期刊
ADVANCED FUNCTIONAL MATERIALS
卷 30, 期 52, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202005324
关键词
3D spheroid printing; cell spheroids; in vitro tissue models; paracrine interaction
类别
资金
- National RD Program
- Bio and Medical Technology Development Program through the National Research Foundation of Korea (NRF) - Ministry of Science and ICT [NRF-2020M3H4A1A02084827, NRF-2015M3A9B3028685]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health and Welfare, Republic of Korea [HC15C0001]
Cell-cell interaction accounts for one of the most influential factors affecting the viability and functionality of cell-based tissue models. In this respect, various methods capable of producing micro-patterns with cell spheroids are introduced to simultaneously improve contact-dependent and -independent cell-cell interactions. However, no method has yet been designed to effectively generate precise 3D patterns with multiple spheroid types. In this study, a new high-precision and convenient 3D spheroid printing technology is developed, designated as 3D bio-dot printing. This new technique is designed to produce cell-laden, non-adhesive micro-pores within 3D structures to allow cell spheroids to be induced at printed sites. Experimental results show that various cell types, including hepatocytes, pancreatic beta-cells, and breast cancer cells, can be employed for the in situ formation of cell spheroids, and 3D freeform structures with multiple spheroid types can be printed. Moreover, this novel technology can also be used for performing 3D invasion assays. More importantly, it ensures that the precise control of spheroid size and position is achieved at micrometer scale. Finally, the usefulness of this novel technology is demonstrated by producing multicellular micro-patterns with primary hepatocyte spheroids and endothelial cells, that exhibit significantly improved long-term hepatic function and drug metabolism.
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