Journal: Frontiers in Physiology

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

doi: 10.3389/fphys.2018.01130

Figure Lengend Snippet: 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.

Article Snippet: Biomimetic in vitro skeletal muscle disease models employing patient-derived human myoblast lines may therefore provide a higher predictive capability than rodent in vivo models.

Techniques: Construct, Migration, Selection, Transplantation Assay, Cell Differentiation, Control, Muscles

Journal: Frontiers in Physiology

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

doi: 10.3389/fphys.2018.01130

Figure Lengend Snippet: Envisioned future of skeletal muscle tissue engineering—a suggested workflow. This schematic presents a skeletal muscle tissue engineering workflow including stage-specific experimental considerations. Initially, the compatibility of biomaterials with potent myogenic cells has to be evaluated. This first step also involves the decision whether the cells will be cultured and grown in a 2D (monolayer on a pliant matrix) or 3D (encapsulation into a pliant matrix) environment. This still represents a static cell culture, where only the first steps in the SMTE approach are addressed. Evaluation of the biophysical matrix properties, biocompatibility and effects of the biomaterial on cell proliferation/differentiation can be evaluated via this process. The second step involves dynamic culture of the evaluated biomaterial and cells, where the main consideration is which stimulation strategy will be implemented into the culture system—ranging from mechanical to electrical stimulation or a combination of both. The third step addresses the functional analysis of the engineered muscle construct via twitch force measurements. At this point, contractile muscle constructs can furthermore be tested for their response to drugs with known effects, which is a prerequisite for later application of engineered muscle tissue in drug screening studies. An ideal setup would involve co-cultures to engineer muscle tissue with built-in vascular and neuronal structures to further enhance muscle maturity and contractility. After successful in vitro evaluation, the final step is the translation into animal models to test for the contribution of the engineered muscle to myogenesis and regeneration in healthy and/or diseased muscle. Ultimately, the knowledge gained from in vivo experiments can also be transferred back to in vitro setups for the generation of disease models.

Article Snippet: Biomimetic in vitro skeletal muscle disease models employing patient-derived human myoblast lines may therefore provide a higher predictive capability than rodent in vivo models.

Techniques: Cell Culture, Encapsulation, Functional Assay, Construct, Drug discovery, In Vitro, In Vivo