Peptidic Hydrogels - In-Situ Gelling Polymers: For Biomedical Applications - page 124

amino acid characteristics are taken full advantage of in creating a rich library of
peptide hydrogel sequences with drastically varied chemistries.
The piece-by-piece amino acid chemical connection during peptide synthesis,
combined with the range of amino acid properties, gives peptide hydrogels tunable
characteristics and capabilities for a multitude of chemical, material or biological
uses. After molecular peptide synthesis, many peptide hydrogels are constructed
with solution assembly mechanisms and can be made in situ with the introduction
of the proper trigger, or change in environment, such as changes in temperature,
pH, or ionic concentration. [ 1 , 2 , 6 , 10 - 18 ]. While the starting peptide sequences
are straightforward to synthesize, the resulting structures after triggered molecular
assembly can take on secondary, tertiary or quaternary structures like peptides and
proteins in nature.
There are many different types of peptide hydrogels presently being researched,
from those created from short peptide sequences that exist as conjugates with
other synthetic polymer constructs [ 11 , 14 , 15 , 19 - 27 ] to hydrogels made from
high molecular weight, protein-like molecules [ 17 , 28 - 35 ]. The focus in this
chapter will be mainly on shorter peptide sequences that can be triggered in situ
to form higher order structure and, consequently, form supramolecular, physical
hydrogels [ 10 , 13 , 36 - 38 ]. These sequences are shorter than typical proteins, and
their solution self-assembling capabilities to form higher order, intra- and inter-
molecular structures can result in a variety of hydrogels with beneficial and inter-
esting material properties such as shear-thinning capabilities for injectable solid
behavior for therapy delivery [ 1 , 13 , 20 , 36 , 39 - 45 ].
Peptide hydrogel structural hierarchy sets them apart from synthetic polymer
hydrogels. Peptides, and their resultant shapes after folding and intermolecular
assembly, are categorized by four different levels of structure: primary, second-
ary, tertiary, and quaternary. With adaptable and precise synthesis methods, pep-
tide structures have the ability to achieve naturally-inspired structures such as
those observed in known protein crystal structures as well as completely new, de
novo designed structures by proper design of a peptide sequence. Starting with
a designed sequence, peptides can be constructed faithfully into a final, desired
structure and function. Additional functional groups or amino acids can be added,
exchanged, or removed from a known natural or designed sequence to change the
final material structure, the kinetics of intermolecular assembly, the material prop-
erties or other behaviors (e.g. biological properties) of the resultant peptide hydro-
gel. The molecular assembly processes designed into peptide hydrogels readily
can be made to be efficient, fast, and easily modified based on the desired hydro-
gel performance environment. From synthesis to assembly, a considerable amount
of organization of intermolecular and intramolecular interactions is needed. Each
structure and its final properties as a hydrogel is defined and affected by these
interactions.
Regardless of final hydrogel structure, the driving forces of peptide assem-
bly into hierarchical structures and materials are physical, non-covalent interac-
tions such as hydrogen bonding and ˀ -stacking, hydrophobic and van der Waals