Biomedical Engineering Reference
In-Depth Information
4 Hydrogel Microenvironments for Construction
of Stem Cell Niche
Hydrogels serve as well-controlled 3-D microenvironment systems for incor-
poration of biochemical and biophysical cues for presentation to stem cells in a
spatiotemporally controlled manner, which allows researchers to deconstruct com-
ponents of the stem cell niche, and to decipher the underlying mechanisms that
regulate stem cell proliferation, differentiation and migration [
44
,
45
]. In recent
years, new variables in hydrogel design, propelled by new tools and techniques,
to incorporate the necessary cues and components to influence stem cell behavior,
have greatly enhanced our understanding of the stem cell microenvironment, and
its relevance for tissue regeneration [
3
].
4.1 Hydrogels as ECM-Mimetic
The native ECM is a 3-D network composed of matrix proteins (e.g. collagen,
fibrin, laminin) that provides structural support framework for anchorage of cells
and naturally sequesters soluble factors. Hydrogels are highly-hydrated networks
of natural or synthetic polymers which resemble the naive ECM, and are therefore
ideal biomaterial scaffold for culture of stem cells [
44
]. Hydrogels can be derived
from natural materials including collagen [
98
,
99
], gelatin [
100
-
102
], fibrin [
103
],
dextran [
104
], hyaluronic acid (HA) [
105
-
107
] and keratin [
108
]. Since native
tissue ECM is likely to compose of many types of matrix proteins, hydrogels
made from decellularized tissue matrix represent an attractive alternative [
109
,
110
]. However, the application of these natural hydrogels is often hampered by
the batch variability and difficulty in the control of material properties includ-
ing degradation, mechanics and bioactivity. These limitations may be overcome
through synthetic modification of these natural materials [
100
,
105
] or the use of
purely synthetic materials such as PEG that allow decoration of ECM ligands to
mimic the native ECM and to support cell adhesion [
111
,
112
]. Among the various
hydrogels, HA-based hydrogels are commonly used for stem cell culture, and have
been shown to support self-renewal and differentiation of hESCs [
107
]. In the
use of synthetic hydrogels such as the PEG for stem cell culture, integrin-specific
adhesion ligands can be incorporated to the hydrogel network, and differential
integrin activation was demonstrated to modulate ESC fate decisions [
113
,
114
].
4.1.1 Matrix Architecture
Hydrogel network and matrix architecture is an important property that is required
to ensure proper nutrient transport for optimal cell growth, and to allow space for
cell movement and to generate cell-cell interactions [
42
,
44
]. The native ECM is
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