| Cardiovascular disease is the leading cause of mortality in the United States, necessitating surgical interventions such as small diameter (I.D. <6 mm) bypass grafting. Although the use of autologous veins as small diameter grafts produces favorable results, their limited availability provides a significant obstacle. Meanwhile, several synthetic materials have demonstrated success as large-diameter vascular grafts, but exhibit poor patency and high failure rates in small-diameter applications. Based on these limitations and the clinical issues associated with them, it is clear that there is a significant need to develop new materials for cardiovascular and blood-contacting applications that could be used to fabricate small-diameter vascular grafts.;Thus, in this thesis we have designed and characterized a new polymer that is composed of both synthetic and natural elements with the goal of generating a material that is appropriate for use in cardiovascular applications. Specifically, we describe the modification of polyurethane (PU), a synthetic polymer with many favorable physical characteristics, with hyaluronic acid (HA), a native glycosaminoglycan that possesses anti-thrombotic properties as well as the ability to modulate endothelial cell proliferation in a molecular weight-dependent manner. The goal of the present work was to assess in detail the impact of 1) HA molecular weight, 2) HA quantity, and 3) the method of HA incorporation (bulk vs. surface-grafted) on the vascular-specific performance of polyurethane-HA (PU-HA) materials, under static conditions and upon exposure to physiological shear stresses. The initial findings presented in this thesis indicate that these PU-HA materials possess many of the physical and biological properties that are necessary for implementation in vascular applications. These materials were able to simultaneously address the three major design criteria in vascular graft fabrication: hemocompatibility, endothelialization, and vascular-appropriate mechanics, which has not been possible with other currently available materials. Moreover, the information presented herein will help the potential clinical translation of these PU-HA materials as a vascular graft product, as we aim to optimize the HA oligosaccharide content, molecular weight and incorporation method that will result in 3-D scaffolds that are hemocompatible and possess both vascular-appropriate mechanics and the ability to support a viable endothelial cell population. |
