Peptidic Hydrogels - In-Situ Gelling Polymers: For Biomedical Applications - page 140

mimetic 3D structures are also highly desirable to better understand the intricate
physical networks that cells need for growth and replication. The inherent fibril-
lar network of the gels provides a similar ECM-like structure on which cells may
anchor, as well as a hydrogel porous enough for growth factors and important bio-
chemical signals to diffuse through [ 11 , 34 , 35 , 37 , 114 - 117 ]. Some of the many
encapsulated cell lines include MSCs [ 73 , 98 ], endothelial cells [ 31 ], chondrocytes
[ 118 ], or fibroblasts [ 99 ]. The Schneider and Pochan groups have successfully
encapsulated MSCs in a 3D environment as seen in Fig. 10 , showing homogenous
distribution of cells with desired cell density and spacing—a feature unavailable in
2D growth environments [ 73 , 97 ]. Additionally, the 3D environment also provides
the starting structure for the cells to deposit ECM [ 73 , 97 ] with the opportunity to
observe in vivo-like behavior recreated in the 3D peptide hydrogel construct.
Because of the nature-inspired origins of peptide hydrogels, the natural degra-
dation of peptide hydrogels is also an important property. This is a feature that
is inherent in peptide hydrogels that is less characteristic in polymeric hydrogels.
Because of the amino acid origins of peptide hydrogels, there is natural degrada-
tion [ 19 , 98 , 115 ] that occurs from enzymes secreted by the body in vivo, without
major immune reactions [ 19 , 37 , 43 , 61 , 67 , 68 ]. Macrophages and neutrophils are
cells typically associated with an immune response in the body that are observed
to have little or no reaction when cultured with hydrogels [ 70 , 84 , 101 ] or in vivo
[ 84 ]. The interaction of enzyme with peptides to affect hydrogel properties is not
surprising, since one of the possible triggers for self-assembly is the introduction
of enzymes to linear peptides as seen by the Xu and Ulijn groups [ 26 , 47 ]. In deg-
radation, however, instead of assembling short peptides into fibrils and hydrogels,
the hydrogels are being broken down into smaller pieces through enzymolysis
[ 115 , 119 , 120 ]. When designing the peptide sequences, specific segments that act
as reaction substrates for enzymes such as MMP13 [ 119 ] or MMP2 [ 120 ] can be
incorporated into the initial peptide synthesis.
The bulk of this chapter explained the hierarchical structures of peptide
sequences and hydrogels constructed with physical solution assembly in an
attempt to discuss the fundamental properties of peptide hydrogels and the molec-
ular foundations thereof. Peptide sequences can be categorized with primary, sec-
ondary, tertiary, and/or quaternary structures, spanning the molecular level through
the hydrogel network. Peptide hydrogels are great candidates in the ever-grow-
ing field of biological and medical applications. Not only are peptide sequences
easy to synthesize, the synthesis process allows for customizable molecular and
material features such as peptide length, amino acid substitution, gelation time,
mechanical properties (e.g. stiffness), or functionalities for cell targeting or encap-
sulations. The natural cytocompatibility and degradability of peptides make pep-
tide hydrogels great candidates for cell encapsulation, 3D growth environments,
tissue scaffolding, and injectable payload delivery. Peptide hydrogels are not
only able to successfully encapsulate cells, but also able to encapsulate proteins
and drugs of varying charge, size, or hydrophobicity. Unlike traditional liquid-
based delivery systems that rely on gelation after injection while simultaneously