Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 84

release kinetics controlled by degradation rate of the polymer used in the
carriers. 59 Another method uses freeze-drying of an emulsion of the lipo-
philic polymer dissolved in methylene chloride and a water phase containing
the different proteins used for encapsulation. The resulting polymer scaf-
folds exhibit quite different pore size distributions and morphologies al-
though the emulsion could affect the stability of the protein. 60
Electrospinning is a simple, versatile technique for generating nanofibers
from a broad range of materials including polymers, composites, and cer-
amics. 61,62 These nanofibers have several advantages for tissue regeneration
such as correct topography (e.g., 3D porosity, nanoscale size, and alignment),
encapsulation and local sustained release of growth factors, and surface
functionalization in order to allow cell adhesion. 63 The electrospinning
technique allows the production of DDS-nanofiber-based scaffolds when
polymeric fibers and protein solution are collected on a plate that is op-
positely charged to the solution involving the metal needle. Release studies
have shown presence of bovine serum albumin for over 30 days, although its
stability and biological activity need to be evaluated. 64
The amino acids in proteins can form covalent bonds with polymer sur-
faces either by a natural mode or be forced to it by using a physiological
method of protein fixation, such as the application of immobilized heparin
to bind heparin-binding domains of certain proteins like FGF-2 or VEGF. 65,66
It is important to guarantee that the binding does not involve amino acids
that are essential for the activity of the protein and that the receptors they
are acting on are accessible within the target cell. The covalent immobil-
ization of insulin 67 and the attachment of EGF 68 have proven that this
method preserves the biological activity of GFs demonstrated by the
stimulation in cell proliferation.
Finally, solid lipids can act as heat extractable porogen templates for
scaffold manufacture. When the temperature increases, lipids melt forming
pores, the polymer precipitates while a non-solvent solution that contains
the proteins invades the new network. This process prevents excessive loss of
encapsulated proteins, but the stability of the GF used at the chosen tem-
peratures must be evaluated. An analogous method can be performed using
gas bubble formation when high pressure carbon dioxide is used as a
solvent. 40

d n 3 r 4 n g | 4

.

4.2.2.4 Lipid-based Systems
Liposomes are microscopic vesicles composed of lipid membranes sur-
rounding discrete aqueous compartments. Their dimensions, composition,
surface charge and structure can be modified to fix the requirements of the
application. Natural and synthetic liposomes have been used both in vitro
and in vivo to deliver proteins for cancer treatment, ocular inflammation,
lung diseases, diabetes and infectious diseases. 69 Some innovative systems
like inhalable liposomes to carry peptides for airway administration to treat
lung diseases 70

or liposomes acoustically disrupted by ultrasound for