Optimizing C2C12 myoblast differentiation using polycaprolactone-polypyrrole copolymer scaffolds.

Advancements in tissue engineering and biomaterial development have the potential to provide a scalable solution to the problem of large-volume skeletal muscle defects. Previous research on the development of scaffolds for skeletal muscle regeneration has focused on strategies for increasing conductivity, which has improved satellite cell attachment and differentiation. However, these strategies usually increase scaffold stiffness, which some studies suggest may be detrimental to myoblast development. In this study, the polymers polypyrrole (PPy) and polycaprolactone (PCL) were synthesized together into a copolymer (PPy-PCL) designed to increase scaffold conductivity without significantly influencing stiffness. Different scaffold groups were fabricated via electrospinning, characterized, and assessed for their suitability for myoblast proliferation and differentiation. The groups included an aligned and random iteration of pure PCL, 10% PPy-PCL, 20% PPy-PCL, and 40% PPy-PCL. Only the 40% PPy-PCL group had a measureable conductivity, and the addition of PPy-PCL had no significant effect on the stiffness of the scaffolds. The PPy-PCL copolymer significantly increased the attachment of C2C12 myoblasts as compared to pure PCL scaffolds, but the concentration of PPy-PCL did not significantly alter cell attachment. In addition, scaffolds with PPy-PCL promoted myoblast differentiation to a greater extent than scaffolds made of PCL as measured by fusion index and number of nuclei per myotube. Aligned scaffolds were superior to random scaffolds in almost all measures. These results suggest that conductivity may not be the key factor in improving skeletal muscle scaffolds. Instead, cell attachment and aligned guidance cues may have a greater impact on myoblast differentiation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 220-231, 2019.