Myocardial infarction is caused by the complete occlusion of coronary artery, leading to loss of downstream myocardium. The lost cardiomyocytes are gradually replaced by fibrous scar tissue, which usually leads to ventricular remolding and arrhythmogenic inhomogeneous electrophysiological distributions. Despite the improved therapeutic strategies, post-infarction heart failure and malignant arrhythmias remain therapeutic challenges. Cardiac engineering of patches and tissues is a promising option to restore infarcted hearts. By seeding cardiac cells onto scaffolds and nurturing their growth in vitro, engineered tissues are expected to generate natural heart structures and functions and can be transplanted to replace fibrous scars. In facts, electrophysiological heterogeneities in the infarct-related region have been identified as determinants of post-infarction arrhythmias. Thus, substantially homogenized electrophysiological properties of engineered tissues is essential for normal beating rhythm and the avoidance of the occurrence of arrhythmias.
Here, super-aligned carbon nanotube sheets (SA-CNTs) are applied to promote electrophysiological homogeneity for in vitro cultured cardiac cells. We found that SA-CNTs can interact with cells and induce the orientation of the growing CMs, and influent the expression and distribution of gap junction protein connexin-43 (CX43), which is essential for synchronous contraction of all adjoining CMs. CMs cultured on SA-CNTs show spontaneous synchronized regular beating rhythms. Which can be explained as (1) accelerated electrophysiological maturation of neonatal rat CMs and reduced beat-to-beat APD (action potential duration) dispersion enabled the cells to generate regular and stable beats; (2) improved intercellular coupling through the increased and lateralized CX43 expression allowed adjacent cells to synchronously contract; (3) reduced cell-to-cell APD dispersions prepared all cells, even those isolated far from each other, to be simultaneously excited upon electrical impulse. Furthermore, SA-CNTs provided an efficient pathway for rapid electronic propagation to all ready-to-excite cells, with stable conductivity and pacing threshold. Therefore, SA-CNT-based cardiac tissue patches achieved the synchronized contraction of all cultured cells with reduced electrophysiological heterogeneity, which provided a potential method to restore the infarcted myocardium and alleviate the electrophysiological heterogeneity in infarct-related regions.