**1. Introduction**

An early attempt of designing a valvular device was made already in 1513 by Leonardo da Vinci, who depicted the appearance of a prosthetic aortic valve to be reproduced in glass material [1].

The first real manufacture of valve substitutes goes back to the '50s of the previous century, when the application in heterotopic position of an aortic mechanical valve by Hufnagel and colleagues triggered the beginning of the surgical therapeutic era of valvulopathies [2]. It was however the contribution of Harken, Starr and Edwards to demonstrate the feasibility of orthotopic valve replacement with these early devices [3]. Since then, several mechanical and bioprosthetic replacements have been proposed as valve substitutes. Still, these solutions are not meeting important prerequisites.

Heart valve tissue engineering and, later, tissue-guided regeneration have been proposed to overcome the limitations associated to current valve substitutes. Principles, preclinical and clinical models of each approach are discussed in this chapter, together to the diverse improv‐ ing strategies for the final achievement of viable and functional aortic valve substitutes.
