Aminated graphene nanosheet stimulates the maturation of hiPSCs-derived cardiomyocytes in vitro and enhances their survival in vivo

Graphene-mediated niches with excellent electroconductibility, good flexibility and convenient modification play a central role in manipulating the cardiogenesis of stem cells. Herein, the graphene derivative matrix of aminated graphene (G-NH₂) was synthesized as a substrate niche to modulate cardiac differentiation of human induced pluripotent stem cells (hiPSCs). The conductivity of G-NH₂ matrix was close to that of native myocardium while the surface roughness of G-NH₂ matrix was much low to present a suitable interface for the adhesion of hiPSCs. The G-NH₂ matrix effectively elevated the maturation of hiPSCs-derived cardiomyocytes based on the evaluation of cardiomyocyte contraction, sarcomere patterns and length, and the content of NCAD (N-cadherin). The molecular mechanism of cardiomyocyte maturation was highly associated with the signaling pathway of PDGF-β. The mature cardiomyocytes derived from G-NH₂ were transplanted into the groin of immunodeficient mice to reveal the better survival and rapid angiogenesis. More importantly, in situ injection into rat hearts of differentiated mature cardiomyocytes exhibited the better performance on residence, survival and proliferation. Consequently, we created an instructive stem cell niche of G-NH₂ matrix that can electrically stimulate various cellular behaviors of hiPSCs in vitro, and the enhanced maturation of hiPSCs-cardiomyocytes manifests favorable activity and function in vivo.