Biomedical Engineering Reference
In-Depth Information
What are the biological implications of using microfabricated hydrogels to fine-
tune the stem cell environment? Firstly, there is an overall improvement of mass
transport to the cell-hydrogel construct due to a smaller diffusion distance [
160
].
Micropatterned hydrogels also offer protection from fluid shear stress in micro-
fluidic perfusion culture systems that are meant to augment mass transport [
161
].
One can also achieve better control over heterotypic cell-cell interactions by being
able to position two or more different cells types at defined locations. For instance,
patterning stellate cells together with ESC can enhance their hepatic differentia-
tion capacity [
162
]. In another configuration, tracks of cell-loaded fibrin hydrogels
were patterned at different distances to investigate interactions between endothe-
lial cells and MSCs in vasculogenesis [
145
].
One of the most notable biological effects enabled by microfabricated hydro-
gels is perhaps the spatial patterning of stem cell differentiation by creating jux-
taposed differential 3D microenvironments. Qi et al., encapsulated mouse EBs
in spatially asymmetrical hybrid hydrogel, where half of the EB was exposed
to gelatin and the other half exposed to PEG. Owing to the differences of the
different hydrogel microenvironments in directing vascular differentiation, they
could spatially direct vasculogenesis in the EBs [
163
]. Khetan and Burdick
employed a different strategy to create an asymmetrical 3D hydrogel micro-
environments by performing UV photolithography on a primary HA hydrogel
crosslinked by enzymatic reactions. Human MSCs could remodel and spread
in areas that were not exposed to UV but remained rounded in UV exposed
regions. This led to the spatially patterning of osteogenic-adipogenic differentia-
tion fates of the hMSCs [
164
].
6 Complexity of Tissue Environment
The tissue environment is dynamic in nature and present spatial and temporal het-
erogeneity in the cellular and matrix composition, and this dynamics is highly
impacted by the type and state of the tissue environment, whether in healthy or
injured/diseased state [
165
]. The level of oxygenation and nutrient supply, oxida-
tive stress and inflammation present in the injured/diseased tissue environment are
likely to affect the mobilization of stem cells from the stem cell niche as well as
the survival and engraftment of exogenous stem cells, and are therefore important
considerations when applying hydrogels to recruit or deliver stem cells to the site
of tissue injury [
165
]. In this aspect, modifying the tissue environment by strate-
gies such as pre-conditioning, anti-inflammation and/or anti-oxidative injury may
be helpful in the transplanted cell survival and engraftment. Modulating the cel-
lular processes and guiding the development of the neotissue formation in parallel
with the changes of the tissue environment would be pivotal in determining the
outcome of the regenerative therapy.
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