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

作　　者：Xin Lei Changmin Shao Xin Shou Keqing Shi Liang Shi Yuanjin Zhao 

机构地区：[1]Translational Medicine Laboratory,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325035,China [2]Wenzhou Institute,University of Chinese Academy of Sciences,Wenzhou 325001,China [3]State Key Laboratory of Bioelectronics,School of Biological Science and Medical Engineering,Southeast University,Nanjing 210096,China [4]Department of Laboratory Medicine,The Eighth Affiliated Hospital,Sun Yat-Sen University,Shenzhen 518033,China

出　　处：《Bio-Design and Manufacturing》2021年第4期842-850,共9页生物设计与制造（英文）

基　　金：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);Wenzhou Institute,University of Chinese Academy of Sciences’s startup fund(No.WIUCASQD2019007).

摘　　要：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 polyeth-ylene 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 uni-form 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.

关 键 词：Drug resistance HYDROGEL POROUS SPHEROID HEPATOMA 

分 类 号：R735.7[医药卫生—肿瘤]