Development of digital organ-on-a-chip to assess hepatotoxicity and extracellular vesicle-based anti-liver cancer immunotherapy

Organ-on-a-chip systems have been increasingly recognized as attractive platforms to assess toxicity and to develop new therapeutic agents. However, current organ-on-a-chip platforms are limited by a “single pot” design, which inevitably requires holistic analysis and limits parallel processing. Her...

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Bibliographic Details
Published in:Bio-design and manufacturing 2022-07, Vol.5 (3), p.437-450
Main Authors: Wu, Guohua, Wu, Jianguo, Li, Zihan, Shi, Shengyu, Wu, Di, Wang, Xuanbo, Xu, Han, Liu, Hui, Huang, Yixiao, Wang, Rending, Shen, Jia, Dong, Zhihong, Wang, Shuqi
Format: Article
Language:English
Subjects:
Biochips
Biomaterials
Biomedical Engineering and Bioengineering
Cancer immunotherapy
Contact angle
Drug development
Drug testing
Drugs
Engineering
Extracellular matrix
Extracellular vesicles
Fibroblasts
Hepatotoxicity
Liver cancer
Mechanical Engineering
Microspheres
Natural killer cells
Research Article
Toxicity
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Summary:Organ-on-a-chip systems have been increasingly recognized as attractive platforms to assess toxicity and to develop new therapeutic agents. However, current organ-on-a-chip platforms are limited by a “single pot” design, which inevitably requires holistic analysis and limits parallel processing. Here, we developed a digital organ-on-a-chip by combining a microwell array with cellular microspheres, which significantly increased the parallelism over traditional organ-on-a-chip for drug development. Up to 127 uniform liver cancer microspheres in this digital organ-on-a-chip format served as individual analytical units, allowing for analysis with high consistency and quick response. Our platform displayed evident anti-cancer efficacy at a concentration of 10 μM for sorafenib, and had greater alignment than the “single pot” organ-on-a-chip with a previous in vivo study. In addition, this digital organ-on-a-chip demonstrated the treatment efficacy of natural killer cell-derived extracellular vesicles for liver cancer at 50 μg/mL. The successful development of this digital organ-on-a-chip platform provides high-parallelism and a low-variability analytical tool for toxicity assessment and the exploration of new anticancer modalities, thereby accelerating the joint endeavor to combat cancer. Graphic abstract
ISSN:2096-5524
2522-8552
DOI:10.1007/s42242-022-00188-1