Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 79

4.2.2 Biomaterials
Biomaterials are synthetic or natural substances with unique properties of
biodegradability and biocompatibility, with the capacity to transport nutri-
ents and metabolites, the ability to regulate cell morphology and differen-
tiation and have the presence of bioactive ligands for cell attachment. All of
them can be chemically or physically modified. 30 The material of choice,
whether it is natural or synthetic, will depend on the application. The most
common biomaterials used in the cardiac repair context has been revised in
Formiga et al. 9 and in Diaz-Herraez et al. 36
Materials from natural sources, such as collagens, or naturally derived
polymers, such as alginate, quitosan, gelatin or hyaluronic acid (HA),
are biologically recognizable but are dicult to purify and could generate
immunogenicity. In contrast, synthetic materials such as the polymers
poly(lactic-co-glycolic) acid (PLGA), polycaprolactone (PCL), poly(ethylene gly-
col) (PEG), poly(vinyl alcohol) (PVA), poly(acrylic acid) (PAA), poly(propylene
fumarate-co-ethylene glycol) [P(PF-co-EG)] and the polyketals present a stable
composition. 34 Although these polymers are tough, their mechanical prop-
erties can be easily manipulated but they lack bioactive sites to interact with
soluble proteins or cells, which could add complexity to the synthesis process
in order to improve specificity.
Polymeric biomaterials are commonly and successfully used for ad-
ministrating small doses of drugs or proteins like GF at defined dose rates
directly to target cells. These DDSs generally contain an aqueous phase with
the soluble molecule embedded in a degradable phase. They can also be
designed to monitor their degradation rates shifting the molecular weight
and co-polymerization ratio, present specific ligand-based signals, and/or
control the release in response to the microenvironment. 30 These last are
called smart delivery systems since they degrade in response to physiological
or disease-specific signals with the advantage of reducing side effects and
increasing ecacy of a variety of therapeutic agents. 37 Polymeric DDSs for
GFs can be built as hydrogels, nano- and microparticles and scaffolds among
others.
The use of lipids in drug delivery is a new trend for the delivery of poorly
soluble drugs and for peptide and protein delivery. Materials used in lipid-
based formulations include fatty acids, glycerides, phospholipids, sphingo-
lipids, waxes and sterols among others. Several lipid-based DDSs have been
developed over the last few years. Among them, liposomes and solid lipid
particulate systems have been used successfully for GF delivery. 38
Below we describe the most used vehicles explored so far for cardiac
protein delivery (Figure 4.1), pitfalls and challenges of this area.

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4.2.2.1 Hydrogels
Hydrogels are three-dimensional cross-linked polymeric networks which are
able to absorb an aqueous solvent and release it in a controlled manner.