The living aortic valve: From molecules to function

Abstract

The aortic valve lies in a unique hemodynamic environment, one characterized by a range of stresses (shear stress, bending forces, loading forces and strain) that vary in intensity and direction throughout the cardiac cycle. Yet, despite its changing environment, the aortic valve opens and closes over 100,000 times a day and, in the majority of human beings, will function normally over a lifespan of 70–90 years. Until relatively recently heart valves were considered passive structures that play no active role in the functioning of a valve, or in the maintenance of its integrity and durability. However, through clinical experience and basic research the aortic valve can now be characterized as a living, dynamic organ with the capacity to adapt to its complex mechanical and biomechanical environment through active and passive communication between its constituent parts. The clinical relevance of a living valve substitute in patients requiring aortic valve replacement has been confirmed. This highlights the importance of using tissue engineering to develop heart valve substitutes containing living cells which have the ability to assume the complex functioning of the native valve.

Bioreactor conditioning of valve scaffolds seeded internally with adult stem cells

“…The latter exhibit good hemodynamics and durability, but are not readily available and eventually fail in the long term due to lack of living cells. Thus, there is a great need for living aortic valve replacements with extended durability [8]. Such constructs could be built by tissue engineering methods, taking into account the complex biology, biochemistry and biomechanics of the valve.…”

Functional Heart Valve Scaffolds Obtained by Complete Decellularization of Porcine Aortic Roots in a Novel Differential Pressure Gradient Perfusion System

“…The latter exhibits good durability, but is not readily available, represents only a small proportion of total valve replacements, and eventually fails in the long term due to lack of living cells. 9 Therefore, one can conclude that there is a great need for living valve replacements for patients of all ages. As has been eloquently said, ''future advances with tissue-engineered heart valves [.]…”

“…12 The aortic valve cusps are exposed to a unique hemodynamic environment, characterized by area-specific shear stress, bending forces and strains in circumferential and radial directions that vary in intensity and direction during each cardiac cycle. 9 To respond to these challenges, cusps have a trilayered (fibrosa, spongiosa, ventricularis) and anisotropic structure (stiffer in the circumferential axis vs. radial axis), which is essential for mechanical durability and stress distribution. 13,14 Currently, the most physiologic valve replacements are considered the homograft valves because of their outstanding valve function and hemodynamics.…”

“…9 Other valve replacement options are the pulmonary autograft valves (i.e., the Ross procedure, whereby the patient's own living pulmonary valve is transplanted into the aortic position) and the human allograft valves (sterilized, cryopreserved cadaveric aortic roots obtained from humans). The latter exhibits good durability, but is not readily available, represents only a small proportion of total valve replacements, and eventually fails in the long term due to lack of living cells.…”

In Search of Living Valve Substitutes

“…Success of these efforts depends on reproducing or emulating the continuing cross talk between the extracellular matrix and specific cellular components, which characterize a living valve (2). In the past, the extracellular matrix (ECM) was thought to consist of …”