Biomedical Engineering Reference
In-Depth Information
cardiomyocyte sheets became integrated with the host tissue and expres-
sion of Cx43 was documented. Electrophysiological experiments showed
the loss of a branch block which is seen in the control groups (no treat-
ment or fi broblast cell sheet grafts), an indication for conductivity improve-
ment in the scar tissue. 37
A similar approach was tested using tissue culture dishes coated with a
thin layer of thrombin-polymerized fi brin. 38,39 The use of fi brin as a culture
substrate with the cell self-assembly strategy has shown promising results
with skeletal muscle cells. 40 The myocytes migrated and proliferated on top
and inside the fi brin gel, produced ECM proteins, and degraded the fi brin
matrix after three to four weeks in vitro . The fi brin degradation rate was
controllable and can be matched to the ECM production rate. Huang et al.
compared the use of fi brin coated dishes by layering cardiomyocytes on top
of the fi brin or embedded inside the thin fi brin layer. The cells plated on
the surface of the fi brin created a uniform monolayer that displayed syn-
chronous contractions of the sheet after 48 hours; however, in the fi brin-
embedded cells, only isolated groups of cells were observed beating. The
authors reported that the embedded cells did not spread or form cell-cell
connections. 39
Synthetic scaffolds have also been used in creating cardiac tissue patches
for cell-based therapy. Vunjak-Novakovic and coworkers demonstrated the
ability to create a cardiac tissue analogue from rat neonatal cardiac cells
cultured in a 3D synthetic scaffold made from a fi brous polyglycolic acid
(PGA) mesh. 41 The effects of cell seeding density and tissue cultivation
conditions were evaluated extensively in these studies. They found that a
high cell seeding density combined with a dynamic culture environment
provided by a rotating bioreactor system improved the structural and func-
tional properties of the engineered cardiac tissue.
Radisic et al. described a biomimetic approach to cardiac tissue engineer-
ing based on a porous solid scaffold. They attempted to address one of the
critical problems in cardiac tissue engineering: the lack of suffi cient oxygen
supply. Cardiac cells and fi broblasts were cultured on a porous poly(glycerol-
sebacate) (biorubber) scaffold with an array of cubically packed parallel
channels which were created using a laser cutting system. In addition to the
highly perfused micro-channel array, the culture medium was also supple-
mented with a perfl uorocarbon (PFC) emulsion - an oxygen carrier to
mimic hemoglobin oxygen delivery. They showed that the increase in oxygen
concentrations also increased cell density and functional properties of the
engineered tissue. 42 Recently Caspi et al. reported on a vascularized cardiac
tissue analogue made from a scaffold composed of 50% poly-L-lactic acid
(PLLA) and 50% polylactic-glycolic acid (PLGA). The vasculature was not
imprinted into the scaffold, but rather it was developed by a co-culture of
vascular cell seeded into the material. They seeded the construct with
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