Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 89

that FGFs have both angiogenic and cardioprotective potential. These factors
could promote resistance to injury (preconditioning), guard against sec-
ondary injury after an acute ischemic insult at the same that accelerate blood
vessel formation which make them candidates for preclinical and clinical
cardiovascular studies. 100
Basic FGF corresponds to a mitotic signal for endothelial cells and Wang
et al., incorporating it into a PLGA scaffold could promote neovascular for-
mation, enhanced blood-flow perfusion and improved myocardial function
in a mini-swine animal model of MI. 101 Intramyocardial administration of
bFGF microspheres injected in the peri-infarcted area can promote the
growth of microvessels and improve left ventricular function and myocardial
viability in the early period of acute myocardial infarction in dogs. 102
Composite fibrin matrices containing FGF-1 or FGF-2 were adsorbed onto
Dacron meshes and then implanted subcutaneously in mice, showing an
increment in the formation of microvessels. 103 On the other hand other
member of the family FGF10 promoted CM differentiation from embryonic
and induced pluripotent stem cells. 104
These studies formed the basis for a further clinical trial, where 335
patients were administrated intravenous and intracoronary FGF2. It was
concluded that a single intracoronary infusion of FGF2 does not improve
exercise tolerance or myocardial perfusion but does show trends toward
symptomatic improvement at 90 days. 23

d n 3 r 4 n g | 4

4.3.2.2 Insulin Growth Factor
IGF-1 is a small growth factor that is bound by IGF-binding proteins in
serum; thus, delivery of the free protein is highly inecient. Delivery of
insulin-like growth factor-1 (IGF-1) enhanced both neonatal myocyte, as well
as cardiac progenitor cell (CPC) ecacy. 14,105 Since, IGF-1 needs to be in the
heart for more than 1 month to cause an effect DDSs are an ideal method to
ensure this. 31
IGF-I embedded in poly( DL -lactide-co-glycolide) microspheres was released
from microsphere formulations for up to 13 days featuring a moderately
pulsatile pattern, depending on the microsphere composition. 106 Biotiny-
lated IGF-1 has been tethered to biotinylated self-assembling peptides using
streptavidin as a linker and was evaluated in vitro and in vivo. 14 In cardio-
myocytes, IGF-1 decreased activation of caspase-3, and increased expression
of cardiac troponin I after experimental myocardial infarction in rats and
an improvement in systolic function. 105 In a mouse model of MI, a single
injection of nanoparticles loaded with IGF-1 was able to avoid apoptosis
of cardiomyocytes, improving ejection fraction after 21 days of treatment. 107
Caplice et al. have an ongoing randomized trial called RESUS-AMI.
This group, currently recruiting patients, is evaluating the safety and
ecacy of a single low dose of intracoronary IGF-1 following percutaneous
coronary

.

intervention for ST-elevation acute MI 108 (clinicaltrials.gov-

NCT01438086).