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A Method Of Preparing A Living Autologous Pericardial Tissue Heart Valve Replacement That Is Modified And Stabilized Using In Vitro Three-dimensional Mechanotransduction
Frantisek Straka1, David Schornik2, Jaroslav Masin1, Elena Filova2, Zuzana Burdikova3, Tomas Mirejovsky1, Hynek Chlup4, Lukas Horny4, Jan Vesely4, Jan Pirk1, Lucie Bacakova2.
1Institute for Clinical and Experimental Medicine, Prague, Czech Republic, 2Dept. of Biomaterials and Tissue Engineering, Institute of Physiology Academy of Sciences, Prague, Czech Republic, 3Department of Biomathematics, Institute of Physiology, Prague, Czech Republic, 4Laboratory of Biomechanics, Faculty of Mechanical Engineering, Czech Technical University, Prague, Czech Republic.

BACKGROUND The objective of our study was to prepare an autologous living pericardial heart valve replacement. In vitro dynamic conditioning was used to modify the pericardial tissue through the process of three-dimensional (3D) mechanotranduction. METHODS Living human pericardium was harvested during heart surgery and a stented heart valve replacement was made from the pericardium. The heart valve replacement was then subjected to the same systemic pressures during repetitive heart contraction-relaxation cycles simulated in a bioreactor using a pulsatile pump. Native aortic heart valves were harvested during heart transplantation and were compared with the autologous human pericardium before and after dynamic conditioning using histological assessment, immunohistochemical analysis and confocal microscopy. The biomechanical properties of both tissues were also compared. RESULTS In vitro dynamic conditioning using an anatomical 3D stent stimulates the living pericardial intersticial cells (PICs) within the autologous pericardium to proliferate and differentiate to an active phenotype (aPICs) which produces and remodels the pericardial extracellular matrix (ECM) giving the pericardial tissue the property of anisotropy similar to that of the normal aortic heart valve. Collagen, elastin and glycosaminoglycan production by PICs is substantially increased (p ≤ 0.001), modifying the pericardial tissue to resemble the tissue of a normal human heart valve. This tissue is stronger, yet soft and pliable, possessing biomechanical properties similar to normal aortic heart valve cusp tissue based on secant elastic modulus (18-27 MPa). Hemodynamic properties measured by echocardiography such as transvalvular Doppler gradient (5-6 mmHg) and valve cusp coaptation were also comparable to the native aortic heart valve. CONCLUSIONS Human living autologous pericardium is a favorable tissue for preparing a heart valve replacement for potential clinical use. This tissue resembles the natural structure of the normal aortic heart valve, and has similar mechanical and hemodynamic properties. PICs are activated to an active myofibroblast-like phenotype through mechanical conditioning allowing the production and remodeling of the pericardial ECM. Acknowledgements: Supported by the Grant Agency of the MH of the CR (No. NT 11270).

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