Supramolecular Soft Biomaterials for Biomedical Applications - In-Situ Gelling Polymers: For Biomedical Applications - page 105

can be categorized in numerous ways depending on the type of polymer and their
structural characteristics. Chemically crosslinked hydrogels are formed by polymer
chains linked permanently by non-reversible covalent bonds. This causes the hydro-
gels to be brittle, at times opaque and not having the self-healing property when the
network is disrupted. These covalent bonds can be made using various reactions
such as Michael type addition, Schiff base formation, thiol-ene photopolymeriza-
tions, free radical photopolymerisation, enzyme-triggered reactions and “click” reac-
tions. Chemical crosslinking can be modulated in order to sufficiently modify the
mechanical properties of hydrogels and it has been frequently used when tough and
stable hydrogels are desired. Unlike traditional chemistry which relies on covalent
interactions, supramolecular chemistry focuses on weaker and reversible non-cova-
lent interactions between molecules. A supramolecular polymer can be defined as an
ordered array of repeating units of monomeric building blocks formed by reversible
and directional non-covalent interactions [ 3 , 4 ]. Supramolecular polymers can form
through various intermolecular interactions such as hydrogen bonding, metal-ligand
complexation, hydrophobic forces, van der Waals forces, ˀ - ˀ interactions and elec-
trostatic effects, together with their synergetic interactions. Important concepts that
have been demonstrated by supramolecular chemistry include molecular self-assem-
bly, folding, molecular recognition, host-guest chemistry, mechanically-interlocked
molecular architectures, and dynamic covalent chemistry. Highly complex func-
tional materials can be built from seemingly simple modular blocks. Supramolecular
chemistry offers possibilities whereby modular structures self-assemble into intri-
cate structures. The extension of these systems beyond the level of the individual
molecule relies on several key non-covalent interactions leading to a directed self-
assembly step. Here, we can observe the development of structures from the pri-
mary molecular level to the secondary polymeric level and further to the tertiary
networked structure. This network structure is the classical example of a hydrogel
structure [ 5 - 7 ]. While offering the dynamic modulation of the intrinsic properties of
the materials, these materials can also be assembled into novel supramolecular struc-
tures such as hydrogels, micelles and vesicles [ 8 ]. In this review, we will highlight
several examples of how the supramolecular hydrogels are prepared through hydro-
gen bonding, ionic and associative interactions, host-guest complexation and metal-
ligand complexation. These interactions have extremely high biomedical relevance
as will be explained in the review. The literature reviewed here is not meant to be
exhaustive but rather meant to be a primer of this research area.
2 Preparation of Supramolecular Hydrogels
2.1 Hydrogen Bonding
Hydrogen bonding is one of the main driving forces that direct the self-assembly
of molecules, and it plays important roles in numerous biomedical applications.
In particular, hydrogen bonding serves as the basis for the formation of a large