Abstract
Heart valve disease is a major health burden, treated by either valve repair or valve replacement, depending on the affected valve. Nearly 300,000 valve replacements are performed worldwide per year. Valve replacement is lifesaving, but not without complications. The in situ tissue-engineered heart valve is a promising alternative to current treatments, but the translation of this novel technology to the clinic still faces several challenges. These challenges originate from the variety encountered in the patient population, the conversion of an implant into a living tissue, the highly mechanical nature of the heart valve, the complex homeostatic tissue that has to be reached at the end stage of the regenerating heart valve, and all the biomaterial properties that can be controlled to obtain this tissue. Many of these challenges are multidimensional and multiscalar, and both the macroscopic properties of the complete heart valve and the microscopic properties of the patient's cells interacting with the materials have to be optimal. Using newly developed in vitro models, or bioreactors, where variables of interest can be controlled tightly and complex mixtures of cell populations similar to those encountered in the regenerating valve can be cultured, it is likely that the challenges can be overcome.