Defining biomechanical endpoints for tissue engineered heart valve leaflets from native leaflet properties

The design and development of functional engineered tissues is dependent on multiple considerations, with biomechanics paramount for load-bearing constructs such as tissue engineered heart valves. As the cryopreserved allograft is the current standard for valve replacement in pediatric patients, identifying and quantifying essential structural–mechanical properties of the native valve leaflet is a crucial step in the engineered valve leaflet design process. Native valve leaflet properties provide an intuitive basis for assessing engineered valvular tissue performance, and can potentially be used as biomechanical endpoints for qualifying engineered leaflets prior to clinical applications. In this short review, we present three analysis techniques that have been used by our lab and others for characterizing heart valve leaflet biomechanical response and discuss the relevance of these properties as candidate endpoints for engineered leaflet tissues. The studies presented herein focused primarily on the aortic valve, which most frequently warrants repair or replacement in the general population and has been useful in our understanding of bioprosthetic heart valve mechanics. However, these analysis techniques are directly applicable for pulmonary and most engineered valve leaflets. Where data is available, initial studies applying these techniques for in vitro assessment of scaffolds and engineered valve leaflets are presented. The development of a tissue engineered heart valve for the pediatric population is conceptually appealing, since few options currently exist due to the lack of growth potential in non-viable prosthetics and size limitations. While significant challenges remain, we believe that a derivative of the current tissue engineered heart valve paradigm will ultimately yield a design suitable for clinical evaluation. The role of biomechanics in this process will be to identify and quantify the structural–mechanical endpoints essential for appropriate heart valve leaflet function, while guiding investigators prior to and during clinical evaluation.