Molecular Gels for Tissue Engineering - Soft Fibrillar Materials: Fabrication and Applications - page 140

supramolecular structures when placed in a solvent. This phenomenon is in
fact not uncommon in nature and can be observed in a variety of chemical and
biological systems. Examples of such molecular aggregates and assemblies include
monolayers, micelles, liposomes, and bilayers. These structures have successfully
found a multitude of clinical applications over the years. Liposomes, for instance,
which are self-folded lipid bilayer vesicles with hydrophilic internal core, have
been employed successfully for intravenous administration of amphotericin B
to combat systemic fungal infections, demonstrating prolonged circulation time
and reduced toxicity [60]. Recent attempts at delivering nucleotide sequences with
self-assembled liposomes for gene therapy have also shown promising results.
Aside from forming simpler two- and three-dimensional aggregates like micelles
and liposomes, several lipids, for example, cholesterols and fatty acids, possess the
ability to self-assemble into more complicated tubules and ribbon-like structures,
which could interconnect via non-covalent interactions, namely hydrogen bonding,
π

aromatic stacking, and van der Waals interaction, and form matrix architec-
tures capable of trapping solvents, leading to the formation of physical molecular
gels [59].
Diacetylene-containing phospholipid 1,2-bis(10,12-tricosadiynoyl)- sn -glycero-3-
phosphocholine (DC 8,9 PC) is able to assemble into hollow cylindrical microtubules
having a diameter of 0.5 μ m and a length of 50-200 μ m with one or more bilay-
ers spontaneously [61]. These microcylinders were employed successfully for the
encapsulation and release of growth factors for nerve regeneration and osteogenic
differentiation [62, 63]. An equimolar mixture of DC 8,9 PC and 1,2-bis(dinonanoyl)-
sn -glycero-3-phosphocholine was found to be able to promote the formation of
lipid nanotubules with sub-100 nm diameter (a value that is 10 times smaller
than the lipid tubules described in previous literature), which transform into
helical ribbons upon heating that interconnect in three dimensions and form a
physical gel [64]. Detailed analysis of the mechanisms and the properties of the
nanotubules formed indicated that the transformation of nanotubule to twisted
ribbon is accompanied by an inversion of the circular dichroism signal, which
implies that the gelation process involves significant molecular reorganization [65].
With a water content of more than 98%, these lipid-based molecular hydrogels
are suitable scaffolding materials for tissue engineering [59]. By combining the
abilities of such lipid tubules to release encapsulated growth factors and generate
biocompatible hydrogels, it is therefore possible to fabricate growth factor-laden
tissue engineering scaffolds that can simultaneously support cell proliferation and
guide cellular differentiation.
Although the use of lipid-based molecular gels in tissue engineering remains
largely unexplored, a successful attempt of achieving cellular growth and at-
tachment on lipid-based molecular gel has been reported. Lukyanova et al . have
developed a microporous, biodegradable, and non-toxic organogel cell culture plat-
formwith the use of a fatty acid, 12-hydroxystearic acid (HSA), as the organogelator
[5]. Two different organic solvents, namely caprylic/capric triglyceride and soy-
bean oil, were gelled with HSA using the particulate leaching method to generate
micropores on the scaffolds to facilitate nutrient distribution and enhance cell

- π