Tissue Engineering And Nanotheranostics

b2815 Tissue Engineering and Nanotheranostics “9.61x6.69”

2 Tissue Engineering and Nanotheranostics

and it is hoped that regenerating or replacing the muscle tissue will

mitigate these negative outcomes. Of the many opportunities for

intervention, two classes are particularly prominent in the clinic. The

first of these is wasting disorders, which result in muscle loss on a

large scale throughout the body. The second is volumetric muscle loss

(VML), which can be the result of injury or surgery.

1.1. W asting Diseases and Disorders

There are several diseases and disorders that can cause muscular wast-

ing, including a class known as muscular dystrophy (MD). Duchenne’s

muscular dystrophy (DMD), for example, is caused by a defective

DMD gene, which encodes the protein dystrophin. Dystrophin is an

integral member of the dystrophin-associated protein complex, which

connects a myocyte’s actin cytoskeleton to the extracellular matrix

(ECM).^1 It is thought that this connection shields the sarcolemma

from excessive stress, especially during eccentric contraction.2,

In DMD, mutations result in a non-functional dystrophin protein,

which is unable to fulfill its mechanical role. This, in turn, is thought

to lead to higher sarcolemmal stresses, eventually resulting in elevated

intracellular Ca2+.^4 Although work is still underway to understand all

of the underlying processes, the end result on the organ level is myo-

cyte death, fat deposition, and fibrosis. Due to these changes to the

muscle tissue, patients with DMD experience pronounced muscle

weakness. The diagnosis is generally made at a young age as the chil-

dren are unable to keep up with their peers, and most of them are

confined to wheelchairs by the age of 10.5,6 Although treatment for

DMD patients is improving, many succumb to respiratory or cardiac

complications by the age of 20. DMD is recessive, and because the

DMD gene is located on the X chromosome, it affects men more

often than women. Female carriers can experience similar symptoms

to males in some cases.^7 In 2015, it was determined that the com-

bined prevalence of DMD and Becker’s muscular dystrophy (BMD)

(another prevalent dystrophy) among boys aged 5–9 was about 2 in

10,000.^8 Although DMD is the most common, there are many other

dystrophies. BMD is very similar to DMD, and results in partially

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