The Development of Heparin-Based Materials to Treat Rotator Cuff Tendon Injuries
Advisor: Johnna S. Temenoff, Ph.D. (Georgia Tech/Emory University)
Robert E. Guldberg, Ph.D. (Georgia Tech)
Alexandra Peister, Ph.D. (Morehouse College)
Manu O. Platt, Ph.D. (Georgia Tech/Emory University)
Anthanassios Sambanis, Ph.D. (Georgia Tech)
The supraspinatus tendon of the rotator cuff is commonly injured due to highly repetitive work and can predispose the tendon to rupture. While surgery can alleviate symptomatic shoulder dysfunction after tendon rupture, the rate of revision surgeries can be very high and do not address the underlying pathophysiology. Commonly cited causes for revision surgeries include poor tendon-bone integration, particularly with degenerative tendon. Tissue engineering strategies, employing the use of multipotent progenitor cells or growth factors, represent potential therapies to improve the outcome of rotator cuff surgery. The use of glycosaminoglycan-based biomaterials in these therapies may enhance the effectiveness of cell and growth factor delivery techniques. Furthermore, understanding the cellular and molecular mediators in tendon overuse can help elucidate the causes for tendon degeneration in order to prevent tendon rupture. Thus the overall goals of this dissertation were to 1) develop heparin-based biomaterials to enhance cell pre-culture and maintain growth factor bioactivity and 2) characterize the histological and enzymatic changes in a supraspinatus tendon overuse model.
To investigate the use of heparin in enhancing dynamic signaling, mesenchymal stem cells (MSCs) were encapsulated in heparin-containing hydrogels and evaluated for differentiation markers when cocultured with a small population of differentiated cells. Since the sulfation level of heparin may have important effects in growth factor presentation and protection, selectively desulfated heparin species were evaluated for their ability to bind and protect proteins. Finally, to develop a tendon overuse model that can become a test bed for testing future targeted therapeutics, an inbred strain of rat was evaluated for tissue damage and protease activity. Together these studies represent a multi-pronged approach to understand how tendon tissues become degenerative and to develop technologies to improve the biological fixation of tendon to bone in order to prevent shoulder dysfunction and the need for revision surgeries.