Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 91

its role in adult heart tissue. Del Re et al. demonstrated that, in response to
stress, endogenous Yap-1 is a critical regulator of cardiomyocyte growth and
survival in the adult mouse myocardium. They also found that a deficiency
in Yap-1 intensifies injury after chronic MI, suggesting that specific targeting
of Yap-1 activation in cardiomyocytes could serve to ameliorate the damage
caused by myocardial ischemia. These findings highlight Yap-1 as a possible
therapeutic target for driving pro-growth and pro-survival phenotype in a cell
autonomous manner in cardiomyocytes of patients suffering a chronic heart
disease. 19 In vitro and in vivo assays with Yap-1 direct injection or its en-
capsulation in DDSs for a release-controlled manner and their character-
ization has not yet been done.

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4.3.3.3 Stromal-cell-derived Factor-1
SDF-1 may be involved in the recruitment of progenitor cells into the
infarcted zone as a result of its chemo-attractant property. Few studies have
been done using DDS for this protein in cardiovascular diseases. Segers et al.
expressed SDF with a protease-resistant signal, followed by a self-assembling
peptide sequence allowing it to be incorporated into a native self-assembling
peptide scaffold. This system allowed the local and sustained delivery of
SDF-1, resulting in an improved cardiac function due to the increase in stem
cell recruitment and capillary density. 119 Another group covalently bound
SDF-1 to a PEGylated fibrinogen patch for controlled release of the protein.
The patch was placed on the surface of the infarct area of the left ventricle.
SDF-1 delivery can improve the rate of c-kit(+) cell homing and improve LV
function in a mouse AMI model. 120 Finally, Purcell et al. injected hydrogels
containing SDF-1 into the ventricle wall of infarcted mice and showed sus-
tained delivery and homing of bone marrow stem cells to the systemic cir-
culation and to the injured area. 121

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4.3.4 Combined Therapies
4.3.4.1 Multiple Growth Factors
Simultaneous activation of diverse signaling pathways by over-expression of
multiple growth factors ensures an appropriate angiogenesis and cause
massive mobilization and homing of stem/progenitor cells from peripheral
circulation, the bone marrow, and the heart. DDSs of multiple growth factors
constitute a novel approach that could accelerate the repair of the infarcted
myocardium.
Zieris et al. used the property of VEGF and FGF2 to bind strongly to
heparin in order to fabricate functionalized PEG-heparin hydrogels for
DDSs. Culture experiments with human umbilical vein endothelial cells
(HUVECs) revealed that this system provides the correct cues to induce
angiogenesis. 122
Sequential delivery of VEGF and PDGF-BB, or IGF-1 and HGF, from al-
ginate hydrogel systems induced the formation of mature vessels and