Molecular Gels for Tissue Engineering - Soft Fibrillar Materials: Fabrication and Applications - page 133

molecular gels. This review discusses the strategies to design gelators and explore
the present and potential applications of molecular gels in tissue engineering. A
list of the gelators discussed in this review can be found in the Appendix at the end
of this review.

4.4.1
Peptide-Based Molecular Gels

Peptide-based hydrogels have been widely studied for tissue engineering to pro-
mote the delivery and the survival of cells for tissue regeneration in injured areas.
Arginine-glycine-aspartic acid (RGD), for instance, is a motif that contributes
to cell adhsesion to extracellular matrix (ECM) and was originally included in
conventional chemical gels to promote cell adhesion and differentiation. There
are generally two types of peptide-based molecular gels: self complementary
alternating amphiphilic peptides [33] and peptides amphiphiles. The ionic self-
complementary alternating amphiphilic peptides system designed by Zhang and
co-workers takes advantage of the self-assembly of these peptides in solution
into structures such as -helices, and coiled coils [17, 33, 34]. Since

synthetic hydrogels are extremely hydrophilic and resist the absorption of pro-
teins and the proper exposure of the specific peptide domains for seeded cells to
bind to [35], the hydrophobic interactions maintaining the peptide-based molec-
ular gels designed above are able to promote proper incorporation and exposure
of specific peptide domains on the gels. Stuppy and co-workers have taken an-
other approach by covalently linking amino acids to other molecules such as
an alkyl chain or an aromatic group, and have designed a family of peptides
named peptide amphiphiles to make certain functional peptide-based hydrogels
[36-38].
Peptides of alternating hydrophilic and hydrophobic amino acid residues tend to
form a

β -sheets, α

-sheet structure. For that reason, alternating amphiphilic-peptide polymers
and oligopeptides can adopt

β

-sheet structures or aggregates. Hierarchical struc-
tures such as tapes, ribbons, fibrils, and fibers can be formed on top of the

β

-sheet
structures under physiological conditions. EAK 16 (AEAEAKAKAEAEAKAK), for
example, a peptide with alternating hydrophilic and hydrophobic residues in a
region of a yeast protein, was found to form an unusual stable macroscopic mem-
brane spontaneously [39]. In the case of arginine-alanine-aspartate (RAD), which
mimics the motif RGD, this has alternating repeat units of positively charged
residues (arginine) and negatively charged residues (aspartate) separated by hy-
drophobic residues (alanine) [33]. These peptides have two surfaces when they form
into a

β

-sheet: the polar surface is composed of ionic side chains and the non-polar
surface is made up of alanine residues. These ionic side chains are complementary
to one another to form a one-dimensional nanostructure. The amino acids bearing
opposite charges give rise to ionic pairs, which serve as non-covalent interactions
to maintain the

β

-sheet structure. The formation and stability of the final assembly
is facilitated by intermolecular hydrogen bonding, intermolecular ionic bonds,

β