Graphene SU-8 platform for enhanced cardiomyocyte maturation and intercellular communication in cardiac drug screening

Cell culture substrates designed for myocardial applications are pivotal in promoting the maturation and functional integration of cardiomyocytes. However, traditional in vitro models often inadequately mimic the diverse biochemical signals and electrophysiological properties of mature cardiomyocytes. Herein, we propose the application of monolayer graphene, transferred onto SU-8 cantilevers integrated with a microelectrode array, to evaluate its influence on the structural, functional, and electro-mechano-physiological properties of cardiomyocytes. The monolayer graphene, prepared using chemical vapor deposition, is adeptly transferred to the target substrates via thermal release tape. The electrical conductivity of these graphene-enhanced SU-8 substrates is about 1600 S/cm, markedly surpassing that of previously reported cell culture substrates. Immunofluorescence staining and Western blot analyses reveal that the electrically conductive graphene significantly enhances cardiomyocyte maturation and cardiac marker expression compared to bare SU-8 substrates. Cardiomyocytes cultured on graphene-transferred substrates exhibit conduction velocity approximately 3.4 times greater than that of the control group. Such improvements in cardiac marker expression, mechano-electrophysiological performance lead to better responsiveness to cardiovascular drugs, such as Verapamil and Isoproterenol. While the graphene monolayer does not fully replicate the complex environment found in native cardiac tissue, its use on SU-8 substrates offers a feasible approach for accelerating cardiomyocyte maturation and facilitating drug screening applications.