Heart valve leaflets have a complex trilayered structure
with layer-specific
orientations, anisotropic tensile properties, and elastomeric characteristics
that are difficult to mimic collectively. Previously, trilayer leaflet
substrates intended for heart valve tissue engineering were developed
with nonelastomeric biomaterials that cannot deliver native-like mechanical
properties. In this study, by electrospinning polycaprolactone (PCL)
polymer and poly(l-lactide-co-ε-caprolactone)
(PLCL) copolymer, we created elastomeric trilayer PCL/PLCL leaflet
substrates with native-like tensile, flexural, and anisotropic properties
and compared them with trilayer PCL leaflet substrates (as control)
to find their effectiveness in heart valve leaflet tissue engineering.
These substrates were seeded with porcine valvular interstitial cells
(PVICs) and cultured for 1 month in static conditions to produce cell-cultured
constructs. The PCL/PLCL substrates had lower crystallinity and hydrophobicity
but higher anisotropy and flexibility than PCL leaflet substrates.
These attributes contributed to more significant cell proliferation,
infiltration, extracellular matrix production, and superior gene expression
in the PCL/PLCL cell-cultured constructs than in the PCL cell-cultured
constructs. Further, the PCL/PLCL constructs showed better resistance
to calcification than PCL constructs. Trilayer PCL/PLCL leaflet substrates
with native-like mechanical and flexural properties could significantly
improve heart valve tissue engineering.