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3D-bioprinted cholangiocarcinoma-on-a-chip model for evaluating drug responses

作     者:Qiong Liu Luis SMille Cesar Villalobos Ingrid Anaya Matthias Vostatek Sili Yi Wanlu Li Junlong Liao Huanghui Wu Yongteng Song Lize Xiong Yu Shrike Zhang Qiong Liu;Luis S.Mille;Cesar Villalobos;Ingrid Anaya;Matthias Vostatek;Sili Yi;Wanlu Li;Junlong Liao;Huanghui Wu;Yongteng Song;Lize Xiong;Yu Shrike Zhang

作者机构:Division of Engineering in MedicineDepartment of MedicineBrigham and Women’s HospitalHarvard Medical SchoolCambridgeMA 02139USA Translational Research Institute of Brain and Brain-Like IntelligenceShanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai 200434China Shanghai Key Laboratory of Anesthesiology and Brain Functional ModulationShanghai 200434China Department of BioengineeringStanford UniversityPalo AltoCA 94305USA Biotechnological Engineering ProgramMonterrey Institute of Technology and Higher Education64849 MonterreyNuevo LeónMexico Molecular BiotechnologyUniversity of Applied Sciences Campus Vienna1100 ViennaAustria Rapid Manufacturing Engineering CenterSchool of Mechatronical Engineering and AutomationShanghai UniversityShanghai 200444China 

出 版 物:《Bio-Design and Manufacturing》 (生物设计与制造(英文))

年 卷 期:2023年第6卷第4期

页      面:373-389页

核心收录:

学科分类:0710[理学-生物学] 080903[工学-微电子学与固体电子学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 0809[工学-电子科学与技术(可授工学、理学学位)] 08[工学] 100602[医学-中西医结合临床] 10[医学] 

基  金:support by the Brigham Research Institute 

主  题:Tumor-on-a-chip Biliary tumor 3D bioprinting Tumor microenvironment Drug screening 

摘      要:Cholangiocarcinoma(CCA)is characterized by heterogeneous mutations and a refractory ***,the development of a model for effective drug screening is urgently *** the established therapeutic testing models for CCA are often ineffective,we fabricated an enabling three-dimensional(3D)-bioprinted CCA-on-a-chip model that to a good extent resembled the multicellular microenvironment and the anatomical microstructure of the hepato-vascular-biliary system to perform high-content antitumor drug ***,cholangiocytes,hepatocytes,and vascular endotheliocytes were employed for 3D bioprinting of the models,allowing for a high degree of spatial and tube-like microstructural ***,it was possible to observe CCA cells attached to the surfaces of the gelatin methacryloyl(GelMA)hydrogelembedded microchannels and overgrown in a thickening manner,generating bile duct stenosis,which was expected to be analogous to the in vivo *** 4000 differentially expressed genes were detected in the CCA cells in our 3D coculture model compared to the traditional two-dimensional(2D)*** screening revealed that the CCA cells grown in the 3D traditional model were more sensitive to the antitumoral prodrug than those in the 2D monoculture due to drug biotransformation by the neighboring functional *** study provides proof-of-concept validation of our bioprinted CCA-on-a-chip as a promising drug screening model for CCA treatment and paves the way for potential personalized medicine strategies for CCA patients in the future.

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