Incremental Stretch Increases Strength and Toughness while Growing Engineered Trileaflet Heart Valves

Tissue engineered
heart valves (TEHVs) represent a promising
method
for fulfilling the needs of young, growing individuals with an insufficient
valve function. Many current approaches that use natural biomaterials
rely on either very long culture times or a secondary polymer network
to create viable mechanical properties. While these materials can
create correct sizes or mechanical properties, issues such as dilation
of grafts still occur when strengthening does not correlate with a
stretch in size. Utilizing an adaptable, mechanical anchorage-based
culture system, we inquired how fibrin with encapsulated stem cells
could be stimulated to both grow and strengthen under an incrementally
increasing stretch (iStretch). We modified our culture system to assess
how the timing and magnitude of stretch affect both linear and planar
tissues, additionally creating leaflet-shaped tissues. In this study,
we show that iStretch stimulates cell alignment and increases tissue
modulus, failure stress, and toughness while achieving a 100% increase
in tissue length. The timing of iStretch increments also drives cell
differentiation, with almost doubling of a remodeling mesenchymal
phenotype achieved with early increments. Planar leaflet tissues stretched
to 50% greater diameter over 14 days increased in cell density and
vimentin expression. When placed in a pulse duplicator system, engineered
trileaflet valves opened completely to a maximal effective orifice
area and coapted with systolic ventricular pressures up to 80 mmHg.
These results demonstrate the potential of iStretch for generating
both rapid growth and the strengthening of engineered tissues.