Lee, Geon Hui Lee, Jae Seo Lee, Gi-Hun Joung, Woo Youl Kim, Soo Hyun Lee, Sang Hoon Park, Joong Yull Kim, Dong-Hwee 2024-01-19T23:34:09Z 2024-01-19T23:34:09Z 2021-09-03 2018-01 1758-5082 https://pubs.kist.re.kr/handle/201004/121862 The engineered three-dimensional (3D) cell cultivation system for the production of multicellular spheroids has attracted considerable attention due to its improved in vivo relevance to cellular communications compared with the traditional two-dimensional (2D) cell culture platform. The formation and maintenance of cell spheroids in a 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 shows limited yield and reduced maintenance periods due to the lack of proper supplies of nutrition as well as intercellular chemical signaling. Here, we develop novel networked concave microwell arrays for the effective construction of 3D multi-cellular spheroids. The proposed method provides a suitable structure for the diffusion of oxygen, water-soluble nutrients and cytokines for cell-cell interactions between the spheroids in neighboring microwells. We have further demonstrated that hepatocyte spheroid cultured networked concave microwells show enhanced cell viability and albumin secretion compared to the un-networked control group over two weeks. Our results reveal that multi-cellular functionality can be tuned up by networking individual 3D spheroids without supplying additional chemicals or biological supplements. We anticipate our result to be useful in high-throughput cellular screening platforms to study cell-cell interactions, in response to diverse chemical stimuli as well as the development of the in vivo mimicking of the customized 3D tissue culture system. English IOP PUBLISHING LTD IN-VITRO EMBRYOID BODIES ALBUMIN TISSUE CHIP COMMUNICATION MICROCHANNEL FABRICATION MODEL FLOW Networked concave microwell arrays for constructing 3D cell spheroids Article 10.1088/1758-5090/aa9876 1 BIOFABRICATION, v.10, no.1 BIOFABRICATION 10 1 scie scopus 000417535300001 2-s2.0-85042300612 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article IN-VITRO EMBRYOID BODIES ALBUMIN TISSUE CHIP COMMUNICATION MICROCHANNEL FABRICATION MODEL FLOW 3D cell culture concave microwell 3D cell spheroid networked microwell hepatocyte spheroid