The Importance of Biophysical and Biochemical Stimuli in Dynamic Skeletal Muscle Models

Classical approaches to engineer skeletal muscle tissue based on current regenerative and surgical procedures still do not meet the  desired outcome for patient applications. Besides the evident need to create functional skeletal muscle tissue for the repair of  volumetric muscle defects, there is also growing demand for platforms to study muscle-related diseases, such as muscular  dystrophies or sarcopenia. Currently, numerous studies exist that have employed a variety of biomaterials, cell types and strategies  for maturation of skeletal muscle tissue in 2D and 3D environments. However, researchers are just at the beginning of understanding  the impact of different culture settings and their biochemical (growth factors and chemical changes) and biophysical cues (mechanical properties) on myogenesis. With this review we intend to emphasize the need for new in vitro skeletal  muscle (disease) models to better recapitulate important structural and functional aspects of muscle development. We highlight the  importance of choosing appropriate system components, e.g., cell and biomaterial type, structural and mechanical matrix properties  or culture format, and how understanding their interplay will enable researchers to create optimized platforms to investigate  myogenesis in healthy and diseased tissue. Thus, we aim to deliver guidelines for experimental designs to allow estimation of the  potential influence of the selected skeletal muscle tissue engineering setup on the myogenic outcome prior to their implementation.  Moreover, we offer a workflow to facilitate identifying and selecting different analytical tools to demonstrate the successful creation of  functional skeletal muscle tissue. Ultimately, a refinement of existing strategies will lead to further progression in understanding  important aspects of muscle diseases, muscle aging and muscle regeneration to improve quality of life of patients and enable the  establishment of new treatment options.