Molecular Gels for Tissue Engineering - Soft Fibrillar Materials: Fabrication and Applications - page 146

is formed by subsequent catalytic dephosphorylation of 2. Both compounds 1
and 3 were found to gelate solvents at 2 wt% and at pH 5-7. Incorporation of
nucleobases was shown to have a protective effect on the dipeptide. Biostability
analysis with proteinase K demonstrated that the presence of nucleobases of-
fers the peptides certain degrees of resistance to enzymatic digestion, suggesting
nucleobase incorporation to be an effective approach for improving the biosta-
bility of peptide-based hydrogelators in vitro and in vivo . Aside from biostability,
the biocompatibility of these nucleopeptides was also investigated. Cell viabilities
were maintained at near 100%, indicating the absence of detrimental cellular
damage. A simple wound-healing assay, as seen in Figure 4.9, was also con-
ducted to investigate the ability of the hydrogelators to maintain cell-matrix
interaction. The lack of inhibitory effect on cell migration, coupled with the high
cell viabilities shown in the in vitro cytotoxic study, suggest promising potential
for such a hydrogel system to be used as a cell culturing platform in tissue
engineering.
Other than peptides, nucleobases or nucleosides can also be incorporated into
lipid-based gelators. A glycosyl-nucleoside lipid LMWG synthesized by Godeau
et al . with double-click chemistry were found to be capable of self-assembling spon-
taneously into supramolecular structures that gel both water and chloroform [82].
This gelator consisted of a lipidic chain, a thymidine, and a

- d -glucopyranoside,
covalently linked together by 1,2,3-triazole bridges. The presence of thymidine
is essential for gel formation as an analog without the nucleoside segment was
unable to gelate water. The importance of nucleosides in stabilizing the gel's
supramolecular structural network was indicated by the lower ultra-violet epsilon
values observed, which suggested the occurrence of

β

stacking events between
the nucleosides. In addition to the presence of nucleosides, the gelation property
of this glycosyl-nucleoside lipid also depends on the nature of the lipid part and the
types of chemical linkage present in the molecule.
Nucleobase incorporation offers additional control over the mode of
supramolecular self-assembly of steroids. Typically, a steroid gel comprises
multiple mesogenic units, stacked in a helical and columnar fashion to form a
central core, with functional groups substituted at the steroid C3 position sticking
outward, resembling a spiral staircase. Introduction of uracil to C3 by Snip et al .
led to the discovery of an excellent gelator [83]. Higher gel stability, as indicated by
a lower sol-gel transition temperature, was obtained with the uracil-substituted
steroid as compared to an analog connected to a uracil moiety with its NH
group substituted with a methyl, suggesting the role of inter-gelator hydrogen
bonding, in addition to aromatic stacking between extended steroid planes, in
stabilizing the organogel. The stability and morphology of the organogel can
be altered by the addition of polynucleotides [84]. A mixture of polynucleotides
with uracil-substituted steroids was found to possess higher gelation ability.
Interestingly, the mixture of polyadenylic acid with steroid formed a well-developed
tape-like fibrous network twisted in a right-angle fashion, while the mixture of
polycytidylic acid with steroid produced only a fibrous network with no helical
structure. This observation demonstrated the effects of complementary interbase

π - π