Development of a fibrin-based tissue-engineered vasculature construct for implantation

Vascular disease has a high prevalence of mortality in western developed countries. Tissue-engineered vessels (TEV's) are being developed to supplement the short supply of available autologous vascular grafts. Biocompatibility, culture time, medium composition, culture conditions and scaffold material all influence development of a site appropriate, functional vessel with adequate mechanical strength. The most commonly used biodegradable scaffold materials for this purpose are potentially immunogenic, show toxic effects from their degradation products, display an inflammatory reaction and demonstrate a slow developmental time line. The specific aim of this project is to identify a scaffold material that best promotes biocompatibility and functionality within a short developmental time period. We developed a small-diameter TEV by mixing ovine vascular smooth muscle cells (OVSMC) into a fibrin gel that is molded around a silastic tube. The degradation rate of the fibrin gel was controlled through the addition of aprotinin in the culture medium. The molded fibrin gel was exposed to a non-pulsed or pulsed condition. Results show that after only 7 days of culture a reactive vessel that constricts to KCl and norepinepherine and dilates to SNAP was created. The concentration of aprotinin and the pulsation significantly influenced the properties of the engineered constructs such as weight, collagen synthesis, cell proliferation, cell density, elasticity, strength and reactivity. The optimal conditions were then chosen to construct TEVs for implantation into external jugular veins 12 week old lambs. These results may have important implications in tissue engineering of small-diameter vessels.