| More than 570,000 coronary artery bypass grafts are implanted each year, creating an important demand for small diameter (<6mm) vascular grafts. For patients who lack an adequate internal mammary artery or healthy saphenous veins as grafting conduit, tissue engineered arteries may prove useful. Mechanical matching of a vascular graft to the surrounding artery is desirable to prevent graft dilation in vivo and to reduce localized changes in blood flow, which could lead to plaque formation. Current engineered arterial tissue fails to match the mechanical properties of native arterial tissue. Specifically, the inferior strength and stiffness of engineered arteries leads to rupture strengths that are lower than those of native arteries, vascular dilation in vivo, and potential difficulty in retaining sutures under arterial stresses.;In an effort to better understand and control the factors that affect engineered tissue strength and stiffness, the research of this thesis dissertation identified collagen as the dominant contributor to the mechanical behavior of engineered arteries and thoroughly characterized the contribution of collagen to engineered tissue mechanics. The impact of collagen density and collagen crosslink density on the mechanical properties of engineered vessels was determined by experimentally manipulating cellular synthesis of collagen and enzymatic activity of a crosslink catalyst, respectively. Collagen density strongly affected the ultimate stiffness of engineered arteries, but collagen crosslink density failed to significantly affect the ultimate stiffness of engineered arteries. The orientation of collagen in engineered arteries was measured using a novel ultrastructural method. A biaxial mechanical model was developed to describe engineered tissue mechanics in terms of the density and orientation of collagen. This model yielded insights into collagen remodeling and suggested that the orientation and undulation of collagen fibers strongly impacted engineered vessel mechanical behavior. The results presented in this dissertation revealed that residual fragments of the polymer scaffold used to support tissue growth negatively impacted the mechanical properties of engineered arteries. Further, obvious differences in compliance between engineered and native vessels emphasized the need for development of functional elastin. Thus, this dissertation has deepened our understanding of the structure and mechanical properties of engineered vessels. |
