Molecular Gels for Tissue Engineering - Soft Fibrillar Materials: Fabrication and Applications - page 136

natural hydrogels [35]. It binds specifically to integrin, a transmembrane protein
that mediates cell adhesion and controls cell adhesion, spread, and migration. The
binding between RGD and its receptors can be controlled by manipulating the
density of RGD incorporated into the peptide amphiphile by altering the number
of RGD peptides added into the amphiphile molecule. High density of RGD was
shown to promote receptor clustering and maximize binding between ligands and
receptors between scaffold and cells [44].
To direct neuronal cell differentiation, a self-assembling artificial scaffold made
froma peptide amphiphile bearing a neurite-promoting lamininmarker isoleucine-
lysine-valine-alanine-valine (IKVAV) was designed [37]. Next to this peptide marker
is a glutamine residue that makes this peptide negatively charged when the pH
was adjusted at 7.4, so that the electrostatic repulsion among peptide molecules
can be overcome by cations, which facilitates the self-assembly of the peptide
when they are exposed to cell suspensions. The -sheet-forming segment in

this peptide is designed as 4 alanine residues and 3 glycine residues and the
hydrophobic tail is composed of an alkyl chain of 16 carbons. When four uniformly
hydrophobic alanine residues are replaced by an alternating serine-leucine-serine-
leucine (SLSL) sequence, the gelation of this new peptide amphiphile takes place at
a lower rate than that for the alanine-containing amphiphiles. The self-assembly is
driven by intermolecular hydrogen bonding, and the unfavorable contact between
hydrophobic segments and water molecules after electrostatic repulsions between
peptide molecules are overcome by cations in the cell culture medium [37]. In
aqueous, salt-free solution, the secondary structures of the IKVAV-bearing peptide
amphiphiles are all dominated by hydrogen-bonded

β

-sheet structure [38]. The
effect of the incorporation of IKVAV epitope was clearly demonstrated by the
promotion of neurite outgrowth and the targeted neural differentiation of neuron
progenitor cells into neuron but not astrocytes, as demonstrated by staining of
cell-type-specific markers.
Heparin-binding peptide amphiphile has been widely used for angiogenesis.
Heparin is a highly sulfated glycosaminoglycan and is able to bind many growth
factors that promote vessel generation including vascular endothelial growth
factor and fibroblast growth factor 2 through the heparin-binding domains. Self-
assembled nanostructure forms in a few seconds by mixing a solution of peptide
amphiphile designed to bind heparin and a solution of heparin with angiogenic
growth factors. Upon changes in the solution pH or the addition of ions with
opposite charges to the peptide amphiphile, the peptide amphiphile molecules
become charged in aqueous solution and self-assemble into

β

-sheet cylindrical
nanostructures [45]. The addition of heparin to the peptide amphiphile eliminated
the charges on the peptide amphiphile molecules and triggered the formation of

β

-
sheet nanostructure, in which the fatty acid tails become hidden in the core and the
peptide segments aggregate through hydrogen bonding. As shown in Figure 4.5,
this nanostructure was shown to stimulate extensive new blood vessel formation on
rat cornea in an in vivo angiogenesis assay [46]. The structure has also been shown
to facilitate islet transplantation [47] with nanogram amounts of growth-factor
proteins, which otherwise cannot induce any detectable angiogenesis.

β