Natural polymeric hydrogel evaluation for skeletal muscle tissue engineering

Although skeletal muscle has a remarkable ability to repair/regenerate after most types of injuries, there is limited regeneration after volumetric muscle loss (VML). A number of scaffold materials have been used in the development of grafts to treat VML, however, there is still a need to better understand the most appropriate material with regards to its ability to maintain mechanical integrity while also supporting myogenesis. Five commonly used natural polymeric materials (Collagen I, Agarose, Alginate, Fibrin, and Collagen Chitosan) used in skeletal muscle tissue engineering grafts were evaluated for their mechanical properties and myogenic capacity. Rheological properties, water absorption rates, degradation stability, tensile characteristics, and the ability to support in vitro myogenesis were compared in all five materials. Collagen, Collagen Chitosan, and Fibrin demonstrated high elasticity and 100% stretch without failure, Agarose was the most brittle (20% max stretch), and Alginate demonstrated poor handleabilty. While Collagen was supportive of myogenesis, overall, Fibrin demonstrated the highest myogenic potential as indicated by the earliest and highest increases in myogenin and myosin heavy chain mRNA in satellite cells along with the most extensive myotube development as evaluated with immunohistochemistry. The findings herein support the notion that under the conditions used in this study, Fibrin is the most suitable scaffold for the development of scaffolds for skeletal muscle tissue engineering. Future studies are required to determine whether the differences in mechanical properties and myogenic potential observed in vitro in the current study translate to better skeletal muscle development in a VML injury model.