Supramolecular Soft Biomaterials for Biomedical Applications - In-Situ Gelling Polymers: For Biomedical Applications - page 106

class of supramolecular hydrogels which have desirable properties such as sen-
sitivity to the environment, facile formation processes and an almost universal
mode of attachment. Here, we will discuss the role of hydrogen bonding on the
different peptides and polymers that can form supramolecular hydrogels. It is well
known that peptides can self-assemble through hydrogen bonding [ 9 , 10 ]. With
self-assembly, the molecules will either co-assemble in a random manner or self-
sort to form an aggregated structure. With growing applications in drug delivery
and tissue engineering areas, there exists a need to control the manner in which
the molecules self-assemble. The use of peptides as hydrogelators in the forma-
tion of the hydrogel can potentially improve the biocompatibility of the hydrogel
as peptides occur naturally in the human body, making it more suitable for any
biomedical application than any other synthetic materials. Morris et al. has devel-
oped a pH-based system that is able to control the self-sorting of naphthalene-
functionalized dipeptide hydrogelators to form self-assembled networks in water
[ 11 ]. By hydrolysing glucono- ʴ -lactone (GdL) to gluconic acid, they were able
to gradually modify the pH level in the system, leading to the formation of the
hydrogels. The pH triggered methodology introduced in this paper utilizes kinetic
self-sorting, which ensures that a self-sorted local energetic minimum is reached
due to its fast formation. The advantage of this technique is that it enables the
preparation of complex structures that would otherwise be difficult to achieve by
conventional chemical reactions. Responsive photo-luminescent dipeptide gels
were reported by Bardelang and colleagues [ 12 ]. Quantum dots (QD) have been
extensively explored for bioimaging applications [ 13 , 14 ]. The incorporation of
QDs into hydrogels has previously been used for the development of materials
for sensing and drug delivery applications [ 15 ]. Here, QDs were incorporated into
soft supramolecular materials, and with the use of ultrasound, QD-gel nanocom-
posites were prepared. In a typical experiment, the mixture of dipeptide with hex-
ane suspensions of CdSe/ZnS QDs covered with trioctylphosphine oxide (TOPO)
as surface ligands forms gels in minutes with the use of ultrasound (Fig. 1 a-c).
The gels are luminescent under UV light and can revert into the sol state by the
application of heat. The ability of these small peptides to generate supramolecular
hydrogels demonstrates great promise for biological applications for which QDs
have also shown a great potential such as biochemical sensing. In another report,
Yang et al. reported the use of enzymes as a tool to regulate both the formation
and the dissociation of self-assembled nanostructures and its subsequent transi-
tion into a supramolecular hydrogel [ 16 ]. This work utilised a kinase/phosphatase
switch to regulate the pentapeptidic hydrogelator, Nap-FFGEY by controlling its
phosphorylation and dephosphorylation. When the kinase is added to Nap-FFGEY,
the self-assembling property of the hydrogel is disrupted. But with addition of a
phosphatase, the self-assembling property of the hydrogel is restored (Fig. 2 ). The
in vivo study done showed that with the subcutaneous injection of the phosphate
in the mice, a supramolecular hydrogel is able to form. Given its biocompatibil-
ity, this suggests the possibility of using minimally invasive methods to introduce
the hydrogel into the body as well as a better and more precise way to control
the hydrogel. Other self-assembled peptide hydrogels have been investigated for