Biomedical Engineering Reference
In-Depth Information
5 Microfabricated Hydrogels
Microtechnologies including microfluidics and micropatterning are fast-evolving
technologies that have become an integral part of constructing stem cell micro-
environments using hydrogels. Besides modulating hydrogel micro-architecture
(e.g. porosity) and composition by changing the polymer or cross-linking chemis-
try, hydrogels can be tuned by using microtechnologies to control their meso-scale
structures. This allows one to reduce the feature size of the hydrogel structures
being formed, which in turn translates to more precise control over the cell locality
in 3-D space.
There are two general approaches to constructing a microfabricated cellu-
lar environment using hydrogels. A more simple approach is to first fabricate the
hydrogel-based micro-structure before seeding cells onto it. For instance, hydro-
gel microwells are frequently constructed for the formation of ESC embryoid bod-
ies (EBs) with controllable sizes [
148
]. 3D projection stereolithography as well
as two-photon laser scanning photolithography (TPLSP) have been used to gener-
ate hydrogel scaffolds of defined architecture, porosity and interconnectivity [
149
,
150
]. The advantage of decoupling hydrogel microfabrication from cell seeding is
that we do not impose any restriction on the fabrication conditions (e.g. pH, tem-
perature). However, control over the positioning of cells is much poorer since cells
are stochastically located within the hydrogel micro-architecture.
The more commonly used approach to have more control over cell locality
in 3D space is to generate cell-laded hydrogel micro-structures. Cells are sus-
pended in the prepolymer before crosslinking is induced to “freeze” the cells in
3D space. UV polymerization of poly(ethylene glycol) diacrylate (PEGDA) is one
of the most commonly used method. UV light can be spatially directed at sub-
millimeter resolution onto a PEGDA solution impregnated with cells to induce
crosslinking via photolithography [
151
] or TPLSP [
152
]. PEGDA-based hydro-
gels can be further modified to include bioactive active ligands, such as RGD
peptides, to improve the bio-functionality or bio-compatibility of the hydrogels
[
151
]. Photopolymerized hydrogels can also be used in conjunction with other
microtechnologies to have an additional degree of control over the 3D multicel-
lular construct. Albrecht et al. used dielectrophoresis (DEP) patterning to control
the relative positions of two or more cell types before immobilizing them in 3D
space by photopolymerized PEG hydrogel [
153
]. Photopatterned hydrogels are
often used to immobilize cells within microfluidic systems [
154
,
155
]. In another
example, a 3D network of carbohydrate glass is printed within cell-laded PEG
hydrogels to serve as a vascular network, which can be independently populated
with endothelial cells [
156
]. Other than PEGDA, a myriad of photopolymerizable
hydrogels have been developed. Typically, these hydrogels are the polymerizable
variants of common hydrogels, such as hyaluronic acid (HA) [
157
], polyvinyl-
alcohol (PVA) [
158
], and gelatin [
159
].
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