chiropractic, Durban Institute of Technology, 2004. 1 v. (various pagings) / Background: Back pain among the golfing population is considered endemic as it has been recommended to golfers that they should attempt to use a state of maximal spinal rotation in their golf swing in order to achieve maximum ball distance. Evidence suggests that maximum spinal rotation range of motion will be more restricted in the golfers with low back pain, even though this maximum rotated position has been considered ideal for developing optimal Club Head Velocity (CHV). Research has demonstrated an approximate 1:3 relation between CHV and air travel (i.e. distance) of the golf ball. An increase in 1mph in CHV would increase air travel of the golf ball by approximately 3 yards. If one considers that CHV is primarily influenced by the strength and power of the torso (low back and abdominal muscles), muscle balance and flexibility, which are responsible for the static and dynamic postural stability of the golf swing, it stands to reason that low back pain, which has been identified as the most common problem affecting amateur golfers, will affect CHV. Objective: The purpose of this investigation was to evaluate the immediate effect of spinal manipulative therapy on club head velocity in amateur golfers suffering from mechanical low back pain in terms of subjective and objective measures.