Through the creation of a 2D and 3D model of human skeletal muscle, structural and functional data can be collected. The initiation mechanisms of Facioscapulohumeral muscular dystrophy’s (FSHD), a genetic dystrophy that causes increasing muscle degeneration, can be identified through the creation of a reproducible model. Here, we share how the details of various facets and properties of the 2D and 3D design affect a human skeletal muscle in vitro. The specifics of how various extracellular matrix play a role in 2D patterning of skeletal muscle is discussed alongside the intricacies of creating a hydrogel based 3D skeletal muscle bundle. While the models have not yet reached optimal design compared to other techniques, this design is close to reaching a state to produce collectible data.