A New Approach to Heart Valve Tissue Engineering Based on the Modification of Human Pericardial Tissue

Abstract The main problem of currently used xenogeneic biological heart valves is the development of degenerative changes leading to valve failure. Reoperation is required in approximately 65% of patients at 15 years after implantation. The challenge of heart valve tissue engineering is to create a new type of biological prosthesis for clinical use. The aim of our study is to construct a living autologous human pericardial heart valve that will have optimal mechanical properties and a similar histological structure as the normal aortic heart valve. Three leaflet heart valve constructs made from human pericardium were attached onto a plastic holder and cultured under dynamic conditions for up to four weeks. After this time conditioned pericardial samples were compared to control unconditioned pericardial samples from the same patient and to that of the normal aortic heart valve. Histological, immunohistochemical and biomechanical assessments were performed. Pericardial interstitial cells (PICs) are able to respond to mechanical stresses by proliferating and differentiating into an active (myofibroblast-like) phenotype and are able to produce new extracellurar matrix (ECM). A threefold increase in PIC number and a twofold increase in smooth muscle actin (SMA) positive cells was observed after dynamic conditioning. These measurements were statistically significant (p<0.001). The histological structure of conditioned pericardium is very similar to the normal aortic heart valve and dynamic conditioning was shown to be important for PIC activation. Uniaxial tensile tests were performed to compare the mechanical properties of conditioned pericardium with the native aortic heart valve. Our results indicate that the secant elastic modulus of pericardium before and after conditioning (13.1 ± 8.3 Mpa) is comparable to the native aortic heart valve. Autologous human pericardium mimics the natural structure of the normal aortic heart valve and has similar mechanical properties. PICs are activated to an active VIC-like phenotype by mechanical conditioning. Our pericardial heart valve construct also possesses optimal hemodynamic properties by echocardiographic measurements similar to the healthy aortic heart valve. Acknowledgements: Supported by the Grant Agency of the Ministry of Health of the Czech Republic (project No. NT 11270.