Tissue-Engineered Tubular Heart Valves Combining a Novel Precontraction Phase with the Self-Assembly Method

Recently, the tubular shape has been suggested as an effective geometry for tissue-engineered heart valves, allowing easy fabrication, fast implantation, and a minimal crimped footprint from a transcatheter delivery perspective. This simple design is well suited for the self-assembly method, with which the only support for the cells is the extracellular matrix they produce, allowing the tissue to be completely free from exogenous materials during its entire fabrication process. Tubular constructs were produced by rolling self-assembled human fibroblast sheets on plastic mandrels. After maturation, the tubes were transferred onto smaller diameter mandrels and allowed to contract freely. This precontraction phase thickened the tissue and prevented further contraction, while improving fusion between the self-assembled layers and aligning the cells circumferentially. When mounted in a pulsed-flow bioreactor, the valves showed good functionality with large leaflets coaptation and opening area. Although physiological aortic flow conditions were not reached, the leaflets could withstand a 1 Hz pulsed flow with a 300 mL/s peak flow rate and a 70 mmHg peak transvalvular pressure. This study shows that the self-assembly method, which has already proven its potential for the production of small diameter vascular grafts, could also be used to achieve functional tubular heart valves.