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Title: Exploring mechano-structural processes in osteoarthritis
Author: Chen, Ying-Chun
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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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.
Supervisor: Gaffney, Eamonn ; Brown, Cameron Sponsor: Taiwan Government
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Osteoarthritis