Biomaterials in cardiac restoration therapy - Biomaterials and Devices for the Circulatory System - page 268

cells. 28 The cells survived in the graft for up to fi ve weeks in both the sub-
cutaneous implantation model as well as on the myocardial scar tissue of
adult rats. Although cells in the graft contracted spontaneously in vitro and
in the subcutaneous implantation, there was no measurable effect on
cardiac function following implantation of the patch on the myocardium.
The study indicated that the size of the implanted graft was too large in
comparison to the infarct size and hence may have damaged the healthy
regions of the cardiac muscle that were also covered by the patch.
Since this initial study, other materials including collagen and Matrigel
have been widely used for cell delivery in myocardial regeneration. 29-32
Zimmermann et al. developed engineered heart tissues (EHTs) from neo-
natal rat heart cell embedded in collagen I, Matrigel and various growth
supplements. 31 The EHTs were shaped as circular rings and subjected to
mechanical strain stimulation during in vitro culture. A multi-loop EHT was
created by fashioning fi ve rings of EHTs together in a unique geometric
confi guration resembling a patch. The multi-loop EHT was sutured onto
the infarcted heart muscle of an adult rat with an MI. They demonstrated
that the multi-loop EHT was integrated and electrically coupled to the
native myocardium. Consequently, they showed that the cardiac systolic and
diastolic function was improved.
Similarly, Kutschka et al. used collagen gels conjugated with matrigel
and growth factors (VEGF, FGF) to deliver fl uorescently labeled cardio-
myoblasts to an adult rat heart. 33 They used in vivo optical biolumines-
cence imaging to evaluate cell survival in the graft after implantation.
Consistent with previous studies, they documented low cell survival rate
when the cardiomyocytes were injected alone, whereas cells seeded on the
collagen matrix showed signifi cant improvements in the survival rate after
eight days. Only 30% of the bioluminescence signal was recorded after
one week without the collagen, and a three-fold enhancement in the
imaging signal was measured with the collagen matrix. One possible
explanation for the improved cell survival was based on the hypothesis
that the porous collagen matrix can better guide vessel ingrowth and thus
improve perfusion to the implanted cells. Interestingly, the cell survival
rate was not signifi cantly affected by the addition of the growth factors to
the collagen matrix. After four weeks only a small fraction of the origi-
nally implanted cells survived in the scar tissue. The surviving cells did not
express connexin-43 (Cx43) and hence did not integrate with the host
myocardium. An improvement in cardiac function was documented, but
the inhibition of cardiac remodeling and wall thinning was the predomi-
nant mechanism for the cardiac improvements, rather than a functional
contribution of the transplanted cells.
Leor et al. investigated alginate sponges as a cell scaffold for myocardial
repair. 34 Alginate scaffolds seeded with fetal cardiomyocytes were

￿ ￿ ￿ ￿ ￿