Microengineered physiological biomimicry: Organs-on-Chips

被引:497
作者
Huh, Dongeun [1 ,2 ,3 ,4 ]
Torisawa, Yu-suke [1 ]
Hamilton, Geraldine A. [1 ]
Kim, Hyun Jung [1 ]
Ingber, Donald E. [1 ,2 ,3 ,4 ,5 ]
机构
[1] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Childrens Hosp Boston, Vasc Biol Program, Dept Pathol, Boston, MA 02115 USA
[4] Childrens Hosp Boston, Vasc Biol Program, Dept Surg, Boston, MA 02115 USA
[5] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA
关键词
3D CELL-CULTURE; DRUG; ABSORPTION; TOXICITY; TISSUES; MODELS;
D O I
10.1039/c2lc40089h
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Microscale engineering technologies provide unprecedented opportunities to create cell culture microenvironments that go beyond current three-dimensional in vitro models by recapitulating the critical tissue-tissue interfaces, spatiotemporal chemical gradients, and dynamic mechanical microenvironments of living organs. Here we review recent advances in this field made over the past two years that are focused on the development of 'Organs-on-Chips' in which living cells are cultured within microfluidic devices that have been microengineered to reconstitute tissue arrangements observed in living organs in order to study physiology in an organ-specific context and to develop specialized in vitro disease models. We discuss the potential of organs-on-chips as alternatives to conventional cell culture models and animal testing for pharmaceutical and toxicology applications. We also explore challenges that lie ahead if this field is to fulfil its promise to transform the future of drug development and chemical safety testing.
引用
收藏
页码:2156 / 2164
页数:9
相关论文
共 45 条
[1]   In vitro zonation and toxicity in a hepatocyte bioreactor [J].
Allen, JW ;
Khetani, SR ;
Bhatia, SN .
TOXICOLOGICAL SCIENCES, 2005, 84 (01) :110-119
[2]   A microfluidic brain slice perfusion chamber for multisite recording using penetrating electrodes [J].
Blake, Alexander J. ;
Rodgers, Frank C. ;
Bassuener, Anna ;
Hippensteel, Joseph A. ;
Pearce, Thomas M. ;
Pearce, Timothy R. ;
Zarnowska, Ewa D. ;
Pearce, Robert A. ;
Williams, Justin C. .
JOURNAL OF NEUROSCIENCE METHODS, 2010, 189 (01) :5-13
[3]   Geometric control of cell life and death [J].
Chen, CS ;
Mrksich, M ;
Huang, S ;
Whitesides, GM ;
Ingber, DE .
SCIENCE, 1997, 276 (5317) :1425-1428
[4]   New technologies and screening strategies for hepatotoxicity: Use of in vitro models [J].
Dambach, DM ;
Andrews, BA ;
Moulin, F .
TOXICOLOGIC PATHOLOGY, 2005, 33 (01) :17-26
[5]   Paper-supported 3D cell culture for tissue-based bioassays [J].
Derda, Ratmir ;
Laromaine, Anna ;
Mammoto, Akiko ;
Tang, Sindy K. Y. ;
Mammoto, Tadanori ;
Ingber, Donald E. ;
Whitesides, George M. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (44) :18457-18462
[6]   Perfused multiwell plate for 3D liver tissue engineering [J].
Domansky, Karel ;
Inman, Walker ;
Serdy, James ;
Dash, Ajit ;
Lim, Matthew H. M. ;
Griffith, Linda G. .
LAB ON A CHIP, 2010, 10 (01) :51-58
[7]   Combination of fluid and solid mechanical stresses contribute to cell death and detachment in a microfluidic alveolar model [J].
Douville, Nicholas J. ;
Zamankhan, Parsa ;
Tung, Yi-Chung ;
Li, Ran ;
Vaughan, Benjamin L. ;
Tai, Cheng-Feng ;
White, Joshua ;
Christensen, Paul J. ;
Grotberg, James B. ;
Takayama, Shuichi .
LAB ON A CHIP, 2011, 11 (04) :609-619
[8]   Cells on chips [J].
El-Ali, Jamil ;
Sorger, Peter K. ;
Jensen, Klavs F. .
NATURE, 2006, 442 (7101) :403-411
[9]  
Esch MB, 2011, ANNU REV BIOMED ENG, V13, P55, DOI [10.1146/annurev-bioeng-071910-124629, 10.1146/annurev-biocng-071910-124629]
[10]   Microengineering of cellular interactions [J].
Folch, A ;
Toner, M .
ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, 2000, 2 :227-+