Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 93

observation should be considered when designing new studies involving
multiple GF administration.

4.4 Growth Factor Delivery Systems and Cell Therapy
The microenvironment of injured myocardium is characterized by high
levels of oxidative stress and the presence of pro-inflammatory cytokines
which directly affects the levels of cell engraftment following transplantation
reducing the ecacy of cell therapy. After 24 h of delivery it has been cal-
culated that the percentage of cell retention within the heart is between 1%
and 20% depending on cell type and delivery method. 130 GF delivery would
help to overcome these issues by providing cues for differentiation and
proliferation controlling the environment of transplanted cells.
Different biomaterials, GFs and cellular sources have been tested in sev-
eral studies to develop a combined therapy for the treatment of MI. The
strategy has several advantages, such as active compounds are released over
time and in close proximity to the transplanted cells, there are high local
concentrations of the compounds, and fewer off-site effects. An extensive
review on this field has been done recently. 74
One example is the delivery of IGF-1 tethered in self-assembling peptide
nanofibers together with cardiac stem cells. This led to a greater improve-
ment of cardiac function after MI and to the development of more mature
myocytes, compared to cells alone. 14 PLGA microspheres releasing HGF and
IGF-1 commitmently induced stem cells into a cardiomyocyte phenotype.
The HGF released could promote adult stem cell cardiomyocyte differen-
tiation and local neoangiogenesis around the graft, while IGF-1 could im-
prove survival of the grafted cells while, at the same time, inducing
proliferation and survival of the cardiac progenitor cells. 74 This strategy has
been used also to induce cardiac differentiation of pluripotent cells like
embryonic stem cells (ESCs) and induced pluripotent stem cells (iPS). Al-
though tough, there have been good results and it continues to be a chal-
lenging approach because of the specific temporal and spatial window in
which these cells are responsive to differentiation. 30
Bone marrow mesenchymal stem cells (BMSCs) were adhered into a bFGF-
loaded polyglycolic acid scaffold impregnated with collagen I hydrogel and
its ecacy in a rat model of MI was studied. The bFGF-BMSC-scaffold group
obtained the highest density vessel formation and the best cardiac function,
leading to a better improvement with respect to the BMSC-scaffold group 1
month after treatment. 131
A porous collagen scaffold incorporate VEGF and FGF in combination with
MSC. The system was tested in a rat model of MI. The group treated with the
GF-MSC scaffold showed a higher angiogenic effect and better cardiac
function compared to the MSC-scaffold group. A higher cell survival in the
GF-scaffold could be responsible of this higher beneficial effect. 132
VEGF was encapsulated in PLGA MP, which were then coated with fibro-
nectin for MSC adhesion. The system was able to enhance in vitro cell

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