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Porous hydrogel arrays for hepatoma cell spheroid formation and drug resistance investigation

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Abstract

Drug resistance is one of the major obstacles in the drug therapy of cancers. Efforts in this area in pre-clinical research have focused on developing novel platforms to evaluate and decrease drug resistance. In this paper, inspired by the structure of hives where swarms live and breed, we propose porous hydrogel arrays with a uniform pore structure for the generation of hepatoma cell spheroids and the investigation of drug resistance. The porous hydrogel arrays were fabricated using polyethylene glycol diacrylate (PEGDA) hydrogel to negatively replicate a well-designed template. Benefiting from the elaborate processing of the template, the prepared porous hydrogel arrays possessed a uniform pore structure. Due to their anti-adhesion properties and the excellent biocompatibility of the PEGDA hydrogel, the hepatoma cells could form well-defined and uniform hepatoma cell spheroids in the porous hydrogel arrays. We found that the resistant hepatoma cell spheroids showed more significant Lenvatinib resistance and a migratory phenotype compared with a two-dimensional (2D) cell culture, which reveals the reason for the failure of most 2D cell-selected drugs for in vivo applications. These features give such porous hydrogel arrays promising application prospects in the investigation of tumor cell spheroid culture and in vitro drug resistance.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (No. 2020YFA0908200), the National Natural Science Foundation of China (Nos. 52073060, 61927805, 81974312, and 81501823), the Natural Science Foundation of Jiangsu Province (No. BE2018707), the Shenzhen Fundamental Research Program (No. JCYJ20190813152616459), the Zhejiang Provincial Natural Science Foundation of China (Nos. LY18H160049 and LQ19H160008), the Medical Scientific Research of Zhejiang Province (No. 2017KY459), Wenzhou Municipal Science and Technology Bureau (No. Y20190203), and Wenzhou Institute, University of Chinese Academy of Sciences’s startup fund (No. WIUCASQD2019007).

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Authors and Affiliations

  1. Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, China

    Xin Lei, Changmin Shao, Keqing Shi & Yuanjin Zhao

  2. Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, China

    Changmin Shao, Xin Shou & Yuanjin Zhao

  3. State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China

    Xin Shou & Yuanjin Zhao

  4. Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, China

    Liang Shi

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  1. Xin Lei
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  2. Changmin Shao
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  3. Xin Shou
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  4. Keqing Shi
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  5. Liang Shi
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Contributions

YJZ was involved in conceptualization; XL was involved in data curation analyzed, investigation, writing—original draft; XL and CMS contributed to formal analysis, validation, writing—review & editing and visualization; XS, LS, and KQS contributed to the project administration and supervision.

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Correspondence to Changmin Shao, Liang Shi or Yuanjin Zhao.

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Lei, X., Shao, C., Shou, X. et al. Porous hydrogel arrays for hepatoma cell spheroid formation and drug resistance investigation. Bio-des. Manuf. 4, 842–850 (2021). https://doi.org/10.1007/s42242-021-00141-8

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  • DOI: https://doi.org/10.1007/s42242-021-00141-8

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