“9.61x6.69” b2815 Tissue Engineering and Nanotheranostics
Engineering Approaches for Creating Skeletal Muscle 19
Much like mechanical strain, electrical fields are able to cause
changes in endothelial cell behavior and preferential alignment. When
human umbilical vein endothelial cells (HUVECs) were exposed to
100–300 mV/mm DC fields, they responded with elongation and
aligned along a vector perpendicular to the applied field.^72 This rea-
lignment of the cells was found to be VEGFR dependent.^72 Along
with the morphological changes, the electrical stimulation caused an
increased release of VEGF from the HUVECs.^72 Fields with strengths
less than 100 mV/mm did not have as profound of an effect on cells,
but the effect was still statistically significant.^72 In general, electrical
stimulation led to increased endothelial cell orientation and increased
VEGF production, both of which are beneficial for angiogenesis.
As their primary role in the body is electrical signal transduction,
it would make sense that electrical stimulation would have an effect
on neurons. However, electrical stimulation alone has not been
enough to cause changes in neurite outgrowth.^73 PC12 cells grown
on collagen-coated culture plastic was stimulated with indium tin
oxide electrodes with a 100 Hz alternating signal generating 50, 100
or 200 mV/mm oscillating fields.^73 While simple electrical stimula-
tion was not able to cause any significant effect in cell behavior, it had
a strong effect on the cells when the culture was supplemented with
nerve growth factor (NGF).^73 It was determined that the electrical
stimulation with NGF could increase average neurite length in cells.^73
Optimum effect was reached with field strength of 100 mV/mm and
100 ng/mL NGF supplementation.^73 In summary, electrical stimula-
tion can be beneficial to neurite development of neurons. However,
addition of other factors like NGF are necessary to see the full effect.
4.2.5. Oxygen tension
In terms of stem cells used in tissue engineering, oxygen tension also
may play a role in development. It has been previously shown that low
oxygen content can preserve MSCs in an undifferentiated state, and a
more recent study shows that hypoxia has a similar effect on muscle
SCs. Decreased oxygen led to faster proliferation, and still allowed
SCs to be differentiated in induction media.^74
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