Heart valve regeneration: the need for systems approaches

Tissue-engineered heart valves are promising alternatives to address the limitations of current valve replacements, particularly for growing children. Current heart valve tissue engineering strategies involve the selection of biomaterial scaffolds, cell types, and often in vitro culture conditions aimed at regenerating a valve for implantation and subsequent maturation in vivo. However, identifying optimal combinations of cell sources, biomaterials, and/or bioreactor conditions to produce functional, durable valve tissue remains a challenge. Despite some short-term success in animal models, attempts to recapitulate aspects of the native heart valve environment based on 'best guesses' of a limited number of regulatory factors have not proven effective. Better outcomes for valve tissue regeneration will likely require a systems-level understanding of the relationships between multiple interacting regulatory factors and their effects on cell function and tissue formation. Until recently, conventional culture methods have not allowed for multiple design parameters to be considered at once. Emerging microtechnologies are well suited to systematically probe multiple inputs, in combination, in high throughput and with great precision. When combined with statistical and network systems analyses, these microtechnologies have excellent potential to define multivariate signal-response relationships and reveal key regulatory pathways for robust functional tissue regeneration.