Our research
is focused on the development of cardiac cell and tissue model systems
that enable 1) a systematic approach to studies of cardiac arrhythmias
in vitro, and 2) a design of electrically safe cell and tissue replacement
therapies in vivo. Microfabricaton techniques and the use of mechanical
and electrical stimulation are employed to reconstitute 2-dimensional
and 3-dimensional cardiac tissue substitutes with controllable architecture
starting with dissociated cells. These substitutes are intended
to mimic the structure of healthy and diseased hearts at multiple
organizational levels from single cell to two- and three-dimensional
cell networks. In addition, microfabricated cocultures of cardiac
and other cell types are used to simulate and systematically study
different scenarios encountered during cellular or tissue cardiomyoplasty,
or cardiac fibrosis in vivo. Immunostaining, protein and gene expression
analysis, and optical recordings with voltage and calcium sensitive
dyes in these systems allow for precise correlation between structure
and function at microscopic and macroscopic spatial scales, as well
as functional evaluation of engineered tissues before and after
potential implantation. The same methods are employed for the analysis
of complicated spatio-temporal changes in electrical activity encountered
in cardiac arrhythmias and fibrillation. Computer models that incorporate
cell-specific ion channels, cardiac cell geometry, distribution
of intercellular connections and discrete tissue microarchitecture
are used to aid the experimental design and the interpretation of
results.
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Isopotential Movie:
Isotropic Monolayer
point stimulus @ center
Isopotential Movie:
Anisotropic Monolayer
point stimulus @ center
Isopotential Movie: Spiral wave multiplication due to field
shock
Phase Movie:
Spiral wave multiplication due to field shock
