Development and Application of a Small Pre-Clinical Animal Model for Juvenile Osteochondritis Dissecans (OCD)

PI’s: Robert Guldberg

Juvenile Osteochondritis Dissecans (OCD) of the knee is an increasingly common condition that predominantly affects adolescent and young adults, and progresses to early onset osteoarthritis. OCD initially involves the formation of an avascular lesion in the subchondral bone with secondary effects in the overlaying articular cartilage. During late stages of this disorder, the lesion becomes unstable and separation of an osteochondral fragment (loose body) ensues. The etiology of OCD is not fully understood, and previous research has been primarily limited to retrospective clinical studies, thus hampering the creation of novel therapeutics. Furthermore, current pre-clinical animal models replicate only late stages of OCD, and their utility in the field is limited. It is the failure to treat OCD in its early stages that results in the progression of this disorder and the onset of osteoarthritis at an early age. Therefore, a new pre-clinical model is needed such that the disease progression mechanisms can be more fully investigated, with a view of developing and testing new therapeutic interventions.

The overall objective of this proposal is to develop a small pre-clinical animal model in order to better tailor diagnosis and treatment of this musculoskeletal disorder. The central hypothesis of this proposal is that a pre-clinical animal model will prove advantageous in testing the efficacy and outcomes of current clinical procedures. We will achieve our objective by creating an initial, localized necrotic lesion near the subchondral bone with a cryogenic insult that will affect the overlaying articular cartilage. We hypothesize that in time this lesion site, if left untreated, would fragment, as seen in late stages of OCD. We will also evaluate the therapeutic benefits of cell delivery coupled with marrow stimulation (current clinical practice) in the animal model, in order to prove its utility within the field.

Publications Salazar-Noratto, G.E., Barry, F.P., Guldberg, R.E., “Application of Biomaterials to In Vitro Pluripotent Stem Cell Disease Modeling of the Skeletal System,” Journal of Materials Chemistry B,.  Salazar-Noratto, G.E., Willett, N., Stevens, H.Y., Lin, A., Gibson, G., Guldberg, R.E., “Pre-Clinical Small Animal Model for Osteochondritis Dissecans of the Knee,” The 61st Annual Meeting of the Orthopaedic Research Society, Las Vegas, Nevada, March 2 Salazar-Noratto, G.E., Xu, M., Stevens, H.Y., Guldberg, R.E., Barry, F., “Robust Method for Scaffold Free 3D Bone Engineering of Patient-Specific Induced Pluripotent Stem Cells,” Tissue Engineering and Regenerative Medicine International Society (TERMIS) Americas Annual Conference and Exhibition, San Diego, California, December 10-14, 2016.

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