The relevance of large strains in functional tissue engineering of heart valves

Background: Exposing the developing tissue to flow and pressure in a bioreactor has been shown to enhance tissue formation in tissue-engineered heart valves. Animal studies showed excellent functionality in these valves in the pulmonary position. However, they lack the mechanical strength for implantation in the high-pressure aortic position. Improving the in vitro conditioning protocol is an important step towards the use of these valves as aortic heart valve replacements. In this study, the relevance of large strains to improve the mechanical conditioning protocol was investigated. Methods: Using a newly developed device, engineered heart valve tissue was exposed to increasing cyclic strain in vitro. Tissue formation and mechanical properties were analyzed and compared to unstrained controls. Results: Straining resulted in more pronounced and organized tissue formation with superior mechanical properties over unstrained controls. Overall tissue properties improved with increasing strain levels. Conclusions: The results demonstrate the significance of large strains in promoting tissue formation. This study may provide a methodological basis for tissue engineering of heart valves appropriate for systemic pressure applications.