4.7 Review

Human organs-on-chips for disease modelling, drug development and personalized medicine

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Summary: This study developed a microfluidic device using organ-on-a-chip technology to replicate the features of human cystic fibrosis (CF) lungs. The device successfully captured CF airway characteristics, including mucus accumulation, increased cilia density, and faster ciliary beating frequency. Additionally, it simulated the inflammatory response and infection levels in CF patients, as well as provided a conducive environment for the growth of Pseudomonas aeruginosa.

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Perspectives on the Evaluation and Adoption of Complex In Vitro Models in Drug Development: Workshop with the FDA and the Pharmaceutical Industry (IQ MPS Affiliate)

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Summary: This article discusses the output from a workshop between FDA and IQ MPS Affiliate on the application of complex in vitro models in pharmaceutical drug development. The workshop aimed to identify barriers to the adoption of microphysiological systems (MPS) technologies and to address evaluation/qualification pathways. The output includes a working definition of MPS, detailed description of case studies, and analysis of breakout sessions.

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Advances in Engineered Three-Dimensional (3D) Body Articulation Unit Models

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Summary: Body articulation units, also known as body joints, are important for body flexibility in the musculoskeletal system. However, they are prone to various pathological conditions such as arthritis. Existing treatment modalities based on anti-inflammatory and analgesic drugs have limitations in terms of cost and recovery. Engineering strategies, such as fabricating body articulation unit models for tissue regeneration and drug development, have emerged as promising solutions. Challenges and difficulties still exist in the clinical application of these models.

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Article Chemistry, Multidisciplinary

Microengineered Multi-Organoid System from hiPSCs to Recapitulate Human Liver-Islet Axis in Normal and Type 2 Diabetes

Tingting Tao et al.

Summary: A new microfluidic multi-organoid system has been developed to replicate the human liver-pancreatic islet axis in both normal and disease states, providing a unique platform for future research and drug development in Type 2 diabetes mellitus.

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Review Anatomy & Morphology

Microphysiological Systems: Stakeholder Challenges to Adoption in Drug Development

Passley Hargrove-Grimes et al.

Summary: This review discusses the obstacles to the widespread adoption of MPS technology and how end-users can help overcome these barriers to achieve broader adoption of the technology.

CELLS TISSUES ORGANS (2022)

Article Chemistry, Multidisciplinary

Ectopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ-on-a-Chip

Girija Goyal et al.

Summary: In this study, researchers successfully cultured human ectopic lymphoid follicles with similar characteristics to lymphoid follicles in a microfluidic chip. These follicles showed improved immune responses to vaccines and can serve as an alternative to non-human primates for preclinical evaluation.

ADVANCED SCIENCE (2022)

Article Chemistry, Multidisciplinary

Biomimetic Human Disease Model of SARS-CoV-2-Induced Lung Injury and Immune Responses on Organ Chip System

Min Zhang et al.

Summary: A biomimetic human disease model on chip has been created to recapitulate lung injury and immune responses induced by SARS-CoV-2, revealing distinctive responses in different cell types and the crucial role of immune cells in alveolar barrier injury and inflammation. The organ chip model closely mirrors human-relevant responses to SARS-CoV-2 infection, providing a unique platform for COVID-19 research and drug development.

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A directional 3D neurite outgrowth model for studying motor axon biology and disease

Xandor M. Spijkers et al.

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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.

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Implementation of a Human Renal Proximal Tubule on a Chip for Nephrotoxicity and Drug Interaction Studies

Marianne K. Vormann et al.

Summary: The Nephroscreen platform, using a combination of cell viability, LDH, and miRNA release, proved to be a robust and predictive method for detecting drug-induced kidney injury. It is compatible with automated pipetting, suitable for long-term experiments, and offers a valuable tool for replacing animal testing and supporting the 3Rs principles.

JOURNAL OF PHARMACEUTICAL SCIENCES (2021)

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)

Article Multidisciplinary Sciences

Modeling alpha-synuclein pathology in a human brain-chip to assess blood-brain barrier disruption

Iosif Pediaditakis et al.

Summary: The authors have developed a human brain-chip model using Organs-on-Chips technology, which recapitulates key features of Parkinson's disease. This model could be used to study the dynamics of cell-cell interactions in human synucleinopathies.

NATURE COMMUNICATIONS (2021)

Article Chemistry, Analytical

Modular 3D In Vitro Artery-Mimicking Multichannel System for Recapitulating Vascular Stenosis and Inflammation

Minkyung Cho et al.

Summary: The study presents a modular multichannel system that mimics the stenosis and inflammation processes in arteries and studies the physical and chemical effects on biomimetic artery models. Through modularization, the system enables reproducible and stable operations, with the flexibility to replace modules for different analytical purposes. This system has the potential to be utilized for comprehensive research on vascular diseases such as atherosclerosis and thrombosis through tunable channel geometry and microfluidic interfacing.

MICROMACHINES (2021)

Article Biochemistry & Molecular Biology

A 3D Renal Proximal Tubule on Chip Model Phenocopies Lowe Syndrome and Dent II Disease Tubulopathy

Sindhu Naik et al.

Summary: Research demonstrates that in a proximal tubule organ on chip model replicating characteristics of Lowe syndrome/Dent II disease, proximal tubule cells lacking OCRL expression upregulate markers associated with epithelial-mesenchymal transition (EMT) and exhibit increased collagen expression and deposition.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Biotechnology & Applied Microbiology

Three-Dimensional In Vitro Lymphangiogenesis Model in Tumor Microenvironment

Youngkyu Cho et al.

Summary: This study proposes a new three-dimensional lymphangiogenesis model in a tumor microenvironment, which can mimic the biochemical and biomechanical characteristics of lymphatic vessels in vivo. By incorporating tumor spheroids, the model reveals microenvironment factors that contribute to tumor metastasis, making it a useful tool for pathological drug screening or disease modeling.

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2021)

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Transferrin receptor targeting by de novo sheet extension

Danny D. Sahtoe et al.

Summary: The challenge of designing polar protein-protein interactions is addressed by a computational approach utilizing complementary geometrically matched beta strands. Specifically designed proteins successfully bind to the human transferrin receptor, enabling drug delivery across the blood-brain barrier. This design strategy offers a general approach for creating binders to protein targets with exposed surface beta edge strands.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

Article Chemistry, Analytical

Facile Patterning of Thermoplastic Elastomers and Robust Bonding to Glass and Thermoplastics for Microfluidic Cell Culture and Organ-on-Chip

Stefan Schneider et al.

Summary: The success of microfluidic research has been largely dependent on PDMS, but its limitations have led to the exploration of PDMS-free systems, with TPE emerging as a promising alternative. A rapid and scalable fabrication method for microfluidic systems based on PC and TPE hybrid material has been developed. The resulting PC/TPE-hybrid material shows improved device handling and biocompatibility, making it suitable for various microfluidic applications.

MICROMACHINES (2021)

Article Pharmacology & Pharmacy

Integrated Isogenic Human Induced Pluripotent Stem Cell-Based Liver and Heart Microphysiological Systems Predict Unsafe Drug-Drug Interaction

Felipe T. Lee-Montiel et al.

Summary: The study focuses on the integration of hiPSC-based liver and cardiac MPSs to study drug-drug interaction, using cisapride and ketoconazole as an example. The results demonstrate how ketoconazole inhibits the metabolic conversion of cisapride in the liver MPS, leading to arrhythmia in the cardiac MPS, highlighting the potential of this integrated approach for screening drug interactions and assessing drug efficacy and toxicity in the same genetic background.

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Article Engineering, Biomedical

A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics

Longlong Si et al.

Summary: The microfluidic bronchial-airway-on-a-chip model, lined with human bronchial-airway epithelium and pulmonary endothelium, can replicate viral infections, cytokine production, and immune cell recruiting, facilitating the rapid identification of antiviral therapeutics and prophylactics with repurposing potential. A variety of drug combinations and treatments were tested on the chip to demonstrate their efficacy in combating infections and the potential for repurposing.

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A novel organ-chip system emulates three-dimensional architecture of the human epithelia and the mechanical forces acting on it

Antonio Varone et al.

Summary: This study presents a new 3D cell-culture system that combines Organ-Chip technology with advantages of three-dimensional organotypic culture. Using microfabrication techniques, a flexible chip was engineered to recreate critical elements of native tissue architecture, offering researchers the possibility to model organs and their functionality more accurately. The Open-Top Chip design successfully addresses common challenges associated with Organs-on-Chip technology, demonstrating its feasibility with primary human skin and alveolar epithelial cells.

BIOMATERIALS (2021)

Article Obstetrics & Gynecology

Three-dimensional microengineered vascularised endometrium-on-a-chip

Jungho Ahn et al.

Summary: A microengineered vascularized endometrium-on-a-chip model has been successfully developed to mimic the complex behaviors of the human endometrium, providing a new in-vitro approach for drug screening and discovery. The model could be a valuable tool for studying female diseases and addressing critical challenges in a personalized manner.

HUMAN REPRODUCTION (2021)

Article Dentistry, Oral Surgery & Medicine

Biomaterial and Biofilm Interactions with the Pulp-Dentin Complex-on-a-Chip

N. S. Rodrigues et al.

Summary: The study utilized a microfluidic device, the tooth-on-a-chip, to investigate the effects of calcium silicate cements on vital pulp therapy and cell proliferation. ProRoot and Biodentine were found to promote cell proliferation, while TheraCal may lead to changes in cell morphology.

JOURNAL OF DENTAL RESEARCH (2021)

Article Engineering, Biomedical

Recapitulating monocyte extravasation to the synovium in an organotypic microfluidic model of the articular joint

Carlotta Mondadori et al.

Summary: This study developed an organotypic microfluidic model to recapitulate the pathological process of the synovium in osteoarthritis patients. The model demonstrated that OA synovial fluid induces monocytes to cross the endothelium and invade the synovial compartment, and the simultaneous blocking of CCR2 and CCR5 pathways is more effective in inhibiting extravasation.

BIOFABRICATION (2021)

Article Multidisciplinary Sciences

High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro

A. L. Gard et al.

Summary: This study integrates human primary airway epithelial cells into a custom-engineered 96-device platform, and applies it to evaluate viral infection kinetics and antiviral agent dosing for influenza A virus and coronavirus infections across various human primary cell populations. This new capability can help address the rapid assessment of therapeutic efficacy against respiratory viruses, including coronaviruses.

SCIENTIFIC REPORTS (2021)

Article Biology

Aorta smooth muscle-on-a-chip reveals impaired mitochondrial dynamics as a therapeutic target for aortic aneurysm in bicuspid aortic valve disease

Mieradilijiang Abudupataer et al.

Summary: Bicuspid aortic valve (BAV) is a common congenital cardiovascular disease associated with thoracic aortic aneurysm (TAA). Insufficiency of NOTCH1 expression is related to BAV-TAA, with impaired mitochondrial dynamics observed. Knockdown of NOTCH1 in HAoSMCs resulted in reduced contractile phenotype and attenuated mitochondrial fusion, which could be partially rescued by mitochondrial fusion activators or fission inhibitor. This study suggests impaired mitochondrial dynamics as a potential therapeutic target for BAV-TAA.
Article Biology

Human immunocompetent Organ-on-Chip platforms allow safety profiling of tumor-targeted T-cell bispecific antibodies

S. Jordan Kerns et al.

Summary: This study demonstrated the unprecedented capability of two human Organs-on-Chips in evaluating the safety profile of T-cell bispecific antibodies targeting tumor antigens, predicting TCB safety liabilities based on target expression and antibody affinity. These novel tools broaden research options for understanding engineered therapeutic antibodies and assessing safety in tissues susceptible to adverse events.
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Forensic Analysis of Human Microbiome in Skin and Body Fluids Based on Geographic Location

Hye-Won Cho et al.

Summary: High-throughput DNA sequencing technologies have facilitated in silico forensic analysis of human microbiome. Microbial communities are influenced by geographic, ethnic, lifestyle, and environmental factors, leading to differences in microbiome distribution across body parts and geographic locations. This study utilized the Forensic Microbiome Database to observe and describe variations in microbiomes from different countries and body parts.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2021)

Article Chemistry, Analytical

A Personalized Glomerulus Chip Engineered from Stem Cell-Derived Epithelium and Vascular Endothelium

Yasmin Roye et al.

Summary: This study engineered a personalized glomerulus chip system using human induced pluripotent stem cells, successfully mimicking the structure and some functions of the glomerular filtration barrier, and modeling glomerular injury and proteinuria. The research has the potential to advance studies of kidney disease mechanisms and the discovery of personalized therapies, and could serve as a blueprint for the development of more personalized organ chip and 'body-on-a-chip' models in the future.

MICROMACHINES (2021)

Article Cell & Tissue Engineering

Human stem cell-based retina on chip as new translational model for validation of AAV retinal gene therapy vectors

Kevin Achberger et al.

Summary: Gene therapies using AAVs show promise in treating or curing retinal diseases, but the development of efficient AAV vectors is slow and costly due to the lack of suitable non-clinical models. Human iPSC-derived retinal organoids faithfully recreate human tissue structure and function, making them essential for translational research. OoC technology allows for the recapitulation of tissue environments and precise control over parameters, with iPSC-based OoC models showing potential as the next generation of screening platforms for gene therapeutic studies.

STEM CELL REPORTS (2021)

Article Engineering, Biomedical

Fungal brain infection modelled in a human-neurovascular-unit-on-a-chip with a functional blood-brain barrier

Jin Kim et al.

Summary: A neurovascular-unit-on-a-chip with a functional blood-brain barrier is able to recapitulate the neurotropism and barrier penetration of the most common pathogen causing fungal meningitis. The model can study how pathogens can penetrate the human BBB and disrupt neuronal homeostasis. This microphysiological model may facilitate the study of brain infection mechanisms by pathogens and the development of drugs for brain diseases.

NATURE BIOMEDICAL ENGINEERING (2021)

Article Microbiology

Clinically Relevant Influenza Virus Evolution Reconstituted in a Human Lung Airway-on-a-Chip

Longlong Si et al.

Summary: Research demonstrates that spontaneous evolution of influenza A virus through both mutation and gene reassortment can be reconstituted in vitro by sequentially passing infected mucus droplets between multiple human lung airway-on-a-chip microfluidic culture devices. This human preclinical model may be useful for studying viral evolution and identifying potential influenza virus variants before they appear in human populations, enabling preemptive design of new and more effective vaccines and therapeutics.

MICROBIOLOGY SPECTRUM (2021)

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.

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Article Pharmacology & Pharmacy

Enteric Coronavirus Infection and Treatment Modeled With an Immunocompetent Human Intestine-On-A-Chip

Amir Bein et al.

Summary: The study using a human intestine-on-a-chip model demonstrated the inflammatory effects of NL63 coronavirus infection on intestinal epithelial and endothelial cells, and identified a potential antiviral drug.

FRONTIERS IN PHARMACOLOGY (2021)

Article Biochemical Research Methods

Construction of a high fidelity epidermis-on-a-chip for scalable in vitro irritation evaluation

Jing Zhang et al.

Summary: 3D skin equivalents have limitations in in vitro safety evaluation models due to troublesome operation procedures and low throughput. Organ-on-a-chip offers a solution by providing an automated and modular way for constructing and detecting skin models. In this research, an integrated epidermis-on-a-chip system was successfully developed, showing histological features similar to normal human epidermis and high barrier function. The system can detect known toxins and non-toxins and predict different irritation responses, providing a potential alternative for in vitro skin irritation evaluation.

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Human Nonalcoholic Steatohepatitis on a Chip

May S. Freag et al.

Summary: NASH, an advanced stage of NAFLD, is a growing global health problem without specific treatments. Researchers have successfully developed a NASH-on-a-chip platform that can mimic NASH progression and test novel anti-NASH drugs.

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On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology

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Robotic fluidic coupling and interrogation of multiple vascularized organ chips

Richard Novak et al.

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Sharon Wei Ling Lee et al.

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Differential Monocyte Actuation in a Three-Organ Functional Innate Immune System-on-a-Chip

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A Microengineered Airway Lung Chip Models Key Features of Viral-induced Exacerbation of Asthma

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

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Sasan Jalili-Firoozinezhad et al.

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Karel Domansky et al.

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Biomechanical Strain Exacerbates Inflammation on a Progeria-on-a-Chip Model

Joao Ribas et al.

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A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle

Shuo Xiao et al.

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

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Aleksander Skardal et al.

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Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro

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