Biomedical Engineering Reference
In-Depth Information
resent another class of naturally derived materials with potential for VEGF
delivery. They are widely used because of their biocompatibility, low toxicity,
relatively low cost, and gentle gelling properties [88, 97]. Alginates are linear
polysaccharide copolymers extracted from seaweed, and consist of (1-4)-
linked beta- D -mannuronic acid (M) and alpha- L -guluronic acid (G) (Fig. 6).
Gelation occurs in the presence of divalent cations (e.g., Ca 2+ ), which ioni-
cally crosslink the carboxylate groups in the poly-G blocks. Modulation of the
crosslinking density by varying the MW of the polymer chains and the M to
G ratio yields gels with controlled mechanical properties and pore sizes [97].
One limitation to the use of alginates is their typically slow and unpredictable
degradation behavior in the body, which is controlled by the loss of diva-
lent cations, dissolution of the gels, and release of high MW polymer strands
that may be difficult for the body to eliminate [88]. To address these restric-
tions, hydrolytically degradable alginate derivatives have been synthesized
by partial oxidation (Fig. 6) and gamma-irradiation [59, 98]. These modified
polymers may also be covalently cross-linked with a variety of agents [98, 99].
Gels formed from polymers with a bimodal MW distribution at various oxi-
dation degrees can be formulated to allow decoupling of pre-gel rheological
properties from the gel mechanical properties, and control of degradation
rate over a wide range [100, 101].
3.2.2
Modulation of Growth Factor Release Kinetics
VEGF release from polymer systems is often controlled by diffusion or poly-
mer degradation, and the desired kinetics are prescribed by the therapeutic
application. The highly hydrated, nanoporous gel networks formed by many
hydrophilic synthetic or natural polymers that are used for VEGF delivery
typically release the factor in a diffusion-controlled manner [30, 88, 97, 102].
The structural integrity and release properties of the swollen networks may
be controlled by crosslinking the polymer chains in a covalent or physical
fashion. Gels formed by covalently-crosslinked networks are termed “chem-
ical gels”, whereas gels generated through secondary forces (e.g., ionic or
H-bonding) are denoted as “physical gels” [102]. The rate and distance of
VEGF diffusion through these hydrogels is governed by the characteristics
of both the network and VEGF. Specifically, the concentration, size, charge,
and crosslinking density of the polymer define the nano-porosity of the net-
work and the extent of water absorption [88, 97, 102], whereas the molecular
properties of VEGF determine the type and strength of interactions with the
polymer. Ionically crosslinked alginate gels represent typical examples of hy-
drogels that release proteins in a diffusion-controlled manner [30, 103]. If the
given hydrodynamic volume of VEGF (roughly correlating with the molecu-
lar weight of 45 kDa[24])islargerelativetotheporesizeofthenetwork
VEGF diffusion will be retarded. If one wants to promote cellular infiltra-
 
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