scholarly journals Microfluidic-Chip-Integrated Biosensors for Lung Disease Models

Biosensors ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 456
Author(s):  
Shuang Ding ◽  
Haijun Zhang ◽  
Xuemei Wang
Keyword(s):  
Lung Diseases ◽  
Three Dimensional ◽  
Drug Efficacy ◽  
Cell Models ◽  
Human Organ ◽  
The Past ◽  
The World ◽  
Future Challenges ◽  
Human Specific

Lung diseases (e.g., infection, asthma, cancer, and pulmonary fibrosis) represent serious threats to human health all over the world. Conventional two-dimensional (2D) cell models and animal models cannot mimic the human-specific properties of the lungs. In the past decade, human organ-on-a-chip (OOC) platforms—including lung-on-a-chip (LOC)—have emerged rapidly, with the ability to reproduce the in vivo features of organs or tissues based on their three-dimensional (3D) structures. Furthermore, the integration of biosensors in the chip allows researchers to monitor various parameters related to disease development and drug efficacy. In this review, we illustrate the biosensor-based LOC modeling, further discussing the future challenges as well as perspectives in integrating biosensors in OOC platforms.

Sensor-free and Sensor-based Heart-on-a-chip Platform: A Review of Design and Applications

2019 ◽  
Vol 24 (45) ◽  
pp. 5375-5385 ◽  
Author(s):  
Hao Wan ◽  
Chenlei Gu ◽  
Ying Gan ◽  
Xinwei Wei ◽  
Kai Zhu ◽  
...  
Keyword(s):  
Drug Efficacy ◽  
Recent Decade ◽  
Toxicity Assessment ◽  
Cell Models ◽  
Basic Definition ◽  
Key Factors ◽  
Human Organs ◽  
New Perspective ◽  
Approved Drugs ◽  
Human Specific

Drug efficacy and toxicity are key factors of drug development. Conventional 2D cell models or animal models have their limitations for the efficacy or toxicity assessment in preclinical assays, which induce the failure of candidate drugs or withdrawal of approved drugs. Human organs-on-chips (OOCs) emerged to present human-specific properties based on their 3D bioinspired structures and functions in the recent decade. In this review, the basic definition and superiority of OOCs will be introduced. Moreover, a specific OOC, heart-on-achip (HOC) will be focused. We introduce HOC modeling in the sensor-free and sensor-based way and illustrate the advantages of sensor-based HOC in detail by taking examples of recent studies. We provide a new perspective on the integration of HOC technology and biosensing to develop a new sensor-based HOC platform.

scholarly journals A 3D Cell Death Assay to Quantitatively Determine Ferroptosis in Spheroids

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 703 ◽  
Author(s):  
Robin Demuynck ◽  
Iuliia Efimova ◽  
Abraham Lin ◽  
Heidi Declercq ◽  
Dmitri V. Krysko
Keyword(s):  
Cell Death ◽  
Three Dimensional ◽  
Drug Efficacy ◽  
Cost Effective ◽  
3D Cultures ◽  
Cell Death Assay ◽  
Tumour Spheroids ◽  
A Cell ◽  
Triton X

The failure of drug efficacy in clinical trials remains a big issue in cancer research. This is largely due to the limitations of two-dimensional (2D) cell cultures, the most used tool in drug screening. Nowadays, three-dimensional (3D) cultures, including spheroids, are acknowledged to be a better model of the in vivo environment, but detailed cell death assays for 3D cultures (including those for ferroptosis) are scarce. In this work, we show that a new cell death analysis method, named 3D Cell Death Assay (3DELTA), can efficiently determine different cell death types including ferroptosis and quantitatively assess cell death in tumour spheroids. Our method uses Sytox dyes as a cell death marker and Triton X-100, which efficiently permeabilizes all cells in spheroids, was used to establish 100% cell death. After optimization of Sytox concentration, Triton X-100 concentration and timing, we showed that the 3DELTA method was able to detect signals from all cells without the need to disaggregate spheroids. Moreover, in this work we demonstrated that 2D experiments cannot be extrapolated to 3D cultures as 3D cultures are less sensitive to cell death induction. In conclusion, 3DELTA is a more cost-effective way to identify and measure cell death type in 3D cultures, including spheroids.

scholarly journals The Importance of Routine Quality Control For Reproducible Pulmonary Measurements By in Vivo Micro-CT

2022 ◽  
Author(s):  
Martina Mambrini ◽  
Laura Mecozzi ◽  
Erica Ferrini ◽  
Ludovica Leo ◽  
Davide Bernardi ◽  
...  
Keyword(s):  
Disease Progression ◽  
Lung Diseases ◽  
Drug Efficacy ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Efficacy Evaluation ◽  
Lung Density ◽  
Before And After ◽  
The Impact

Abstract Micro-Computed Tomography (CT) imaging provides densitometric and functional assessment of lung diseases in animal models, playing a key role either in understanding disease progression or in drug discovery studies.The generation of reliable and reproducible experimental data is strictly dependent on a system’s stability. Quality Controls (QC) are essential to monitor micro-CT performance but, although QC procedures are standardized and routinely employed in clinical practice, detailed guidelines for preclinical imaging are lacking. In this work, we propose a routine QC protocol for in vivo micro-CT, based on three commercial phantoms. To investigate the impact of a detected scanner drift on image post-processing, a retrospective analysis using twenty-two healthy mice was performed and lung density histograms used to compare the Area Under Curve (AUC), the skewness and the kurtosis before and after the drift. As expected, statistically significant differences were found for all the selected parameters [AUC: 532 ± 31 vs. 420 ± 38 (p < 0.001); skewness: 2.3 ± 0.1 vs. 2.5 ± 0.1 (p < 0.001) and kurtosis: 4.2 ± 0.3 vs. 5.1 ± 0.5 (p < 0.001)], confirming the importance of the designed QC procedure to obtain a reliable longitudinal quantification of disease progression and drug efficacy evaluation.

scholarly journals Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure

Gut ◽  
2020 ◽  
pp. gutjnl-2019-319960 ◽  
Author(s):  
Huayu Yang ◽  
Lejia Sun ◽  
Yuan Pang ◽  
Dandan Hu ◽  
Haifeng Xu ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Liver Failure ◽  
Human Liver ◽  
Three Dimensional ◽  
3D Bioprinting ◽  
Heparg Cells ◽  
Liver Functions ◽  
Human Specific

ObjectiveShortage of organ donors, a critical challenge for treatment of end-stage organ failure, has motivated the development of alternative strategies to generate organs in vitro. Here, we aim to describe the hepatorganoids, which is a liver tissue model generated by three-dimensional (3D) bioprinting of HepaRG cells and investigate its liver functions in vitro and in vivo.Design3D bioprinted hepatorganoids (3DP-HOs) were constructed using HepaRG cells and bioink, according to specific 3D printing procedures. Liver functions of 3DP-HOs were detected after 7 days of differentiation in vitro, which were later transplanted into Fah-deficient mice. The in vivo liver functions of 3DP-HOs were evaluated by survival time and liver damage of mice, human liver function markers and human-specific debrisoquine metabolite production.Results3DP-HOs broadly acquired liver functions, such as ALBUMIN secretion, drug metabolism and glycogen storage after 7 days of differentiation. After transplantation into abdominal cavity of Fah-/-Rag2-/- mouse model of liver injury, 3DP-HOs further matured and displayed increased synthesis of liver-specific proteins. Particularly, the mice acquired human-specific drug metabolism activities. Functional vascular systems were also formed in transplanted 3DP-HOs, further enhancing the material transport and liver functions of 3DP-HOs. Most importantly, transplantation of 3DP-HOs significantly improved the survival of mice.ConclusionsOur results demonstrated a comprehensive proof of principle, which indicated that 3DP-HO model of liver tissues possessed in vivo hepatic functions and alleviated liver failure after transplantation, suggesting that 3D bioprinting could be used to generate human liver tissues as the alternative transplantation donors for treatment of liver diseases.

scholarly journals Multi-Organs-on-Chips: Towards Long-Term Biomedical Investigations

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 675 ◽  
Author(s):  
Yi Zhao ◽  
Ranjith Kankala ◽  
Shi-Bin Wang ◽  
Ai-Zheng Chen
Keyword(s):  
Real Time ◽  
Three Dimensional ◽  
Drug Efficacy ◽  
Dynamic Responses ◽  
Physical Parameters ◽  
Real Time Monitoring ◽  
Multiple Organs ◽  
On Chip

With advantageous features such as minimizing the cost, time, and sample size requirements, organ-on-a-chip (OOC) systems have garnered enormous interest from researchers for their ability for real-time monitoring of physical parameters by mimicking the in vivo microenvironment and the precise responses of xenobiotics, i.e., drug efficacy and toxicity over conventional two-dimensional (2D) and three-dimensional (3D) cell cultures, as well as animal models. Recent advancements of OOC systems have evidenced the fabrication of ‘multi-organ-on-chip’ (MOC) models, which connect separated organ chambers together to resemble an ideal pharmacokinetic and pharmacodynamic (PK-PD) model for monitoring the complex interactions between multiple organs and the resultant dynamic responses of multiple organs to pharmaceutical compounds. Numerous varieties of MOC systems have been proposed, mainly focusing on the construction of these multi-organ models, while there are only few studies on how to realize continual, automated, and stable testing, which still remains a significant challenge in the development process of MOCs. Herein, this review emphasizes the recent advancements in realizing long-term testing of MOCs to promote their capability for real-time monitoring of multi-organ interactions and chronic cellular reactions more accurately and steadily over the available chip models. Efforts in this field are still ongoing for better performance in the assessment of preclinical attributes for a new chemical entity. Further, we give a brief overview on the various biomedical applications of long-term testing in MOCs, including several proposed applications and their potential utilization in the future. Finally, we summarize with perspectives.

Stem cells of the oesophageal epithelium

2002 ◽  
Vol 115 (9) ◽  
pp. 1783-1789
Author(s):  
John P. Seery
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
Epithelial Stem Cells ◽  
The Past ◽  
The World

Cancers arising in the oesophageal epithelium are among the most common fatal tumors in the world. Despite this, comparatively little is known about the cell biology and organization of this tissue. Recently, in vitro and in vivo techniques developed over the past 30 years for the study of the epidermis have been applied to the study of the oesophageal epithelium. This approach, combined with data from previous histochemical studies, has lead to the identification and isolation of putative oesophageal epithelial stem cells. Oesophageal epithelial stem cells demonstrate several unusual properties, and their identification may facilitate studies on oesophageal carcinogenesis.

scholarly journals The hurdles of nanotoxicity in transplant nanomedicine

Nanomedicine ◽  
2019 ◽  
Vol 14 (20) ◽  
pp. 2749-2762 ◽  
Author(s):  
Amber Nagy ◽  
Nicholas L Robbins
Keyword(s):  
Regulatory Agencies ◽  
The Past ◽  
Future Challenges ◽  
Transplant Medicine

Nanomedicine has matured significantly in the past 20 years and a number of nanoformulated therapies are cleared by regulatory agencies for use across the globe. Transplant medicine is one area that has significantly benefited from the advancement of nanomedicine in recent times. However, while nanoparticle-based therapies have improved toxicological profiles of some drugs, there are still a number of aspects regarding the biocompatibility and toxicity of nanotherapies that require further research. The goal of this article is to review toxicological profiles of immunosuppressant therapies and their conversion into nanomedicine formulations as well as introduce future challenges associated with current in vitro and in vivo toxicological models.

scholarly journals In Vivo Assessment of Drug Efficacy against Plasmodium falciparum Malaria: Duration of Follow-Up

2004 ◽  
Vol 48 (11) ◽  
pp. 4271-4280 ◽  
Author(s):  
Kasia Stepniewska ◽  
Walter R.J. Taylor ◽  
Mayfong Mayxay ◽  
Ric Price ◽  
Frank Smithuis ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Failure Rate ◽  
Drug Efficacy ◽  
Plasmodium Falciparum Malaria ◽  
Value Assessment ◽  
Randomized Controlled ◽  
The Past

ABSTRACT To determine the optimum duration of follow-up for the assessment of drug efficacy against Plasmodium falciparum malaria, 96 trial arms from randomized controlled trials (RCTs) with follow-up of 28 days or longer that were conducted between 1990 and 2003 were analyzed. These trials enrolled 13,772 patients, and participating patients comprised 23% of all patients enrolled in RCTs over the past 40 years; 61 (64%) trial arms were conducted in areas where the rate of malaria transmission was low, and 58 (50%) trial arms were supported by parasite genotyping to distinguish true recrudescences from reinfections. The median overall failure rate reported was 10% (range, 0 to 47%). The widely used day 14 assessment had a sensitivity of between 0 and 37% in identifying treatment failures and had no predictive value. Assessment at day 28 had a sensitivity of 66% overall (28 to 100% in individual trials) but could be used to predict the true failure rate if either parasite genotyping was performed (r 2 = 0.94) or if the entomological inoculation rate was known. In the assessment of drug efficacy against falciparum malaria, 28 days should be the minimum period of follow-up.

scholarly journals Brain Organoids—A Bottom-Up Approach for Studying Human Neurodevelopment

2019 ◽  
Vol 6 (1) ◽  
pp. 9 ◽  
Author(s):  
Eyal Karzbrun ◽  
Orly Reiner
Keyword(s):  
Human Brain ◽  
Three Dimensional ◽  
Human Stem Cells ◽  
In Vitro Systems ◽  
Brain Organoid ◽  
Specific Disorders ◽  
Bioengineering Techniques ◽  
Human Specific

Brain organoids have recently emerged as a three-dimensional tissue culture platform to study the principles of neurodevelopment and morphogenesis. Importantly, brain organoids can be derived from human stem cells, and thus offer a model system for early human brain development and human specific disorders. However, there are still major differences between the in vitro systems and in vivo development. This is in part due to the challenge of engineering a suitable culture platform that will support proper development. In this review, we discuss the similarities and differences of human brain organoid systems in comparison to embryonic development. We then describe how organoids are used to model neurodevelopmental diseases. Finally, we describe challenges in organoid systems and how to approach these challenges using complementary bioengineering techniques.

scholarly journals Three Dimensional Capacitive Control System using Arduino Uno

2019 ◽  
Vol 8 (11S) ◽  
pp. 6-10
Keyword(s):  
Control System ◽  
Human Computer Interaction ◽  
Three Dimensional ◽  
Human Computer Interactions ◽  
The Past ◽  
The World ◽  
Arduino Uno ◽  
Computer Interaction ◽  
Computer Interactions

Technology has grown vastly in all directions of the world. The influence it has had on the world over the past 50 years has been exponential and the need for further growth is demanding. Human Computer interaction these days exists in various forms. Ever since the computer has dominated the business age, there have been huge leaps in progress towards science. These days a person need to use a series of multiple peripheral devices to simply send data from one system to another. However the existing devices used for Human computer interactions are limited in their potential and capabilities. More devices would thus require a more sophisticated touchless control system. This system however has been deemed to be too expensive and furthermore it requires a lot of skill to control and maintain. Thus the proposed system would need to be fairly cheap to produce and simple enough that the users will not be intimidated by its complexity and design

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