b2815 Tissue Engineering and Nanotheranostics “9.61x6.69”16 Tissue Engineering and Nanotheranosticsthat the effect of a soft substrate on endothelial cells comes from more
emphasis on the cell–cell junctions rather than substrate adhesions.
This seems to lead to the beginning of more stable vascular networks.
Neurons can rely on a number of factors to guide their direction
of regrowth. It has been shown many times that nanotopographies
or nanofibers have the potential to direct and enhance neuronal axon
growth.62,63 In a paper demonstrating the effect of substrate mechan-
ics on cell behavior, researchers showed that substrate stiffness can
have a large effect on both neurons and glial cells.^63 The substrates
were made out of a tunable poly(e-caprolactone) triacrylate (PCLTA)
polymer and patterned with various dimensions of microscale
grooves.^63 Rat PC12 pheochromocytoma cells, chosen to represent
neurons, were cultured on these substrates for up to 7 days.^63 It was
found that neuron proliferation was enhanced on substrates with a
lower stiffness of 7 kPa when compared to the substrates at 10 kPa.^63
Interestingly, rat Schwann cell precursor line cells (SpL201) pre-
ferred the higher stiffness.^63 It was proposed that, in the body,
Schwann cells may have a mechanical cushioning effect on the neu-
rons.^63 This leads to the possibility that the best approach for engi-
neering skeletal muscle involves choosing a particular order of
introducing cells to the culture to best utilize their stiffness and
other properties.
4.2.3. Mechanical stimulation
Numerous studies have been done on the effects of mechanical forces
on myoblasts and their precursors. The mechanical load is often
applied to a deformable substrate on which the cells are grown. Two
primary modes of uniaxial stretching have been investigated, cyclic
and static. It was discovered that a 10% periodic cyclic strain could
enhance the differentiation of human skeletal myoblasts, as demon-
strated by vast increases in miR-1, miR-133a, miR-206, and myo-
genic transcription factors Mef-2C.^64 The strain waveform of 10%
strain at 0.5 Hz was applied for 1 h at a time with 5 h in between each
session for 14 days.^64 Interestingly, another study has shown that
myogenic differentiation of bone-derived human MSCs was enhanced
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