Figure 2.

Differences in experimental design of skeletal muscle tissue engineering approaches influence outcome. The choice of the biomaterial and its biophysical properties influence the TE construct in terms of cell adhesion, migration, morphology, proliferation, and differentiation. Notably, differentiation of muscle cells into contractile myofibers is highly dependent on factors such as matrix elasticity, porosity or the availability of growth factors within the construct. The selection of the appropriate cell type is of equal importance as it partially predetermines which scientific questions can be answered using a given SMTE approach. Thus, changing cell types within the same SMTE setup can increase its application range, from studies on different stages in myogenesis or disease modeling to transplantation or cellular gene therapy. Finally, application of external stimuli to cells embedded in biomaterials greatly enhances myogenic maturation. Patterning of the biomaterial via provision of defined topographical cues can drive cell differentiation and further enables control over cell/myofiber arrangement. As engineered muscles are required to create sufficiently large contractile forces upon transplantation, the importance of dynamic culture systems using such stimulation strategies has been unambiguously shown. GF, growth factors; ESCs, embryonic stem cells; iPSCs, induced pluripotent stem cells; MSCs, mesenchymal stem cells; SM interstitial cells, skeletal muscle interstitial cells.