Matrix-mediated formation & innervation of skeletal myotubes

The field of tissue engineering utilizes combinations of cells, biomaterials, and therapeutic molecules in order to generate therapies and better understand the emergent behaviors involved in tissue formation and diseases. One of the goals of tissue engineering is to be able to recapitulate the in vivo microenvironment of cells in vitro. As such, a lot of attention has been focused on the development of materials that are able to present various aspects of the cell microenvironment so that the specific roles of each property can be probed. The overall goal of this thesis is to develop advanced matrices for the formation and innervation of skeletal muscle. This thesis discusses the development of advanced bioactive matrices to be able to study the role of a variety of extracellular matrix properties on skeletal muscle formation and, ultimately, innervation. The role of polysaccharide mediated pores will be investigated in Chapter 2. Myogenic differentiation will be decoupled from matrix stiffness in an aligned microchanneled matrix in Chapter 3. In Chapter 4, the role of matrix stiffness on neural organoid development and, its ability to innervate and control the actuation of skeletal muscle will be investigated. The results of this thesis will be useful in developing a better understanding of how matrix properties mediate skeletal myotube formation and innervation. Additionally, the results will provide a method to be able to study the emergent behaviors involved in myotube formation and neuromuscular diseases