Articular cartilage is the soft tissue found at the end of long bones within the joint capsule and plays an important role in load transmission and facilitating joint motion. However, traumatic injury delivered to joints generates extreme supraphysiologic shear and compressive forces which result in joint inflammation and significant damage to both cartilage tissue and chondrocytes. Chronic persistence of post-injury changes often results in the development of post-traumatic osteoarthritis (PTOA). Treatment options for cartilaginous injuries are limited due to the lack of vasculature or lymphatics, which limit the transport of anabolic cytokines to injured areas. Furthermore, development of disease modifying treatments is hindered by the lack of suitable PTOA models to conduct experimental trials upon as current models are unable to accurately model the post-injury joint environment, thereby limiting their translational relevance.Thus, the overall goal of this thesis was to generate an ex vivo model of PTOA that could more closely capture the characteristics of an injured synovial joint. This was achieved by demonstrating that simultaneous compressive and shear forces delivered to cartilage generated a profile of chondrocyte damage that is more physiologically relevant to what is expected in vivo (Chapter 1). Secondly, by assessing changes in cartilage mechanical properties pre- and post-injury and relating these changes to resulting chondrocyte damage, to evaluate chondrocyte sensitivity to mechanical loading (Chapter 2). Finally, the effect of negatively altering the lubricating qualities of synovial fluid on the relationship between local shear strains and cellular damage was also assessed (Chapter 3). Collectively, this work offers crucial insight into the mechanisms behind the early stages of PTOA pathogenesis and provides a physiologically relevant model to be utilized for future testing of potential PTOA therapeutics.