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Mechanisms of Cardiac Valve Failure and the Development of Tissue Engineered Heart Valves

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Cardiac Fibrosis and Heart Failure: Cause or Effect?

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 13))

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Abstract

Calcification of the aortic valve results in valvular dysfunction and is an important cause of morbidity and mortality. Our understanding of the process of aortic valve calcification has changed from a passive wear and tear process to that of an actively regulated process with known molecular mediators. Prior to calcification of the valve, activated valvular interstitial cells coordinate maladaptive extracellular matrix remodeling of the leaflets. Bioprosthetic heart valves used to surgically replace stenotic aortic valves have excellent hemodynamic profiles and are anti-thrombogenic. However, they fail due to similar mechanisms as native aortic valves and thus durability is a limiting factor. Mechanical prostheses necessitate anticoagulation. Ideal heart valve substitutes would be non-thrombogenic, maintain excellent hemodynamics, but would be durable and may hold the promise of growth. The basics of tissue engineering include fabricating a scaffold onto which autologous cells may be incorporated. The cells then transform the scaffold to autologous tissue with the ability to function in its desired location in the body. Popular scaffolds are decellularized allografts or xenogeneic aortic valves as they have the complex structure of the aortic valve still intact. Recellularization with valvular endothelial cells has been successful but avenues for recellularizing valvular interstitial cells are still being pursued. Alternative methods for generating scaffolds include three dimensional bioprinting and electrospinning.

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Helder, M., Simari, R. (2015). Mechanisms of Cardiac Valve Failure and the Development of Tissue Engineered Heart Valves. In: Dixon, I., Wigle, J. (eds) Cardiac Fibrosis and Heart Failure: Cause or Effect?. Advances in Biochemistry in Health and Disease, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-17437-2_21

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