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Scalable Formation of Highly Viable and Functional Hepatocellular Carcinoma Spheroids in an Oxygen‐Permeable Microwell Device for Anti‐Tumor Drug Evaluation
Journal article

Scalable Formation of Highly Viable and Functional Hepatocellular Carcinoma Spheroids in an Oxygen‐Permeable Microwell Device for Anti‐Tumor Drug Evaluation

Jianyu He, Chang Zhou, Xiaolei Xu, Zhenzhen Zhou, Mathieu Danoy, Marie Shinohara, Wenjin Xiao, Dong Zhu, Xiuying Zhao, Xiaobin Feng, …
Advanced healthcare materials, v 11(18), pp e2200863-n/a
21 Sep 2022

Abstract

anti‐tumor drug screening human hepatocellular carcinoma microwell arrays oxygen‐permeable microwells tumor spheroids
For high‐throughput anti‐cancer drug screening, microwell arrays may serve as an effective tool to generate uniform and scalable tumor spheroids. However, microwell arrays are commonly anchored in non‐oxygen‐permeable culture plates, leading to limited oxygen supply for avascular spheroids. Herein, a polydimethylsiloxane (PDMS)‐based oxygen‐permeable microwell device is introduced for generating highly viable and functional hepatocellular carcinoma (HCC) spheroids. The PDMS sheets at the bottom of the microwell device provide a high flux of oxygen like in vivo neighboring hepatic sinusoids. Owing to the better oxygen supply, the generated HepG2 spheroids are larger in size and exhibit higher viability and proliferation with less cell apoptosis and necrosis. These spheroids also exhibit lower levels of anaerobic cellular respiration and express higher levels of liver‐related functions. In anti‐cancer drug testing, spheroids cultured in PDMS plates show a significantly stronger resistance against doxorubicin because of the stronger stem‐cell and multidrug resistance phenotype. Moreover, higher expression of vascular endothelial growth factor‐A produces a stronger angiogenesis capability of the spheroids. Overall, compared to the spheroids cultured in conventional non‐oxygen‐permeable plates, these spheroids can be used as a more favorable model for early‐stage HCCs and be applied in high‐throughput anti‐cancer drug screening. A polydimethylsiloxane (PDMS)‐based oxygen‐permeable microwell device is introduced for generating highly viable and functional hepatocellular carcinoma (HCC) spheroids. The PDMS sheets of the microwell device provide high flux oxygen and function like in vivo neighboring hepatic sinusoids in terms of oxygen supply. The generated spheroids can be used as a favorable model mimicking early‐stage avascular HCCs for high‐throughput drug screening.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Engineering, Biomedical
Materials Science, Biomaterials
Nanoscience & Nanotechnology
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