Here, we introduce a facile, scalable engineering approach to enable long-term development and maturation of organoids. We have redesigned the configuration of conventional organoid culture to develop a platform that converts single injections of stem cell suspensions to radial arrays of organoids that can be maintained for extended periods without the need for passaging. Using this system, we demonstrate accelerated production of intestinal organoids with significantly enhanced structural and functional maturity, and their continuous development for over 4 weeks. Furthermore, we present a patient-derived organoid model of inflammatory bowel disease (IBD) and its interrogation using single-cell RNA sequencing to demonstrate its ability to reproduce key pathological features of IBD. Finally, we describe the extension of our approach to engineer vascularized, perfusable human enteroids, which can be used to model innate immune responses in IBD. This work provides an immediately deployable platform technology toward engineering more realistic organ-like structures in a dish.

在这里，我们介绍了一种简便、可扩展的工程方法，以实现类器官的长期开发和成熟。我们重新设计了传统类器官培养的配置，以开发一个平台，将干细胞悬浮液的单次注射转化为类器官的放射状阵列，无需传代即可维持较长时间。使用该系统，我们展示了结构和功能成熟度显着提高的肠道类器官的加速生成，以及它们持续发育超过 4 周的时间。此外，我们提出了一种源自患者的炎症性肠病 (IBD) 类器官模型，并使用单细胞 RNA 测序对其进行审讯，以证明其重现 IBD 关键病理特征的能力。最后，我们描述了我们的方法的扩展，以设计血管化、可灌注的人类肠，可用于模拟 IBD 中的先天免疫反应。这项工作提供了一种可立即部署的平台技术，用于在培养皿中设计更逼真的类器官结构。