Articular cartilage is a remarkable tissue with mechanical performance that surpasses engineering standards. Collagen, the most abundant protein in cartilage, plays an important role in this performance. Building on observations of collagen structural changes at the earliest stages of osteoarthritis, we here explore the role of collagen in the disease process. Specifically, we focus on the material properties and organization of collagen fibrils in the cartilage surface, seeking to answer three key questions: • What are the physical changes to collagen in early osteoarthritis? • How do physical changes relate to osteoarthritic progression mechanistically? • Can we detect early, irreversible changes to cartilage intraoperatively to facilitate early treatment? Ten human tibial plateaus were characterised by atomic force microscopy and Raman spectroscopy, with clinical and histological scoring used for comparison. Minimal changes were found in the collagen molecules themselves, yet a marked increase in intra-fibrillar crosslinking was observed. A bottom-up numerical model of the collagen fibril network was then implemented to specifically explore the relationship between fibril interactions and mechanics in osteoarthritis. Simulating two different fibril configurations, we established that high connectivity is critical to the resistance to, and recovery from, loading. Osteoarthritis-like bundled configurations were produced by networks with sparse interactions, and identified as a mechanically irreversible stage in disease progression. Coupling the model with experimental results, we argue that the intra-fibril changes appear to link to disease initiation and it is the inter-fibril interactions that drives the disease. Finally, a pilot study was conducted to explore the potential for quantitative intraoperative imaging to detect irreversible collagen-related changes in the cartilage surface. Based on spectral analysis of the available light from standard arthroscopic equipment, it may be possible to advance arthroscopy from a qualitative to quantitative assessment tool.

Early knee osteoarthritis (EKOA) is common, hard to treat and can be debilitating for symptomatic individuals. Whilst end-stage osteoarthritis is treated reliably with knee replacement surgery, such surgery is not routinely offered to those with less severe OA as it is associated with a poorer outcome. These patients are said to be in a 'treatment gap' and they are the primary focus of this thesis. A series of large epidemiological studies were designed to clarify the natural history of symptomatic EKOA. A prospective cohort study including 1,634 symptomatic knees with EKOA found that malalignment was the most potent risk factor for structural progression. A subsequent study, which included a detailed assessment of lower limb alignment, established that this structural progression was driven by the alignment of the proximal tibia. Using semi-quantitive MRI analysis it was found that the increased structural progression seen in subjects with proximal tibia vara, was due to more full thickness cartilage loss in the central medial tibia. These are novel observations which have implications for future research as the alignment of the proximal tibia can be corrected with surgery. Following this epidemiological description of EKOA, attention was turned to intervention and treatment. A systematic review of the literature identified moderate to very low quality evidence to support the role of surgery in treating symptomatic EKOA. A single-centre prospective cohort study for patients undergoing a novel neutralising high tibial osteotomy was established and excellent early (1yr) and mid-term (3-5 years) clinical outcomes are reported. A retrospective study was designed to investigate whether full thickness cartilage loss on magnetic resonance imaging, but not on plain film radiographs, is sufficient to warrant proceeding to unicompartmental knee arthroplasty (UKA). Outcomes for this cohort of patients were excellent, highlighting the usefulness of MR for the early identification of patients suitable for UKA. In summary, this thesis has reported the natural history of symptomatic EKOA and identified proximal tibia vara as a potent risk factor for structural progression. The paucity of trials investigating subjects with this disease has been highlighted and surgical interventions which are safe and clinically effective have been identified. The direction of future research in this area has been proposed.

Knee osteoarthritis is an incurable degenerative joint disease that affects millions of people in Canada. Characterized by stiffness and knee pain in the early stages, it can cause loss of function and mobility. Most treatment options are either not sustainable, such as pain medications and steroid injections, or invasive, such as knee replacement surgery. While therapeutic options, such as physiotherapy, have been shown to have a positive effect on pain and activity levels over time, minimal immediate relief has been observed. Moreover, these treatments or combinations of treatments can be costly. Alternatively, offloading knee orthoses are a cost-effective option that provides immediate pain relief when worn. Offloading knee orthoses, however, have low patient compliance rates. To improve patient compliance and optimize patient benefit, current orthosis designs must be enhanced to improve comfort, increase the perceived effect and be adjustable to the patient. Consequently, this thesis presents the design, fabrication and testing of an offloading knee orthosis joint designed to enhance comfort and perceived effect. This improvement is achieved by developing a novel modular orthosis that features an offloading mechanism intended to relieve the load on the joint through an offloading moment solely during stance phase and reduce the moment during swing phase when offloading is not needed. The evaluation of the proposed orthosis design was achieved by fabricating an experimental prototype and performing mechanical testing. Three-point bending tests demonstrated a generated offloading moment of 3.36 Nm, creating a noticeable offloading effect during stance, and reduced the moment to less than 0.5 Nm after 35° of knee flexion, thus, increasing comfort during swing phase and sitting when offloading forces are not needed.

Thesis (M.A.)--Kent State University, 2009-07-07. / Title from PDF t.p. (viewed March 3, 2010). Advisor: Mary Ann Stephens. Keywords: need for independence; osteoarthritis; spousal support; person-environment fit. Includes bibliographical references (p. 37-42).

Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.

Thesis (M.A.)--University of Tennessee, Knoxville, 2007. / Title from title page screen (viewed on June 2, 2008). Thesis advisor: Lee Meadows Jantz. Vita. Includes bibliographical references.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

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