Intramyocardial Injection of a Synthetic Hydrogel
with Delivery of bFGF and IGF1 in a Rat Model of Ischemic Cardiomyopathy
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Abstract
It
is increasingly appreciated that the properties of a biomaterial
used in intramyocardial injection therapy influence the outcomes of
infarcted hearts that are treated. In this report the extended in
vivo efficacy of a thermally responsive material that can deliver
dual growth factors while providing a slow degradation time and high
mechanical stiffness is examined. Copolymers consisting of <i>N</i>-isopropylacrylamide, 2-hydroxyethyl methacrylate, and
degradable methacrylate polylactide were synthesized. The release
of bioactive basic fibroblast growth factor (bFGF) and insulin-like
growth factor 1 (IGF1) from the gel and loaded poly(lactide-<i>co</i>-glycolide) microparticles was assessed. Hydrogel with
or without loaded growth factors was injected into 2 week-old infarcts
in Lewis rats and animals were followed for 16 weeks. The hydrogel
released bioactive bFGF and IGF1 as shown by mitogenic effects on
rat smooth muscle cells in vitro. Cardiac function and geometry were
improved for 16 weeks after hydrogel injection compared to saline
injection. Despite demonstrating that left ventricular levels of bFGF
and IGF1 were elevated for two weeks after injection of growth factor
loaded gels, both functional and histological assessment showed no
added benefit to inclusion of these proteins. This result points to
the complexity of designing appropriate materials for this application
and suggests that the nature of the material alone, without exogenous
growth factors, has a direct ability to influence cardiac remodeling