Models of 3-Dimensional Heart
Muscle In Vitro - We are interested
in evaluating the feasibility of utiizing different strategies to
promote the
formation of functional heart muscle in vitro. Our group has
developed
three models of heart muscle in vitro. The first model is based
on the
self-organizatin of primary cardiac myocytes. Our second model is
based
on the utilization of biodegradable fibrin gel. Our third model
is based
on the utilization of polymeric scaffolds. Our work is primarily
focused
on understanding the interaction of isolated cardiac cells with
different
materials and defining optimal conditions for maximal functionality.
Phenotypic Modulation of Tissue
Engineered Heart Muscle - A
signficant amount of our research is focused on utilizing chemical,
mechanical
and electrical stimulation to modulate the phenotype of tissue
engineered heart
muscle in vitro. We are interested in simulating a phyiological
environment to support the viability of 3-dimensional heart muscle in
vitro. Chemical, mechanical and electrical stimulation protocols
are
being utilized to maintain and improve the contractile performance of
our
3-dimensional heart muscle. We have already obtained a
significant
improvement in contractile performance of cardioids using thyroid
hormone. We obtained an improvement in active force, specific
force, time
to peak tension, half relaxation time, frequency of spontaneous
contractility
and electrical pacing characteristics. We are also evaluating the
effect
of mechanical loading and electrical stimulation on the contractility
of tissue
engineered constructs.
Angiogenesis and
Micro-Perfusion - The ability to engineer three
dimensional cardiac tissue equivalents is often limited by the lack of
a
vasculature. We are working towards a model to promote the
organization
of endothelial cells to form capillaries within the 3-dimensional
architecture
of the construct. Our fundamental hypothesis is that the
endothelial
cells can be stimulated with various growth factors to form
capillaries.
The endothelial cells are already present in the contractile tissue
constructs
that we engineer. Upon formation of a capillary network within
the tissue
construct, we are primarily interested in developing micro-perfuion
systems to
perfuse the newly formed vasculature. We anticipate that this
will result
in the long term viability of our tissue engineered constructs.
Models of Cell Based Cardiac
Pumps In Vitro- We have developed a method
to engineer a cell based cardiac pump that is capable of generating
hydrostatic
pressure upon electrical stimulation. The pump consists of a
lumunal
tubular scaffold that is fabricated from polymeric material. The
properties of the tubular scaffold can be controlled to modulate the
elastic
modulus. The tubular scaffold is seeded with primary cardiac
myocytes.
Upon electrical stimulation, the cell monolayer tend to contract
generating
radially stresses on the tubular structure resulting in displacement of
the
structure. Pumps that have been engineered this way have been
able to
generate a hydrostatic pressure of 0.1-0.2 mmHg.
Tissue Engineered Heart Valves-
We are interested in
utilizing scaffold based strategies to engineer a functional heart
valve
substitute that can be seeded with patient derived myofibroblast cells
allowing
for the formation of personalized heart valves. Our work is
focused on
developing fabrication strategies to engineer planar scaffolds with
mechanical
properties that match the properties of normal heart valves. We
are also
focusing our efforts on translating our fabrication technology to
engineer
3-dimensional tri-leaflet valves. We are working towards the
isolation and
culture of myofibroblasts that have been derived from umbilical cord or
placental tissue of donor sheeps. Our methodology will result in
the
formation of a tissue engineered heart valve with direct clinical
applications
for pediatric patients.
Vascular Tissue Engineering
- We are evaluating the feasibility of utilizing
human derived vascular smooth muscle cells to engineer both solid and
tubular
constructs. The motivation for utilizing solid constructs is to
provide a
model to investigate the basic physiology of the smooth muscle
cells. The
motivation for utilizng a tubular structure is to replicate the
geometry of a blood
vessel thereby promoting the feasibility for clinical applicibility.