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Assembly of Multi‐Spheroid Cellular Architectures by Programmable Droplet Merging
Author(s) -
Cui Haijun,
Wang Xianxian,
Wesslowski Janine,
Tronser Tina,
Rosenbauer Jakob,
Schug Alexander,
Davidson Gary,
Popova Anna A.,
Levkin Pavel A.
Publication year - 2021
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202006434
Subject(s) - multicellular organism , spheroid , materials science , regenerative medicine , throughput , nanotechnology , wnt signaling pathway , tissue engineering , cell , computer science , cell culture , biology , microbiology and biotechnology , biomedical engineering , signal transduction , engineering , telecommunications , genetics , wireless
Artificial multicellular systems are gaining importance in the field of tissue engineering and regenerative medicine. Reconstruction of complex tissue architectures in vitro is nevertheless challenging, and methods permitting controllable and high‐throughput fabrication of complex multicellular architectures are needed. Here, a facile and high‐throughput method is developed based on a tunable droplet‐fusion technique, allowing programmed assembly of multiple cell spheroids into complex multicellular architectures. The droplet‐fusion technique allows for construction of various multicellular architectures (double‐spheroids, multi‐spheroids, hetero‐spheroids) in a miniaturized high‐density array format. As an example of application, the propagation of Wnt signaling is investigated within hetero‐spheroids formed from two fused Wnt‐releasing and Wnt‐reporter cell spheroids. The developed method provides an approach for miniaturized, high‐throughput construction of complex 3D multicellular architectures and can be applied for studying various biological processes including cell signaling, cancer invasion, embryogenesis, and neural development.

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