scholarly journals A Decade of Organs-on-a-Chip Emulating Human Physiology at the Microscale: A Critical Status Report on Progress in Toxicology and Pharmacology

Micromachines ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 470
Author(s):  
Mario Rothbauer ◽  
Barbara E.M. Bachmann ◽  
Christoph Eilenberger ◽  
Sebastian R.A. Kratz ◽  
Sarah Spitz ◽  
...  
Keyword(s):  
Academic Research ◽  
Basic Research ◽  
In Vitro Models ◽  
Status Report ◽  
Chip Technology ◽  
Organ Systems ◽  
Future Drug ◽  
Pharmacology And Toxicology ◽  
Organ On A Chip

Organ-on-a-chip technology has the potential to accelerate pharmaceutical drug development, improve the clinical translation of basic research, and provide personalized intervention strategies. In the last decade, big pharma has engaged in many academic research cooperations to develop organ-on-a-chip systems for future drug discoveries. Although most organ-on-a-chip systems present proof-of-concept studies, miniaturized organ systems still need to demonstrate translational relevance and predictive power in clinical and pharmaceutical settings. This review explores whether microfluidic technology succeeded in paving the way for developing physiologically relevant human in vitro models for pharmacology and toxicology in biomedical research within the last decade. Individual organ-on-a-chip systems are discussed, focusing on relevant applications and highlighting their ability to tackle current challenges in pharmacological research.

scholarly journals Advanced in vitro models of vascular biology: Human induced pluripotent stem cells and organ-on-chip technology

2019 ◽  
Vol 140 ◽  
pp. 68-77 ◽  
Author(s):  
Amy Cochrane ◽  
Hugo J. Albers ◽  
Robert Passier ◽  
Christine L. Mummery ◽  
Albert van den Berg ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Vascular Biology ◽  
In Vitro Models ◽  
Chip Technology ◽  
On Chip ◽  
Induced Pluripotent

scholarly journals 3D bioprinting of complex tissues in vitro: state-of-the-art and future perspectives

2022 ◽  
Author(s):  
Yi Xiang ◽  
Kathleen Miller ◽  
Jiaao Guan ◽  
Wisarut Kiratitanaporn ◽  
Min Tang ◽  
...  
Keyword(s):  
State Of The Art ◽  
In Vitro Models ◽  
Future Perspectives ◽  
Precise Control ◽  
Broad Variety ◽  
3D Printed ◽  
Pharmacology And Toxicology ◽  
Increasing Demand ◽  
Tissue Models

AbstractThe pharmacology and toxicology of a broad variety of therapies and chemicals have significantly improved with the aid of the increasing in vitro models of complex human tissues. Offering versatile and precise control over the cell population, extracellular matrix (ECM) deposition, dynamic microenvironment, and sophisticated microarchitecture, which is desired for the in vitro modeling of complex tissues, 3D bio-printing is a rapidly growing technology to be employed in the field. In this review, we will discuss the recent advancement of printing techniques and bio-ink sources, which have been spurred on by the increasing demand for modeling tactics and have facilitated the development of the refined tissue models as well as the modeling strategies, followed by a state-of-the-art update on the specialized work on cancer, heart, muscle and liver. In the end, the toxicological modeling strategies, substantial challenges, and future perspectives for 3D printed tissue models were explored.

scholarly journals Breaking the Third Wall: Implementing 3D-Printing Technics to Expand the Complexity and Abilities of Multi-Organ-on-a-Chip Devices

Micromachines ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 627
Author(s):  
Yoel Goldstein ◽  
Sarah Spitz ◽  
Keren Turjeman ◽  
Florian Selinger ◽  
Yechezkel Barenholz ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cfd Simulation ◽  
Cost Effective ◽  
In Vitro Models ◽  
3D Print ◽  
Biological Compatibility ◽  
3D Printed ◽  
Organ On A Chip

The understanding that systemic context and tissue crosstalk are essential keys for bridging the gap between in vitro models and in vivo conditions led to a growing effort in the last decade to develop advanced multi-organ-on-a-chip devices. However, many of the proposed devices have failed to implement the means to allow for conditions tailored to each organ individually, a crucial aspect in cell functionality. Here, we present two 3D-print-based fabrication methods for a generic multi-organ-on-a-chip device: One with a PDMS microfluidic core unit and one based on 3D-printed units. The device was designed for culturing different tissues in separate compartments by integrating individual pairs of inlets and outlets, thus enabling tissue-specific perfusion rates that facilitate the generation of individual tissue-adapted perfusion profiles. The device allowed tissue crosstalk using microchannel configuration and permeable membranes used as barriers between individual cell culture compartments. Computational fluid dynamics (CFD) simulation confirmed the capability to generate significant differences in shear stress between the two individual culture compartments, each with a selective shear force. In addition, we provide preliminary findings that indicate the feasibility for biological compatibility for cell culture and long-term incubation in 3D-printed wells. Finally, we offer a cost-effective, accessible protocol enabling the design and fabrication of advanced multi-organ-on-a-chip devices.

scholarly journals Design and Fabrication of Low-Cost Microfluidic Chips and Microfluidic Routing System for Reconfigurable Multi-(Organ-on-a-Chip) Assembly

Micromachines ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1542
Author(s):  
Sadeq Abu-Dawas ◽  
Hawra Alawami ◽  
Mohammed Zourob ◽  
Qasem Ramadan
Keyword(s):  
Low Cost ◽  
In Vitro Models ◽  
Specific Cell ◽  
Microfluidic Chips ◽  
Cell Tissue ◽  
Custom Design ◽  
Specialized Equipment ◽  
Organ On A Chip ◽  
Fluidic Routing

A low-cost, versatile, and reconfigurable fluidic routing system and chip assembly have been fabricated and tested. The platform and its accessories were fabricated in-house without the need for costly and specialized equipment nor specific expertise. An agarose-based artificial membrane was integrated into the chips and employed to test the chip-to-chip communication in various configurations. Various chip assemblies were constructed and tested which demonstrate the versatile utility of the fluidic routing system that enables the custom design of the chip-to-chip communication and the possibility of fitting a variety of (organ-on-a-chip)-based biological models with multicell architectures. The reconfigurable chip assembly would enable selective linking/isolating the desired chip/compartment, hence allowing the study of the contribution of specific cell/tissue within the in vitro models.

scholarly journals Biofabrication of advanced in vitro and ex vivo cancer models for disease modeling and drug screening

2021 ◽  
pp. FDD62
Author(s):  
Kylie G Nairon ◽  
Aleksander Skardal
Keyword(s):  
Disease Modeling ◽  
Ex Vivo ◽  
Human Tumor ◽  
In Vitro Models ◽  
Tissue Type ◽  
Organ On A Chip ◽  
Vitro Model ◽  
Model Platform ◽  
Simple Systems

Bioengineered in vitro models have advanced from 2D cultures and simple 3D cell aggregates to more complex organoids and organ-on-a-chip platforms. This shift has been substantial in cancer research; while simple systems remain in use, multi-tissue type tumor and tissue chips and patient-derived tumor organoids have grown rapidly. These more advanced models offer new tools to cancer researchers based on human tumor physiology and the potential for interactions with nontumor tissue physiology while avoiding critical differences between human and animal biology. In this focused review, the authors discuss the importance of organoid and organ-on-a-chip platforms, with a particular focus on modeling cancer, to highlight oncology-focused in vitro model platform technologies that improve upon the simple 2D cultures and 3D spheroid models of the past.

scholarly journals In vitro generation of human pluripotent stem cell derived lung organoids

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Briana R Dye ◽  
David R Hill ◽  
Michael AH Ferguson ◽  
Yu-Hwai Tsai ◽  
Melinda S Nagy ◽  
...  
Keyword(s):  
Human Lung ◽  
Upper Airway ◽  
Fetal Lung ◽  
Cell Types ◽  
Structural Features ◽  
In Vitro Models ◽  
Basal Cells ◽  
3 Dimensional ◽  
Organ Systems

Recent breakthroughs in 3-dimensional (3D) organoid cultures for many organ systems have led to new physiologically complex in vitro models to study human development and disease. Here, we report the step-wise differentiation of human pluripotent stem cells (hPSCs) (embryonic and induced) into lung organoids. By manipulating developmental signaling pathways hPSCs generate ventral-anterior foregut spheroids, which are then expanded into human lung organoids (HLOs). HLOs consist of epithelial and mesenchymal compartments of the lung, organized with structural features similar to the native lung. HLOs possess upper airway-like epithelium with basal cells and immature ciliated cells surrounded by smooth muscle and myofibroblasts as well as an alveolar-like domain with appropriate cell types. Using RNA-sequencing, we show that HLOs are remarkably similar to human fetal lung based on global transcriptional profiles, suggesting that HLOs are an excellent model to study human lung development, maturation and disease.

scholarly journals Recent progress in translational engineered in vitro models of the central nervous system

Brain ◽  
2020 ◽  
Vol 143 (11) ◽  
pp. 3181-3213 ◽  
Author(s):  
Polyxeni Nikolakopoulou ◽  
Rossana Rauti ◽  
Dimitrios Voulgaris ◽  
Iftach Shlomy ◽  
Ben M Maoz ◽  
...  
Keyword(s):  
Large Scale ◽  
Induced Pluripotent Stem Cell ◽  
In Vitro Models ◽  
Model Systems ◽  
Success Rates ◽  
Recent Developments ◽  
Practical Guidelines ◽  
Organ On A Chip ◽  
Induced Pluripotent

Abstract The complexity of the human brain poses a substantial challenge for the development of models of the CNS. Current animal models lack many essential human characteristics (in addition to raising operational challenges and ethical concerns), and conventional in vitro models, in turn, are limited in their capacity to provide information regarding many functional and systemic responses. Indeed, these challenges may underlie the notoriously low success rates of CNS drug development efforts. During the past 5 years, there has been a leap in the complexity and functionality of in vitro systems of the CNS, which have the potential to overcome many of the limitations of traditional model systems. The availability of human-derived induced pluripotent stem cell technology has further increased the translational potential of these systems. Yet, the adoption of state-of-the-art in vitro platforms within the CNS research community is limited. This may be attributable to the high costs or the immaturity of the systems. Nevertheless, the costs of fabrication have decreased, and there are tremendous ongoing efforts to improve the quality of cell differentiation. Herein, we aim to raise awareness of the capabilities and accessibility of advanced in vitro CNS technologies. We provide an overview of some of the main recent developments (since 2015) in in vitro CNS models. In particular, we focus on engineered in vitro models based on cell culture systems combined with microfluidic platforms (e.g. ‘organ-on-a-chip’ systems). We delve into the fundamental principles underlying these systems and review several applications of these platforms for the study of the CNS in health and disease. Our discussion further addresses the challenges that hinder the implementation of advanced in vitro platforms in personalized medicine or in large-scale industrial settings, and outlines the existing differentiation protocols and industrial cell sources. We conclude by providing practical guidelines for laboratories that are considering adopting organ-on-a-chip technologies.

Repetitive Transcranial Magnetic Stimulation of the Brain

2016 ◽  
Vol 23 (1) ◽  
pp. 82-94 ◽  
Author(s):  
Alexander Tang ◽  
Gary Thickbroom ◽  
Jennifer Rodger
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Therapeutic Potential ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Experimental Studies ◽  
Basic Research ◽  
In Vitro Models ◽  
In Vivo Studies

Since the development of transcranial magnetic stimulation (TMS) in the early 1980s, a range of repetitive TMS (rTMS) protocols are now available to modulate neuronal plasticity in clinical and non-clinical populations. However, despite the wide application of rTMS in humans, the mechanisms underlying rTMS-induced plasticity remain uncertain. Animal and in vitro models provide an adjunct method of investigating potential synaptic and non-synaptic mechanisms of rTMS-induced plasticity. This review summarizes in vitro experimental studies, in vivo studies with intact rodents, and preclinical models of selected neurological disorders—Parkinson’s disease, depression, and stroke. We suggest that these basic research findings can contribute to the understanding of how rTMS-induced plasticity can be modulated, including novel mechanisms such as neuroprotection and neurogenesis that have significant therapeutic potential.

scholarly journals Organ-on-a-chip technology for nanoparticle research

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Shawn Kang ◽  
Sunghee Estelle Park ◽  
Dan Dongeun Huh
Keyword(s):  
Targeted Drug Delivery ◽  
New Technologies ◽  
Engineered Nanoparticles ◽  
Preclinical Models ◽  
Modeling And Analysis ◽  
Concise Review ◽  
Chip Technology ◽  
Efficacy Assessment ◽  
Organ On A Chip

AbstractThe last two decades have witnessed explosive growth in the field of nanoengineering and nanomedicine. In particular, engineered nanoparticles have garnered great attention due to their potential to enable new capabilities such as controlled and targeted drug delivery for treatment of various diseases. With rapid progress in nanoparticle research, increasing efforts are being made to develop new technologies for in vitro modeling and analysis of the efficacy and safety of nanotherapeutics in human physiological systems. Organ-on-a-chip technology represents the most recent advance in this effort that provides a promising approach to address the limitations of conventional preclinical models. In this paper, we present a concise review of recent studies demonstrating how this emerging technology can be applied to in vitro studies of nanoparticles. The specific focus of this review is to examine the use of organ-on-a-chip models for toxicity and efficacy assessment of nanoparticles used in therapeutic applications. We also discuss challenges and future opportunities for implementing organ-on-a-chip technology for nanoparticle research.

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