Well documented shortcomings of current heart valve substitutes – biological and mechanical prostheses make them imperfect choices for patients diagnosed with heart valve disease, in need for a cardiac valve replacement. Regenerative Medicine and Tissue Engineering represent the research grounds of the next generation of valvular prostheses – Tissue Engineering Heart Valves (TEHV). Mimicking the structure and function of the native valves, TEHVs are three dimensional structures obtained in laboratories encompassing scaffolds (natural and synthetic), cells (stem cells and differentiated cells) and bioreactors. The literature stipulates two major heart valve regeneration paradigms, differing in the manner of autologous cells repopulation of the scaffolds; in vitro, or in vivo, respectively. During the past two decades, multidisciplinary both in vitro and in vitro research work was performed and published. In vivo experience comprises preclinical tests in experimental animal model and cautious limited clinical translation in patients. Despite initial encouraging results, translation of their usage in large clinical scenarios represents the most important challenge that needs to be overcome. This review purpose is to outline the most remarkable preclinical and clinical results of TEHV evaluation along with the lessons learnt from all this experience.

The inherent limitations of current heart valve substitutes create the premise for the Tissue Engineered Heart Valve (TEHV), considered the perfect substitute. We aimed to compare in vitro hemodynamic performances of our TEHV, the conventional prosthetic valve and similar porcine valves, by ultrasonography and geometry resulting in six valve models analysis. In a bioreactor, pulmonary and aortic physiology were replicated thus hemodynamic characteristics were tested. Using ultrasound, transvalvular pressure gradients and flow were measured and used to calculate their valvular functional area (VFA) and using a high-speed camera, the geometric peak opening area (GOA) was assessed. The obtained results were normalized to the diameter of the biological prosthesis in order to increase the measurement’s accuracy. The ultrasound revealed normal function of all valves and physiologic transvalvular pressure gradients. The TEHV scaffold revealed absence of laceration or dehiscence, and performances in accordance with the control prostheses. The GOA was facile to obtain and the normalized values proved to be greater than the calculated functional area in all analyzed cases and the peak opening areas resulted lesser for the aortic conditions for all six used valves prototypes. To our knowledge, this is the first study to use bioreactors, for in vitro evaluation of heart valves.