scholarly journals Modelling Human Physiology on-Chip: Historical Perspectives and Future Directions

Micromachines ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1250
Author(s):  
Sirjana Pun ◽  
Li Cai Haney ◽  
Riccardo Barrile
Keyword(s):  
Precision Medicine ◽  
Animal Experiments ◽  
3D Bioprinting ◽  
Animal Testing ◽  
Historical Perspectives ◽  
Wide Range ◽  
Drug Treatments ◽  
Potential Alternative ◽  
On Chip

For centuries, animal experiments have contributed much to our understanding of mechanisms of human disease, but their value in predicting the effectiveness of drug treatments in the clinic has remained controversial. Animal models, including genetically modified ones and experimentally induced pathologies, often do not accurately reflect disease in humans, and therefore do not predict with sufficient certainty what will happen in humans. Organ-on-chip (OOC) technology and bioengineered tissues have emerged as promising alternatives to traditional animal testing for a wide range of applications in biological defence, drug discovery and development, and precision medicine, offering a potential alternative. Recent technological breakthroughs in stem cell and organoid biology, OOC technology, and 3D bioprinting have all contributed to a tremendous progress in our ability to design, assemble and manufacture living organ biomimetic systems that more accurately reflect the structural and functional characteristics of human tissue in vitro, and enable improved predictions of human responses to drugs and environmental stimuli. Here, we provide a historical perspective on the evolution of the field of bioengineering, focusing on the most salient milestones that enabled control of internal and external cell microenvironment. We introduce the concepts of OOCs and Microphysiological systems (MPSs), review various chip designs and microfabrication methods used to construct OOCs, focusing on blood-brain barrier as an example, and discuss existing challenges and limitations. Finally, we provide an overview on emerging strategies for 3D bioprinting of MPSs and comment on the potential role of these devices in precision medicine.

scholarly journals New Endeavors of (Micro)Tissue Engineering: Cells Tissues Organs on-Chip and Communication Thereof

2021 ◽  
pp. 1-15
Author(s):  
Haysam M.M.A.M. Ahmed ◽  
Liliana S. Moreira Teixeira
Keyword(s):  
Tissue Engineering ◽  
Food Additives ◽  
Market Potential ◽  
Model Systems ◽  
Human Model ◽  
Human Stem Cells ◽  
Animal Testing ◽  
Preclinical Research ◽  
On Chip

The development of new therapies is tremendously hampered by the insufficient availability of human model systems suitable for preclinical research on disease target identification, drug efficacy, and toxicity. Thus, drug failures in clinical trials are too common and too costly. Animal models or standard 2D in vitro tissue cultures, regardless of whether they are human based, are regularly not representative of specific human responses. Approaching near human tissues and organs test systems is the key goal of organs-on-chips (OoC) technology. This technology is currently showing its potential to reduce both drug development costs and time-to-market, while critically lessening animal testing. OoC are based on human (stem) cells, potentially derived from healthy or disease-affected patients, thereby amenable to personalized therapy development. It is noteworthy that the OoC market potential goes beyond pharma, with the possibility to test cosmetics, food additives, or environmental contaminants. This (micro)tissue engineering-based technology is highly multidisciplinary, combining fields such as (developmental) biology, (bio)materials, microfluidics, sensors, and imaging. The enormous potential of OoC is currently facing an exciting new challenge: emulating cross-communication between tissues and organs, to simulate more complex systemic responses, such as in cancer, or restricted to confined environments, as occurs in osteoarthritis. This review describes key examples of multiorgan/tissue-on-chip approaches, or linked organs/tissues-on-chip, focusing on challenges and promising new avenues of this advanced model system. Additionally, major emphasis is given to the translation of established tissue engineering approaches, bottom up and top down, towards the development of more complex, robust, and representative (multi)organ/tissue-on-chip approaches.

scholarly journals Bioprinting for Liver Transplantation

2019 ◽  
Vol 6 (4) ◽  
pp. 95 ◽  
Author(s):  
Christina Kryou ◽  
Valentina Leva ◽  
Marianneza Chatzipetrou ◽  
Ioanna Zergioti
Keyword(s):  
Direct Writing ◽  
Liver Tissue Engineering ◽  
Liver Model ◽  
Cell Structures ◽  
Wide Range ◽  
Ink Jet ◽  
Functional Complex ◽  
On Chip ◽  
2D And 3D

Bioprinting techniques can be used for the in vitro fabrication of functional complex bio-structures. Thus, extensive research is being carried on the use of various techniques for the development of 3D cellular structures. This article focuses on direct writing techniques commonly used for the fabrication of cell structures. Three different types of bioprinting techniques are depicted: Laser-based bioprinting, ink-jet bioprinting and extrusion bioprinting. Further on, a special reference is made to the use of the bioprinting techniques for the fabrication of 2D and 3D liver model structures and liver on chip platforms. The field of liver tissue engineering has been rapidly developed, and a wide range of materials can be used for building novel functional liver structures. The focus on liver is due to its importance as one of the most critical organs on which to test new pharmaceuticals, as it is involved in many metabolic and detoxification processes, and the toxicity of the liver is often the cause of drug rejection.

scholarly journals Organ-on-Chip: Playing LEGO® With Mini-Organs to Reduce Animal Testing and Make Medicines Safer

2020 ◽  
Vol 8 ◽  
Author(s):  
Julia Rogal ◽  
Madalena Cipriano ◽  
Peter Loskill
Keyword(s):  
Animal Experiments ◽  
Beating Heart ◽  
Laboratory Animals ◽  
Fat Tissue ◽  
Animal Testing ◽  
Small Plastic ◽  
The Future ◽  
On Chip ◽  
Better Than

Have you ever pictured yourself as a LEGO®-mini-figure? That is pretty cool, right?! But now, instead of picturing yourself as an astronaut, superhero, or elf-figure, try to imagine your own body being miniature and built from LEGO®–one brick for each of your organs. Sound weird? Let us explain why a mini LEGO®-version of you could be extremely useful and could become reality in the future. Such technology might help end testing that uses laboratory animals and help your doctors understand your disease. We use people’s cells and small plastic housings to build mini-organs the size of small LEGO®-bricks, such as a beating heart or energy-storing fat tissue. Similar to playing LEGO®, we can also connect different organ-bricks and study how they talk and work with each other. In this article, we will tell you how this all works and why it is so much better than animal experiments.

scholarly journals A fast and reliable method for monitoring genomic instability in the model organism Caenorhabditis elegans

2021 ◽  
Author(s):  
Merle Marie Nicolai ◽  
Barbara Witt ◽  
Andrea Hartwig ◽  
Tanja Schwerdtle ◽  
Julia Bornhorst
Keyword(s):  
Caenorhabditis Elegans ◽  
Animal Experiments ◽  
Model Organism ◽  
Animal Testing ◽  
C Elegans ◽  
Testing Strategies ◽  
Genotoxic Agents ◽  
Genotoxicity Testing

AbstractThe identification of genotoxic agents and their potential for genotoxic alterations in an organism is crucial for risk assessment and approval procedures of the chemical and pharmaceutical industry. Classically, testing strategies for DNA or chromosomal damage focus on in vitro and in vivo (mainly rodent) investigations. In cell culture systems, the alkaline unwinding (AU) assay is one of the well-established methods for detecting the percentage of double-stranded DNA (dsDNA). By establishing a reliable lysis protocol, and further optimization of the AU assay for the model organism Caenorhabditis elegans (C. elegans), we provided a new tool for genotoxicity testing in the niche between in vitro and rodent experiments. The method is intended to complement existing testing strategies by a multicellular organism, which allows higher predictability of genotoxic potential compared to in vitro cell line or bacterial investigations, before utilizing in vivo (rodent) investigations. This also allows working within the 3R concept (reduction, refinement, and replacement of animal experiments), by reducing and possibly replacing animal testing. Validation with known genotoxic agents (bleomycin (BLM) and tert-butyl hydroperoxide (tBOOH)) proved the method to be meaningful, reproducible, and feasible for high-throughput genotoxicity testing, and especially preliminary screening.

Isolated hemoperfused heart model of slaughterhouse pigs

2001 ◽  
Vol 24 (4) ◽  
pp. 215-221 ◽  
Author(s):  
D. Modersohn ◽  
S. Eddicks ◽  
C. Grosse-Siestrup ◽  
I. Ast ◽  
S. Holinski ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Animal Experiments ◽  
Laboratory Animals ◽  
Coronary Perfusion ◽  
Balloon Catheters ◽  
Wide Range ◽  
Infusion Of Norepinephrine

A model of hemoperfused slaughterhouse pighearts is described providing a wide range of applications which leads to a reduction in animal experiments. The size of a pigheart, heart rate, coronary perfusion, metabolism, etc. are more comparable to conditions in patients than those in hearts of small laboratory animals. Global heart function can be assessed either by measuring stroke volume, ejection fraction, Emaxetc. in the working model or by measuring intraventricular pressure with balloon catheters in the isovolumetric model. Regional cardiac function can be measured by sonomicrometry and ischemic and non-ischemic areas can be compared. Local metabolic changes are measurable as well with microdialysis. Cardiac function can be kept on any given functional level by infusion of norepinephrine in spite of the fact that functional parameters are lower without adrenergic drive in vitro than in vivo. Stable heart function can be maintained for several hours with only 500 to 1000 ml of blood because the blood is permanently regenerated by a special dialysis system. This model can be applied in many research projects dealing with reperfusion injuries, inotropic, antiarrhythmic or arrhythmogenic effects of certain drugs, immunological rejection, evaluation of imaging systems (NMR, echocardiography etc.) or cardiac assist devices.

Abstract MP207: A Precision Medicine Approach For Non-invasive, Longitudinal, And Quantitative Monitoring Of Cardiac Tissue-engineered Scaffolds

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Carmen Gil ◽  
Connor Evans ◽  
Lan Li ◽  
Merlyn Vargas ◽  
Gabriella Kabboul ◽  
...  
Keyword(s):  
Contrast Agents ◽  
Precision Medicine ◽  
Cardiac Tissue ◽  
Ct Imaging ◽  
3D Bioprinting ◽  
Au Nps ◽  
Non Invasive ◽  
Functional Features

3D bioprinting has revolutionized personalized and precision medicine by enabling the manufacturing of tissue constructs that precisely recapitulate the cellular and functional features of native tissues. In cardiac regenerative medicine, printed scaffolds have shown tremendous potential in repairing damaged heart, however, their clinical applications have been limited by the lack of precise noninvasive tools to monitor the patch function following implantation. By integrating state-of-the-art 3D bioprinting and photon-counting computed tomography (PCCT), this study introduces a new approach for bioengineering defect-specific scaffolds and monitoring their function. We prepared distinct CT-visible bioinks containing a variety of molecular or nanoparticle (NP) contrast agents, including iodine and gadolinium molecules, Au NPs, Gd 2 O 3 NPs, and iodine-loaded liposomes ( Fig 1A-B ). In vitro release experiments showed relatively rapid diffusion-controlled depletion of molecular contrast agents from scaffolds. In contrast, NP agents showed more stable encapsulation and only a partial, degradation-mediated release for up to 3 weeks of incubation ( Fig 1C-D ). Next, PCCT imaging was performed on various scaffold geometries printed using bioinks laden with Gd 2 O 3 or Au NPs. Results demonstrated CT visibility with differential contrast between different patch regions that corresponded to the designed geometries ( Fig 1E ). Finally, we evaluated the in vivo CT imaging of bioprinted patches after their subcutaneous implantation in a mouse model. CT images demonstrated adequate signal from implanted grafts ( Fig 1F ). Together, these results establish a novel precision medicine platform for non-invasive monitoring of medical devices which can open new prospects for a broad range of tissue engineering applications. Figure 1. 3D Bioprinting of CT-visible cardiac patches. A-B: Design of bioinks functionalized with molecular (left) and nanoparticle (right) CT contrast agents ( A ) and their bioprinting ( B ). C-D: In vitro release of contrast agents from printed patches. E: CAD design (left), CT image (middle), and PCCT material decomposition (right) for multi-contrast bioprinted scaffolds. F: In vivo CT imaging of printed patch, laden with Au NPs, implanted subcutaneously into a mouse torso.

scholarly journals Versatile electrical stimulator for providing cardiac-like electrical impulses in vitro

2020 ◽  
Author(s):  
Stefano Gabetti ◽  
Giovanni Putame ◽  
Federica Montrone ◽  
Giuseppe Isu ◽  
Anna Marsano ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Animal Experiments ◽  
Cost Effective ◽  
Culture Conditions ◽  
Animal Testing ◽  
Electrical Stimulator ◽  
Electrical Impulses ◽  
Reliable Methods

In the perspective of reliable methods alternative to in vivo animal testing for cardiac tissue engineering (CTE) research, the versatile electrical stimulator ELETTRA has been developed. ELETTRA delivers controlled and stable cardiac-like electrical impulses, and it can be coupled to already existing bioreactors for providing in vitro combined biomimetic culture conditions. Designed to be cost-effective and easy to use, this device could contribute to the reduction and replacement of in vivo animal experiments in CTE.

scholarly journals Biologia futura: animal testing in drug development—the past, the present and the future

2020 ◽  
Vol 71 (4) ◽  
pp. 443-452
Author(s):  
Miklós Sántha
Keyword(s):  
Drug Development ◽  
In Silico ◽  
Experimental Testing ◽  
Animal Experiments ◽  
Animal Testing ◽  
Culture Methods ◽  
Veterinary Research ◽  
Safety Studies ◽  
Ancient Times

AbstractAnimal experiments have served to improve our knowledge on diseases and treatment approaches since ancient times. Today, animal experiments are widely used in medical, biomedical and veterinary research, and are essential means of drug development and preclinical testing, including toxicology and safety studies. Recently, great efforts have been made to replace animal experiments with in vitro organoid culture methods and in silico predictions, in agreement with the 3R strategy to “reduce, refine and replace” animals in experimental testing, as outlined by the European Commission. Here we present a mini-review on the development of animal testing, as well as on alternative in vitro and in silico methods, that may at least partly replace animal experiments in the near future.

In Vitro Toxicity: Mechanisms, Alternatives and Validation — A Report from the 19th Annual Scientific Meeting of the Scandinavian Society for Cell Toxicology

2002 ◽  
Vol 30 (3) ◽  
pp. 307-308
Author(s):  
Anna Forsby
Keyword(s):  
Animal Experiments ◽  
Scientific Meeting ◽  
In Vitro Cytotoxicity ◽  
Annual Scientific ◽  
In Vitro Toxicity ◽  
In Vitro Tests ◽  
Mechanisms Of Toxicity ◽  
Scandinavian Society ◽  
Wide Range

The Scandinavian Society for Cell Toxicology (SSCT) has arranged annual scientific meetings since 1983. These workshops were the forum for the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) programme. Along with the MEIC programme, which was completed in 1998, a wide range of topics relating to cytotoxicity have been discussed. The meetings have also given an opportunity for graduate students and young scientists to present their work to an international audience. At the same time, experts in the fields of in vitro toxicity have been invited as speakers. The 19th SSCT scientific meeting, which was held in 2001 at Sørup Manor in Ringsted, Denmark, was no exception. The meeting consisted of four sessions: mechanisms of toxicity; environmental toxicological testing; alternatives to animal experiments; and validation of in vitro tests.

scholarly journals In Situ LSPR Sensing of Secreted Insulin in Organ-on-Chip

Biosensors ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 138
Author(s):  
María A. Ortega ◽  
Júlia Rodríguez-Comas ◽  
Ozlem Yavas ◽  
Ferran Velasco-Mallorquí ◽  
Jordina Balaguer-Trias ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Metabolic Diseases ◽  
Disease Modeling ◽  
Localized Surface Plasmon ◽  
Animal Testing ◽  
Novel Approach ◽  
On Chip ◽  
External Stimuli

Organ-on-a-chip (OOC) devices offer new approaches for metabolic disease modeling and drug discovery by providing biologically relevant models of tissues and organs in vitro with a high degree of control over experimental variables for high-content screening applications. Yet, to fully exploit the potential of these platforms, there is a need to interface them with integrated non-labeled sensing modules, capable of monitoring, in situ, their biochemical response to external stimuli, such as stress or drugs. In order to meet this need, we aim here to develop an integrated technology based on coupling a localized surface plasmon resonance (LSPR) sensing module to an OOC device to monitor the insulin in situ secretion in pancreatic islets, a key physiological event that is usually perturbed in metabolic diseases such as type 2 diabetes (T2D). As a proof of concept, we developed a biomimetic islet-on-a-chip (IOC) device composed of mouse pancreatic islets hosted in a cellulose-based scaffold as a novel approach. The IOC was interfaced with a state-of-the-art on-chip LSPR sensing platform to monitor the in situ insulin secretion. The developed platform offers a powerful tool to enable the in situ response study of microtissues to external stimuli for applications such as a drug-screening platform for human models, bypassing animal testing.

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