Early Osteoarthritis: A multi-scale structural and mechanical investigation

Abstract

In this work, the bovine patella has been used to study the changes in the cartilage, calcified cartilage, and subchondral bone during the early stages of the development of the disease osteoarthritis (OA). The bovine patella was first validated as a model for intact human cartilage. The bovine patella exhibited proliferative and progressive degenerative changes that were shown to relate to human osteoarthritis. Then, using this bovine model, the degenerative changes in the cartilage were correlated with changes in the mechanical properties and mineral content of the calcified cartilage and subchondral bone. Most significantly, this work showed that during the earliest phases of osteoarthritis, where the cartilage is largely intact with only mild surface fibrillation, the underlying calcified tissues are altered. The increased ratio of calcium to phosphorous with OA development suggests an increase in carbonate-substituted hydroxyapatite at the osteochondral junction. Following on from this work, the changes in mechanical properties of the calcified tissues with early OA were more broadly explored using three scales of mechanical testing, namely macroscopic three point bending, microhardness indentation, and nanoindentation. Mechanical changes were shown to occur concurrently with articular surface changes before the cartilage was completely degenerated and lost. The subchondral bone initially decreases in stiffness relative to the calcified cartilage as the cartilage begins to display surface irregularities and fissuring. This change then reverses as the bone subsequently increases in stiffness with more advanced cartilage fissuring and erosion. Conversely, significant changes in the ratio of calcified cartilage to subchondral bone stiffness were not observed at the micro or nano scales. In the last part of this work, the osteochondral junction was examined using light and electron microscopy to analyse the new bone growth at the osteochondral junction as seen in OA. Regions of the calcified cartilage appear to be resorbed and filled in with bone spicules originating in the subchondral bone. These spicules resemble the structure of developing osteons in bone remodelling and become more bony and less vascular with disease progression. However, their frequency and morphology do not otherwise change with early degeneration. This thesis provides, for the first time, a deeper understanding of the structural, mechanical, and mineral changes occurring in the calcified tissues in the early stages of osteoarthritis. It provides new insights into the mechanobiological feedback loop of degenerative change between the cartilage and bone. While this experimental study did not resolve whether changes first occur in the bone or the cartilage, it does demonstrate that structural, mechanical, and mineralisation changes occur in the calcified cartilage and subchondral bone concurrently with mild micro-level articular cartilage fibrillation. The structural and mechanical data generated in this work will be of potential relevance to researchers endeavouring to create biomimetic osteochondral grafts or accurate computer models of the joint tissues that embody the complexities of the soft-hard osteochondral junction.