Small Animal Model of Osteochondritis Dissecans
Cobb, Destiny August
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Juvenile Osteochondritis Dissecans (JOCD) is a joint disorder that predominantly affects athletic children and adolescents. It is characterized by the formation of osteochondral loose bodies which cause pain and swelling in the affected area, limit the patient’s activity level, and in some cases requires surgery to fix or remove loose bodies depending on the stage to which the disorder has progressed. There is interest in developing preclinical animal models of the disorder to be used as a tool for developing regenerative therapeutics for treating the disorder. The objective of this project is to develop a small animal model of JOCD using Lewis rats. The model is being developed through a series of pilot studies with iterative modifications made to the procedure. The surgical procedure aims to mechanically and chemically induce an initial lesion just below that subchondral bone, which would have a secondary effect on the overlaying cartilage over time. By drilling into the left medial femoral condyle, we are to create a 1 mm deep and 1mm wide defect. The right leg serves as the contralateral control. Pilot studies have relied on an injection of various doses of monosodium iodoacetate (MIA, in saline), a glycolytic inhibitor, into the cauterized drilled defect to induce the initial necrosis. The current procedure is being modified to create a thermal insult. 3 weeks post-surgery, the animals are euthanized and the morphology and integrity of the articular cartilage, including the thickness, volume, and attenuation, of both the left and right femurs are examined using EPIC-μCT. This is followed by histological analysis. Additionally, diseased and healthy human biopsy cores provided by Children’s Healthcare of Atlanta are being analyzed in a similar manner to provide a standard by which the model can be compared and its efficacy evaluated.