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Biofabrication. 2017 Nov 6. doi: 10.1088/1758-5090/aa9876. [Epub ahead of print]

Networked concave microwell arrays for constructing 3-D cell spheroids.

Author information

KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Korea (the Republic of).
School of Mechanical Engineering, College of Engineering, Chung-Ang University, Seoul, Seoul, Korea (the Republic of).
School of Biomedical Engineering, College of Health Science, Korea University, Seoul, Korea (the Republic of).
Biomaterials Research Center, Korea Institute of Science and Technology, 39-1Hawolgok-dong, Seongbuk-gu, Seoul, 136-791, Korea, Seoul, KOREA, REPUBLIC OF.
Biomedical Engineering Department, Korea University, 126-1 Anam-dong 5ga, Sungbuk-gu, Seoul, 136-705, Korea, Seoul, KOREA, REPUBLIC OF.
Chung-Ang University, Seoul, KOREA, REPUBLIC OF.
KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, R&D Center #410, Seoul, 02841, Korea (the Republic of).


The engineered three-dimensional (3-D) cell cultivation system for the production of multicellular spheroids has attracted considerable attention due to its improved in vivo relevance to cellular communications compared to the traditional two-dimensional (2-D) cell culture platform. The formation and maintenance of cell spheroids in healthy condition is the critical factor for tissue engineering applications such as the repair of damaged tissues, the development of organ replacement parts, and preclinical drug tests. However, culturing spheroids in conventional isolated single wells show limit ted yield and maintenance periods due to the lack of proper supplies of nutrition as well as intercellular chemical signaling. Here we develop the novel networked concave microwell arrays for effective construction of 3-D multi-cellular spheroids. The proposed method provides a suitable structure for the diffusion of oxygen, water-soluble nutrients, and cytokines for cell-cell interactions among the spheroids in neighboring microwells. We have further demonstrated in hepatocyte spheroids-cultured networked concave microwells showed enhanced cell viability and albumin secretion compared to the un-networked control group for two weeks. Our results reveal multi-cellular functionality could be tuned up by networking individual 3-D spheroids without supplying additional chemicals or biological supplements. We anticipate our result to be used in high-throughput cellular screening platforms to study cell-cell interactions in response to diverse chemical stimuli as well as development of in vivo mimicking customized 3-D tissue culture system.


3D cell culture; 3D cell spheroid; Concave microwell; Networked microwell; hepatocyte spheroid


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