Electrically conductive graphene/polyacrylamide hydrogels produced by mild chemical reduction for enhanced myoblast growth and differentiation.

Graphene and graphene derivatives, such as graphene oxide (GO) and reduced GO (rGO), have been extensively employed as novel components of biomaterials because of their unique electrical and mechanical properties. These materials have also been used to fabricate electrically conductive biomaterials that can effectively deliver electrical signals to biological systems. Recently, increasing attention has been paid to electrically conductive hydrogels that have both electrical activity and a tissue-like softness. In this study, we synthesized conductive graphene hydrogels by mild chemical reduction of graphene oxide/polyacrylamide (GO/PAAm) composite hydrogels to obtain conductive hydrogels. The reduced hydrogel, r(GO/PAAm), exhibited muscle tissue-like stiffness with a Young's modulus of approximately 50kPa. The electrochemical impedance of r(GO/PAAm) could be decreased by more than ten times compared to that of PAAm and unreduced GO/PAAm. In vitro studies with C2C12 myoblasts revealed that r(GO/PAAm) significantly enhanced proliferation and myogenic differentiation compared with unreduced GO/PAAm and PAAm. Moreover, electrical stimulation of myoblasts growing on r(GO/PAAm) graphene hydrogels for 7days significantly enhanced the myogenic gene expression compared to unstimulated controls. As results, our graphene-based conductive and soft hydrogels will be useful as skeletal muscle tissue scaffolds and can serve as a multifunctional platform that can simultaneously deliver electrical and mechanical cues to biological systems.

STATEMENT OF SIGNIFICANCE: Graphene-based conductive hydrogels presenting electrical conductance and a soft tissue-like modulus were successfully fabricated via mild reduction of graphene oxide/polyacrylamide composite hydrogels to study their potential to skeletal tissue scaffold applications. Significantly promoted myoblast proliferation and differentiation were obtained on our hydrogels. Additionally, electrical stimulation of myoblasts via the graphene hydrogels could further upregulate myogenic gene expressions. Our graphene-incorporated conductive hydrogels will impact on the development of new materials for skeletal muscle tissue engineering scaffolds and bioelectronics devices, and also serve as novel platforms to study cellular interactions with electrical and mechanical signals.