☆ 4.7 Review

Gut-on-a-Chip Models: Current and Future Perspectives for Host-Microbial Interactions Research

BIOMEDICINES (2023)

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Review Biotechnology & Applied Microbiology

The revolution of PDMS microfluidics in cellular biology

Soumyabrata Banik et al.

Summary: Microfluidics revolutionizes cellular biology research by providing control over the physicochemical environment and enabling high-throughput cellular analysis. The introduction of PDMS as a structural material has made microfluidic technology more accessible and widely applicable in various biological fields. This review emphasizes the innovative applications of PDMS-based microfluidic systems in pre-clinical biological research, enhancing sensitivity and diagnostic effectiveness in cell-based assays.

CRITICAL REVIEWS IN BIOTECHNOLOGY (2023)

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Article Chemistry, Analytical

Effects of Porous Size and Membrane Pattern on Shear Stress Characteristic in Gut-on-a-Chip with Peristalsis Motion

Pannasit Borwornpiyawat et al.

Summary: The study investigates the shear stress behavior in a gut-on-a-chip device with porous membrane subjected to peristalsis motion using CFD simulation. The results show that the average shear stress on the porous membrane is higher than that of the flat membrane in the stationary microchannel. However, during cyclic deformation, the porous membrane with smaller pore size experiences greater variation of shear stress.

MICROMACHINES (2023)

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Article Toxicology

Dose and route dependent effects of the mycotoxin deoxynivalenol in a 3D gut-on-a-chip model with flow

Franziska Poeschl et al.

Summary: This study demonstrates the effects of DON in a gut-on-a-chip model, which incorporates the effects of intestinal flow. DON causes dysfunction of intestinal barrier, with lower concentrations inducing TEER increase and higher concentrations leading to barrier disruption and IL-8 secretion.

TOXICOLOGY IN VITRO (2023)

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Article Toxicology

Systematic comparison of transcriptomes of Caco-2 cells cultured under different cellular and physiological conditions

Janneke Elzinga et al.

Summary: There is a need for standardized in vitro models of the human intestinal tract to study intestinal health without using animals. The Caco-2 cell line is a widely accepted and characterized model for studying intestinal drug transport, host-microbe interactions, and toxicity. We investigated the effect of different experimental variables on gene expression using transcriptome analysis of Caco-2 cells grown on permeable membranes. Our analysis revealed a weak association between experimental variables and gene expression, possibly due to heterogeneity in cell culture practice and inadequate reporting. This highlights the need for improved reporting protocols and serves as a template for future comparative studies.

ARCHIVES OF TOXICOLOGY (2023)

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Review Biochemistry & Molecular Biology

Intestinal organoids as advanced modeling platforms to study the role of host-microbiome interaction in homeostasis and disease

Ji-Su Ahn et al.

Summary: After birth, animals are colonized by a diverse community of microorganisms, with the gut containing the largest microbiome. In recent years, there has been extensive research on the importance of gut microbiome and its metabolites in host health, particularly with the emergence of the gut-brain axis. The development of organoid culture systems has provided a valuable tool for studying intestinal pathophysiology and host-microbe interactions, allowing insights into the roles of pathobionts and commensal symbionts.

BMB REPORTS (2023)

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Article Chemistry, Medicinal

A Novel In Vitro Membrane Permeability Methodology Using Three-dimensional Caco-2 Tubules in a Microphysiological System Which Better Mimics In Vivo Physiological Conditions

Yuki Hagiwara et al.

Summary: The aim of this study was to develop an in vitro drug permeability methodology that accurately mimics the gastrointestinal environment using a three-dimensional (3D) Caco-2 tubules and a microphysiological system. The methodology was confirmed by measuring the permeability of propranolol and subsequently applied to solifenacin and bile acids. This model provides an alternative testing system for drug absorption in a closely resembling environment to the human gastrointestinal tract.

JOURNAL OF PHARMACEUTICAL SCIENCES (2022)

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Article Biochemical Research Methods

High performance inkjet printed embedded electrochemical sensors for monitoring hypoxia in a gut bilayer microfluidic chip

Muhammad Asad Ullah Khalid et al.

Summary: This study proposes a simple, low-cost inkjet printing technique for embedded electrochemical sensors to monitor dissolved oxygen and reactive oxygen species on a gut bilayer microfluidic chip platform. The sensors demonstrate high sensitivity and low detection limits, and can be used to quantify barrier tight junctions and evaluate protein expression. In addition, this platform has potential applications in bioavailability assays, drug transport studies, and other fields.

LAB ON A CHIP (2022)

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Article Oncology

Standardizing Patient-Derived Organoid Generation Workflow to Avoid Microbial Contamination From Colorectal Cancer Tissues

Mattia Marinucci et al.

Summary: The use of patient-derived organoids (PDO) has become increasingly important in cancer research. In this study, we tested different washing solutions to prevent contamination in organoid cultures and found that phosphate-buffered saline (PBS) and PBS with penicillin/streptomycin reduced the contamination rate, while PBS with Primocin completely eliminated contamination. Interestingly, the addition of penicillin/streptomycin negatively impacted organoid growth.

FRONTIERS IN ONCOLOGY (2022)

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Review Gastroenterology & Hepatology

Gut microbiota-motility interregulation: insights from in vivo, ex vivo and in silico studies

Barbora Waclawikova et al.

Summary: The human gastrointestinal tract is populated by trillions of microbes that play a significant role in regulating intestinal physiology, including gut motility. Understanding the inter-regulatory mechanisms between the microbiota and bowel function is crucial for addressing gut dysmotility and associated diseases.

GUT MICROBES (2022)

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Article Nanoscience & Nanotechnology

Contributions of the microbiome to intestinal inflammation in a gut-on-a-chip

Min Seo Jeon et al.

Summary: This study presents a microfluidic-based gut model that can mimic the structure and function of the human intestine and enable co-culture of human and microbial cells. The gut-on-a-chip demonstrated the ability to recapitulate in vivo relevance epithelial cell differentiation and restore barrier function when co-cultured with probiotics, providing insights into the interaction between the intestinal microbiome and human health.

NANO CONVERGENCE (2022)

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Article Multidisciplinary Sciences

Simulation and modeling of physiological processes of vital organs in organ-on-a-chip biosystem

Sadegh Seidi et al.

Summary: Organ-on-a-chip biosystems are microfluidic devices that mimic the functions of different organs and create physiological models. They have diverse applications in the field of biomedicine and are crucial for disease modeling and drug development.

JOURNAL OF KING SAUD UNIVERSITY SCIENCE (2022)

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Article Radiology, Nuclear Medicine & Medical Imaging

Overview of Application of Nanomaterials in Medical Domain

Jiabo Lan

Summary: The application of nanomaterials in the medical field is a forefront hotspot, offering new possibilities for disease treatment with its high drug loading rate, better biocompatibility, and targeted transportation.

CONTRAST MEDIA & MOLECULAR IMAGING (2022)

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Review Gastroenterology & Hepatology

Gastric organoids: Advancing the study of H. pylori pathogenesis and inflammation

Sulaimon Idowu et al.

Summary: Traditional models for studying Helicobacter pylori infection have limitations in understanding cancer initiation and translating results due to genetic differences. The development of gastric organoids provides advantages in mimicking human stomach and long-term culture. This review discusses the advantages and limitations of existing models and the application of gastric organoids in studying H. pylori pathogenesis.

HELICOBACTER (2022)

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Article Gastroenterology & Hepatology

Modeling colorectal cancer: A bio-resource of 50 patient-derived organoid lines

Rebekah M. Engel et al.

Summary: Patient-derived colorectal cancer organoids (PDCOs) have the potential utility in personalized cancer medicine, as they recapitulate key characteristics of the primary tumor and can be used as a powerful tool for cancer research.

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY (2022)

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Article Immunology

Microbial regulation of intestinal motility provides resistance against helminth infection

Mati Moyat et al.

Summary: The study suggests that the complex bacterial microbiota plays a crucial role in host resistance against intestinal helminths, as the lack of a diverse bacterial microbiota reduces the host's ability to resist worm infections.

MUCOSAL IMMUNOLOGY (2022)

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Article Microbiology

Interactions between Enterohemorrhagic Escherichia coli (EHEC) and Gut Commensals at the Interface of Human Colonoids

Fernando H. Martins et al.

Summary: The interactions between gut microbiota and pathogens are found to impact the outcome of infection. This study demonstrates that certain gut commensals can enhance the virulence and lesion formation of Enterohemorrhagic Escherichia coli (EHEC). Additionally, the different commensal bacteria have different impacts on the metabolic landscape, suggesting that microbiota compositions can modulate EHEC-mediated disease to varying degrees.

MBIO (2022)

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Article Multidisciplinary Sciences

Tissue extracellular matrix hydrogels as alternatives to Matrigel for culturing gastrointestinal organoids

Suran Kim et al.

Summary: Gastrointestinal tissue-mimetic matrices are feasible alternatives to Matrigel for organoid culture and transplantation, providing a suitable microenvironment for the development and function of gastrointestinal organoids comparable or superior to those grown in Matrigel.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

Endothelial inflammation and neutrophil transmigration are modulated by extracellular matrix composition in an inflammation-on-a-chip model

Rebecca B. Riddle et al.

Summary: Inflammatory diseases are characterized by excessive neutrophil infiltration, but lack of accurate in vitro and in vivo models hinders drug development. This study developed a 3D in vitro inflammation-on-a-chip model to mimic neutrophil migration across endothelium and extracellular matrix. The composition of the extracellular matrix was found to significantly affect neutrophil transmigration and response to inhibitors, providing potential for disease-specific drug development.

SCIENTIFIC REPORTS (2022)

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Article Chemistry, Analytical

Partitioning of Small Hydrophobic Molecules into Polydimethylsiloxane in Microfluidic Analytical Devices

Patricia M. Rodrigues et al.

Summary: Polydimethylsiloxane (PDMS) is commonly used in microfluidics. This study investigated the effects of variables such as concentration, solvent pairing, and residence time on molecule partitioning into PDMS. Different surface/bulk modifications were tested, and it was found that reducing PDMS hydrophobicity did not directly affect molecule partitioning. This research highlights the importance of pre-assessing molecule absorption and considering alternative materials in microfluidic fabrication.

MICROMACHINES (2022)

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Review Gastroenterology & Hepatology

Organ-on-Chip Approaches for Intestinal 3D In Vitro Modeling

Joana Pimenta et al.

Summary: The combination of microfluidics technology with cell culture has led to the development of organs-on-chip models that mimic the proliferative and differentiated compartments of the intestinal epithelium, long-term maintenance of commensals, and intraluminal perfusion of organoids. These systems show closer transcriptomic profile and functionality to the intestine in vivo. The design flexibility of microfluidic technology enables the simultaneous incorporation of multiple components, potentially allowing applications in disease modeling, host-microbiota studies, stem cell biology, drug testing, and personalized medicine.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2022)

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Article Cell Biology

Chitosan Oligosaccharides Regulate the Occurrence and Development of Enteritis in a Human Gut-On-a-Chip

Bolin Jing et al.

Summary: A human gut-on-a-chip microsystem was established to investigate the effects of chitosan oligosaccharides (COS) on human enteritis. The study demonstrated that COS can reduce intestinal epithelial injury, protect the intestinal barrier, and decrease inflammation.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

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Article Biotechnology & Applied Microbiology

Investigation of Antimicrobial and Cytotoxic Properties and Specification of Silver Nanoparticles (AgNPs) Derived From Cicer arietinum L. Green Leaf Extract

Ayse Baran et al.

Summary: This study investigated the synthesis of silver nanoparticles using chickpea leaf extract and characterized their physical and chemical properties. The biologically synthesized silver nanoparticles showed strong antimicrobial activity and low cytotoxicity.

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2022)

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Article Peripheral Vascular Disease

In vitro grafting of hepatic spheroids and organoids on a microfluidic vascular bed

Flavio Bonanini et al.

Summary: This study introduces a platform for routine grafting of liver and other tissues on an in vitro grown microvascular bed. The platform allows the formation of a stable, perfusable vascular network by inducing angiogenesis between two main lateral vessels. It has the potential to replace animals with an in vitro alternative for routine grafting of spheroids, organoids, or (patient-derived) explants.

ANGIOGENESIS (2022)

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Article Engineering, Biomedical

Immunoresponsive microbiota-gut-on-chip reproduces barrier dysfunction, stromal reshaping and probiotics translocation under inflammation

Vincenza De Gregorio et al.

Summary: We propose an immune-responsive human Microbiota-Intestine axis on-chip that can replicate the structure and topography of the microbiota and simulate the complex extracellular microenvironment of the intestine. By integrating cell populations involved in the inflammatory response and intestinal commensal microbiota, we demonstrated the important role of the microbiota in immune response and inflammation.

BIOMATERIALS (2022)

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Article Multidisciplinary Sciences

Live probiotic bacteria administered in a pathomimetic Leaky Gut Chip ameliorate impaired epithelial barrier and mucosal inflammation

Soyoun Min et al.

Summary: In this study, a pathomimetic Leaky Gut Chip was developed to mimic increased epithelial permeability and intestinal inflammation. The effectiveness of probiotic intervention was evaluated using this chip, and it was found that probiotic bacteria could improve barrier function, reduce the expression of inflammatory markers, and decrease the production of pro-inflammatory cytokines.

SCIENTIFIC REPORTS (2022)

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Article Biotechnology & Applied Microbiology

Primary exploration of host-microorganism interaction and enteritis treatment with an embedded membrane microfluidic chip of the human intestinal-vascular microsystem

Wei Zhao et al.

Summary: Intestinal flora imbalance affects the host's intestinal health. This study developed an in vitro gut-on-a-chip model using a microfluidic-based organ chip, which simulated the immune system and blood flow shear stress. The model exhibited the morphology and function of the intestine and can be used for studying intestinal ecology, host and intestinal flora interactions, and medication assessment.

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2022)

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Article Multidisciplinary Sciences

Bacteriophages evolve enhanced persistence to a mucosal surface

Wai Hoe Chin et al.

Summary: The majority of viruses in the gut are bacterial viruses known as bacteriophages, which coevolve with gut bacteria. This study investigated the evolutionary interactions between bacteriophages, bacterial hosts, and the mammalian gut mucosa. The researchers found that bacteriophages can evolve in response to a mammalian-derived mucosal environment.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Article Engineering, Biomedical

Bioengineered Co-culture of organoids to recapitulate host-microbe interactions

Min Beom Kim et al.

Summary: The recent increase in complex physiological host-microbe interactions has led to a demand for in vitro models that replicate the microbial microenvironment in the human body. Organoids, an in vitro culture system that closely mimics the structure, function, and genetic features of human organs, are emerging as a promising tool for studying host-microbe interactions. Co-cultures of organoids with microbes show great potential in simulating complex host-microbe interactions and advancing related fields. This review provides an overview of bioengineering approaches for microbe-co-cultured organoids and highlights the latest developments in their applications for studying human physiology and pathophysiology.

MATERIALS TODAY BIO (2022)

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Review Medicine, General & Internal

Role of gut microbiota-derived signals in the regulation of gastrointestinal motility

Zhipeng Zheng et al.

Summary: The gut microbiota plays a significant role in regulating GI motility through interactions with the enteroendocrine system, enteric nervous system, intestinal smooth muscle, and immune system.

FRONTIERS IN MEDICINE (2022)

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Article Biochemical Research Methods

Microfluidic system for immune cell activation and inflammatory cytokine profiling: Application to screening of dietary supplements for anti-inflammatory properties

Qasem Ramadan et al.

Summary: A versatile and reconfigurable microfluidic chip was developed for immune cell culture and quantification of multi-cytokine secretion. The chip includes three fluidic layers for perfusion, cell culture, and cytokine capture, enabling time-resolved detection of secreted cytokines. THP-1 cells were treated with lipopolysaccharides, docosahexaenoic acid (DHA), and curcumin to study their effects on cytokine secretion.

BIOMICROFLUIDICS (2022)

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Article Cell Biology

Stand by me: Fibroblasts regulation of the intestinal epithelium during development and homeostasis

Neta Felsenthal et al.

Summary: The epithelium of the small intestine consists of crypts and villi, with intrinsic cell behaviors and coordination between epithelium and fibroblasts playing crucial roles in tissue morphogenesis and gene expression.

CURRENT OPINION IN CELL BIOLOGY (2022)

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Article Biochemistry & Molecular Biology

A versatile multiplexed assay to quantify intracellular ROS and cell viability in 3D on-a-chip models

Camilla Soragni et al.

Summary: Reactive oxygen species (ROS) play important roles in cell signaling and oxidative stress. However, quantifying ROS directly in vivo is challenging, and most studies are conducted in vitro. This study developed a multiplexed assay to quantify ROS and cell viability in organ-on-a-chip models. The results showed that organ-on-a-chip models are more efficient in scavenging ROS compared to 2D cell culture. Additionally, the assay could differentiate different cell phenotypes based on oxidative stress level and detect higher levels in tumor cells. This study helps unravel the mechanisms behind oxidative stress and ROS accumulation.

REDOX BIOLOGY (2022)

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Article Multidisciplinary Sciences

4D live imaging and computational modeling of a functional gut-on-a-chip evaluate how peristalsis facilitates enteric pathogen invasion

Aleix Boquet-Pujadas et al.

Summary: This study reveals the significant role of mechanical cues in the invasion of enteropathogens and highlights the acceleration of tissue destruction and invasion by peristalsis. The activation of virulence genes in bacteria and facilitation of parasite penetration were also observed under local tension. This work introduces a framework for studying mechanobiology on deformable tissues.

SCIENCE ADVANCES (2022)

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Article Immunology

An autologous colonic organoid-derived monolayer model to study immune: bacterial interactions in Crohn's disease patients

Hamish Ck Angus et al.

Summary: This study developed a new autologous colonic monolayer model to study the complexity of CD, revealing impaired epithelial integrity in monolayers derived from CD donors compared to non-IBD donors, with higher variability in CD donors.

CLINICAL & TRANSLATIONAL IMMUNOLOGY (2022)

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Article Biotechnology & Applied Microbiology

Systematic evaluation of colorectal cancer organoid system by single-cell RNA-Seq analysis

Rui Wang et al.

Summary: Patient-derived organoids can faithfully recapitulate the gene expression signatures of colorectal cancer cells in vivo, while organoids derived from normal tissues exhibit some tumor-like features but retain normal genomic features. Conditioned medium outperforms chemical-defined medium in long-term culture of tumor epithelial cells, and interchanging the culture medium does not significantly alter the transcriptome characteristics of the organoids.

GENOME BIOLOGY (2022)

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Review Biochemistry & Molecular Biology

Microbiota in health and diseases

Kaijian Hou et al.

Summary: The role of microbiota in health and disease is significant, contributing to homeostasis and immune regulation. Dysbiosis of microbiota can lead to disease progression, associated with dysregulation of community composition, modulation of host immune response, and induction of chronic inflammation. Clinical approaches utilizing microbiota, such as microbiota modulation and fecal microbial transplantation, can be effective for disease treatment.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2022)

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Article Engineering, Biomedical

Properties and Applications of PDMS for Biomedical Engineering: A Review

Ines Miranda et al.

Summary: This review provides an overview of the properties of PDMS and its applications in the field of micro and nanoengineering. PDMS is widely used in biomedical applications due to its excellent optical, electrical, and mechanical properties, as well as biocompatibility. The introduction of the soft-lithography technique has facilitated the rapid prototyping of micro and nanostructures using PDMS, leading to advances in microfluidics, electronics, and biomedicine.

JOURNAL OF FUNCTIONAL BIOMATERIALS (2022)

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Article Chemistry, Physical

Biosynthesis of AgNPs onto the urea-based periodic mesoporous organosilica (AgxNPs/Ur-PMO) for antibacterial and cell viability assay

Amir Hasanzadeh et al.

Summary: Nano-size silver particles stabilized on urea-based periodic mesoporous organosilica, using Euphorbia leaf extract as a green reducing agent; physical and chemical properties of organosilica materials analyzed through various techniques; promising biocompatibility and antibacterial effects of designed material demonstrated through in vitro cytotoxicity test.

JOURNAL OF COLLOID AND INTERFACE SCIENCE (2021)

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Article Chemistry, Analytical

Turn-On Fluorescence Sensing of Oxygen with Dendrimer-Encapsulated Platinum Nanoparticles as Tunable Oxidase Mimics for Spatially Resolved Measurement of Oxygen Gradient in a Human Gut-on-a-Chip

Hyein Lee et al.

Summary: Turn-on fluorescence sensing of O-2 using Pt dendrimer-encapsulated nanoparticles (DENs) was successfully demonstrated in a 3D human intestinal epithelial layer on a gut-on-a-chip platform. The study showed that the oxidase-mimetic activity of Pt DENs can be tuned, with the optimal Pt2+/dendrimer ratio of 1320 exhibiting a 117-fold increase in activity compared to a ratio of 200. This research provides a simple and effective approach for spatially resolved imaging of O-2 in microphysiological environments.

ANALYTICAL CHEMISTRY (2021)

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Article Engineering, Biomedical

Dynamic flow and shear stress as key parameters for intestinal cells morphology and polarization in an organ-on-a-chip model

Chiara A. M. Fois et al.

Summary: The study found that using dynamic flow rate can maintain constant cell shear stress and promote cell polarization during cultivation. Caco-2 cells can achieve cell differentiation and form specific structures under both dynamic and constant flow rate conditions, with gene expression unaffected by dynamic flow rate.

BIOMEDICAL MICRODEVICES (2021)

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Review Biochemistry & Molecular Biology

Biobanking of human gut organoids for translational research

Francesca Perrone et al.

Summary: The development of human organoid culture models offers opportunities for generating three-dimensional miniature organs that mimic in vivo conditions, contributing to drug discovery and personalized treatment. However, establishing a living organoid biobank requires greater coordination, resources, and expertise compared to traditional tissue repositories, facing various challenges and complexities.

EXPERIMENTAL AND MOLECULAR MEDICINE (2021)

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Article Multidisciplinary Sciences

Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity

Samaneh K. Sarvestani et al.

Summary: This study successfully developed an induced human UC-derived organoid (iHUCO) model using induced pluripotent stem cells (iPSCs) to recapitulate disease histological and functional features, and confirmed the role of CXCL8/CXCR1 in the pathogenesis of UC.

NATURE COMMUNICATIONS (2021)

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Review Biochemistry & Molecular Biology

The Progress of Intestinal Epithelial Models from Cell Lines to Gut-On-Chip

Shafaque Rahman et al.

Summary: Research on intestinal function models helps to understand intestinal physiology and functions in health and disease states. However, the translation to human in vivo situation remains problematic due to the failure of these models to fully reflect the complex in vivo environment. Although traditional models are still in use, more sophisticated intestinal models have been developed in recent years.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Multidisciplinary Sciences

SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip

Yaqiong Guo et al.

Summary: The research team developed an intestinal infection model on a chip that recapitulates the pathophysiology induced by SARS-CoV-2 at the organ level, providing insights into the intestinal barrier injury caused by viral infection. The model reconstructs key features of the intestinal epithelium-vascular endothelium barrier through 3D co-culture, offering a unique and rapid platform for COVID-19 research.

SCIENCE BULLETIN (2021)

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Article Nanoscience & Nanotechnology

Comparative study of the transcriptomes of Caco-2 cells cultured under dynamic vs. static conditions following exposure to titanium dioxide and zinc oxide nanomaterials

Kornphimol Kulthong et al.

Summary: The study utilized a gut-on-chip in vitro system and found that under dynamic conditions, intestinal epithelial cells showed increased sensitivity to TiO2 and ZnO nanomaterials, with significantly different gene expression levels. This suggests that shear stress may be a major factor in cell susceptibility.

NANOTOXICOLOGY (2021)

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Article Pharmacology & Pharmacy

A 3D microfluidic liver model for high throughput compound toxicity screening in the OrganoPlate®

Kristin M. Bircsak et al.

Summary: This study presents the development, automation, and validation of a 3D, microfluidic liver-on-a-chip system for high-throughput hepatotoxicity screening. The model consists of iPSC-derived hepatocyte aggregates co-cultured with endothelial cells and macrophages in a microchannel platform. With automation protocols and robust statistical analysis, the model demonstrated stable cell viability and functionality over time, making it a promising tool for hepatotoxicity screening and compound prioritization.

TOXICOLOGY (2021)

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Article Multidisciplinary Sciences

Transcriptome comparisons of in vitro intestinal epithelia grown under static and microfluidic gut-on-chip conditions with in vivo human epithelia

Kornphimol Kulthong et al.

Summary: Dynamic culture conditions in gut-on-chip devices can mimic the in vivo intestinal environment and impact the gene expression of Caco-2 cells. The study shows that under dynamic culture conditions, gene expression patterns similar to those of the intestines in vivo were observed.

SCIENTIFIC REPORTS (2021)

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Article Immunology

Harnessing Colon Chip Technology to Identify Commensal Bacteria That Promote Host Tolerance to Infection

Francesca S. Gazzaniga et al.

Summary: This study described methods for developing microfluidic organ-on-a-chip models of small and large intestine, focusing on host-microbiome interactions in the mouse Colon Chip. The study successfully demonstrated the effects of infection on epithelial cells and the symbiosis between microbiome bacteria and intestinal epithelium in the Colon Chips by populating them with complex living microbiome samples from mice or humans.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2021)

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Review Chemistry, Multidisciplinary

Biomaterials for Three-Dimensional Cell Culture: From Applications in Oncology to Nanotechnology

Tarek Sayde et al.

Summary: Three-dimensional cell culture has transformed cellular biology research by allowing for analysis of cellular behavior and responses to microenvironment stimuli. The use of hydrogel scaffold-based models can produce multicellular tumor spheroids when growing cancer cells, providing a platform to study tumor development and toxicity assessment. However, the biggest challenge lies in the reproducibility of the system's components, particularly the multicellular tumor spheroids.

NANOMATERIALS (2021)

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Article Oncology

Non-matrigel scaffolds for organoid cultures

Savneet Kaur et al.

Summary: Organoids are 3D cell cultures derived from tissue-resident or embryonic stem cells on hydrogels with defined growth factors. Matrigel is commonly used, but other natural and synthetic hydrogel scaffolds are being explored due to its limitations. Developing customized hydrogels for organoid cultures is crucial for various therapeutic and pharmaceutical applications.

CANCER LETTERS (2021)

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Article Multidisciplinary Sciences

Characterization of an engineered live bacterial therapeutic for the treatment of phenylketonuria in a human gut-on-a-chip

M. Tyler Nelson et al.

Summary: Engineered bacteria, or synthetic biotics, utilize synthetic biology tools for therapeutic purposes and require translational testing to predict their function in the human body. Gut-on-a-chip microfluidics technology allows for characterization of strain function within a simulated human gastrointestinal tract, providing a framework to predict the function of candidate strains in vivo.

NATURE COMMUNICATIONS (2021)

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Review Microbiology

Organoids and organs-on-chips: Insights into human gut-microbe interactions

Jens Puschhof et al.

Summary: In vitro co-culture models are important tools for studying interactions between microbiota and intestinal tissues. These models can replicate specific processes of microbe-epithelia interactions. By using different models of bacterial, viral, and parasitic infections, the advantages of each culture model can be highlighted.

CELL HOST & MICROBE (2021)

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Article Biochemistry & Molecular Biology

A Microfluidic 3D Endothelium-on-a-Chip Model to Study Transendothelial Migration of T Cells in Health and Disease

Luuk de Haan et al.

Summary: Recruitment of T cells plays a crucial role in inflammatory responses, with a newly developed assay providing insights into T cell dynamics under flow conditions. This study demonstrates T cell responses to various stimuli and offers a comprehensive approach for studying immunological processes.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Biochemical Research Methods

Intestinal organoid cocultures with microbes

Jens Puschhof et al.

Summary: This protocol outlines methods for co-culturing human small intestinal and colon organoids with microbes, including microinjection and exposure to bacteria. It provides detailed protocols for assessing cell viability and growth kinetics, as well as spatial relationships using microscopy techniques. Considerations for evaluating the impact of bacteria on gene expression and mutations through sequencing are also discussed.

NATURE PROTOCOLS (2021)

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Article Food Science & Technology

Bioengineering approaches to simulate human colon microbiome ecosystem

Dalila Roupar et al.

Summary: This review discusses the applications of in vitro models in simulating human colon microbiome dynamics, highlighting the characteristics, functionalities, applications, advantages, and disadvantages. While various models representing specific colon parts have been developed, none can fully replicate all key conditions found in the human colon, indicating a need for further improvement in experimental setups to create more realistic operating systems.

TRENDS IN FOOD SCIENCE & TECHNOLOGY (2021)

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Article Gastroenterology & Hepatology

A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal Permeability

Athanasia Apostolou et al.

Summary: This study developed a microphysiological Colon Intestine-Chip platform that can mimic properties of human intestinal epithelium. It highlights the importance of endothelium and in vivo tissue-relevant dynamic microenvironment in establishing a tight monolayer of differentiated, polarized, organoid-derived intestinal epithelial cells, providing insights into the mechanism of interleukin 22 in the human epithelial barrier.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2021)

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Article Gastroenterology & Hepatology

Ileal Derived Organoids From Crohn's Disease Patients Show Unique Transcriptomic and Secretomic Signatures

Barbara Joanna Niklinska-Schirtz et al.

Summary: Using PDOs, the study investigated the epithelial-specific transcriptional and secretome signatures of the ileum in CD patients, identifying disease profiles and potential druggable targets. By analyzing DE genes, candidate small molecules were found to potentially reverse different CD phenotypes, and the secretome of PDOs showed both similarity and diversity in the levels and types of soluble factors released. The study concluded that targeting the epithelium could reverse stricturing phenotype and improve outcomes.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2021)

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Article Biochemical Research Methods

Simulating drug concentrations in PDMS microfluidic organ chips

Jennifer Grant et al.

Summary: A combined simulation and experimental approach is described to predict the spatial and temporal concentration profile of a drug in a PDMS Organ Chip, allowing for drug testing without prior knowledge of partition coefficient or diffusion rate in PDMS.

LAB ON A CHIP (2021)

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Article Biochemical Research Methods

High throughput transepithelial electrical resistance (TEER) measurements on perfused membrane-free epithelia

A. Nicolas et al.

Summary: The instrument introduced can measure TEER of perfused epithelial tubes, showing higher sensitivity to certain stimuli and allowing measurement of multiple tubes in less than a minute. Additionally, it enables time-lapse data acquisition to observe the effects on the channels.

LAB ON A CHIP (2021)

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Article Biochemical Research Methods

High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows†

H. Azizgolshani et al.

Summary: Drug development lacks predictive and human-relevant in vitro models. The Organ-on-chip (OOC) technology provides advanced culture capabilities to generate human-based tissue in vitro, but faces challenges in throughput and compatibility. This study presents an OOC platform with advanced culture capabilities supporting multiple human tissue models for drug screening and gene expression analysis.

LAB ON A CHIP (2021)

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Article Biochemical Research Methods

Developing an advanced gut on chip model enabling the study of epithelial cell/fibroblast interactions

Marine Verhulsel et al.

Summary: A new gut on chip model has been developed for co-culture of primary epithelial and stromal cells, mimicking the structure and topography of the mouse gut. The collagen scaffold is rigidified by threose-based post-polymerization treatment to maintain its structure and cytocompatibility. Mouse organoids deposited into crypts are able to epithelialize the scaffold and form a polarized epithelial monolayer, demonstrating proper cell segregation along the crypt-villus axis. Fluid shear stress application allows long-term culture of the intestinal epithelium in this biomimetic tool.

LAB ON A CHIP (2021)

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Article Immunology

Mechanical Stimuli Affect Escherichia coli Heat-Stable Enterotoxin-Cyclic GMP Signaling in a Human Enteroid Intestine-Chip Model

Laxmi Sunuwar et al.

INFECTION AND IMMUNITY (2020)

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Article Multidisciplinary Sciences

Mutational signature in colorectal cancer caused by genotoxic pks+E. coli

Cayetano Pleguezuelos-Manzano et al.

NATURE (2020)

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Review Gastroenterology & Hepatology

Abnormal gut motility in inflammatory bowel disease: an update

G. Bassotti et al.

TECHNIQUES IN COLOPROCTOLOGY (2020)

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Article Gastroenterology & Hepatology

Lactobacillus reuteri maintains intestinal epithelial regeneration and repairs damaged intestinal mucosa

Haiqin Wu et al.

GUT MICROBES (2020)

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Article Multidisciplinary Sciences

Patient-derived small intestinal myofibroblasts direct perfused, physiologically responsive capillary development in a microfluidic Gut-on-a-Chip Model

Kristen M. Seiler et al.

SCIENTIFIC REPORTS (2020)

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Article Biology

Duodenum Intestine-Chip for preclinical drug assessment in a human relevant model

Magdalena Kasendra et al.

ELIFE (2020)

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Article Biotechnology & Applied Microbiology

Establishment and Application of Peristaltic Human Gut-Vessel Microsystem for Studying Host-Microbial Interaction

Bolin Jing et al.

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2020)

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Article Immunology

A Human 2D Primary Organoid-Derived Epithelial Monolayer Model to Study Host-Pathogen Interaction in the Small Intestine

Thomas Roodsant et al.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2020)

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Article Chemistry, Analytical

Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip

Yong Cheol Shin et al.

MICROMACHINES (2020)

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Article Biochemistry & Molecular Biology

Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells

Elena Naumovska et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Cell Biology

Characterization of Human Colon Organoids From Inflammatory Bowel Disease Patients

Emilie d'Aldebert et al.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2020)

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Article Biotechnology & Applied Microbiology

A Theoretical and Experimental Study to Optimize Cell Differentiation in a Novel Intestinal Chip

Nicky Langerak et al.

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2020)

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Review Biotechnology & Applied Microbiology

Human Microphysiological Models of Intestinal Tissue and Gut Microbiome

Steven N. Steinway et al.

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2020)

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Article Chemistry, Multidisciplinary

IFlowPlate-A Customized 384-Well Plate for the Culture of Perfusable Vascularized Colon Organoids

Shravanthi Rajasekar et al.

ADVANCED MATERIALS (2020)

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Article Multidisciplinary Sciences

Homeostatic mini-intestines through scaffold-guided organoid morphogenesis

Mikhail Nikolaev et al.

NATURE (2020)

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Article Nutrition & Dietetics

Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function

Tanja Suligoj et al.

NUTRIENTS (2020)

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Review Immunology

Mucins in Intestinal Mucosal Defense and Inflammation: Learning From Clinical and Experimental Studies

Jensine A. Grondin et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Article Multidisciplinary Sciences

Development of a human primary gut-on-a-chip to model inflammatory processes

Claudia Beaurivage et al.

SCIENTIFIC REPORTS (2020)

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Review Cell Biology

Extracellular Matrix Mechanical Properties and Regulation of the Intestinal Stem Cells: When Mechanics Control Fate

Lauriane Onfroy-Roy et al.

CELLS (2020)

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Article Materials Science, Multidisciplinary

Visualization of Bacterial Colonization and Cellular Layers in a Gut-on-a-Chip System Using Optical Coherence Tomography

Lu Yuan et al.

MICROSCOPY AND MICROANALYSIS (2020)

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Article Biochemical Research Methods

Neutrophilic infiltration in organ-on-a-chip model of tissue inflammation

Nikolce Gjorevski et al.

LAB ON A CHIP (2020)

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Article Gastroenterology & Hepatology

Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology

Alexandra Sontheimer-Phelps et al.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2020)

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Article Pediatrics

The mucosal-luminal interface: an ideal sample to study the mucosa-associated microbiota and the intestinal microbial biogeography

Walid Mottawea et al.

PEDIATRIC RESEARCH (2019)

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Article Multidisciplinary Sciences

Long-term in vitro 3D hydrogel co-culture model of inflammatory bowel disease

Rasha H. Dosh et al.

SCIENTIFIC REPORTS (2019)

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Article Microbiology

Species-specific enhancement of enterohemorrhagic E-coli pathogenesis mediated by microbiome metabolites

Alessio Tovaglieri et al.

MICROBIOME (2019)

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Review Biochemistry & Molecular Biology

Dysbiosis Disrupts Gut Immune Homeostasis and Promotes Gastric Diseases

Devinder Toor et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

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Article Engineering, Biomedical

A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip

Sasan Jalili-Firoozinezhad et al.

NATURE BIOMEDICAL ENGINEERING (2019)

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Article Multidisciplinary Sciences

Self-organized intestinal epithelial monolayers in crypt and villus-like domains show effective barrier function

Gizem Altay et al.

SCIENTIFIC REPORTS (2019)

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Review Microbiology

Regional Diversity of the Gastrointestinal Microbiome

Kristina Martinez-Guryn et al.

CELL HOST & MICROBE (2019)

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Article Microbiology

Bioengineered Human Organ-on-Chip Reveals Intestinal Microenvironment and Mechanical Forces Impacting Shigella Infection

Alexandre Grassart et al.

CELL HOST & MICROBE (2019)

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Article Engineering, Biomedical

A three-dimensional immunocompetent intestine-on-chip model as in vitro platform for functional and microbial interaction studies

Michelle Maurer et al.

BIOMATERIALS (2019)

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Article Biochemistry & Molecular Biology

Development of a Gut-on-a-Chip Model for High Throughput Disease Modeling and Drug Discovery

Claudia Beaurivage et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

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Article Immunology

Evaluating Shigella flexneri Pathogenesis in the Human Enteroid Model

Sridevi Ranganathan et al.

INFECTION AND IMMUNITY (2019)

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Article Immunology

Human Intestinal Enteroids as a Model System of Shigella Pathogenesis

Benjamin J. Koestler et al.

INFECTION AND IMMUNITY (2019)

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Article Biotechnology & Applied Microbiology

A Robust Longitudinal Co-culture of Obligate Anaerobic Gut Microbiome With Human Intestinal Epithelium in an Anoxic-Oxic Interface-on-a-Chip

Woojung Shin et al.

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2019)

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Article Multidisciplinary Sciences

Human Intestinal Morphogenesis Controlled by Transepithelial Morphogen Gradient and Flow-Dependent Physical Cues in a Microengineered Gut-on-a-Chip

Woojung Shin et al.

ISCIENCE (2019)

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Review Immunology

Interactions Between the Gut Microbiota and the Host Innate Immune Response Against Pathogens

Hong-Yu Cheng et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Article Biochemistry & Molecular Biology

Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22

Qihang Hou et al.

CELL DEATH AND DIFFERENTIATION (2018)

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Article Chemistry, Multidisciplinary

Implementation of a dynamic intestinal gut-on-a-chip barrier model for transport studies of lipophilic dioxin congeners

Kornphimol Kulthong et al.

RSC ADVANCES (2018)

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Article Multidisciplinary Sciences

Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids

Magdalena Kasendra et al.

SCIENTIFIC REPORTS (2018)

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Review Cell Biology

Mechanical Force-Driven Adherens Junction Remodeling and Epithelial Dynamics

Diana Pinheiro et al.

DEVELOPMENTAL CELL (2018)

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Article Multidisciplinary Sciences

Intestinal barrier dysfunction orchestrates the onset of inflammatory host-microbiome cross-talk in a human gut inflammation-on-a-chip

Woojung Shin et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

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Review Physiology

Intestinal in vitro and ex vivo Models to Study Host-Microbiome Interactions and Acute Stressors

Sarah C. Pearce et al.

FRONTIERS IN PHYSIOLOGY (2018)

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Article Gastroenterology & Hepatology

Formation of Human Colonic Crypt Array by Application of Chemical Gradients Across a Shaped Epithelial Monolayer

Yuli Wang et al.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2018)

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Article Biochemistry & Molecular Biology

Mechanisms regulating intestinal barrier integrity and its pathological implications

Chaithanya Chelakkot et al.

EXPERIMENTAL AND MOLECULAR MEDICINE (2018)

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Article Gastroenterology & Hepatology

A High-Throughput Organoid Microinjection Platform to Study Gastrointestinal Microbiota and Luminal Physiology

Ian A. Williamson et al.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2018)

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Article Gastroenterology & Hepatology

Enhanced Utilization of Induced Pluripotent Stem Cell-Derived Human Intestinal Organoids Using Microengineered Chips

Michael J. Workman et al.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2018)

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Article Cell Biology

T84 monolayers are superior to Caco-2 as a model system of colonocytes

Sarah Devriese et al.

HISTOCHEMISTRY AND CELL BIOLOGY (2017)

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Article Cell & Tissue Engineering

Emulating Host-Microbiome Ecosystem of Human Gastrointestinal Tract in Vitro

Gun-Seok Park et al.

STEM CELL REVIEWS AND REPORTS (2017)

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Article Multidisciplinary Sciences

Membrane-free culture and real-time barrier integrity assessment of perfused intestinal epithelium tubes

Sebastiaan J. Trietsch et al.

NATURE COMMUNICATIONS (2017)

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Article Cell & Tissue Engineering

Emulating Host-Microbiome Ecosystem of Human Gastrointestinal Tract in Vitro

Gun-Seok Park et al.

STEM CELL REVIEWS AND REPORTS (2017)

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Article Multidisciplinary Sciences

Human Gut-On-A-Chip Supports Polarized Infection of Coxsackie B1 Virus In Vitro

Remi Villenave et al.

PLOS ONE (2017)

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Article Multidisciplinary Sciences

Microscale Bioreactors for in situ characterization of GI epithelial cell physiology

Cait M. Costello et al.

SCIENTIFIC REPORTS (2017)

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Review Gastroenterology & Hepatology

The extracellular matrix in IBD: a dynamic mediator of inflammation

Aaron C. Petrey et al.

CURRENT OPINION IN GASTROENTEROLOGY (2017)

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Article Engineering, Biomedical

Microfluidic gut-on-a-chip with three-dimensional villi structure

Kyu-Young Shim et al.

BIOMEDICAL MICRODEVICES (2017)

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Review Microbiology

The role of gut microbiota in health and disease: In vitro modeling of host-microbe interactions at the aerobe-anaerobe interphase of the human gut

Julius Z. H. von Martels et al.

ANAEROBE (2017)

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Review Immunology

Roles of the intestinal microbiota in pathogen protection

Carles Ubeda et al.

CLINICAL & TRANSLATIONAL IMMUNOLOGY (2017)

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Article Biochemistry & Molecular Biology

Small molecule absorption by PDMS in the context of drug response bioassays

B. J. van Meer et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2017)

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Article Gastroenterology & Hepatology

Current Understanding of Dysbiosis in Disease in Human and Animal Models

Arianna K. DeGruttola et al.

INFLAMMATORY BOWEL DISEASES (2016)

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Article Chemistry, Medicinal

Functional Characterization of Cholera Toxin Inhibitors Using Human Intestinal Organoids

Domenique D. Zomer-van Ommen et al.

JOURNAL OF MEDICINAL CHEMISTRY (2016)

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Article Multidisciplinary Sciences

A microfluidics-based in vitro model of the gastrointestinal human-microbe interface

Pranjul Shah et al.

NATURE COMMUNICATIONS (2016)

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Article Gastroenterology & Hepatology

Enterohemorrhagic Escherichia coli Reduces Mucus and Intermicrovillar Bridges in Human stem Cell-Derived Colonoids

Julie In et al.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2016)

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Article Physiology

Salmonella-infected crypt-derived intestinal organoid culture system for host-bacterial interactions

Yong-Guo Zhang et al.

PHYSIOLOGICAL REPORTS (2014)

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Article Cell Biology

Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation

Hyun Jung Kim et al.

INTEGRATIVE BIOLOGY (2013)

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Article Biochemical Research Methods

Comparison of the Caco-2, HT-29 and the mucus-secreting HT29-MTX intestinal cell models to investigate Salmonella adhesion and invasion

Melanie Gagnon et al.

JOURNAL OF MICROBIOLOGICAL METHODS (2013)

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Review Multidisciplinary Sciences

Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications

Toshiro Sato et al.

SCIENCE (2013)

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Article Biochemical Research Methods

Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow

Hyun Jung Kim et al.

LAB ON A CHIP (2012)

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Article Gastroenterology & Hepatology

Long-term Expansion of Epithelial Organoids From Human Colon, Adenoma, Adenocarcinoma, and Barrett's Epithelium

Toshiro Sato et al.

GASTROENTEROLOGY (2011)

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Review Biotechnology & Applied Microbiology

Epithelial Cell Coculture Models for Studying Infectious Diseases: Benefits and Limitations

Benjamin L. Duell et al.

JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY (2011)

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Article Multidisciplinary Sciences

Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro

Jason R. Spence et al.

NATURE (2011)

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Review Gastroenterology & Hepatology

Microflora Modulation of Motility

Eamonn M. M. Quigley

JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY (2011)

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Review Cell Biology

The effects of mechanical forces on intestinal physiology and pathology

Christopher P. Gayer et al.

CELLULAR SIGNALLING (2009)

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Review Biochemistry & Molecular Biology

The Caco-2 cell monolayer: usefulness and limitations

Huadong Sun et al.

EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY (2008)

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Article

Adapting Cell-Based Assays to the High-Throughput Screening Platform: Problems Encountered and Lessons Learned

C MADDOX et al.

Journal of the Association for Laboratory Automation. (2008)

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Article Biochemical Research Methods

PDMS absorption of small molecules and consequences in microfluidic applications

Michael W. Toepke et al.

LAB ON A CHIP (2006)

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Review Cell Biology

The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics

Y Sambuy et al.

CELL BIOLOGY AND TOXICOLOGY (2005)

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