Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/ijms18112348
Keywords
in vitro cancer model; inkjet cell printing; microtissue array; cancer drug discovery; electrospinning; nanofibrous membrane
Funding
- Pionner Research Center Program through the National Research Foundation of Korea - Ministry of Science, ICT & Future Planning [NRF-2012-0009666]
- Ministry of Education [NRF-2017R1A6A1A03015562]
- Robot Industry Fusion Core Technology Development Project through the Ministry of Trade, industry & Energy (MI, Korea) [10048358]
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In general, a drug candidate is evaluated using 2D-cultured cancer cells followed by an animal model. Despite successful preclinical testing, however, most drugs that enter human clinical trials fail. The high failure rates are mainly caused by incompatibility between the responses of the current models and humans. Here, we fabricated a cancer microtissue array in a multi-well format that exhibits heterogeneous and batch-to-batch structure by continuous deposition of collagen-suspended Hela cells on a fibroblast-layered nanofibrous membrane via inkjet printing. Expression of both Matrix Metalloproteinase 2 (MMP2) and Matrix Metalloproteinase 9 (MMP9) was higher in cancer microtissues than in fibroblast-free microtissues. The fabricated microtissues were treated with an anticancer drug, and high drug resistance to doxorubicin occurred in cancer microtissues but not in fibroblast-free microtissues. These results introduce an inkjet printing fabrication method for cancer microtissue arrays, which can be used for various applications such as early drug screening and gradual 3D cancer studies.
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