Organogenesis in microcapsules: developing an efficient and scalable organoid culture platform

 产品说明：该项目的目标是使用核-壳解耦的水凝胶微胶囊开发有效且可扩展的类器官培养平台。类器官是来源于多能干细胞或器官祖细胞的仿器官多细胞结构，近年来已成为基础干细胞生物学研究和潜在治疗药物开发的重要系统。世界各地的研究小组在为各种器官衍生类器官方面取得了重要进展;然而，类器官的大规模培养或生产（其工业和临床应用的先决条件）仍然是一个挑战。 目前通过将干细胞或祖细胞包埋在大量细胞外基质（ECM）水凝胶中的类器官培养系统具有有限的传质表面积，并且不适合大规模生产。我们建议开发一个基于微胶囊的，可扩展的类器官培养平台。微胶囊具有核-壳结构，其中核由支持类器官生长的ECM组成，并且壳形成坚固的球形微胶囊，使得能够在搅拌的生物反应器中悬浮培养。与传统的在散装ECM水凝胶中培养相比，微胶囊具有更高的传质表面积与体积比，并且可以通过双流体静电共喷雾以大速率（> 10，000/min）连续生产。这项研究的预期成果是开发一种新的类器官培养方法，不仅将促进目前在许多研究小组中进行的研究，而且还将加速和促进类器官技术的转化。

 DESCRIPTION: The objective of this project is to develop an efficient and scalable organoid culture platform using core-shell decoupled hydrogel microcapsules. Organoids, organ-mimicking multicellular structures derived from pluripotent stem cells or organ progenitors, have recently emerged as an important system for both studies of fundamental stem cell biology and development of potential therapeutics. Research groups worldwide have made important progress in deriving organoids for various organs; however large-scale culture or production of organoids, a prerequisite for their industrial and clinical applications, has remained a challenge. Current organoid culture systems by embedding the stem or progenitor cells in bulk extracellular matrix (ECM) hydrogels have limited surface area for mass transfer and are not suitable for large-scale productions. We propose to develop a microcapsule-based, scalable organoid culture platform. The microcapsules have a core-shell structure where the core consists of ECM that supports the growth of the organoids and the shell forms robust spherical microcapsules, enabling suspension culture in stirred bioreactors. Compared with conventional culture in bulk ECM hydrogels, the microcapsules have a much higher surface-to-volume ratio for mass transfer and can be produced continuously at a large rate (>10,000/min) by a two-fluidic electrostatic cospraying. The anticipated outcome of this research is the development of a new organoid culture method that will not only facilitate the studies currently performed in numerous research groups but also accelerate and contribute to the translation of organoid technologies.