Directed differentiation of human pluripotent stem cells to kidney organoids brings the prospect of drug screening, disease modelling and the generation of tissue for renal replacement. Currently, these applications are hampered by organoid variability, nephron immaturity, low throughput and limited scale. Here, we apply extrusion-based three-dimensional cellular bioprinting to deliver rapid and high-throughput generation of kidney organoids with highly reproducible cell number and viability. We demonstrate that manual organoid generation can be replaced by 6- or 96-well organoid bioprinting and evaluate the relative toxicity of aminoglycosides as a proof of concept for drug testing. In addition, three-dimensional bioprinting enables precise manipulation of biophysical properties, including organoid size, cell number and conformation, with modification of organoid conformation substantially increasing nephron yield per starting cell number. This facilitates the manufacture of uniformly patterned kidney tissue sheets with functional proximal tubular segments. Hence, automated extrusion-based bioprinting for kidney organoid production delivers improvements in throughput, quality control, scale and structure, facilitating in vitro and in vivo applications of stem cell-derived human kidney tissue.

人类多能干细胞定向分化为肾脏类器官带来了药物筛选、疾病建模和肾脏替代组织生成的前景。目前，这些应用受到类器官变异性、肾单位不成熟、低通量和规模有限的阻碍。在这里，我们应用基于挤出的三维细胞生物打印来快速、高通量地生成具有高度可重现的细胞数量和活力的肾脏类器官。我们证明手动生成类器官可以用 6 孔或 96 孔类器官生物打印代替，并评估氨基糖苷类的相对毒性，作为药物测试的概念证明。此外，三维生物打印能够精确操纵生物物理特性，包括类器官大小、细胞数量和构象，随着类器官构象的改变，每个起始细胞数的肾单位产量显着增加。这有助于制造具有功能性近端管状段的均匀图案化肾组织片。因此，用于肾脏类器官生产的基于挤出的自动化生物打印技术可以改善通量、质量控制、规模和结构，促进干细胞衍生的人类肾脏组织的体外和体内应用。