Peptidic Hydrogels - In-Situ Gelling Polymers: For Biomedical Applications - page 139

hydrogel. Peptide hydrogels can be introduced by injection [ 27 , 33 , 34 , 45 , 48 , 68 ,
72 ] or surgical placement [ 26 , 29 , 37 ]. While injection is a common delivery tac-
tic, most polymer material hydrogels being injected are liquids that are designed to
be crosslinked covalently in vivo [ 45 , 68 ]. This requires additional external stimuli
to trigger gelation after injection. For example, a gel pre-cursor is injected, and
gelation is then triggered using UV [ 105 , 106 ], a crosslinking chemical, or infrared
light [ 107 ]. Not only does external stimuli increase the possibility of contamina-
tion or side effects, these delayed crosslinking steps do not guarantee uniformity in
gel structures or payload distribution. In the cases when peptides are injected as a
liquid, usually a biological stimulus in vivo is used to cause desired secondary and
quaternary structure formation i.e. gelation. These gelation stimuli include using
body temperature [ 108 ], cell environments [ 15 , 55 ], or native enzymes [ 109 ].
An alternative to liquid injection that is made possible by some physical pep-
tide hydrogels is the idea of an injectable solid. The Pochan and Schneider groups
are able to take advantage of the structural organization of MAX gels to inject
solids that have already assembled because the hydrogels have shear-thinning
behavior and reheal at the cessation of shear forces. This advantage is the result
of the physical crosslinking of the hydrogel nanostructures, causing the hydrogel
to break up into smaller domains of intact gel when undergoing shear. Because
the system is not chemically cross-linked, when shear forces cease, the nanofibrils
remake physical crosslink contacts and do not need the introduction of another
trigger to reform a hydrogel network. As a shear-thinning and rehealing hydrogel
is injected through a syringe, only the hydrogel at the edges, along the surface of
the syringe, experiences shear, leaving the rest of the hydrogel intact. This creates
a plug flow of hydrogel [ 37 , 41 ]. The resultant plug flow allows the hydrogel to
protect payloads from shear and maintain the distribution and viability of cells,
drugs, or proteins encapsulated within [ 29 , 37 , 41 , 72 ].
Besides drugs and large molecules, peptide hydrogels are also used in the deliv-
ery of cells [ 41 , 43 , 45 , 73 , 96 - 99 ]. MSCs are encapsulated for injection in hopes
of influencing or better understanding stem cell differentiation, with the goal of
depositing the cells in a specific-cell type deficient area [ 73 , 97 , 98 ]. Instead of
encapsulating cells for cell growth, the Hartgerink group cultures ESCs and their
E 2 (SL) 6 E 2 GRGDS hydrogel separated by a permeable membrane [ 43 ]. The sep-
arated peptide hydrogels act as sponges, harnessing secreted growth factors and
secretomes from ESCs. Then, the protein-infused peptide hydrogels are injected in
vivo or used for tissue culture at a later time with concurrent release of or metabo-
lism of the infused ESC proteins.
In addition to delivery, peptide hydrogels are ideal for tissue scaffolding and
3D cell growth environments. 3D environments can be used to provide a work-
ing model of systems within the body that may be hard to observe and difficult to
mimic in vitro. Some of these systems include the culture of endothelial stem cells
[ 31 ], blood vessel formation [ 63 ], chondrocyte development [ 11 ], and stem cells
of many types [ 73 , 98 ]. 3D environments also provide a more natural environment
than 2D cell culturing methods with ability to control material details in 3D such as
morphology and matrix stiffnesses [ 1 , 61 , 110 - 113 ]. Extracellular matrix (ECM)