Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 86

oxide) triblock co-polymer). VEGF-loaded core-shell nanoparticles and their
gel improved heart function particularly with regard to ejection fraction and
cardiac output. A minimal difference in neovascularization was observed
between the core-shell nanoparticles and their gel. 73

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4.3 Growth Factor Drug Delivery Systems for Cardiac
Applications
Several alternative strategies are being investigated to complement the cur-
rent pharmacological therapies for myocardial diseases, including re-
activation of cardiomyocytes (CMs) cell cycle activity and reduction of
myocardial cell death. To improve regeneration of the damaged heart area
two main strategies in the cell therapy field have been developed. The first
aims at recruiting or promoting the homing of endogenous or circulating
stem cells at the periphery or inside the damaged zone which improves the
innate repair capacity of heart tissue. The second seeks for building a new
tissue with a new population of functional and beating cardiomyocytes, with
cell-cell communications, secreted factors and induction of neoangiogen-
esis. GFs play an essential role in both approaches and their administration
together with cytokines and extracellular matrix molecules could help to
reduce inflammation, promote cell survival, and promote recruitment and
differentiation of progenitor cells towards cardiac lineages ensuring a suc-
cessful result of this type of treatment. 74
Below we review a group of GFs described as having a role in angiogenesis,
remodeling, differentiation and proliferation processes within the heart
after an infarction. 9,36 In vitro pre-clinical and clinical studies have been
developed for almost all of them with different outcomes constituting an
important field of research and a promising therapy for patients, especially
for those who are not surgical candidates.

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4.3.1 Angiogenesis
Infarcted myocardium is an ischemic and inflammatory environment hostile
to most cells. New treatment strategies seek to enhance angiogenesis in
order to increase survival of cardiac cells, remodeling of the tissue, stem cell
engraftment and differentiation. GFs, by promoting the formation of new
functional vessels help to decrease ischemia, improving cardiac perform-
ance after infarction. 30,75

4.3.1.1 Vascular Endothelial Growth Factor
VEGF is a key regulator of angiogenesis but its systemic injection could lead
to hyperpermeable vessels, hypotension, induction of tumor growth, and
uncontrolled neovascularization in non-target tissues. DDSs of angiogenic