Maturation and synchronisation of heart cells, including cardiomyocytes and fibroblasts, are essential to develop functional biomimetic cardiac tissues for regenerative medicine and drug discovery. Synchronisation of cells in the biomimetic cardiac tissue requires the structural integrity and functional maturation of cardiomyocytes with other cell types. However, it is challenging to synchronise the beating of macroscale cardiac tissues and induce maturation of cardiomyocytes derived from stem cells. Here, we developed a simple assembly technology to modulate cell–cell interactions by combining layer-by-layer (LBL) deposition and centrifugation of cells with collagen type I to control cell–cell interactions for the preparation of cardiac macro tissues (CMTs). We found that maturation of cardiomyocytes in CMTs was largely enhanced by growth factors FGF-4 and ascorbic acid, but synchronisation of cardiac beating required LBL deposition of cardiomyocytes and cardiac fibroblasts in addition to the growth factors during the maturation process. Our findings have important implications because incorporation of cardiac fibroblasts into the cardiomyocyte layer is a prerequisite for synchronised beating of macroscale cardiac tissues in addition to growth factors to facilitate maturation of stem cell-derived cardiomyocytes.

中文翻译：

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使用逐层沉积来调节心肌细胞和成纤维细胞的相互作用有助于心脏宏组织的同步化。

心脏细胞（包括心肌细胞和成纤维细胞）的成熟和同步对于开发功能性仿生心脏组织以进行再生医学和药物开发至关重要。仿生心脏组织中细胞的同步需要心肌细胞与其他细胞类型的结构完整性和功能成熟。然而，同步化大型心脏组织的搏动并诱导源自干细胞的心肌细胞的成熟是具有挑战性的。在这里，我们开发了一种简单的组装技术，可以通过层与层（LBL）沉积和I型胶原蛋白的离心分离相结合来控制细胞之间的相互作用，从而调节细胞与细胞之间的相互作用，从而制备心脏宏组织（CMT）。我们发现生长因子FGF-4和抗坏血酸大大增强了CMT中心肌细胞的成熟，但是心脏搏动的同步性要求在成熟过程中除了生长因子外还需要心肌细胞和心脏成纤维细胞的LBL沉积。我们的发现具有重要意义，因为将心肌成纤维细胞掺入心肌细胞层是同步刺激大型心脏组织跳动的先决条件，此外还需要促进干细胞衍生的心肌细胞成熟的生长因子。