Resources

Evaluation of in vitro human alveolar and bronchial microphysiological systems to predict the permeability and absorption of inhaled pulmonary medications

The lung is the most vulnerable internal organ to infection and injury due to its constant exposure to inhaled particles and pathogens from the environment. Coinciding with this, respiratory diseases are a leading cause of death and disability.

Human liver microphysiological system for predicting the drug-induced liver toxicity of differing drug modalities

Novac et al

The liver is one of the organs most susceptible to drug toxicity and drug-induced liver injury (DILI). With more than 750 FDA-approved drugs known to have a degree of DILI risk, better preclinical models are required to de-risk new therapeutics earlier in the drug development process.​ We assess whether a Liver MPS model could be used to understand the detailed mechanistic aspects of liver toxicity.

Microphysiological system for studying fatty liver disease and its impact on drug-induced liver injury

Kostrzewski et al

As a result of the increased prevalence of diabetes, obesity, and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease in developed countries. Using better in vitro models to fast-track therapeutic development but also accurately assess DILI risk in NASH patients ahead of the clinic is critical. Here, we show the potential of an in vitro 3D NASH model to accurately identify any DILI-associated risks.

Application of a gut–liver-on-a-chip device and mechanistic modeling to the quantitative in vitro pharmacokinetic study of mycophenolate mofetil

Milani et al., 2022

This study shows how an in vitro gut-liver multi-organ model can quantitatively recapitulate the in vivo metabolism of a drug. By combining Organ-on-a-chip with in silico modeling, the study also demonstrates the potential of multi-organ models for quantitative estimation of PK parameters of a drug and its metabolites.

Pharmacokinetics in mice… or a microfluidic device!

Are you still using xenograft models? Looking for more translatable results? Discover how our oncology services can help you today.

Pros and cons of preclinical models of Non-Alcoholic Steatohepatitis

This infographic was made by Biotechniques to help educate people on our NASH-in-a-box kit and how it sets a new standard in the search for an approved NASH therapeutic.

In Focus: Modeling NASH disease – organ-on-a-chip technologies

This short animation describes how our NASH-in-a-box kit enhances your chance of successfully developing NASH therapeutics by recreating our industry-proven NASH model in your laboratory. Created by Biotechniques.

Every Breath You Take: Predicting Inhaled Drug ADME Using Lung-on-a-Chip

Webinar Series 5 Episode 2

In this webinar, Lead Scientist, Dr Emily Richardson describes novel alveolar and bronchial lung-on-a-chip, or lung MPS, models. She demonstrates how to predict drug pharmacokinetics, allowing for more rapid, precise, and cost-effective compound analysis.

Organ-on-a-Chip Models of Fatty Liver Disease

15-Minute Tech Blast – In this podcast developed by Biotechniques, our Lead Scientist Gareth Guenigault discussed NAFLD & NASH and their growing prevalence both in terms of cases and economic factors.

MPS World Summit Round-up

Find out what you missed at the inaugural MPS World Summit and why we hope to see you there next year.

Biotechnology: Bringing New Treatments to Market

A snapshot of research and tools focused on early drug discovery that could eventually bring more effective treatments to patients. Featuring insights from Product Manager, Dr Audrey Doubourg.

This article is taken from Lab Manager, June 2022.

Drug Discoveries Without Animal Testing

Dr Abbas discusses how OOC technology can help reduce the reliance on animal testing.

This article is taken from BioSpecturm Asia, June 2022.

Why two organs are better than one

Abbas, Kostrzewski & Hughes

This poster demonstrates how a gut-liver MPS can improve oral bioavailability predictions by mimicking human oral and IV regimens. Thus improving the in vitro to in vivo translation of drug efficacy and safety.

Alveolar and bronchial human microphysiological systems for use in respiratory infection research and therapeutics evaluation

Richardson et al

This poster shows the use of two lung models (alveolar and bronchial), which both generate physiologically-relevant phenotypes, to improve preclinical therapeutic evaluation and lung disease models.

Primary vs. Stem-Like Cells in 3D Cultures

Dr Ovidiu Novac discusses cell choices in 3D cell cultures.

This article is taken from Biocompare, June 2022.

A microfluidic system that replicates pharmacokinetic (PK) profiles in vitro improves prediction of in vivo efficacy in preclinical models

Singh et al., 2022

This publication demonstrates the Microformulators capability to incorporate replicated PK exposures into cellular assays to improve in vitro–in vivo translation understanding. This is demonstrated through comparisons to traditional fixed dose in vitro studies and in vivo xenograft models.

A Breath of Fresh Air: Novel approaches to human lung disease modelling for accelerated drug discovery

Webinar Series 5 Episode 1

In this webinar, Professor Wojciech Chrzanowski, University of Sydney, and Dr Emily Richardson, CN Bio, discuss how to accelerate therapeutic discovery and evaluation for respiratory infection and lung injuries, using lung MPS models.

Normalization of organ-on-a-chip samples for mass spectrometry based proteomics and metabolomics via dansylation-based assay

Gallagher et al

This poster shows the combined use of MS-based proteomics and metabolomics with organ-on-a-chip to better assess the classification of biological replicates in toxicity studies.

Harnessing the power of multimodal imaging to explore ASO distribution in cells, complex in vitro models and tissue

Alex et al

This recent poster from GSK and collaborators features data from our PhysioMimix™ OOC and Liver (MPS-LC12) plates. The results demonstrate that the distribution of ASOs into Kupffer cells and circular or cuboidal hepatocytes cultured in 3D can be detected using imaging.

Bridging Gaps in Translational Biology

Petreus et al

Developing effective oncology therapies involves defining the right schedules to minimize side effects and maximise efficacy. This requires an accurate understanding of the pharmacokinetic/pharmacodynamics PK/PD relationship of the compound(s). Animal and human PKs can differ significantly and many failures of novel therapies are due to a missing physiologically relevant link between preclinical and clinical data.​

The lung in crisis

Fighting back against pathogens, infections, and inflammation with predictive in vitro respiratory models that accelerate drug discovery.

Animal Models and Microfluidic Tools with a Human Touch

Humanized in vivo and in vitro systems are becoming more clinically relevant and facilitating better decisions earlier in drug development – featuring CEO, Dr David Hughes.

This article is taken from GEN Engineering News, May 2022.

New Model Will Support Drug Discovery for Liver Disease NASH

Dr Audrey Doubourg discusses the therapeutic challenges of NASH and how our NASH-in-a-box kit will help to advance drug discovery.

This article is taken from Technology Networks, April 2022.

CN is believing

Our CEO, Dr David Hughes chats to PharamTimes about our game-changing organ-on-a-chip technology.

This article is taken from PharmaTimes Magazine, March 2022.

Opinionated Science: What is Body-on-a-Chip Technology

Our CEO Dr David Hughes joins Assistant Professor Martin Trapecar at the John Hopkins University of Medicine to share their expert insights of Body-on-a-Chip technologies.

Debunking the 9 Myths of Organ-on-a-Chip Technology

What do you think you know about OOC?

Assessing drug-induced liver injury using a sensitive and selective human liver microphysiological system and clinical biomarkers

Novac et al

Drug-induced liver injury (DILI) is the most common cause of acute liver failure and a leading cause of compound attrition in drug development. In this poster, we demonstrate the potential of a liver MPS to better predict toxicity and improve in vitro to in vivo translation.

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Novac et al., 2022

This study demonstrates the capability of a human liver MPS to generate clinically-relevant, high-content data (six endpoint EC50 curves). A broad set of known severely and mildly hepatotoxic compounds to accurately predict human DILI and its mechanism versus conventional approaches.

Exploration and Application of a Liver-on-a-Chip Device in Combination with Modelling and Simulation for Quantitative Drug Metabolism Studies

Docci et al., 2022

This publication explores the potential of the PhysioMimix liver model for investigating drug candidates for hepatic disease. This study integrates mathematical modeling with experimental liver-on-a-chip studies and demonstrates how this approach supports the generation of high-quality data from complex in vitro cellular systems.

ORGAN-ON-A-CHIP – A Novel Way to Accurately Test Delivery of Non-Standard Formulations

A deep dive into our Lung-on-a-chip system with our CEO Dr David Hughes.

This article is taken from Drug Development, January/February 2022.

A pressing Need for Accurate Preclinical Models of Metabolic Disease

How using organ-on-a-chip (OOC) can more accurately recapitulate the physiology and functions of the human body by culturing under flow perfusion – to mimic the blood – in 3D.

This article is taken from European Biopharmaceutical Review January 2022, pages 28-31.

Multiorgan microphysiological systems as tools to interrogate interorgan crosstalk and complex diseases

Trapecar, 2022

A review of the state of multi-organ microphysiological systems in 2021. Overviews of currently available multi-organ MPS and the different technologies, cells and physiological cues used. Discusses approaches for systems biology integration and how MPS can be more readily adopted in the wider research community.

β2-spectrin (SPTBN1) as a therapeutic target for diet-induced liver disease and preventing cancer development

Rao et al., 2021

This study shows the effect of the presence of β2-spectrin (SPTBN1) in the promotion of sterol regulatory element (SRE)–binding protein (SREBP)–stimulated lipogenesis. These findings suggest SPTBN1 could be a potential target for a therapeutic against NASH and liver cancer.

Predicting Drug Bioavailability with the Modern-Day Toolkit

Animal models continue to be used in bioavailability research but limitations are serious and difficult to overcome. Find out how OOC can help solve your PK/PD and bioavailability issues.

This article is taken from International Biopharmaceutical Industry Winter 2021, pages 14-17.

De-risking drug-induced liver injury through the predictive power of organ-on-a-chip

Unfortunately, it is not uncommon that DILI (Drug-induced liver injury) is only first identified in the clinic. Find out how our systems can help you identify it in your lab.

Improved prediction of oral bioavailability using a gut-liver microphysiological system

Abbas, Kostrzewski & Hughes

Central to the development of new drugs is an understanding of their pharmacokinetic properties, in particular their bioavailability. Here, we demonstrate the potential of a true 2-organ gut-liver MPS to better predict human bioavailability and improve in vitro to in vivo correlation.

Reduce, Refine… Replace?

How to use organ-on-a-chip technologies to make drug discovery more efficient with VP – Science and Technology, Dr Tomasz Kostrzewski.

This article is taken from The Medicine Maker, December 2021.

From Dose to Circulation: Determination of Drug Oral Bioavailability Using a Gut-Liver Microphysiological System

Webinar Series 4 Episode 4

In this webinar, Dr. Yassen Abbas discusses how CNBio’s gut-liver MPS can be used for in vitro determination of oral bioavailability. This application has been validated with drugs with known human bioavailability and with a mathematical model developed to enable prediction of oral bioavailability in silico.

Drug metabolism in a gut-liver microphysiological system

Abbas, Kostrzewski & Hughes

Studies investigating the efficacy and safety of candidate drugs use a variety of animal models to translate research from the bench to clinical trials and then to the clinic. Here, we demonstrate the potential of multi-organ MPS models for improved predictions of in vivo drug absorption and hepatic clearance rates.

Hype or hope – microphysiological systems?

This article in DDW examines MPS (microphysiological systems/organ-on-a-chip) in drug discovery and their place in the preclinical ‘toolbox’.

This article is taken from Drug Discovery World, October 2021.

Fighting Toxic Chemicals: Evaluating the Safety of Cobinamide as a Neutralizing Agent

Webinar Series 4 Episode 3:

This webinar outlines how Boss’ lab used CN Bio’s DILI Services to investigate the hepatotoxicity of two cobinamide formulations.

Pharmacokinetic profiles revisited in 3D microfluidic tumour models

Petreus et al

The efficacy or toxicity of a drug is dependent on the concentration at the target. Current preclinical models mainly rely on in vivo animal studies which often lack translatability to the human. Here, we demonstrate the potential of a new in vitro MPS approach to better predict human PK and improve in vitro to in vivo translational relevance.

Making a difference with disruptive organ-on-a-chip technology

Why do most drugs fail and how can OOC help? This article features CEO David Hughes and Chairman Maureen Coleman.

This article is taken from Busines & Industry, September 2021.

Changing Times, Why Pharmacokinetics Matter in Drug Discovery

Ready to unlock new human-relevant information through our new Oncology Service? This blog discusses all the challenges in drug discovery today and why our Oncology Services could be the missing tool in your toolbox.

Modelling human liver fibrosis in the context of non-alcoholic steatohepatitis using a microphysiological system

Kostrzewski et al., 2021

It was shown in this study that the MPS NASH model, composed of a primary cell co-culture in various conditions, is able to model different characteristics of clinical NASH, including advanced disease with a quantifiable fibrosis phenotype as well as pharmaceutical intervention.

Predictive DILI Models: Human Liver Microphysiological System for Studying Acute and Chronic Drug-Induced Liver Toxicity

Webinar Series 4 Episode 2:

In this webinar, CN Bio Senior Scientist Dr. Ovidiu Novac discusses how a human liver microphysiological system (MPS), or Liver-on-a-chip, can be used to understand the causality and mechanistic aspects of drug-induced liver injury (DILI).

The economic impact of the UK’s New Approach Methodologies sector

CN Bio data is included in this Cebr report to help demonstrate how Britain can show leadership in the field of NAMs (New Approach Methodologies).

This article is taken from A Cebr report for Animal Free Research UK, September 2021.

Organ-on-chip applications in drug discovery: an end user perspective

Clapp et al., 2021

A review that evaluates OOC systems and their application in drug discovery, specifically how they surpass 2D culture and in vivo models in predicting drug efficacy and toxicity. Also highlights the issue of generalisability as OOC are yet to be globally used.

Predicting human drug permeability with a gut microphysiological system

Bray et al

Preclinical drug absorption studies are a key step when developing when therapeutics as they determine how much of orally-administered drug reaches the systemic circulation. Here, we show how we developed and characterized a gut MPS closely aligned to the human small intestine, using the PhysioMimix™ Single-Organ system, and demonstrated its utility to predict drug permeability.

Microphysiological systems of the human liver, gut and linked liver-gut, to assess human drug absorption, metabolism and bioavailbility

Kostrzewski et al

This poster demonstrates the potential of human MPS models for liver, gut, and multi-organ (connecting gut with liver) for the investigation of human PK parameters, drug absorption and metabolism, and bioavailability.

Liver-on-Chip and In Silico Modeling for Quantitative Drug Metabolism Studies

Webinar Series 4 Episode 1:

This webinar examines the benefits of combining Liver-on-a-chip with in silico modeling to explore clinical PK predictions of specific reference drugs, including investigations into the intrinsic clearance determinations for high metabolically stable compounds and the quantitation of fractions metabolized by specific enzymes.

Of Mice and Men – Will human organ-on-a-chip disease models replace animal use?

The aim of organ-on-a-chip (OOC) technology is to more accurately replicate human physiology in vitro to overcome the relevance limitations of current approaches, and the field is progressing at a rapid pace!

Bringing Life to PK Profiles: In Vivo-Relevance From an In Vitro Environment.

Webinar Series 3 Episode 4:

In this webinar, we introduce a new MPS platform designed to address these challenges: the PhysioMimix™ PK – a novel microformulator developed by CN Bio

2D, or Not 2D

Improving pre-clinical drug metabolism and safety predictions of novel therapeutics through fully humanised research can expedite research immensely.

This article is taken from Innovations in Pharmaceutical Technology Spring/Summer 2021, pages 49-51.

Formulating a New Approach to Pharmacokinetics and Cell State Control

Webinar Series 3 Episode 3:

In this webinar, Professor John Wikswo discusses the need for better approaches to efficiently and better predict pharmacokinetics in vitro.

IP-10 (CXCL10) Can Trigger Emergence of Dormant Breast Cancer Cells in a Metastatic Liver Microenvironment

Clark et al., 2021

This study elucidated using our MPS platform that CXCR3 ligands were elevated in growing populations of metastatic cancer cells while remaining at physiological levels in the dormant cancer cell site. Upon stimulation with IP-10, dormant cancer cells resulted in a dose-dependent emergence with the metastatic environment playing a significant role.

Gut-Liver Physiomimetics Reveal Paradoxical Modulation of IBD-Related Inflammation by Short-Chain Fatty Acids

Trapecar et al., 2020

A multi-organ model of ulcerative colitis connecting the gut, liver and circulating Treg and Th17 cells. By integrating immune cells, the effect of microbiome-derived short-chain fatty acids on inflammatory bowel disease can be studied.

The characterisation of a human two organ on a chip ( lung-Liver) system

Dalrymple et al

This poster demonstrates the potential of human lung and lung-liver MPS models for drug metabolism and toxicity studies.

Pathologically Scarred by Fibrosis: How To Model and Quantify Human NASH in a Microphysiological System

Webinar Series 3 Episode 2:

In this webinar, Dr Samantha Peele, AstraZeneca, and Dr Gareth Guenigault, CN Bio, discuss how to better recreate NASH in vitro, using liver MPS models, to improve the quantification of liver fibrosis.

NAFLD vs MAFLD: could a name change impact the progression of liver disease research?

Read this article to understand why a name change has been discussed in an attempt to reflect its underlying pathology.

Towards a Body-on-a-Chip: The Value of Multi-Organ MPS for Human-Relevant Drug Assessment

Webinar Series 3 Episode 1:

In this webinar, Dr Tomasz Kostrzewski, VP – Science & Technology explores how single-and multi-organ MPS can be incorporated into your drug discovery and development workflows to increase in vitro to in vivo translation of preclinical assays.

Engineering Mucosal Barriers: From Organoids to Organs-on-Chips with Professor Linda Griffith

Webinar Series 2 Episode 4:

In this webinar, Professor Linda Griffith, MIT, explores how the explosion of interest in the human microbiome, especially but not only in the gut, has driven new interests in building human mucosal barrier models.

Flowing to the Beat of Your Heart

How Mimicking Blood Flow Makes Organ-on-a-Chip Technology Even More Life-like.

Multi-Organ in vitro organ-on-chip models for intestinal drug absorption and metabolism

Bray et al

The development of more translationally relevant in vitro intestinal models is key to better predicting drug absorption earlier in the drug development process. Here, we demonstrate the potential of a gut MPS, and a simple gut-liver MPS, for preclinical ADME investigation.

Gut-liver organ-on-a-chip combined with in silico modeling as a promising tool for investigation of mycophenolate mofetil pharmocokinetics

Milano et al

This poster demonstrates the potential of a true 2-organ gut-liver MPS for ADME applications and is more relevant in vitro to in vivo translation of drug efficacy and toxicity.

A Microphysiological Model of Metastatic Progression: Using systems to model metastatic progression

Webinar Series 2 Episode 3:

In this webinar, Dr Amanda Clark, University of Pittsburgh, discusses how to use a Liver MPS to model metastatic progression, evaluate therapeutics and improve our understanding of the bidirectional crosstalk that occurs between host tissue cells and metastatic cancer cells.

3D Cell Based Assays: Tips for Success

This article discusses previous data yielded from cell-based assays (CBAs) and how best to utilise them.

This article is taken from Biocompare, February 2021.

Sitting down with… CN Bio

In this article in DDW our CEO David Hughes discusses everything CN Bio.

This article is taken from Drug Discovery World, January 2022.

How a novel in vitro Liver-on-a-Chip model of fatty liver disease is being used to help prevent a global healthcare crisis.

Find out how our Liver-on-a-chip is being used to help find a therapeutic treatment for NASH.

Primary human colonic mucosal barrier crosstalk with super oxygen-sensitive Faecalibacterium prausnitzii in continuous culture

Zhang et al., 2021

This study evaluated the ability of MPS to facilitate long-term co-culture of human gut cells and a microbe. Thus, demonstrated the potential of MPS to facilitate understanding of precise interaction between the human gut and the complex network of surrounding microbiome.

Life in the Fastlane

How a Partnership between the FDA and Organ-on-a-Chip Developers Has the Potential to Fast-track Drug Development.

Testing on Humans How to Predict Hepatotoxicity and Drug Clearance Ahead of Clinical Trials Using Liver-on-a-Chip

Webinar Series 2 Episode 2:

In this webinar, Dr Tomasz Kostrzewski discusses the need for better preclinical in vitro approaches for investigational toxicology, drug metabolism, and safety.

Characterizing the reproducibility in using a liver microphysiological system for assaying drug toxicity, metabolism and accumulation

Rubiano et al., 2020

This study demonstrated the ability of the CN Bio’s PhysioMimix liver model to generate reproducible results from experiments assaying metabolism, drug toxicity and intracellular accumulation. The results from the paper showed that the liver MPS can be routinely used in general drug evaluation applications.

The Rhythm of Life: Using Microfluidics To Mimic Blood Flow in Single- and Multi-Organ-on-a-Chip Models

Webinar Series 2 Episode 1:

In this webinar, Dr Graham Broder and Ms. Alysha bray discuss what Organ-on-a-Chip models are and their importance to model human biology in vitro.

A Regulators Viewpoint: Establishing Strategies To Evaluate Microphysiological Systems for Drug Development

Webinar Series 1 Episode 4

In this webinar, Dr Alexandre Ribeiro, FDA, discusses Regulators’ strategies to evaluate and establish MPS for preclinical drug development.

Go with the Flow: Application of Microfluidic 3D Liver Chip Models To Genotoxicity Testing

Webinar Series 1 Episode 3

Join Dr Renato Cardoso and Dr Thalita Zanoni, Charles River Laboratory (Montreal- Canada) to discuss the current challenges of existing preclinical in vitro methods and the use of a Liver MPS for better genotoxicity testing.

The Scars of Fat: The Transability of 3D NASH Microtissues To Model Human/murine NASH

Webinar Series 1 Episode 2

Join Dr Michele Vacca, University of Cambridge, to discuss the use of in vitro 3D human and murine NASH models to better understand NASH disease mechanisms.

Cell-Based Assays in 2D and 3D

Are you thinking about adopting 3D cell cultures? This article compares traditional 2D cell cultures to 3D cell cultures.

This article is taken from Biocompare, September 2020.

PhysioMimix Single-organ System Animation

An introduction to the CN Bio PhysioMimix Organ-on-a-chip technology, focusing on our PhysioMimix Single-organ System. This animation demonstrates how our microphysiological system works and how to create liver-on-a-chip and gut-on-a-chip models.

An Introduction to Organ-On-a-Chip

Webinar Series 1 Episode 1

In this webinar, Mrs. Vaish Manoharan-Jayarajah discusses the revolutionary technology behind Organ-on-a-Chip systems.

Bone morphogenetic protein 8B promotes the progression of Non-Alcoholic Steatohepatitis

Vacca et al., 2020

Collaborative publication with the University of Cambridge using the NASH model to bridge knowledge gaps and confirm prior discoveries. This study teases apart the complex, overlapping and multi-faceted inflammatory pathways involved in liver fibrosis to identify key, potentially “druggable”, players in NASH.

Microphysiological Systems Emerging as Powerful Tools for Drug Discovery

A new class of in vitro is expected to assist drug discovery by providing robust physiologically relevant data at crucial stages of R&D.

This article is taken from European Biopharmaceutical Review July 2020, pages 48-51.

A Microphysiological System for Studying Non-alcoholic Steatohepatitis

Kostrzewski et al., 2019

A study that used MPS to resemble key features of human liver tissues with NASH/NAFLD. This study highlighted success in creating an in vitro 3D model for NASH disease modeling, thus facilitating the understanding of the complex mechanism underlying this disease.

Comparing an in vitro Organ-on-Chip model of Non-Alcoholic Steatohepatitis to murine models and liver tissue from patients

Kostrzewski et al

Currently available preclinical in vitro and in vivo NAFLD/NASH models have a range of limitations and do not fully represent the key aspects of the human disease state. This study demonstrates the potential of an in vitro liver MPS model, which recreates and maintains the key markers of the disease, for the assessment of new anti-NASH therapies.

Investigating the PK/PD/efficacy relationship of PI3K inhibitors in vitro, enabled by a microfluidic addition and removal device

Singh et al

Characterizing the relationship between pharmacokinetics (PK), pharmacodynamics (PD), and efficacy is critical in the discovery and development of new drugs, schedules, and combinations. This study explores an in vitro methodology using a device capable of recapitulating in vivo PK-like profiles in vitro.

“Liver-on-a-Chip” Cultures of Primary Hepatocytes and Kupffer Cells for Hepatitis B Virus Infection

Ortega-Prieto et al., 2019

Despite the exceptional infectivity of the hepatitis B virus (HBV) in vivo, where only three viral genomes can result in a chronicity of experimentally infected chimpanzees, most in vitro models require several hundreds to thousands of viral genomes per cell in order to initiate a transient infection.

The PNPLA3 I148 variant enhances the disease phenotype of hepatic stellate cells in an in vitro model of non-alcoholic fatty liver disease

Kostrzewski et al

This study demonstrates the potential for a 3D in vitro NAFLD model to (i) explore the molecular mechanisms that underlie the development of human NAFLD, notably the role of PNPLA3 I148 in the severity of the disease; (ii) to analyze the efficacy of novel anti-NAFLD therapeutics against a range of different target pathways.

In vitro assessment of combination dosing regimen with in vivo-like pharmacokinetic concentration profiles enabled by a microfluidic addition and removal device

Golby et al

The pharmacokinetic (PK) profile is a determining factor in both the safety and efficacy of a drug or therapeutic regimen. PK profiles can vary significantly between patients and between humans and pre-clinical animal species.​

Here we describe a device capable of recapitulating PK-like profiles in vitro and explore the effects of PK on the treatment of non-small-cell lung carcinoma in mono and combination therapy.

Interconnected microphysiological systems for quantitative biology and phamarcology studies

Edington et al., 2018

A proof-of-principle study that demonstrates microphysiological systems are capable of modeling multiple organs enabling pharmacological testing of drugs and assessing organ-organ cross-talk, this was done through measuring functional biomarkers for the liver and brain and TEER for the gut and lungs over time.

Perfused human hepatocyte microtissues identify reactive metabolite-forming and mitochondria-perturbing hepatotoxins

Rowe et al., 2018

Undetected hepatoxicity is a major cause of high drug attrition in drug development and drug-related clinical morbidity. This study shows the potential of a liver MPS in mechanistic toxicology and detecting clinical levels of hepatic toxicity earlier in the drug development process.

3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection

Ortega-Prieto et al., 2018

With more than 240 million people infected, hepatitis B virus (HBV) is a major health concern. The inability to mimic the complexity of the liver using cell lines and regular primary human hepatocyte (PHH) cultures pose significant limitations for studying host/pathogen interactions.

Integrated gut and liver microphysiological systems for quantitative in vitro pharmacokinetics studies

Tsamandouras et al., 2017

There is a need for more physiologically-relevant in vitro models to better investigate the efficacy and pharmacokinetics (PK) of compounds in the early stages of drug development. Here, we demonstrate the potential of a multi-organ (gut-liver) MPS combined with quantitative mechanistic modeling to accurately assess the PK of new therapeutics.

Integrated assessment of diclofenac biotransformation, pharmacokinetics and omics-based toxicity in a 3D human liver-immunocompetent co-culture system

Sarkar et al., 2017

The paper demonstrates how 3D liver MPS may serve as preclinical investigational platforms for the discovery of a set of clinically-relevant biomarkers, including potential reactive metabolites, endogenous bile acids, excreted proteins, and cytokines to predict early drug-induced liver toxicity in humans.

Integrated gut/liver microphysiological systems elucidates inflammatory inter-tissue crosstalk

Chen et al., 2017

Animal models are the only way to understand the complex systemic effects of drugs in organisms; however, they often fail to translate to humans. Here, we demonstrate the potential of a multi-organ model to study inflammatory organ crosstalk between the gut and liver.

Fully human in vitro gut-liver model of non-alcoholic steatohepatitis

Kostrzewski et al

Non-Alcoholic Fatty Liver Disease (NAFLD) represents a wide spectrum of liver abnormalities with the most severe cases involving progressive liver injury in the form of Non-Alcoholic Steatohepatitis (NASH). NASH is the liver manifestation of the metabolic syndrome, with close association with insulin resistance, obesity and Type 2 diabetes. The interaction between the liver and the gut (the “gut-liver axis”), is now known to play a critical role in NAFLD onset and progression. Using in vitro human NASH liver and NASH gut/liver MPS models this study shows the potential of such models for the exploration of complex molecular mechanisms and organ-to-organ crosstalk in disease state.

Microphysiological systems for studying interactions between the liver, gut and immune system

Kostrzewski et al

This study demonstrates the potential of in vitro Liver MPS linked to another MPS (gut or immune cells) for the assessment drug efficacy and ADME properties.

Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated MPS

Maass et al., 2017

Typically scaling for MPS systems is designed upon allometric scaling and not function. This study outlines a new multi-functional scaling method for multi-organ MPS platform design. Explored in this study are Gut-Liver and Gut-Liver-Kidney models.

Quantitative Assessment of Population Variability in Hepatic Drug Metabolism Using a Perfused Three-Dimensional Human Liver Microphysiological System

Tsamandouras et al., 2017

A study which demonstrates the variation of hepatocyte drug metabolism over different donor sets and how this data can be best interpreted translationally using modelling and simulation frameworks. Five donors’ abilities to metabolise six drugs were evaluated alongside metabolism gene and functional viability analysis.

Modeling Therapeutic Antibody-Small Molecule Drug-Drug Interactions Using a Three-Dimensional Perfusable Human Liver Coculture Platform

Long et al., 2016

TBC

Three-dimensional human cell culture model for studying Non-Alcoholic Fatty Liver Disease

Kostrzewski et al

Non-Alcoholic Fatty Liver Disease (NAFLD) is a growing concern worldwide and is set to become the most predominant cause of chronic liver disease. There are currently no FDA-approved drugs for the treatment of NAFLD and there is a clear requirement for better models to understand disease progression and the molecular pathways underlying the disease. Here, we demonstrate the potential of a 3D human Liver MPS to mimic in vitro the liver microarchitecture and support hepatic functions over extended periods of culture, allowing the continual accumulation of fat deposits in the hepatocytes.

Identification And Evaluation Of Patient Serum Isolates As A Source Of Inoculum For 3D in Vitro Cell Culture: A Tool For Drug Discovery

Large et al

Hepatitis B Virus (HBV) is currently a leading healthcare problem affecting more than 240 million people worldwide, despite the availability of a highly effective vaccine. Drug therapies are available on the market for the treatment of HBV, but these rarely provide a cure.

Here, we demonstrate the potential of an in vitro 3D liver MPS to study HBV infection and treatment.

Quantitative systems pharmacology approaches applied to MPS: Data interpretation and Multi-MPS integration

Yu et al., 2015

These studies demonstrate the use of MPS for in vitro-to-in vivo translation of pharmacology data.

Metabolite profiling and pharmacokinetic evaluation of hydrocortisone in a perfused 3D human liver bioreactor

Sarkar et al., 2015

Study using glucocorticoids to demonstrate their anti-inflammatory proterties in liver cells cultured with lipopolysaccharied (LPS).

Three-dimensional perfused cell culture enhances the infectability of primary human hepatocytes with Hepatitis B virus

Kostrzewski et al

Research into the biology and treatment of hepatitis B virus (HBV) requires an in vitro infection model that fully supports all the steps of the HBV life cycle and accurately recapitulates virus-host interactions. However, the molecular mechanisms underlying HBV infection remain poorly understood. Here, we show the potential of a perfused 3D cell culture system over standard 2D cell culture to investigate the infectivity of PHH by HBV.

Morphological behaviour and metabolic capacity of cryopreserved human primary hepatocytes cultivated in a perfused multiwell device

Vivares et al., 2015

This study evaluated the viability of a human liver model when cultured on a microfluidic LiverChip™ system. Findings highlighted the system’s ability to maintain healthy morphology and metabolic capacity over the 7-day period in culture, displaying well-differentiated and viable structures of human hepatocytes. This outlined the potential of MPS to be employed as a platform for quantitative prediction in drug studies.

Addressing the Challenges of Low Clearance in Drug Research

Di and Obach, 2015

Current tools available in vitro for early metabolite identification and ADME exploration are limited in low clearance compounds often leading to gross overestimations of clearance. This paper explores improved methodologies in vitro which focus on more accurate in vitro results for low clearance compounds.