Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 81

hydroxypropylcellulose (HPC) hydrogel for a clinical trial 44 as well as platelet
derived growth factor-BB (PDGF-BB), 45 suggesting the necessity of improving
direct loading. Variations on the cross-linking density, 46 the amount of
cross-linking agent 47 or the charge of functional groups 43 could help to

modify the releasing rate of proteins contained in hydrogels.
The incorporation of carriers within the hydrogels systems could help to
extend the delivery period of time of proteins. The carriers are usually de-
signed as particles containing the molecule of interest in the middle or as
implants where the protein is dispersed within the polymeric network.
Carries can be built with different biodegradable and non-biodegradable
materials. The presence of a concentration gradient in the target site is
mandatory when using a non-biodegradable carrier, in contrast to bio-
degradable carriers which release molecules along with the degradation of
the hydrogel system. 48,49
Proteins can also be covalently attached to hydrogels by the reaction of the
different side chain functionalities of polymers with the amino acids of the
GFs. For instance, PVA hydrogels have two neighboring hydroxyl groups
which can be used to attach peptide sequences. On the other hand, PEG-
based gels need a cell adhesion mediating peptide previous the incorpor-
ation of GFs. In the literature, it is also reported the covalent binding of PEG
to epidermal growth factor (EGF), bFGF and TGF-b2. 34,50
Hydrogels can be provided with enzymatic motifs to simulate ECM be-
havior allowing progressively release of GFs due to the matrix metallopro-
teinase (MMP)-mediated degradation. Zisch's group immobilized an
adhesion peptide (RGD) and VEGF within a metallo-proteinase-sensitive
synthetic hydrogel networks. An active VEGF liberation was confirmed from
these hydrogels by incubation with MMP-2 or plasmin. Besides, when im-
planted subcutaneously in rats, these VEGF-containing matrices were com-
pletely remodeled into native vascularized tissue. 51
A wide variety of hydrogels have been used to improve heart function after
infarction. Gelatin hydrogels loaded with FGF-2 injected via the intramyo-
cardial route in animal models of myocardial infarction seem to induce
significant angiogenesis and improve left ventricular function. Moreover,
alginate hydrogels alone or loaded with GFs have been demonstrated to be
effective therapeutic systems when injected in the cardiac muscle after
myocardial infarction. 6,32,52-54

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4.2.2.2 Microparticles and Nanoparticles
Microparticles can be classified as particles between 1 and 1000 mm while
nanoparticles are those within a nanoscale (10-1000 nm). These systems
seek to avoid the limitations of intravenous administration of therapeutic
proteins. Same design parameters as liposomes need to be pursued here.
Device biocompatibility and size are some of them.
Particles prepared with biodegradable polymers like PLGA have been
widely used to deliver GFs to the heart due to its excellent biocompatibility