Exploring the role of biological factors in skeletal muscle tissue engineering

A number of conditions both congenital and acquired, such as volumetric muscle loss (VML) and muscular dystrophy can be treated through skeletal muscle tissue engineering. To optimize regeneration in skeletal muscle tissue constructs, the appropriate biological factors with properties such as increasing differentiation and proliferation, aiding in satellite cell activation, improving cell survival and inducing angiogenesis should be used in conjunction with taking into consideration and manipulating the effects that certain systems such as the immune system and the gut microbiome have on skeletal muscle regeneration. These biological factors include IGF-1, VEGF, HGF, myostatin inhibitors, PDGF-B, FGF-2 (also known as bFGF), insulin, and androgens. In skeletal muscle tissue engineering, these biological factors stimulate the utilized cell sources (myoblasts and satellite cells) and injured skeletal muscle tissue to promote regeneration. The purpose of this review is to discuss the specific effects of these biological factors on the utilized cells and their usage in skeletal muscle tissue engineering. The effects that the aforementioned systems have on skeletal muscle regeneration and potential methods to manipulate these systems for improved regeneration will also be discussed. The paper will also highlight the challenges associated with the use of these biological factors. The use of bacteriophages to modulate the levels of gut bacteria that influence muscle regeneration, as well as incorporating polarized M2 macrophages into in vitro tissue constructs to blunt host immunosurveillance mechanisms are proposed, which do not yet appear in the scientific literature.