Despite significant progress in the development of renal tissue, recapitulation of perfusable complex renal tubular tissue with clinically relevant cellular heterogeneity is still remaining a challenge. In this study, using coaxial 3D cell-printing technique, we present microfluidic hollow tubes to realize tubular/vascular renal parenchyma composed of renal tubular epithelial and endothelial cells, respectively. We developed a functional hybrid bioink that inherits microenvironments for vascularized native kidney tissue with rapidly crosslinkable character to optimize cell functionality and retain the predefined hollow tubular structure. In addition, the novel bioink and 3D coaxial cell-printing technique provided a complex tube with tunable feature of monolayer and bilayer structure across the length of printed tube. Through prototyping a vascularized renal proximal tubule-on-a-chip, we showed its applicability to novel microfluidic renal tissue models. The renal subcapsular transplantation of the hollow tubes showed a long-term graft survival with the therapeutic capability of the tubular constructs in in vivo model of renal disease, which serves their applicability in regenerative medicine.

中文翻译：

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晚期肾小管组织类似物的三维细胞打印。

尽管在肾组织的发育方面取得了显着进展，但具有临床相关细胞异质性的可灌注复杂肾小管组织的概括仍是一个挑战。在这项研究中，使用同轴3D细胞打印技术，我们提出了微流体空心管，以实现分别由肾小管上皮细胞和内皮细胞组成的肾小管/血管肾实质。我们开发了一种功能性混合生物墨水，该墨水继承了具有快速可交联特性的血管化天然肾脏组织的微环境，从而优化了细胞功能并保留了预定的中空管状结构。另外，新颖的生物墨水和3D同轴细胞打印技术提供了一种复杂的管，在整个打印管的长度上具有可调节的单层和双层结构特征。通过原型化血管化的肾近端小管上芯片，我们显示了其对新型微流控肾组织模型的适用性。中空管的肾囊下移植显示了长期的移植物存活，并且在肾病的体内模型中具有管状构建体的治疗能力，这使其在再生医学中具有适用性。