Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 87

factors localize and prolong the effect to a microenvironment, minimizing
the negative side effects. 59,76-80
For cardiac applications, VEGF has been successfully loaded into a wide
variety of natural and synthetic materials using diverse methods. VEGF has
been covalently incorporated into collagen gels scaffolds 81 and fibrin
matrices, 82 encapsulated in gelatine 83 and PLGA microparticles, liposomes 84
or alginate gel matrices. 85 For most cases VEGF retained its bioactivity after
DDS preparation and improved angiogenic performance in vitro.
VEGF-DDS ecacy has been widely evaluated in animal models. Some of
those studies have proved the effect of this GF in the treatment of ischemic
disease in mice using alginate matrices, 85 the improvement of vascularity
and cardiac function in MI model 84 and the restoration of perfusion from
hind limb ischemia, preventing severe necrosis in mice, when embedded in
PLG scaffolds containing the microspheres with VEGF. 85 Also our group,
demonstrated the improvement in vasculogenesis and tissue remodeling
when PLGA and PEG-PLGA microparticles loaded with VEGF-A were de-
livered in a rat model of cardiac ischemia. 86,87

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4.3.1.2 Placental Growth Factor
PIGF is a member of the cysteine-knot family that can modulate the activity
of VEGF. Gene inactivation experiments in mice showed that loss of PIGF
correlated with impaired angiogenesis, but on its own PIGF cannot initiate
endothelial cell stimulation and only enhances the effects of the available
low concentrations of endogenous VEGF. 10 PIGF can stimulate the recruit-
ment and activation of monocytes, which is an essential step in the process
of formation of mature vascular networks. In animal models, systemic ad-
ministration of recombinant PIGF-1 protected from induced ischemic le-
sions in the heart without affecting heart rate. 88,89
PIGF is a potential candidate for DDS for angiogenesis; nevertheless,
further in vitro and in vivo experiments need to be done with PIGF alone and
in combination with VEGF which would probably be more effective in the
treatment of cardiovascular diseases.

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4.3.1.3 Platelet-derived Growth Factor
PDGF corresponds to a mitotic and motility signal for smooth muscle cells
and pericytes during angiogenesis, as well as a chemo-attractant that in-
duces VEGF expression in cardiac endothelial cells. Intramyocardial in-
jection of PDGF has cardio-protective effect in mice, reducing the extent of
myocardial injury following coronary occlusion. 90
Several DDSs for PDGF have been examined, hydrogels that could be
enzymatically degraded, 91 PLGA-nanoparticles 92 or porous scaffold devices
made by entrapping PDGF-BB in PLG microspheres through a standard
double-emulsion process. 93 Under optimal conditions, the encapsulation
eciency of PDGF-BB can reach 87% while maintaining bioactivity.