“9.61x6.69” b2815 Tissue Engineering and Nanotheranostics
Engineering Approaches for Creating Skeletal Muscle 3
functional dystrophin. Therefore, the symptoms of BMD are generally
not as serious as those of DMD. Other notable dystrophies include
myotonic, congenital, Emery–Dreifuss, facioscapulohumeral, limb-girdle,
distal, and oculopharyngeal. Other conditions of clinical concern are
cachexia and sarcopenia. Cachexia is a loss of body weight due to
chronic disease, such as cancer. Much of this lost weight is the result of
muscle wasting.^9 Sarcopenia is age-related muscle loss and weakness.^10
Each of these diseases and disorders are systemic, affecting the entire
body through faulty genetics or disease (although the primary symp-
toms may be more specific). Because of this, treatment strategies will
differ from muscle loss caused in only one location.
1.2. V olumetric Muscle Loss
Significant amounts of muscle tissue can be lost through either trau-
matic injury or surgery. Often classified as VML, such a wound can be
very difficult for the body to heal.^11 Severe injuries such as those sus-
tained in vehicular accidents or combat that cause substantial damage
to the soft tissues are a major source of this problem. Bullet wounds
can also cause VML injury, both in combat and in civilian conflict.
Because of the inherent nature and unpredictability of such events,
patients sustaining such traumatic wounds are generally handled on a
case-by-case basis.^12 Various surgical procedures can also result in mus-
cle loss, such as tumor ablation and limb salvage. These procedures are
intended to remove soft tissue sarcomas in muscle, and necessitate
injury to the affected organ.11,13 VML has a large potential for negative
impact on a patient’s quality of life. Even if the wound is closed
quickly and without infection, permanent deformity and disability may
result. Ideally, wound healing in muscle proceeds in a similar manner
to other connective tissues. The mechanical forces tear apart the tis-
sue, rupturing the myoblasts and capillaries in the wound area.14,
A hematoma forms as the body attempts to contain the injury.
Inflammation follows over the course of several days, and immune
cells are recruited to remove debris and prevent spread of any infec-
tion.^15 To prevent further mechanical trauma and restore integrity to
the tissue, fibroblasts begin depositing dense ECM within the
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