Nano/microscale topographically designed alginate/PCL scaffolds for inducing myoblast alignment and myogenic differentiation

For regenerating skeletal muscle tissue, cell alignment and myotube formation in a scaffold are required. To achieve this goal, various studies have focused on controlling the myoblast orientation by manipulating the topographical structures of scaffolds. In the present study, a combined process involving electrospinning and three-dimensional (3D) printing was used to obtain a hierarchical structure consisting of microscale and nanoscale topographical structures by using alginate nanofibers and a polycaprolactone (PCL)-fibrillated microstrut. In the structure, a micropatterned PCL strut, which was obtained using 3D printing and a leaching process supplemented with a sacrificial material, was employed for not only enhancing the mechanical stability, but also inducing myotube formation, while highly aligned alginate nanofibers fabricated using a modified electrospinning process facilitated myoblast attachment and alignment. The cell orientation and myotube formation of C2C12 cells cultured in the 3D hierarchical structure were significantly better than those of two controls (alginate-coated PCL strut and alginate nanofiber-deposited PCL strut, not fibrillated). These results confirm that the hierarchical scaffold has immense potential as a biomaterial for muscle-tissue regeneration.