Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States of America.
Department of Materials Science & Engineering, Carnegie Mellon University, Pittsburgh, PA, United States of America.
Biofabrication. 2022 Mar 16;14(2). doi: 10.1088/1758-5090/ac58be.
Here we report the 3D bioprinting of a simplified model of the heart, similar to that observed in embryonic development, where the heart is a linear tube that pumps blood and nutrients to the growing embryo. To this end, we engineered a bioinspired model of the human heart tube using freeform reversible of embedding of suspended hydrogels 3D bioprinting. The 3D bioprinted heart tubes were cellularized using human stem cell-derived cardiomyocytes and cardiac fibroblasts and formed patent, perfusable constructs. Synchronous contractions were achieved ∼3-4 days after fabrication and were maintained for up to a month. Immunofluorescent staining confirmed large, interconnected networks of sarcomeric alpha actinin-positive cardiomyocytes. Electrophysiology was assessed using calcium imaging and demonstrated anisotropic calcium wave propagation along the heart tube with a conduction velocity of ∼5 cm s. Contractility and function was demonstrated by tracking the movement of fluorescent beads within the lumen to estimate fluid displacement and bead velocity. These results establish the feasibility of creating a 3D bioprinted human heart tube and serve as an initial step towards engineering more complex heart muscle structures.
在这里，我们报告了一种简化的心脏 3D 生物打印模型，类似于胚胎发育过程中观察到的心脏，即线性管状结构，用于将血液和营养物质泵送到生长中的胚胎。为此，我们使用自由形态可逆嵌入悬浮水凝胶 3D 生物打印技术，设计了一种类人心脏管的生物仿生模型。使用人源干细胞来源的心肌细胞和心脏成纤维细胞对 3D 生物打印的心脏管进行细胞化，形成有功能的、可灌注的结构。在制造后约 3-4 天实现了同步收缩，并能维持长达一个月。免疫荧光染色证实了具有较大、相互连接的肌节肌钙蛋白阳性心肌细胞网络。通过钙成像评估了电生理学特性，证明了沿心脏管的各向异性钙波传播，传播速度约为 5cm/s。通过跟踪管腔内部荧光珠的运动来估计流体位移和珠体速度，证明了收缩性和功能。这些结果确立了创建 3D 生物打印人类心脏管的可行性，并为构建更复杂的心肌结构迈出了最初的一步。
