Behavior of valvular interstitial cells on trilayered nanofibrous substrate mimicking morphologies of heart valve leaflet

Abstract

Heart valve tissue engineering could be an alternative to the current bioprosthetic heart valves and their limitations, especially for pediatric patients. However, heart valve tissue engineering remains challenging because leaflets — the primary component of a heart valve — have three diversely oriented layers — circumferential, random and radial. In order to mimic the orientations, we first designed three novel collectors to fabricate three nanofibrous layers with those orientations from a polymeric biomaterial in an electrospinning system. Then, we devised a novel direct electrospinning technique to develop a unified trilayered nanofibrous (TN) substrate comprising those oriented layers. The TN substrate supported the growth and orientations of seeded porcine valvular interstitial cells (PVICs) and their deposited collagen fibrils. After one month culture, the obtained trilayered tissue construct (TC) exhibited increased tensile properties over its TN substrate. Most importantly, the developed TC did not show any sign of shrinkage. Gene expression pattern of the PVICs indicated the developing stage of the TC. Their protein expression pattern was quite similar to that of leaflets.