b2815 Tissue Engineering and Nanotheranostics “9.61x6.69”
14 Tissue Engineering and Nanotheranostics
recovery of grip strength.^55 A similar study using a variety of cells,
including fibroblasts, endothelial cells, and myoblasts, also showed
similar results in terms of vascularization.^56 It is possible that the use
of multiple cell types, or at least prior induction of stem cells along
different lineages, may be necessary to obtain the complexity needed
for formation of both vasculature and myofibers.
All of these approaches, both in vitro and in vivo, show some
promise. However, to precisely control the outcomes of these types of
experiments, many engineering factors must be considered. Cells are
responsive to both chemical and physical stimuli, opening many pos-
sible routes to modifying their behavior. These engineering factors are
summarized in Table 1 and also described below.
4.2.2. Scaffolding materials
Fully formed myofibers are very specifically arranged with a high
degree of alignment within skeletal muscle tissue, so it comes as no
surprise that beneficial effects can be generated by providing the cells
with a patterned substrate.^57 It has been discovered that aligned
Table 1. Over view of engineering factors for tissue engineering of skeletal muscle.
Various factors leading to improved differentiation or function are highlighted.
Myoblasts Endothelial cells Neurons
Substrate
properties
12 kPa stiffness
nanofibers +
microchannels →
alignment and
differentiation58,59
200 Pa → vasculature
2500 Pa →
proliferation^60
7 kPa stiffness +
microchannels →
proliferation^63
Mechanical
stimulation
Cyclic stretching or
static strain →
alignment and
differentiation64,66
Cyclic stretching →
perpendicular
alignment and
angiogenesis^67
Equibiaxial stretching
→ neurite out-
growth^70
Electrical
stimulation
0.2 V/m 1 Hz
4 ms → increasing
contractility^71
100–300 mV/mm
DC field →
perpendicular
alignment and
angiogenesis^72
NGF necessary + 100–
200 mV/mm at 100
Hz (sinusoid) →
neurite elongation^73
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