Organ-on-a-Chip (OoC) technology represents a groundbreaking advancement in biomedical research, offering a transformative approach to mimic the complex microenvironments and physiological functions of human organs in vitro. These microfluidic devices incorporate small structures designed for cell culture, creating precise biochemical and mechanical stimuli to recreate physiologically relevant conditions. By integrating microfluidic and bioengineering techniques, OoC platforms aim to recapitulate tissue architecture and simulate key organ functions, making them invaluable tools for preclinical drug testing and disease modeling[1].
Since its inception in the early 2010s [2], OoC technology has witnessed rapid evolution and garnered increasing interest from the biomedical community. Traditional 2D petri dish cultures and animal models have inherent limitations in replicating human physiology accurately. In contrast, OoC systems offer a more representative in vitro model, bridging the gap between preclinical and clinical outcomes in drug development and disease studies.
3D cell culture definitely offers great advantages over 2D cell culture. It facilitates cell differentiation and tissue organization getting closer to physiological conditions of living organisms.
However, 3D cells organization brings new challenges to overcome:
Microfluidic systems are essential for relevant 3D cell culture models due to their ability to mimic physiological conditions and provide precise control over the microenvironment [3]. Unlike traditional static cultures, microfluidic systems allow for dynamic flow of culture medium, ensuring uniform nutrient distribution and waste removal throughout the cellular construct [4]. This continuous perfusion maintains cell viability and function over extended periods, closely resembling the nutrient exchange observed in vivo. Additionally, microfluidic platforms enable the establishment of spatial gradients of signaling molecules, such as growth factors and oxygen, which play crucial roles in cellular behavior and differentiation [5]. By accurately replicating these complex microenvironments, microfluidics enhances the fidelity of 3D cell culture models, making them more physiologically relevant for biomedical research and drug development.
OoC platforms are micro-engineered chips designed to emulate the essential functions of organs and tissues in vitro. Unlike traditional cell culture plates or animal models, the primary goal of OoC is not to replicate entire organs but to mimic specific organ functions for targeted studies. These platforms offer a balance between complexity and controllability, providing researchers with well-defined, physiologically relevant environments to study organ-specific phenomena.
At the core of OoC platforms are three fundamental characteristics [2]:
To realize these characteristics, OoC platforms leverage a combination of engineering principles and cell biology techniques. These chips are linked to microfluidic systems to enable effective cell perfusion and regulate diverse stimulus modalities. By carefully manipulating these factors, researchers can tailor OoC platforms to model specific organ functions and pathophysiological conditions accurately.
Preclinical animal models have been essential for drug development but struggle to accurately predict human responses due to limitations in mimicking human physiology and genetics. Also, recent studies have questioned their predictive ability and highlighted ethical concerns, high costs, and low yields. Disease-specific OoC models provide unique insights into disease progression, pathophysiology, and potential therapeutic interventions. By faithfully mimicking the physical, behavioral, and structural characteristics of tissues and organs, OoC platforms offer a robust approach for studying disease mechanisms and testing novel treatments [9].
Drug screening frequently faces challenges in finding cost-effective and physiologically relevant solutions, as traditional animal models continue to dominate preclinical evaluation. The limited scalability associated with animal testing means that only a fraction of potential drug candidates from extensive molecular libraries can be thoroughly assessed. OoC technology represents a paradigm shift in drug screening, offering superior physiological relevance compared to traditional cell cultures (Fig. 3). Microfluidic chips embedded in OoC platforms facilitate the generation of biochemical gradients, concentration, allowing researchers to study cellular responses to drug compounds with unprecedented detail. OoC platforms serve as invaluable tools for evaluating drug pharmacokinetics, toxicity profiles, and potency, thereby streamlining the drug development process and reducing reliance on animal models [10], [11].
Compared to traditional preclinical models, OoC platforms offer enhanced predictability and accuracy in evaluating drug toxicity Integrated sensors within OoC devices enable real-time monitoring of cellular responses to drug compounds, facilitating the identification of adverse effects and potential safety issues. By reconstructing complex tissue microenvironments and simulating organ functions, OoC technology enhances the assessment of drug-induced toxicity and improves the efficiency of drug candidate selection processes [13], [14].
OoC technology has revolutionized the field of biomedical research by providing advanced platforms for modeling complex organ systems in vitro. These organ models, fabricated using microfluidic devices, faithfully replicate the structural and functional characteristics of human organs, offering unprecedented insights into disease mechanisms, drug responses, and toxicity profiles. Here, we delve into some of the key organ models developed in OoC platforms, highlighting the associated cell types and disease models:
The lung-on-chip model was one of the first milestone of OoC technologies with the “breathing lung” developed in 2010 [15] by theWyss institute of Harvard University. As air quality continues to decline globally, resulting in an increase in respiratory diseases, there is a growing need for in vitro lung models like OoC technologies [16]. The lung-on-chip model comprises epithelial cells, endothelial cells, and immune cells, mimicking the alveolar-capillary interface. This model is instrumental in studying respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. By exposing the lung model to environmental toxins, pathogens, and drug compounds, researchers can elucidate disease pathogenesis and evaluate therapeutic interventions.
The liver-on-chip model incorporates hepatocytes, Kupffer cells, stellate cells, and endothelial cells, or human pluripotent stem cells derivatives (Fig.4) recapitulating hepatic functions and interactions. It is a valuable tool for studying liver diseases including hepatitis, fatty liver disease, and drug-induced liver injury. The liver model facilitates the assessment of drug metabolism, hepatotoxicity, and drug-drug interactions, aiding in the development of safer and more effective medications. [3], [17].
The kidney-on-a-chip model consists of renal epithelial cells, endothelial cells, and immune cells, resembling the nephron structure and function. Researchers utilize this model to investigate kidney diseases such as acute kidney injury, polycystic kidney disease, and diabetic nephropathy. By simulating glomerular filtration, tubular reabsorption, and interstitial inflammation, the kidney model enables the study of disease mechanisms and the screening of potential therapeutics.
The heart-on-chip model incorporates cardiomyocytes, fibroblasts, endothelial cells, and cardiac progenitor cells, replicating the myocardial tissue architecture. It serves as a valuable platform for studying cardiovascular diseases including arrhythmias, myocardial infarction, and heart failure [19], [20]. By subjecting the heart model to mechanical strain, electrical stimulation, and drug compounds, researchers can assess cardiac function, drug cardiotoxicity, and the efficacy of cardiac therapies (Fig. 5).
The brain-on-chip model comprises neurons, astrocytes, microglia, and endothelial cells, mimicking the neural network and blood-brain barrier (Fig. 6). It facilitates the study of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and stroke. By recapitulating neuronal connectivity, synaptic function, and neuroinflammatory responses, the brain model offers insights into disease pathogenesis and potential neuroprotective strategies.
These organ models in OoC platforms represent sophisticated tools for disease modeling, drug screening, and toxicity testing. By integrating multiple cell types within physiologically relevant microenvironments, OoC technology holds immense promise for advancing our understanding of human biology and accelerating the development of novel therapeutics. Moreover, the advent of multi-organs-on-chip models allows for the integration of multiple organ models (heart-liver[22], liver kidney[23], brain-liver[24], etc.) enabling the study of complex organ interactions and systemic responses to drugs and diseases (Fig. 7). These sophisticated OoC platforms represent powerful tools for disease modeling, drug screening, and toxicity testing, promising to revolutionize biomedical research and therapeutic development.
Recreating the intricate multicellular interactions and tissue-organ interfaces found in vivo remains a major challenge in OoC technology. While current models capture certain aspects of organ physiology, they often lack the complexity and heterogeneity of native tissues. Incorporating immune cells, structural cells, lymphatic system and other stromal components into OoC are the key direction to enhance the physiological relevance of these models and improve their predictive value for drug testing and disease modeling.
Despite significant advancements, OoC technology still faces challenges related to reproducibility, scalability, and standardization. Variability in cell sources, culture conditions, and microfabrication processes can affect experimental outcomes and hinder comparability between studies. The lack of standardized protocols and regulatory guidelines poses significant barriers to the widespread adoption of OoC technology in preclinical research and drug development. Collaborative initiatives involving academia, industry, and regulatory agencies are needed to establish consensus on experimental methodologies, validation criteria, and ethical considerations. Clear regulatory pathways for OoC-based assays and devices are essential to ensure their acceptance and integration into mainstream biomedical research and clinical practice.
Despite the challenges, OoC technology holds immense promise for advancing our understanding of human biology and disease mechanisms. Future research directions include integrating multiple organ models to simulate systemic physiology, enhancing predictive capabilities through computational modeling and artificial intelligence[12], and advancing personalized medicine by using patient-derived cells and tissues. Continued investment in technological innovation, material study and regulatory support will be crucial to realizing the full potential of OoC technology and translating it into clinical applications for improving human health.
In conclusion, organ-on-a-chip technology represents a groundbreaking approach to biomedical research, offering unprecedented opportunities to model human physiology and disease in vitro. By integrating microfabrication techniques, advanced cell culture methods, and innovative sensing technologies, OOC platforms enable researchers to recapitulate the complexities of human organs and tissues with remarkable fidelity. The burgeoning interest in personalized and precision medicine, coupled with advancements in novel therapeutics, has fueled the research of OoC technology in both academic institutions and pharmaceutical industries. Despite remaining challenges related to reproducibility, scalability, and regulatory approval, ongoing advancements and collaborative efforts hold promise for revolutionizing drug discovery, disease modeling, and personalized medicine in the years to come, leading to a valuable impact on human health[1].
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Coronavirus (SARS-CoV2) diagnostic through microfluidics
In this report, we identify the following two main purposes for the 3D cell market
At the beginning of the third millennium, due to prolonged aging, neurodevelopmental disorders are growing and a much deeper understanding of the brain is necessary.
The liver is involved in more than 300 vital functions, but is mainly known for being part of the digestive tract, where it has the extremely important role of metabolizing both xenobiotics and nutrients (carbohydrates and lipids).
A heart-on-chip is a microfluidic chip reproducing the mechanisms of a heart, in order to test medicine quickly and observe the reaction of heart cells. Great care is given to mimic the mechanics of a heart in an artificial structure, lined with live heart cells.
While many animal models have been used to study lung diseases, they lack sufficient similarity with human systems, leaving gaps in what is possible in animal-based platforms.
The lung is the main organ of respiration whose function is to facilitate gas exchange in and out of the blood stream.
It could be extremely interesting to build a human-on-chip that will model the interactions between different organs, but it is also essential to develop simulations of tissue-tissue interfaces and more generally of local organ behavior.
Multi-organs on chip could also allow us to witness the side effects of certain drugs on different organs, not limited to those that the treatment targets.
Since 2012, more and more people, companies or lab, have worked on the organ-on-a-chip. These cell cultures can, thanks to microfluidics, mimic the cells microenvironment of the human body. Thus, these chips could become wonderful search accelerators and we can hope that, in ten years, they could replace the animal testing. Finally, organs on chips could lead us to personalized medicine.
Cell culture consists in growing cells in an artificial environment in order to study their behavior in response to their environment[1]. Different kinds of cell cultures can be found nowadays, and some would be more suited than others depending on its properties and applications.
Organ-on-chip companies developping innovative technologies
Although we take part in various research projects such as artificial photosynthesis, pathogen detection and stem cell differentiation, the ultimate goal of our entrepreneurial adventure is to accelerate anti-aging research.
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