The present study describes our efforts to
develop a cardiac patch that can be locally implanted into a myocardial
infraction. The requirements of
restoring the contractile function of the diseased heart using a cardiac patch
must aspire to true tissue integration with the host myocardium and synchronous
contraction thereafter. In the present work, we
describe the development of a 3D bioartificial cardiac muscle with defined
geometry and cellular organization that enables better host-tissue
integration. We hypothesized that mechanical stimulation can be used to
regulate cell-mediated functional reorganization of the tissue constructs and
that this stimulation would initiate the cardiomyocytes to reorient into
longitudinal configuration, causing tissue reorganization and subsequent
phenotypic changes to the cells. The mechanical stimulation is imparted by a
bioreactor system that is designed to mimic the natural myocardial wall motion.
We prepared engineered constructs from neonatal rat cardiac cells, smooth
muscle cells and reconstituted collagen for use in the bioreactor system. After
an initial period of cellular compaction, the constructs were inserted into the
bioreactor and cyclically strained. We controlled the organization of cells in
the tissue constructs by applying up to 12.5% cyclic radial strain at a 1-Hz
frequency with a precisely controlled duty cycle. The results demonstrate that
the strain stimulation guides cellular orientation in the direction of applied
strain (i.e., in the circumferential direction). The cellular and morphological
reorganization is highly dependent on the amplitude of the strain stimulation.
The stimulated constructs exhibited a cardiac phenotype and increased protein
content. In conclusion, the cellular reorganization produces defined cellular
organization and structural characteristics that are similar to that of the
mature native tissue.
