BIOMIMETIC MATERIALS FOR ENGINEERING OF NEURAL TISSUES: CONTROL OF CELL ADHESION AND GUIDING NEURAL CELL OUTGROWTH WITH PEPTIDE-CONJUGATED POLYMER STRUCTURES - Biologically-Responsive Hybrid Biomaterials - page 345

nanofibrous hydrogels using self-assembly of IKVAV based peptide
amphiphiles. The biomimetic scaffolds can be triggered to polymerize in situ ,
with the addition of an aqueous buffer solution. They showed IKVAV motifs
could direct differentiation in neural progenitor cells while simultaneously
inhibiting astrocyte differentiation. Further support for this scaffold in CNS
repair was provided with a spinal cord compression model. In vivo treatment
with IKVAV self-assembled nanofibers reduced astrogliosis, cell death and
recruited oligodendrocytes at the injection site [39]. Regeneration of both
ascending and descending axons as well as behavioral changes was observed.
Accompanying literature with IKVAV-hyaluronic acid conjugates, also
demonstrate axonal ingrowth/regeneration, glial cell invasion and neovasculari-
zation in the rat cerebellum [40].
Alternatively, Behnke et al., 2007 used a repeating peptide sequence of
RADA-16 (Figure 4) to develop self-assembled nanoscaffolds [28]. Using a
severed optic nerve in vivo model, RADA-16 was injected into the site of injury
and was later shown to induce axon regeneration. Lesioned hamsters partially
recovered lost vision as determined by behavioral tests. The self-assembled
nanostructures were also found to be non-toxic and did not elicit an
inflammatory response in brain. Follow up studies showed these same scaffolds
supported neuronal migration [41].
The physiochemical properties of hydrogels also make them excellent
candidates for caging cells. In traumatic brain injury (TBI) or spinal cord lesions,
cavities formed from mechanical damage or tumor removal can lead to severe
functional loss. Stem cell therapy has emerged as a viable avenue of research to
replenish lost neurons [42]. These approaches generally involve harvesting
neural progenitor cells, in vitro expansion/differentiation and subsequent re-
implantation into the defect. Preliminary investigations with peptide hydrogels
have shown promise for use in cell encapsulation techniques. Hydrogels, such as
those described by Semino et al. were used to entrap neural progenitor cells [41].
In another instance, globular domains derived from laminin were coupled to
keratin hydrogels. Neurosphere forming cells adhered to the hybrid keratin
constructs and proliferated at a high survival rate [43].
In summary, functionalized hydrogels with optimum epitope densities
provide a tunable approach to filling void defects as well as delivery of biologics.
The chemical and mechanical properties of hydrogels can be modified to elicit
cell-specific behavior such as attachment, neurite extension, migration and cell
differentiation.