Biomedical Engineering Reference
In-Depth Information
The rheological and mechanical properties of biodegradable, binary algi-
nate systems may be readily adjusted to the physical demands prescribed
by the injection procedure and injection site [139]. Binary gels designed to
exhibit both a high stiffness and a high strain at failure will likely allow pro-
longed release of VEGF in response to mechanically dynamic environments.
In contrast, less rigid or brittle gels may lead to accelerated release and fail-
ure due the strains imposed on the vehicle in the body. Covalent linkage
of cell-adhesion peptides to alginate may allow for control over blood ves-
sel formation by affecting endothelial cell invasion and proliferation [152],
and modulating mural cell properties that stabilize neovessels [153]. Impor-
tantly, the gel stiffness may modify the cell phenotype directly and thus VEGF
signaling and blood vessel formation [154]. This characteristic may be partic-
ularly useful to improve growth factor production when nonviral VEGF gene
delivery approaches are used to promote vascularization [155]. While hydro-
gels enable growth factor release over a time-frame of days to approximately
a month [30, 68, 95], microspheres made from aliphatic polyesters may be de-
signed to release drugs over this time frame or longer [110, 130]. However,
long-term release is dependent on growth factor stability in the device [69].
Porous 3-D PLGA scaffolds may be suitable for various therapeutic needs
that benefit from structural support. For example, healing of diabetic ulcers
or enhancing angiogenesis in the lower limbs secondary to diseases such as
diabetes may benefit from the controlled sequential delivery of angiogenic
growth factors from this form of vehicle [67]. These systems additionally pro-
vide 3-D support structures that may be readily seeded with cells that can
participate in regeneration. This approach may be particularly useful in the
treatment of patients with a reduced number of competent cells caused, for
example, by aging, disease, or irradiation therapy [156, 157]. In these cases,
the therapeutic efficacy of VEGF delivery may be enhanced by transplantation
of responsive cell populations that are able to actively participate in blood
vessel regeneration (e.g., endothelial cells, bone marrow derived stem cells,
endothelial progenitor cells circulating in the blood) [158-160].
4.2
Bone Regeneration
4.2.1
Therapeutic Significance of VEGF
Significant bone loss caused by accidents, sports injuries, or diseases such as
osteoporosis is frequently associated with severely impaired or nonhealing
defects. Major economic issues arise from an increasingly aged population
that typically exhibits slower healing of fractures, and this leads to a demand
for new therapies to promote bone formation. Bone formation (osteogenesis)
has long been appreciated to be dependent on vascularization, but not until
