Tissue Engineering And Nanotheranostics

“9.61x6.69” b2815 Tissue Engineering and Nanotheranostics

Engineering Approaches for Creating Skeletal Muscle 17

by periodic strain, although the differentiation was accompanied by a

decrease in proliferation.^65 Static strain has also been shown to have

beneficial effects on myoblast cultures, leading to enhanced myofiber

fusion.^66 Strain was applied to a 3D fibrin gel culture of C2C12 myo-

blasts for 6 days. Each day consisted of 6 h at 10% strain followed by

18 h at 3% strain. The stimulation also increased expression of crucial

markers like MyoG and desmin, and increased cell alignment parallel

to the strain direction.^66 In summary, both cyclic and static strains

have the potential to increase differentiation and fusion of myoblasts

into myofibers, although cyclic stretching may better mimic the

in vivo conditions.

Although endothelial cells are not primarily load-bearing cells in

the skeletal muscle, various researchers have found that they respond

to mechanical stretching. When BAECs were cyclically and uniaxially

stretched they aligned perpendicularly to the direction of stretch.^67

Some researchers suggest that this perpendicular orientation reduces

the strain on the cells.^68 Stretching the collagen gel on which the

BAECs were cultured was enough to increase the number of vascular

sprouts into the gel as much as vascular endothelial growth factor

(VEGF) treatment.^67 This response was determined to occur through

Rho-associated protein kinase (ROCK)-dependent pathways.^67

Interestingly, VEGF and cyclic strain had a negative interaction with

each other in the 3D environment, resulting in less sprouting than

when either was done alone.^67 Conversely, in a 2D monolayer environ-

ment, VEGF plus the stretching had an additive effect.^67 This points

to the necessity of testing both types of environments, as the 2D cul-

ture may not necessarily behave the same way as a 3D system. Overall,

mechanical stimulation was able to improve vascular sprouting.

Neurons are not typically thought of as being highly involved

with mechanical forces, however, they have the ability to be very

responsive to applied strain. It has been demonstrated that when neu-

rons are cultured in such a way that the nerve body and the axon are

attached to different, sliding surfaces, the axons can be lengthened by

slowly moving the surfaces apart.^69 This phenomenon is known as

axon stretch growth. The neurons could be stretched at 42 mm per

hour.^69 Therefore, neurons are definitely capable of compensating for

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