Molecular Gels for Tissue Engineering - Soft Fibrillar Materials: Fabrication and Applications - page 134

hydrophobic interactions, overlapping interactions between individual peptides,
and coordination of intermolecular ionic bonds by salt ions [33].
Unlike self-complementary alternating amphiphilic peptides, peptide am-
phiphiles, or peptide-based molecules that can self-organize into nano-fibers, were
designed in such a way to ensure that they first assembles into one-dimensional
nanostructures under physiological conditions and then into three-dimensional
networks possessing a strong hydrophobic nature. A typical peptide amphiphile is
composed of four domains: a hydrophobic tail, a -sheet-forming segment, charged

group(s), and bioactive epitope(s). The first three domains ensure the amphiphilic
nature of the gel and the molecular packing within a cylindrical geometry formed
by the gelator molecules, which allows for high density of biological signals to
present on the fiber surface. The last domain is variable and is used to display
different peptides of interest on the surface of the three-dimensional network
and to carry out designed functions such as enhancing cell adhesion [24]. The
applications of these two types of peptide-based gels in tissue engineering are
discussed below.

β

4.4.1.1 Self-Complementary Alternating Amphiphilic Peptides
Self-assembling peptide nano-fiber scaffolds (SAPNS) designed by the Zhang
group used alternating positively and negatively charged l -amino acids to generate
a scaffold when they are exposed to physiological solutions such as saline, culture
media, and cerebrospinal fluid [34]. With the hamster optic tract bridge model as
a model for injuries, treatments with SAPNS was shown to reconnect brain tissue
after acute injury [34]. Newly grown axons were found to reconnect to the damaged
tissues and facilitate the functional return of vision. With over 99% water content,
SAPNS is highly hydrated and can fill an irregular injured area before it forms a
molecular nano-fiber scaffold. For this reason, SAPNS was proposed as a candidate
for tissue regeneration in irregular injured areas such as those found in damaged
optic nerves.
The scaffolds made by biopolymer materials like polylactic acid are composed
of very fine nanofibers in the range of 10-100 μ m [40]. Self-assembling peptides
such as RAD16-I were interweaved to make a scaffold, and its ability to pro-
mote rat liver progenitor cell differentiation and function were evaluated [41].
Compared to scaffolds made of fibers whose diameters are in the micrometer
range, the scaffolds made of RAD16-I peptide, possessing fibers 10-20 nm in
diameter, are thinner by 3 orders of magnitude than conventional microfibers,
enabling the diameter of the fibers to be close to that of the cells for im-
proved cell encapsulation. The scaffold was also demonstrated to promote the
proliferation of normal progenitor cells and enhance cell differentiation. Cells in
adherent cultures divide exponentially but lack the expression of surface mark-
ers for mature hepatocytes; in contrast, liver progenitor cells in amphiphilic
peptide-based scaffold cultures show non-exponential cell growth but display a
characteristic hepatocyte morphology and generate cells with mature hepatocyte
markers [41].