Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 94

proliferation and survival, but further studies are required to demonstrate its
in vivo ecacy. 133 Lately our group encapsulated NRG in PLGA MP. The
particles were next coated with collagen and/or poly- D -lysine for adipose
derived stem cells (ADSC) adhesion and studied in vivo in a rat model of MI.
The system was well integrated in the peri-infarcted area 2 weeks after
treatment demonstrating its biocompatibility. This work, although pre-
liminary, has yielded favorable results that require further studies that
should focus in the e cacy of this treatment. 134
Finally, there is an ongoing phase I clinical trial named ALCADIA that
aims to evaluate the safety and ecacy of autologous human cardiac-derived
stem cells (hCSCs) combined with a gelatin hydrogel sheet incorporating
bFGF in severe refractory heart failure patients with chronic ischemic car-
diomyopathy with left ventricular dysfunction (15% r LVEF r 35%) 135
(clinicaltrials.gov-NCT00981006).

d n 3 r 4 n g | 4

4.5 Conclusions
Cardiovascular diseases (CVDs) remain the biggest cause of deaths world-
wide, even though they are largely preventable. Occlusion of arteries, pri-
marily as a result of atherosclerosis leads to a deprivation of oxygen and in
tissues like the heart the ischemia produces an infarct that could result in
permanent muscle damage and probably death.
After an ischemic event, the heart tries to heal and recover the muscle
function but this process is highly inecient, leading to heart failure. There
are several treatment options for myocardial ischemia, including drugs,
bypass grafting surgery or transplant. Many novel therapies include the
delivery of different cellular types, proteins, like GFs or the genes that en-
codes for those factors.
The localized delivery of exogenous GFs is believed to be therapeutically
effective for the replication of cardiac cellular components involve in both
development and in the healing process, thus making them important fac-
tors for protein therapy. Different studies have helped to elucidate the
principal GFs needed to promote heart regeneration, even though much
detailed investigations on their signaling pathways, binding properties, half-
life, dosage and timing of administration are needed.
DDSs of GFs for cardiac repair have been developed; however, all of them
face major challenges, such as avoiding an initial burst of GF, achieving
proper controlled release over time, degradation and loss of bioactivity of
GF due to manufacturing methods, low eciency of encapsulation, bio-
availability of GF as recombinant proteins or high concentrations of GF
loaded into the devices which normally exceed those seen in the body.
Cardiac repair is a complex process that implicates angiogenic signals
along with cardiomyocyte proliferation, differentiation and remodeling, and
thus involves different GFs and cell types whose participation is perfectly
synchronized. In order to mimic the natural microenvironment of the heart,
the development of systems with the ability to engraft different cell types

.