Biomedical Engineering Reference
In-Depth Information
7 Advanced Hydrogel Systems for Stem Cell Delivery
To better tailor stem cell therapies to the dynamic complexity of the tissue envi-
ronment [
165
], whether in healthy or injured state, multi-phased and multi-func-
tional hydrogel systems are being developed for stem cell delivery [
43
,
44
,
47
].
7.1 Multi-phased Hydrogels
The spatial organization of cells and biomolecules and the relative distribution in
the hydrogel network are important in guiding the cellular processes including cell
proliferation, differentiation and tissue morphogenesis towards the de novo forma-
tion of complex hierarchical tissue. Utilization of techniques including co-culture/
co-encapsulation of different cells [
147
], photopatterning [
166
], and multi-phased/
multi-layered hydrogel systems [
167
,
168
] may aid in the spatially controlled
organization of multiple cell types and bioactive molecules and facilitate the pro-
gress towards better organization and functionality of newly-generated complex
tissue in vivo.
A notable study in this direction is the development of a three-layer PEG-based
hydrogel to direct differentiation of single population of MSCs into multiple,
spatially distinct phenotypes within the 3-D scaffold [
167
]. The three-layer PEG
hydrogel with chondroitin sulfate and MMP-sensitive peptides in the top layer,
chondroitin sulfate in the middle layer, and hyaluronic acid in the bottom layer,
creates the zonal organization (superficial, transitional and deep zones) of the
native-like articular cartilage. This study suggests the possibility of regenerating
complex tissues from a single stem cell population by spatially varying the bioma-
terial composition to direct stem cell differentiation into multiple distinct pheno-
types. Other studies utilize bilayered hydrogel matrices for co-culture of stem cells
with committed somatic cells to direct stem cell differentiation [
169
,
170
].
Towards this end, design of multi-phased hydrogel systems that allow directed
stem cell differentiation to multiple lineages or co-culture/co-encapsulation of
multiple cell types or biomolecules may improve the spatial organization of the
newly generated tissue in vivo.
7.2 Multi-functional Hydrogels
During tissue injury, oxidative stress and inflammatory processes are always pre-
vailing, making the tissue environment at the injury sites highly unfavorable for
the introduction of therapeutic cells including stem cells. Oxidative stress is asso-
ciated with increased production of oxidizing species including the production of
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