基于微流控芯片的体外三维肝脏生理模型的构建及应用  

Construction and Application of 3D Microfluidic Liver-On-A-Chip

作　　者：卢雪萍 赵亮[1] 汪夏燕[1] 郭广生[1] Xueping Lu;Liang Zhao;Xiayan Wang;Guangsheng Guo(Center of Excellence for Environmental Safety and Biological Effects,Faculty of Environment and Life,Department of Chemistry,Beijing University of Technology,Beijing 100124,China)

机构地区：[1]北京工业大学、环境安全与生物效应卓越中心、环境与生命学部、化学系,北京100124

出　　处：《化学进展》2023年第9期1357-1368,共12页Progress in Chemistry

基　　金：国家自然科学基金项目(No.22174007,22127805);北京市卓越青年科学家项目(BJJWZYJH01201910005017)资助。

摘　　要：肝脏是身体内最重要器官之一,是生化代谢和合成过程最主要的器官。因此,深入了解肝脏生理生化过程、病理机制等,对于研究、预防、诊断、治疗肝脏相关或代谢相关疾病具有重要意义。肝脏体外培养模型是研究肝脏相关生物学机制的重要实验基础。传统体外细胞培养难以重现肝脏复杂的生理结构和微环境,且缺乏肝脏组织构造的基本三维特征。更重要的是,平面培养过程中细胞的组织形态架构、基因表达、物质代谢过程等与体内相比具有较大差异。微流控技术可以通过精巧设计与布局在微通道结构中培养相应细胞来模拟肝脏的生理结构,结合三维细胞培养技术,可以在微流控芯片上实现更类似于体内肝脏微环境以及与其他组织器官相互作用的体外肝器官模型。本文总结了基于微流控技术构建体外三维肝脏芯片的方法和最新进展,包括基于多孔膜培养、水凝胶培养、细胞团簇培养及生物打印的三维肝脏模型。进一步,我们也探讨了三维培养的肝脏芯片在重塑肝脏生理结构、探究机理和病理机制以及药物筛选和毒性测试方面的应用,并对三维肝脏微流控器官芯片的潜在价值及其面临的挑战进行了展望。As the largest internal organ in the human body,the liver plays an essential role in the metabolism.The liver or relevant diseases are one of the leading causes of death in the world,with the number of cases surging each year.Therefore,an in-depth understanding of the physiological and biochemical processes and pathological mechanisms of the liver is of great significance for the research,prevention,diagnosis,and treatment of liver-related or metabolism-related diseases.The in vitro liver culture model is an important experimental platform for the study of liver-related biological mechanisms.However,the traditional two-dimensional in vitro cell culture model makes it difficult to reproduce the complex physiological structure and microenvironment of the liver,and lack of disease characteristics.More importantly,the cell structure,gene expression,substance metabolism,and so on in the process of planar culture are significantly different from those in vivo.Microfluidic technology can simulate the physiological structure of liver by designing appropriate micro-structure,providing a microenvironment more like that in vivo by combining with three-dimensional liver tissue culture.Therefore,this paper summarizes the methods and latest progress in constructing 3D liver chips in vitro based on microfluidic technology,including porous membrane culture,hydrogel culture,cell spheroid-based culture,and 3D bioprinting.The applications of 3D cultured liver microchips in remodeling liver physiological structure,exploring mechanism and pathological mechanism,drug screening,and toxicity testing are further summarized.Finally,the potential value and challenges of 3D liver-on-a-chip are discussed.

关 键 词：微流控芯片 三维培养 器官芯片 肝脏芯片 药物筛选 

分 类 号：R446.5[医药卫生—诊断学]