Biomedical Engineering Reference
In-Depth Information
Development of biomimetic delivery strategies that provide VEGF locally,
and in an appropriately timed fashion offer great potential for recreation
of damaged nerve functions. Recent data indicate that chronic delivery of
VEGF may delay progression of brain-related degenerative diseases [27]. Sys-
temic VEGF delivery would prove ineffective for these applications because
of its inability to cross the blood-brain barrier, and implantation of sus-
tained release vehicles into the brain may overcome this issue and other
limitations of bolus delivery. Combined delivery of VEGF with neurotrophic
factors such as NGF may further improve the functions of regenerated
Polymeric Delivery Systems
Polymeric guidance channels, microspheres, and hydrogels may all be useful
for long-term release of VEGF. A widely explored strategy to treat periph-
eral nerve and spinal cord injuries is to physically guide neuronal outgrowth
by utilizing conduits typically prepared from biodegradable polymers (e.g.,
PLGA [179, 180] or magnetically aligned collagen or fibrin gels [181, 182]).
These grafts are placed across lesions and may exhibit either single or mul-
tiple lumens, and serve to support axonal outgrowth, allow the generation of
growth factor diffusion gradients, and minimize the infiltration of scar tis-
sue [183]. The release of growth factors from these grafts may render them
more effective, as shown with PLGA conduits that released NGF [184]. By
varying the approach to factor incorporation, and the PLGA composition,
different release kinetics could be readily achieved.
Microspheres are versatile, injectable systems for delivery of neurotrophic
growth factors, and the release kinetics with this system may be readily tai-
lored. Long-term release of neurotrophic growth factors has, for example,
been achieved with PLGA microspheres [185-187], and alginate and chitosan
microspheres may also prove valuable for this application [188]. Furthermore,
microspheres may be used in composite systems for multiple growth factor
delivery, and incorporated into hydrogel systems that physically direct growth
of regenerating nerves. The latter approach yields contact guiding neuro-
trophic matrices [186], whose effectiveness may potentially be improved by
incorporation of additional microspheres that release synergistically acting
The performance of polymeric VEGF delivery systems may be further
improved by modulation of cellular interactions, transplantation of cells,
and delivery of condensed DNA encoding neurotrophic growth factors. Ax-
onal outgrowth may be controlled by providing interfaces that present nerve
cell specific recognition motifs, and the modification of hydrogels (e.g., al-
regeneration may prove useful [189-191]. These hydrogels may either be
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