Biomedical Engineering Reference
In-Depth Information
used alone, or as a filling of solid nerve conduits. Cellular therapies may
particularly aid patients with decreased neural cell signaling activity due
to deficits in VEGF supply, and may utilize both mature neural cell types
(e.g., glial cells, olfactory ensheathing cells) and progenitor cells (e.g., neu-
ral stem cells, glial progenitor cells) [180, 183, 187]. For example, neural stem
cells can be seeded onto appropriately designed PLGA scaffolds that emu-
late their spatial arrangement into the gray and white matter of the spinal
cord, and implantation of these constructs mediated functional recovery sub-
sequent to spinal cord injuries [180]. In the future, nonviral gene therapy
approaches may become an option to obtain prolonged presentation of neu-
rotrophic factors, and could be achieved with localized delivery of polyca-
tion/plasmid DNA complexes to damaged nerve tissue. For example, poly-
cationic polyaminoethyl propylene phosphate (PPE-EA) may mediate gene
transfer in the brain, and display prolonged gene expression, lower cytotoxic-
ity, and better nervous tissue compatibility as compared to other condensing
agents [192].
5
Summary and Future Directions
Current strategies of growth factor delivery for tissue regeneration most com-
monly rely on bolus injections, but this approach typically fails to restore
compromised tissue functions. Delivery from polymeric systems may over-
come the limitations associated with bolus delivery by supplying the growth
factor in a well-controlled, localized, and sustained manner to the defect site.
Polymeric delivery vehicles have traditionally been developed by modulating
physicochemical characteristics. However, it has now become clear that the
appropriate mimicry of certain biologic signaling events is useful to achieve
full function from the delivered growth factors.
Originally examined solely for its role in blood vessel formation, VEGF
has recently been attributed potential in other tissue regeneration therapies.
At present, therapeutic angiogenesis, bone regeneration, and nerve regenera-
tion represent the best understood application areas for VEGF delivery from
polymeric delivery systems. In the body, VEGF is delivered from a sophis-
ticated, biologic delivery system, whose functionalities may be mimicked by
the polymer systems to obtain increased signaling activities from the deliv-
ered VEGF. Simulation of the ECM binding and sequestering of VEGF by
polymer systems may not only enable control over the temporal and spatial
availability of VEGF, but also enhance the effectiveness of signal transduction.
ECM molecules furthermore contain cell recognition motifs that are critical
to both the cellular interactions with the delivery system and the signaling
functions of VEGF. Incorporation of these motifs into the polymer delivery
vehicle may more appropriately prime host cells to the delivered factor. A key
