Review
Biotechnology & Applied Microbiology
Lucie A. Low, Christine Mummery, Brian R. Berridge, Christopher P. Austin, Danilo A. Tagle
Summary: OoCs, also known as microphysiological systems or 'tissue chips', have the potential to be informative at multiple stages of drug discovery and development, providing insights into normal human organ function and disease pathophysiology, as well as predicting the safety and efficacy of investigational drugs in humans. The field of OoCs has seen significant advances in recent years, but there are still challenges and opportunities that need to be addressed to fully realize their potential for translational research.
NATURE REVIEWS DRUG DISCOVERY
(2021)
Article
Biophysics
Anna Grazia Monteduro, Silvia Rizzato, Giusi Caragnano, Adriana Trapani, Gianluigi Giannelli, Giuseppe Maruccio
Summary: Current in-vitro 2D cultures and animal models have limitations in recapitulating human physiology, but microphysiological systems and organ-on-chip technologies are emerging as novel tools for high-throughput research and drug development. This review provides an introduction to major themes in this field and discusses the significance, limitations, and future prospects of these technologies.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Pharmacology & Pharmacy
Felipe T. Lee-Montiel, Alexander Laemmle, Verena Charwat, Laure Dumont, Caleb S. Lee, Nathaniel Huebsch, Hideaki Okochi, Matthew J. Hancock, Brian Siemons, Steven C. Boggess, Ishan Goswami, Evan W. Miller, Holger Willenbring, Kevin E. Healy
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.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Genetics & Heredity
Donald E. Ingber
Summary: This Review discusses the types of single and multiple human organ-on-a-chip (organ chip) microfluidic devices and their diverse applications for disease modeling, drug development, and personalized medicine. It also addresses the challenges that must be overcome for organ chips to reach their full potential and discusses recent advances in the field.
NATURE REVIEWS GENETICS
(2022)
Article
Medicine, Research & Experimental
Andres Rubiano, Amruta Indapurkar, Ryosuke Yokosawa, Alina Miedzik, Barry Rosenzweig, Ayesha Arefin, Chloe M. Moulin, Keri Dame, Neil Hartman, Donna A. Volpe, Murali K. Matta, David J. Hughes, David G. Strauss, Tomasz Kostrzewski, Alexandre J. S. Ribeiro
Summary: The study characterized the reproducibility of liver microphysiological systems (MPSs) in predicting hepatic drug effects through experiments on drug toxicity, metabolism, and intracellular accumulation. The results demonstrated that the liver MPS can reliably produce consistent experimental outcomes for drug evaluation applications, showing better stability and functionality compared to other culture platforms. The study also provided general considerations and recommendations for using liver MPSs in drug development.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2021)
Article
Engineering, Biomedical
Hyemin Kim, Ilkyun Im, Jang Su Jeon, Eun-Hye Kang, Hyang-Ae Lee, Seongyea Jo, Ji-Woo Kim, Dong-Hun Woo, Young Jae Choi, Hyo Jin Kim, Ji-Seok Han, Byoung-Seok Lee, Jong-Hoon Kim, Sang Kyum Kim, Han-Jin Park
Summary: This study aims to generate liver organoids with high drug metabolic ability using human pluripotent stem cells. The fully differentiated organoids exhibit cellular polarity, hepatobiliary structures, and remarkable drug metabolic function. They can also successfully model Wilson's disease and provide an advanced tool for studying hepatic drug metabolism and diseases.
Article
Pharmacology & Pharmacy
Ayesha Arefin, Melissa Mendoza, Keri Dame, M. Iveth Garcia, David G. Strauss, Alexandre J. S. Ribeiro
Summary: We investigated the properties of engineered heart tissues (EHTs) made with different tissue casting batches and lines of differentiated hPSC-cardiomyocytes. The contractile outputs of EHTs were measured using a video-optical assay and compared with monolayers of hPSC-cardiomyocytes cultured in two-dimensional cultures. The drug-induced contractile responses were similar between monolayers and EHTs, and showed a close relationship with calcium kinetics.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Yi Yang, Yin Chen, Liang Wang, Shihui Xu, Guoqing Fang, Xilin Guo, Zaozao Chen, Zhongze Gu
Summary: The combination of organ-on-a-chip technology and physiologically based pharmacokinetic modeling has the potential to improve drug development and personalized medicine.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Ying Luo, Xiaoxiao Li, Yawei Zhao, Wen Zhong, Malcolm Xing, Guozhong Lyu
Summary: Drugs that pass expensive preclinical studies may still fail to prove their efficacy in clinical trials, making it challenging to discover new drugs. Organs-on-chips (OCs) provide accurate insights into organ functions and pathophysiology, allowing for precise prediction of drug safety and effectiveness in the body. OCs are faster, more economical, and more precise than traditional preclinical cell cultures, animal studies, and even human clinical trials. This paper outlines the nature and significance of OCs, discusses their manufacturing materials and methodology, explores their applications in drug screening and disease modeling and treatment, and presents their future perspective.
Review
Biotechnology & Applied Microbiology
Mario Rothbauer, Christoph Eilenberger, Sarah Spitz, Barbara E. M. Bachmann, Sebastian R. A. Kratz, Eva I. Reihs, Reinhard Windhager, Stefan Toegel, Peter Ertl
Summary: The development of advanced in vitro organotypic tissue constructs requires the re-creation of physiological cellular microenvironments that resemble complex in vivo architectures. Organ-on-a-chip technology has been increasingly used in recent years to create improved models for organs and tissues in human health and disease, providing control over soluble cues, biophysical signals, and biomechanical forces necessary for proper organotypic functions. The combination of organ-on-a-chip technology with 3D bioprinting and additive manufacturing techniques allows for unprecedented control over tissue structures and the generation of anisotropic constructs, similar to in vivo tissue architectures.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Immunology
Iris Aparici Herraiz, Hugo R. Caires, Oscar Castillo-Fernandez, Nuria Sima, Lourdes Mendez-Mora, Ruth M. Risueno, Jetsumon Sattabongkot, Wanlapa Roobsoong, Aurora Hernandez-Machado, Carmen Fernandez-Becerra, Cristina C. Barrias, Hernando A. del Portillo
Summary: Plasmodium vivax is a widely distributed malaria parasite, with a high disease burden in Southeast Asia. Recent evidence suggests that besides the liver, the spleen and bone marrow may also serve as sources of chronic erythrocytic infections. The origin of these infections remains controversial, and further research is needed to understand and eliminate them.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Multidisciplinary Sciences
Jintao Li, Jie Chen, Hua Bai, Haiwei Wang, Shiping Hao, Yang Ding, Bo Peng, Jing Zhang, Lin Li, Wei Huang
Summary: Microfluidic-based organs-on-chips (OoCs) are an advanced technology in biomedical and chemical research, offering unique properties for biomedical applications. However, the amount of data generated by OoC systems has surpassed manual analysis capabilities. Deep learning, a new area in machine learning, can automatically analyze big data and has successful applications in various fields. The integration of deep learning in OoCs shows great potential for drug development, disease modeling, and personalized medicine.
Review
Cell Biology
Leandra S. Baptista, Constance Porrini, Gabriela S. Kronemberger, Daniel J. Kelly, Cecile M. Perrault
Summary: Medicine today faces the challenge of increasing untreatable diseases and a decrease in successful drug development. In vitro preclinical tests, particularly using 3D cell culture and human stem cell biology, can help predict the potential of new drugs and avoid expensive clinical trial phases. Integrating organoid culture with microsystems, such as microphysiological systems or organ-on-a-chip, can improve drug development by emulating physiological conditions and reducing costs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Yonghong Luo, Haocheng Lu, Daoquan Peng, Xiangbo Ruan, Yuqing Eugene Chen, Yanhong Guo
Summary: Liver-humanized mice, established by reconstituting mouse liver with human hepatocytes, have emerged as an attractive animal model to study drug metabolism and evaluate therapeutic effects in human liver due to their ability to replicate enzymatic features of human hepatocytes. However, the uncertain replication of metabolic profiles compared to humans limits their application in studying metabolic disorders.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Review
Chemistry, Analytical
Leslie Donoghue, Khanh T. Nguyen, Caleb Graham, Palaniappan Sethu
Summary: This review discusses tissue chips and microphysiological systems, highlighting their basic definitions, major organs/tissues, critical parameters, and microfluidic approaches. It addresses current shortcomings and future directions of these technologies.
Article
Critical Care Medicine
Safak Mert, Beyza Bulutoglu, Christopher Chu, Maggie Dylewski, Florence M. Lin, Yong-Ming Yu, Martin L. Yarmush, Robert L. Sheridan, Korkut Uygun
Summary: This study observed significant metabolic and lipid changes in liver and muscle tissues of severe burn injury rats, indicating potential liver-muscle crosstalk during hypermetabolism, where the tissues may exacerbate each other's metabolic pathologies through excessive utilization of certain metabolites.
JOURNAL OF BURN CARE & RESEARCH
(2021)
Article
Dermatology
Mengjie Wu, Andrey Ethan Rubin, Tianhong Dai, Rene Schloss, Osman Berk Usta, Alexander Golberg, Martin Yarmush
Summary: The study optimized PEF parameters to achieve the best disinfection efficacy for Pseudomonas aeruginosa infection in a stable mouse burn wound model. Results showed that PEF treatment reduced bacterial load, decreased inflammatory signs, and modulated inflammatory responses in infected burn wounds, suggesting PEF treatment as a potent candidate for antimicrobial therapy for P. aeruginosa burn infections.
ADVANCES IN WOUND CARE
(2021)
Article
Engineering, Biomedical
Aylin Acun, Ruben Oganesyan, Korkut Uygun, Heidi Yeh, Martin L. Yarmush, Basak E. Uygun
Summary: The extracellular matrix of the liver changes with age, affecting cell function, and donor age should be considered an important factor for bioengineering liver substitutes.
Article
Chemistry, Multidisciplinary
Hwan June Kang, Suneel Kumar, Arielle D'Elia, Biraja Dash, Vikas Nanda, Henry C. Hsia, Martin L. Yarmush, Francois Berthiaume
Summary: The combination of AGEs and RAGE triggers pro-inflammatory signals that inhibit the proliferative phase of skin wound healing. A new coacervate system has been developed to reverse AGE-mediated changes, accelerate diabetic wound healing, and provide a potential therapeutic approach.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Engineering, Biomedical
Nida Tanataweethum, Allyson Trang, Chaeeun Lee, Jhalak Mehta, Neha Patel, Ronald N. Cohen, Abhinav Bhushan
Summary: The development of insulin resistance in the liver is crucial in the development of type 2 diabetes. Excess white adipose tissue is detrimental to insulin sensitivity, while transplantation of brown adipose tissue can restore it. However, the communication between liver and adipose tissue is still not fully understood. This study reports the development of an integrated insulin resistant liver-adipose organ-on-chip and shows that brown adipocytes can restore insulin sensitivity and suppress glucose production and lipogenesis.
BIOMEDICAL MATERIALS
(2022)
Article
Medicine, Research & Experimental
Camilo Rey-Bedon, Peony Banik, Aslihan Gokaltun, O. Hofheinz, Martin. L. Yarmush, M. Korkut Uygun, O. Berk Usta
Summary: This study investigates the impact of fatty liver on drug-drug interactions. Dysregulation of enzyme systems observed in fatty liver may increase the risk of unexpected drug interactions. An in vitro model was developed to study enzyme regulation in fatty liver, and it was found that fatty liver might exacerbate drug interactions related to CYP2B6 and CYP2C9 enzymes.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Engineering, Biomedical
Beyza Bulutoglu, Aylin Acun, Sarah L. Deng, Safak Mert, Elise Lupon, Alexandre G. Lellouch, Curtis L. Cetrulo, Basak E. Uygun, Martin L. Yarmush
Summary: Elastin-like peptides (ELPs) are a versatile platform for tissue engineering and drug delivery. In this study, therapeutic molecules are genetically fused to ELPs and applied to wound healing. The results show that the fused molecules retain their bioactivity and the application of these ELP nanoparticles significantly promotes wound closure in diabetic mice.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Nanoscience & Nanotechnology
Muhammad R. Haque, Caitlin R. Wessel, Daniel D. Leary, Chengyao Wang, Abhinav Bhushan, Faraz Bishehsari
Summary: Pancreatic ductal adenocarcinoma (PDAC) is highly heterogeneous, which hampers treatment and clinical trials. Patient-derived organoids (PDOs) have opened the door for personalized medicine. This study developed a tumor-chip device that replicates the PDAC tumor microenvironment and validated its application in drug testing.
MICROSYSTEMS & NANOENGINEERING
(2022)
Article
Cell & Tissue Engineering
Chengyao Wang, Andrea Cancino, Jasmine Baste, Daniel Marten, Advait Anil Joshi, Amreen Nasreen, Abhinav Bhushan
Summary: This study investigated the regulation of gut bacteria by oxygen by creating a dual-oxygen environment in a microfluidic device. The results showed that under a specific oxygen gradient, bacterial strains significantly upregulated mucin proteins and modulated intestinal transporters and transcription factors, providing evidence of the role of oxygen in bacterial-epithelial signaling. This work presents a novel strategy to study intestine-microbiome signaling and intestinal tissue engineering and offers a new perspective on the indirect effects of gut bacteria on tissues, including tumors.
CELLULAR AND MOLECULAR BIOENGINEERING
(2022)
Article
Microbiology
Christopher B. Forsyth, Lijuan Zhang, Abhinav Bhushan, Barbara Swanson, Li Zhang, Joao Mamede, Robin M. Voigt, Maliha Shaikh, Phillip A. Engen, Ali Keshavarzian
Summary: The COVID-19 pandemic originated in Wuhan, China in 2020 and led to numerous deaths and long-term symptoms in survivors. Research suggests that the spike protein S1 on the surface of the virus may play a significant role in the pathogenesis of COVID-19 and the development of long-term symptoms.
Article
Engineering, Biomedical
A. Aslihan Gokaltun, Letao Fan, Luca Mazzaferro, Delaney Byrne, Martin L. Yarmush, Tianhong Dai, Ayse Asatekin, O. Berk Usta
Summary: This study developed a novel biocompatible, self-healable, and on-demand dissoluble supramolecular hybrid hydrogel burn dressing. By leveraging the interactions of a custom-designed cationic copolymer with cucurbit[7]uril and electrostatic interactions with clay nanosheets coated with an anionic polymer, the dressing achieved enhanced mechanical properties and fast on-demand dissolution. The dressing showed high mechanical strength (>50 kPa), rapid self-healing (within 1 minute), and quick dissolution (4-6 minutes) using an amantadine hydrochloride solution. It did not have any adverse effects on human dermal fibroblasts or epidermal keratinocytes in vitro and did not elicit any immune or inflammatory response in vivo murine experiments.
BIOACTIVE MATERIALS
(2023)
Review
Biochemical Research Methods
Maryan Arrieta, Barbara Swanson, Louis Fogg, Abhinav Bhushan
Summary: Analysis of breath VOCs using the Cyranose 320 e-nose showed varying sensitivity and specificity results. Linear models yielded smaller ranges for mean sensitivity and specificity compared to nonlinear models. Further exploration of linear models for point of care testing is warranted.
JOURNAL OF BREATH RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Frederick R. Adler, Alexander R. A. Anderson, Abhinav Bhushan, Paul Bogdan, Jose Javier Bravo-Cordero, Amy Brock, Yun Chen, Edna Cukierman, Kathleen E. DelGiorno, Gerald V. Denis, Meghan C. Ferrall-Fairbanks, Zev Jordan Gartner, Ronald N. Germain, Deborah M. Gordon, Ginger Hunter, Mohit Kumar Jolly, Loukia Georgiou Karacosta, Karthikeyan Mythreye, Parag Katira, Rajan P. Kulkarni, Matthew L. Kutys, Arthur D. Lander, Ashley M. Laughney, Herbert Levine, Emil Lou, Pedro R. Lowenstein, Kristyn S. Masters, Dana Pe'er, Shelly R. Peyton, Manu O. Platt, Jeremy E. Purvis, Gerald Quon, Jennifer K. Richer, Nicole C. Riddle, Analiz Rodriguez, Joshua C. Snyder, Gregory Lee Szeto, Claire J. Tomlin, Itai Yanai, Ioannis K. Zervantonakis, Hannah Dueck
Summary: Collective cell behavior plays a crucial role in all stages of cancer progression. Exploring how this behavior emerges through cell-cell interactions and decision-making is essential for advancing our knowledge of cancer biology and developing new therapeutic approaches. This article summarizes an interdisciplinary discussion on multicellular behavior in cancer, highlights insights from other scientific disciplines, and identifies future research directions.
Article
Materials Science, Biomaterials
A. Aslihan Gokaltun, Luca Mazzaferro, Martin L. Yarmush, O. Berk Usta, Ayse Asatekin
Summary: This study introduces a novel, simple, fast, and scalable method for enhancing PDMS surface hydrophilicity and preventing nonspecific adsorption by incorporating a surface-segregating zwitterionic copolymer during fabrication.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Muhammad R. Haque, Caitlin R. Wessel, Daniel D. Leary, Chengyao Wang, Abhinav Bhushan, Faraz Bishehsari
