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Tuesday, Feb 19, 2013

8:30 AM9:30 AM Goergen Hall 101

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BME PhD Proposal Seminar: Youssef Farhat

Assessing the Role of Matrix Turnover Proteins in Models of Flexor Tendon Healing

Professor Hani Awad, Ph.D.

Abstract:

Over 100 million people across the developed world will develop scars each year as a result of injuries and surgeries. Because scars lack the functional, material and aesthetic properties of the tissues they replace, they can be disfiguring and even disabling. A potent example of how scar tissue can be disabling is seen after damage to the flexor tendons of the hand. Such injuries often result in adhesions, which are scars that adhere tendons to the surrounding tissue in a way that limits hand function. To make matters worse, the inferior strength of tendon scar tissue can lead to re-rupture, requiring another surgical intervention. Therefore, there is a definite need to understand the biological processes underlying scar tissue formation in the flexor tendons. A body of literature as well as our own work suggests that the inflammatory growth factor, TGF-β1, promotes scar tissue formation by suppressing extracellular matrix turnover during tendon healing. Furthermore, our preliminary data suggests that the master inhibitor of matrix degradation, PAI-1, mediates some of TGF-β's pro-scarring effects. In the proposed studies, we will (1) characterize TGF-β1's effects on matrix turnover proteins in tenocytes cultured in vitro, and (2) evaluate the use of neutralizing antibodies against PAI-1 as a novel therapeutic for the prevention of flexor tendon adhesions in vivo. These aims will contribute to the development of pharmacologic and biologic agents aimed at preventing scar tissue, the like of which do not exist in the present time.