Ongoing research efforts aim at improving the creation of tissue-engineered heart valves for in vivo systemic application. Hence, in vitro studies concentrate on optimising culture protocols incorporating biological as well as biophysical stimuli for tissue development. Important lessons can be drawn from valvulogenesis to mimic natural valve development in vitro. Here, we review the up-to-date status of valvulogenesis, focussing on the biomolecular and biophysical regulation of semilunar valve development. In addition, we discuss potential benefits of incorporating concepts derived from valvulogenesis, as well as alternative approaches, in tissue-engineering protocols, to improve in vitro valve development. The combined efforts from clinicians, cell biologists and engineers are required to implement and evaluate these approaches to achieve optimised protocols for heart-valve tissue engineering.
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