This is a basic scientific investigation of the patho-mechanistic etiology of post-traumatic osteoarthritis(PTOA) with particular emphasis on the role of acute mechanical damage. The long-term objectives of thestudy are to: 1)determine how acute mechanical damage is linked to PTOA; 2) determine how acutemechanical damage affects the tolerance of articular cartilage to injury-associated changes in the long-termloading environment within a joint; and 3) investigate novel therapeutic options specifically designed to treattissue-level and cellular-level damage associated with acutely impacted cartilage. A series of in vitroinvestigations will study the relative contribution of both acute damage and chronic loading abnormalities tocartilage degeneration. Potential adverse synergisitic interaction between these injury-associated residualswill also be investigated. Another in vitro study will investigate the role of matrix damage in the the cascadeof injury propagation into surrounding uninjured cartilage. Finally, an established in vivo model will be usedto investigate the patho-mechanistic link between acute mechanical damage, chronic abnormal loading, andthe progression of PTOA, accounting for whole-joint effects that cannot be tested in parametric in vitrostudies. The second part of the study will investigate therapeutic options that mechanically stabilize matrixdamage and deliver targeted Pharmaceuticals into acutely damaged areas that foster chondrocytic anabolicmetabolism and prevent chondrocyte apoptosis. These therapies will be studied in vitro, in a parametricstudy design that investigates treatment effectiveness with respect to impact energy and timing of treatment.To determine whole-joint effects, an in vivo porcine model of impact injury will be employed to study thesame treatments. Post-traumatic osteoarthritis is a major cause of pain and dysfunction in a relatively youngpatient population. Therefore, it is also a major source of medical expenditure. Understanding the basicmechanisms that cause PTOA will facilitate development of more effective treatments. This study not onlywill further understanding the etiology of this devastating disease, it will provide new knowledge in a differenttreatment approach, focused on treating the acute mechanical damage.This study will investigate why injured joints develop arthritis. Furthermore, this study will investigate newtreatment options that could potentially reduce or prevent arthritis in an injured joint.
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