Biomedical Engineering Reference
In-Depth Information
tion into the delivery vehicle, it is often not desirable to decrease the pore
size to regulate VEGF release kinetics, as this may inhibit tissue regenera-
tion [104, 105].
VEGF release from degrading polymeric systems is determined by the rate
of degradation and subsequent dissolution [97, 106, 107]. Hydrolysis is fre-
quently exploited as the mechanism to regulate degradation of the polymer
system,asthisprocesstypicallyoccursataconsistentratethatisnotin-
fluenced by local conditions. The molecular weight (MW) distribution and
chemical structure of the polymer provide means to readily adjust the VEGF
release rate to the specific regenerative needs [108, 109]. For example, de-
livery systems made from PLGA degrade through hydrolysis of the back-
bone ester linkages, and the biodegradation rate of PLGA vehicles can be
modified on the basis of their MW and molar ratio of lactic and glycolic
acid [106, 110-112]. The release rate from vehicles created with naturally
derived ECM components that degrade by enzymatic cleavage can also be
controlled. For example, growth factor release from collagen, gelatin, and chi-
tosan can depend on enzymatic degradation rather than diffusion [97], and
may be decreased by additional crosslinking of the polymer network to slow
degradation and dissolution [68, 93, 96, 113].
The desire to control the release of multiple growth factors with distinct
kinetics from a single delivery device has motivated the creation of com-
posite systems. A combination of microspheres with a second matrix is an
example of these more complex systems. Microspheres may be equipped with
differential release properties by fabricating them in different sizes [114],
utilizing different natural and synthetic materials (e.g., alginate [56, 95],
gelatin [68], collagen [115], and PLGA [67, 77]), and/or retroactively altering
them by physicochemical modification (e.g., crosslinking [68, 93] or coating
with a second material [95]). The subsequent incorporation of these micro-
spheres into a second matrix (e.g., a synthetic hydrogel matrix [68] or PLGA
scaffolds [67]), which may have been equally modified may ultimately lead to
a wide spectrum of release kinetics.
3.2.3
Mechanical Properties
Growth factor delivery systems are required to withstand physical forces
present at the diseased tissue site. Upon placement into the body, the poly-
meric vehicles must be able to bear loads and maintain the structural prop-
erties critical to the release of the growth factors (e.g., the pore size of
hydrogels enabling diffusion) and tissue formation (e.g., provision of space
for cellular invasion). At the same time, they often need to effectively trans-
duce biomechanical stimuli to the surrounding cells and tissues. Such signals
may be critical to the cellular response to growth factor supply [116-119],
and may directly induce cellular proliferation and differentiation [116, 117].
 
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