ABSTRACT
This chapter discusses the biological processes involved in skeletal muscle repair and regeneration, the use of tissue engineering technologies to reconstitute bioengineered muscle tissues in vitro and in vivo, and challenges and future directions in the field of regenerative muscle therapy. 22.1 Biology of Skeletal Muscle RegenerationSkeletal muscle is the most abundant tissue in our body comprising nearly 45% of the total body weight. The main characteristic of muscle tissue is its ability to contract by coordinated activity of aligned bundles of multinucleated and striated muscle cells called myofibers. The contractile function of muscle is supported by a
network of nerves, blood vessels, and extracellular matrix. When functioning properly, skeletal muscle has the capacity to mount a robust regenerative response to exercise or injury by sequentially preparing, and then repairing, the area of tissue damage; a process that involves a pool of endogenous progenitors, termed “satellite cells.” In this section of the chapter, we will discuss important biological aspects of skeletal muscle development and repair, including skeletal myogenesis, muscle regeneration in acute trauma and chronic degenerative disease, and the roles that satellite cells, non-myogenic cell types, extracellular matrix, and mechanical loading play in muscle regeneration. 22.1.1 Overview of Skeletal MyogenesisSkeletal myogenesis (Fig. 22.1), i.e., the formation of skeletal muscle, is a fundamental and complex process that occurs during both muscle development and repair. During early development, a major portion of skeletal muscle in the body of vertebrates, including the trunk and limbs, is derived from the paraxial mesodome of the somite [25]. This process is driven by primary progenitor cells that co-express two paired-box transcription factors, Pax3 and Pax7 [61], which control expression of a family of myogenic regulatory factors (MRF), including myoblast determination protein (MyoD), myogenic factor 5 (Myf5), muscle-specific regulatory factor 4 (MRF4), and myogenin, all of which coordinately initiate and regulate the myogenic program [17]. Pax3 and Pax7 are also expressed in satellite cells, a group of small mononuclear progenitor cells located between the basal lamina and sarcolemma of individual myofibers in postnatal skeletal muscle [22]. Satellite cells are responsible for maintenance, growth and regeneration of adult skeletal muscle [19]. Upon activation by exercise or injury, satellite cells proliferate and either commit to myogenic differentiation, yielding a pool of mononucleated myoblasts, or forestall differentiation and self-renew, ultimately returning to quiescence. Similar to their embryonic ancestors, myogenic differentiation of satellite cells relies on the coordinated expression of the four MRFs [22].
