Biomedical Engineering Reference
In-Depth Information
peroxides and free radicals that can damage all components of the cell, includ-
ing proteins, lipids and DNA. Inflammation involves the production of cytokines
including tumor necrosis factor-alpha (TNF-
ʱ
) and interleukin-1
ʱ
/
ʲ
, and recruit-
ment of inflammatory cells including monocytes and macrophages that are capa-
ble of secreting MMPs involved in matrix degradation. Both oxidative stress and
inflammation can trigger cell death by mechanisms of apoptosis or necrosis, impli-
cating these processes as important considerations when delivering cells in inject-
able hydrogels to the site of tissue injury.
In view of these considerations, various strategies by means of functionaliza-
tion or loading of the hydrogel with anti-oxidants or anti-inflammatory agents and
receptor blocking agents against oxidative stress and/or inflammation were devel-
oped [
171
-
174
]. A notable study in this direction is the development of thermo-
sensitive chitosan hydrogel conjugated covalently with glutathione, a well-known
anti-oxidant peptide molecule [
171
]. This functionalized hydrogel with anti-oxi-
dant property are capable of scavenging reactive oxygen species (ROS) including
oxygen radicals (superoxide and hydroxyl radicals) and was shown to enhance the
survival of cardiomyocytes in the presence of hydrogen peroxide (H
2
O
2
) inducing
oxidative stress [
171
]. Similarly, ferulic acid has been incorporated into the chi-
tosan-gelatin-glycerophosphate hydrogel [
172
] or poly (anhydride-ester) nanogel
[
173
] to improve the ROS scavenging capacity. Although H
2
O
2
induces oxidative
stress, it has been used as oxidant in the oxidative coupling reaction in the enzy-
matically cross-linked material systems such as HA-Tyr and Gtn-HPA, and it was
found that the HRP-catalyzed cross-linking mechanism utilizing very low amount
of H
2
O
2
in the oxidative coupling reaction preconditioned the NSCs encapsulated
in 3-D Gtn-HPA hydrogel and enhanced the oxidative stress resistance and sur-
vival of these cells, which might be potentially applied for neural regeneration
[
100
]. Some biopolymers also possessed natural antioxidant capability. One exam-
ple is the polymer pullulan, a carbohydrate glucan, known to exhibit potent anti-
oxidant capabilities, and was recently demonstrated in a study that pullulan-based
hydrogels were effective in delivery of MSCs and enhanced survival and engraft-
ment in a high ROS environment in an ischemic excisional wound model in mouse
[
175
].
Towards this end, the development of hydrogels that can modulate the tissue
environment for enhanced survival and engraftment of the exogenous stem cells
delivered, or even recruit endogenous adult stem cells to the tissue site of injury, is
most likely to improve the outcome of the regenerative therapy.
8 Conclusions and Perspectives
Hydrogel-based culture platforms, coupled with advanced hydrogel designs and
fast-evolving microtechnologies, have the greatest potential in constructing com-
plex artificial stem cell microenvironments. Specific bioactive niche components
may be incorporated into the microenvironment to modulate and manipulate stem
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