Journal ArticleDOI
Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow
Hyun Jung Kim,Dongeun Huh,Geraldine A. Hamilton,Donald E. Ingber,Donald E. Ingber,Donald E. Ingber +5 more
TLDR
This gut-on-a-chip recapitulates multiple dynamic physical and functional features of human intestine that are critical for its function within a controlled microfluidic environment that is amenable for transport, absorption, and toxicity studies, and hence it should have great value for drug testing as well as development of novel intestinal disease models.Abstract:
Development of an in vitro living cell-based model of the intestine that mimics the mechanical, structural, absorptive, transport and pathophysiological properties of the human gut along with its crucial microbial symbionts could accelerate pharmaceutical development, and potentially replace animal testing. Here, we describe a biomimetic ‘human gut-on-a-chip’ microdevice composed of two microfluidic channels separated by a porous flexible membrane coated with extracellular matrix (ECM) and lined by human intestinal epithelial (Caco-2) cells that mimics the complex structure and physiology of living intestine. The gut microenvironment is recreated by flowing fluid at a low rate (30 μL h−1) producing low shear stress (0.02 dyne cm−2) over the microchannels, and by exerting cyclic strain (10%; 0.15 Hz) that mimics physiological peristaltic motions. Under these conditions, a columnar epithelium develops that polarizes rapidly, spontaneously grows into folds that recapitulate the structure of intestinal villi, and forms a high integrity barrier to small molecules that better mimics whole intestine than cells in cultured in static Transwell models. In addition, a normal intestinal microbe (Lactobacillus rhamnosus GG) can be successfully co-cultured for extended periods (>1 week) on the luminal surface of the cultured epithelium without compromising epithelial cell viability, and this actually improves barrier function as previously observed in humans. Thus, this gut-on-a-chip recapitulates multiple dynamic physical and functional features of human intestine that are critical for its function within a controlled microfluidic environment that is amenable for transport, absorption, and toxicity studies, and hence it should have great value for drug testing as well as development of novel intestinal disease models.read more
Citations
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Journal ArticleDOI
Microfluidic organs-on-chips
TL;DR: A microfluidic cell culture device created with microchip manufacturing methods that contains continuously perfused chambers inhabited by living cells arranged to simulate tissue- and organ-level physiology has great potential to advance the study of tissue development, organ physiology and disease etiology.
Journal ArticleDOI
TEER Measurement Techniques for In Vitro Barrier Model Systems
Balaji Srinivasan,Aditya Reddy Kolli,Mandy B. Esch,Hasan E. Abaci,Michael L. Shuler,James J. Hickman +5 more
TL;DR: The aim of this article is to review the different TEER measurement techniques and analyze their strengths and weaknesses, determine the significance of TEER in drug toxicity studies, and examine the various in vitro models and microfluidic organs-on-chips implementations using TEER measurements in some widely studied barrier models.
Journal ArticleDOI
25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine
Nasim Annabi,Nasim Annabi,Ali Tamayol,Ali Tamayol,Jorge Alfredo Uquillas,Jorge Alfredo Uquillas,Mohsen Akbari,Mohsen Akbari,Luiz E. Bertassoni,Luiz E. Bertassoni,Chaenyung Cha,Chaenyung Cha,Gulden Camci-Unal,Gulden Camci-Unal,Mehmet R. Dokmeci,Mehmet R. Dokmeci,Nicholas A. Peppas,Ali Khademhosseini,Ali Khademhosseini +18 more
TL;DR: The development of advanced hydrogel with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light‐sensitive, composite, and shape‐memory hydrogels, and a number of potential applications and challenges in the utilization in regenerative medicine are reviewed.
Journal ArticleDOI
Organs-on-chips at the frontiers of drug discovery
TL;DR: The new opportunities for the application of organ-on-chip technologies in a range of areas in preclinical drug discovery, such as target identification and validation, target-based screening, and phenotypic screening are examined.
Journal ArticleDOI
A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice
Dongeun Huh,Daniel C. Leslie,Daniel C. Leslie,Benjamin D. Matthews,Jacob P. Fraser,Samuel Jurek,Geraldine A. Hamilton,Kevin S. Thorneloe,Michael Allen McAlexander,Donald E. Ingber,Donald E. Ingber,Donald E. Ingber +11 more
TL;DR: The human lung on a microfluidic chip is recreated and shown that it not only mimics lung function in response to IL-2 and mechanical strain but also successfully predicts the activity of a new drug for pulmonary edema.
References
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