Biomedical Engineering Reference
In-Depth Information
Mechanically competent VEGF delivery systems may be designed on the ba-
sis of the estimated mechanical thresholds that the vehicles may encounter
in situ.
The mechanical competence of hydrogels is almost entirely controlled by
the selected polymer and the type and density of cross-links in the sys-
tem [120]. Furthermore, the conditions under which the hydrogel network is
formed (e.g., temperature, pH, medium), actively influence mechanical per-
formance [97, 120]. The strength of alginate gels, for example, may be raised
by increasing the concentration of G residues and the alginate concentration
of the polymer [121, 122]. Additionally, the mechanical characteristics of algi-
nate hydrogels may be readily controlled by covalently cross-linking the indi-
vidual alginate chains with different types and concentrations of crosslinking
molecules [123]. Similarly, the mechanical characteristics of other hydrogel
matrices such as collagen, chitin, fibrin, and PEG directly correlate with their
respective polymer concentration [124-127] and may be further modified by
chemical crosslinking [128, 129].
The mechanical strength of solid VEGF delivery systems fabricated from
aliphatic polyesters (e.g., PLGA) is prescribed by the polymer MW, crys-
tallinity, and the molar ratio of the individual monomer components (e.g.,
lactide and glycolide). Matrices made from the homopolymers
L
-PLA or PGA,
as well as copolymers with a high ratio of one monomer are crystalline and
exhibitameltingpoint,whereasthosepreparedfrom
D
,
L
-PLA and copoly-
mers with less than 90% of one monomer display amorphous properties and
undergo glass transition above a critical temperature (
T
g
) [106, 130]. More
crystalline polymers usually exhibit increased physical strength [130]. Since
the
T
g
of the amorphous polymers is typically higher than the body tempera-
ture, the respective delivery systems maintain a glassy structure once placed
in the body [106, 130, 131], although the absorption of significant amounts of
water may decrease
T
g
to less than 37
◦
C for certain polymers [132].
The mechanical capacity of polymers is often enhanced by the formation
of composite structures composed of (1) oriented reinforcing units, such as
fibrils,fibers,orextendedchaincrystalsand(2)theuseofbindingmatri-
ces of the same chemical structure [133]. An alternative that mediates im-
proved mechanical performance while providing space for cellular invasion
is the deposition of a bonelike mineral film on the interior pore surfaces of
PLGA scaffolds (Fig. 8) [134, 135]. This approach not only leads to increased
compressive moduli, but also confers the scaffolds with osteoconductive char-
acteristics and the ability to modulate proliferation and differentiation of
multipotent stem cells [134-137].
The size and mechanical characteristics of a delivery system furthermore
prescribe its delivery route (i.e., whether it may be surgically inserted into the
repair site or injected in a minimally invasive manner). Typically, polymer
scaffolds and compact implants are inserted in an invasive fashion, whereas
microspheres and gels can be readily applied through injections. The utility of
