Current status of tissue engineering for cardiovascular structures

Abstract

Various vascular and valvlular grafts are commonly used in the treatment of cardiovascular disease. Current prosthetic or bioprosthetic materials lack growth potential, and therefore, subsequent replacement further defeats the concept of primary repair early in pediatric cardiac patients. Tissue engineering is a new discipline that offers the potential to create replacement structures from autologous cells and biodegradable polymer scaffolds. Because tissue-engineering constructs contain living cells, they may have the potential for growth, self-repair, and self-remodeling. Cardiac valve leaflets and large conduits in the pulmonary ciruulation have been made with this tissue-engineering approach in lambs. Venous conduits were also created in dogs. Mixed cell populations of endothelial cells and fibroblasts were isolated from explanted peripheral arteries or vein. A synthetic biodegradable scaffold con-sisting of polyglactin and polyglycolic acid fibers was seeded in vitro with mixed cultured cells. After one week, these autologous cell/polymer constructs were reimplanted in animals. Each animal was then followed periodically by echocardiography and angiography. The animals were sacrificed, and the implanted tissues were examined histologically, biochemically, and biomechanically. A 4-hydroxyproline assay was performed to evaluate the collagen content. The implanted conduit diameters increased as the animals grew during the study period. Histologically, the biodegradable polymer scaffold was completely degraded. Collagen analysis of the constructs showed the development of an extracellular matrix. Immunohistochemical staining demonstrated elastin fiber in the matrix and factor VIII on the inner surface of the conduits. In conclusion, a tissue-engineering approach to constructing cardiovascular structures is feasible using cells of either arterial or venous origin. In these tissue-engineered autografts, transplanted autologous cells generated the proper matrix over the polymer scaffold under physiologic conditions.