Functional tissue engineering of the aortic heart valve.

INTRODUCTION Aortic heart valve dysfunction is commonly treated with replacement of the valve. To overcome the shortcomings of currently used mechanical valves, xenografts and homografts, efforts are being made to create fully autologous heart valve replacements using the concepts of tissue engineering. To this end autologous cells are seeded onto pre-shaped biodegradable scaffolds and cultured under conditions that mimic the physiological valve environment. This includes mechanical and/or biochemical conditioning in bioreactors to enhance tissue formation and organization. The scaffold provides initial anchorage and support for the cells, until they have produced and reorganized their own extra cellular matrix (ECM) to form a functional tissue. Ideally, the rate of tissue formation is proportional to the rate of scaffold degradation. Moreover, the engineered tissue should meet and maintain the specific mechanical behavior and load bearing properties of the native aortic heart valve. To date, tissue engineered heart valves show promising results when used to replace the pulmonary valve in animal studies [1,2]. The mechanical properties of these valves, however, are insufficient to withstand the functional demands on the high-pressure, aortic side of the circulation. To satisfy these demands, and hence to develop a functional, load-bearing aortic heart valve, our studies aim at improving ECM architecture and properties via optimal mechanical conditioning protocols. The present study concentrates on relationships between mechanical conditioning, tissue formation and ECM remodeling using an in-vitro model system of engineered heart valve material.