Mass production of lumenogenic human embryoid bodies and functional cardiospheres using in-air-generated microcapsules

Sebastiaan Robert van Loo, Simone A. ten Den, Nuno Araújo-Gomes, Vicent de Jong, Rebecca Snabel, Maik Raphaël Schot, José Manuel Rivera Arbelaez, Gert Jan Veenstra, Robert Passier, Tom Kamperman, J. Leijten*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Organoids are engineered 3D miniature tissues that are defined by their organ-like structures, which drive a fundamental understanding of human development. However, current organoid generation methods are associated with low production throughputs and poor control over size and function including due to organoid merging, which limits their clinical and industrial translation. Here, we present a microfluidic platform for the mass production of lumenogenic embryoid bodies and functional cardiospheres. Specifically, we apply triple-jet in-air microfluidics for the ultra-high-throughput generation of hollow, thin-shelled, hydrogel microcapsules that can act as spheroid-forming bioreactors in a cytocompatible, oil-free, surfactant-free, and size-controlled manner. Uniquely, we show that microcapsules generated by in-air microfluidics provide a lumenogenic microenvironment with near 100% efficient cavitation of spheroids. We demonstrate that upon chemical stimulation, human pluripotent stem cell-derived spheroids undergo cardiomyogenic differentiation, effectively resulting in the mass production of homogeneous and functional cardiospheres that are responsive to external electrical stimulation. These findings drive clinical and industrial adaption of stem cell technology in tissue engineering and drug testing.

Original languageEnglish
Article number6685
JournalNature communications
Early online date21 Oct 2023
Publication statusPublished - Dec 2023


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