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Common respiratory diseases: respiratory diseases are among the leading cause of deaths worldwide. Chronic respiratory conditions including COPD and asthma affect most people. All respiratory diseases have symptoms varying from mild to severe and can also be life-threatening.

Common respiratory diseases: respiratory diseases are among the leading cause of deaths worldwide. Chronic respiratory conditions including COPD and asthma affect most people. All respiratory diseases have symptoms varying from mild to severe and can also be life-threatening.

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Recently, organ-on-a-chip models, which are microfluidic devices that mimic the cellular architecture and physiological environment of an organ, have been developed and extensively investigated. The chips can be tailored to accommodate the disease conditions pertaining to many organs; and in the case of this review, the lung. Lung-on-a-chip models...

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... Lungs are indeed crucial for healthy living and poorly functioning lungs and leads to a wide range of clinical conditions. Figure 1 illustrates the most common pulmonary diseases in the world. According to The Global Impact of Respiratory Disease published by the Forum of International Respiratory Societies, the number of deaths due to respiratory diseases remains enormous [55]. ...

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... The study of cell-blood flow, cell-gas flow, and cell-cell interactions in the respiratory tract has important implications for physiological studies and drug delivery ( Figure 5(Ab)) [185,186]. Therefore, establishing an OoC model of lung cancer is important for understanding the treatment and pathogenesis of lung cancer ( Figure 5(Aa)) [187][188][189][190]. A typical lung-on-a-chip platform consists of two microfluidic channels, which are separated by a porous extracellular matrix, with lung tumor cells integrated into pulmonary epithelial cells and pulmonary microvascular endothelial cells distributed on both sides [191][192][193]. ...
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Although many studies have focused on oncology and therapeutics in cancer, cancer remains one of the leading causes of death worldwide. Due to the unclear molecular mechanism and complex in vivo microenvironment of tumors, it is challenging to reveal the nature of cancer and develop effective therapeutics. Therefore, the development of new methods to explore the role of heterogeneous TME in individual patients’ cancer drug response is urgently needed and critical for the effective therapeutic management of cancer. The organ-on-chip (OoC) platform, which integrates the technology of 3D cell culture, tissue engineering, and microfluidics, is emerging as a new method to simulate the critical structures of the in vivo tumor microenvironment and functional characteristics. It overcomes the failure of traditional 2D/3D cell culture models and preclinical animal models to completely replicate the complex TME of human tumors. As a brand-new technology, OoC is of great significance for the realization of personalized treatment and the development of new drugs. This review discusses the recent advances of OoC in cancer biology studies. It focuses on the design principles of OoC devices and associated applications in cancer modeling. The challenges for the future development of this field are also summarized in this review. This review displays the broad applications of OoC technique and has reference value for oncology development.
... Recently, by developing a microphysiological system using an organ-on-a-chip, efforts are being made to solve the problems of the existing drug development method, which requires huge development costs for a long time and the limitations of animal experiments due to differences between species [1][2][3]. Organs under study are being studied in various ways, such as Lung-on-a-chip [4], Glomerulus-on-a-chip [5], and Heart-on-a-chip [6]. 2 of 12 Chip research on proximal tubules is also being actively conducted. In various studies, patterns are made using soft lithography, and research using tubule-on-a-chip made with PDMS is in progress [7,8]. ...
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... Epi, endo The epithelial stimulation with inflammatory cytokine tissue necrosis factor alpha [221,222] Epi (line) The toxicity due to the silica nanoparticles in the pulmonary region [198,223] Epi, endo Pulmonary oedema caused via the interleukin-2 which is detected by the leakage of fluids [120,224] Epi, endo The infiltration from the neutrophils [225,226] Epi (line), endo, immune Virus infection (SARS-CoV-2), inflammation [227] Epi, endo, cancer Lung cancer [212] Epi COPD induced by smoke [228] Epi (line), endo, immune Asthma, COPD [191,229] Epi Mechanical injury to airway cells [230] Epi (line), endo, immune, bacteria Cystic fibrosis, inflammation, bacterial infection [231] Epi, endo, immune Virus infection (influenza, pseudotyped SARS-CoV-2), inflammation [232] Skin Keratinocyte Model for wound healing, inflammation, repair, irritation, ageing and shear stress studies [233] Gut Epi (org), endo Intestinal differentiation [145] Epi (line), endo The epithelium infected by virus coxsackie B1 The pathogen-induced injury [234] Epi (line), endo The peristaltic mechanical deformation-induced bacterial out-growth [235,236] Epi (line), bacteria Host-microbiome interactions (to clinically simulate effects of microbiome metabolites on host) [237] Epi (line) The loss of the barrier function caused by staurosporine and aspirin [238] Epi (line), endo, lymphatic, endo, immune, bacteria Bacterial infection and inflammation [144] Epi (line) Enteric virus infection (to clinically mimic infection-associated injury) [239] Gut Epi (org), immune Inflammatory bowel disease (IBD) [240] Epi (org), endo, immune, virus Enteric virus infection [241] Epi (line), endo, virus SARS-CoV-2 virus infection [242] Epi (org), bacteria Bacterial infection, mechano-sensitivity (to clinically mimic Shigella infection) [243] Epi (line), endo, Radiation injury [244] Kidney ...
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Over the decades, conventional in vitro culture systems and animal models have been used to study physiology, nutrient or drug metabolisms including mechanical and physiopathological aspects. However, there is an urgent need for Integrated Testing Strategies (ITS) and more sophisticated platforms and devices to approach the real complexity of human physiology and provide reliable extrapolations for clinical investigations and personalized medicine. Organ-on-a-chip (OOC), also known as a microphysiological system, is a state-of-the-art microfluidic cell culture technology that sums up cells or tissue-to-tissue interfaces, fluid flows, mechanical cues, and organ-level physiology, and it has been developed to fill the gap between in vitro experimental models and human pathophysiology. The wide range of OOC platforms involves the miniaturization of cell culture systems and enables a variety of novel experimental techniques. These range from modeling the independent effects of biophysical forces on cells to screening novel drugs in multi-organ microphysiological systems, all within microscale devices. As in living biosystems, the development of vascular structure is the salient feature common to almost all organ-on-a-chip platforms. Herein, we provide a snapshot of this fast-evolving sophisticated technology. We will review cutting-edge developments and advances in the OOC realm, discussing current applications in the biomedical field with a detailed description of how this technology has enabled the reconstruction of complex multi-scale and multifunctional matrices and platforms (at the cellular and tissular levels) leading to an acute understanding of the physiopathological features of human ailments and infections in vitro.
... Viral infection can induce asthma exacerbation, seasonal flu and outbreaks of COVID-19. Asthma is considered a common chronic disease, and is present in 14% of all children worldwide and affects approximately 334 million people worldwide (Shrestha et al., 2020). Bronchopneumonia associated with seasonal influenza virus is one of the infectious diseases with the highest mortality rate. ...
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Viral infectious diseases remain a global public health problem. The rapid and widespread spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) has had a severe impact on the global economy and human activities, highlighting the vulnerability of humans to viral infectious diseases and the urgent need to develop new technologies and effective treatments. Organ-on-a-chip is an emerging technology for constructing the physiological and pathological microenvironment of human organs in vitro and has the advantages of portability, high throughput, low cost, and accurate simulation of the in vivo microenvironment. Indeed, organ-on-a-chip provides a low-cost alternative for investigating human organ physiology, organ diseases, toxicology, and drug efficacy. The lung is a main target organ of viral infection, and lung pathophysiology must be assessed after viral infection and treatment with antiviral drugs. This review introduces the construction of lung-on-a-chip and its related pathophysiological models, focusing on the in vitro simulation of viral infection and evaluation of antiviral drugs, providing a developmental direction for research and treatment of viral diseases.
... Organ on a chip can either be a single cell or multiple cell type in nature and has a microfluidics device for the continuous supply of nutrients and removal of waste. These devices can mimic the cellular architecture, microenvironment, and tissue-tissue interfaces of an organ and thus can be used to study various lung diseases such as lung cancer, COPD, and asthma [158,159]. Techniques such as lithography-based microfabrication, thermoplastic technique, and 3D bioprinting are used for the fabrication of the lung on a chip model. ...
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Tobacco smoking has been established to contribute to the pathogenesis of various respiratory diseases including chronic obstructive pulmonary disease (COPD), lung cancer, and asthma. However, major hurdles in mechanistic studies on the role of smoking in human lungs remain in part due to the lack of ex vivo experimental models and ambiguous data from animal models that can best recapitulate the architecture and pathophysiology of the human lung. Recent development of the lung organoid culture system has opened new avenues for respiratory disease research as organoids are proving to be a sophisticated ex vivo model that functionally and structurally mimics the human lungs better than other traditionally used models. This review will discuss how recent advances in lung organoid systems may help us better determine the injurious and immunological effect of smoking on human lungs and will provide some suggestions for future research directions.
... Additionally, the expression level of U87 exceeded the one of RPMI 2650. Apart from more intricate techniques such as microfluidic 3D cell culture, air-liquid interface culture models of the respiratory tract are currently the most promising in vitro approach to mimic in vivo conditions in rather high-throughput experiments [83][84][85]. The most important characteristic of this model is that cells are cultured on a supporting membrane, so that the apical side is exposed to air while the basolateral side is in contact with nourishing medium. ...
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Nose-to-brain delivery presents a promising alternative route compared to classical blood–brain barrier passage, especially for the delivery of high molecular weight drugs. In general, macromolecules are rapidly degraded in physiological environment. Therefore, nanoparticulate systems can be used to protect biomolecules from premature degradation. Furthermore, targeting ligands on the surface of nanoparticles are able to improve bioavailability by enhancing cellular uptake due to specific binding and longer residence time. In this work, transferrin-decorated chitosan nanoparticles are used to evaluate the passage of a model protein through the nasal epithelial barrier in vitro. It was demonstrated that strain-promoted azide–alkyne cycloaddition reaction can be utilized to attach a functional group to both transferrin and chitosan enabling a rapid covalent surface-conjugation under mild reaction conditions after chitosan nanoparticle preparation. The intactness of transferrin and its binding efficiency were confirmed via SDS-PAGE and SPR measurements. Resulting transferrin-decorated nanoparticles exhibited a size of about 110–150 nm with a positive surface potential. Nanoparticles with the highest amount of surface bound targeting ligand also displayed the highest cellular uptake into a human nasal epithelial cell line (RPMI 2650). In an air–liquid interface co-culture model with glioblastoma cells (U87), transferrin-decorated nanoparticles showed a faster passage through the epithelial cell layer as well as increased cellular uptake into glioblastoma cells. These findings demonstrate the beneficial characteristics of a specific targeting ligand. With this chemical and technological formulation concept, a variety of targeting ligands can be attached to the surface after nanoparticle formation while maintaining cargo integrity. Graphical abstract
... The microfluidic device, as a bioreactor, was called "organon-a-chip". After more than 10 years of development, these organ-on-a-chips have successfully been used to reproduce many tissues and organs (Oleaga et al., 2016;Wu et al., 2020;Rothbauer et al., 2021) such as lung (Stucki et al., 2015;Shrestha et al., 2020), liver (Banaeiyan et al., 2017;Moradi et al., 2020), kidney (Zhou et al., 2016;Lee and Kim, 2018), and skin (Wufuer et al., 2016;Lee et al., 2017). These precisely constructed models are used to clarify physiological phenomena that are difficult to dynamically observe, systematically evaluate, and quantify in vivo, and can serve as effective tools for high-throughput screening of therapeutic drugs. ...
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Biological studies typically rely on a simple monolayer cell culture, which does not reflect the complex functional characteristics of human tissues and organs, or their real response to external stimuli. Microfluidic technology has advantages of high-throughput screening, accurate control of the fluid velocity, low cell consumption, long-term culture, and high integration. By combining the multipotential differentiation of neural stem cells with high throughput and the integrated characteristics of microfluidic technology, an in vitro model of a functionalized neurovascular unit was established using human neural stem cell-derived neurons, astrocytes, oligodendrocytes, and a functional microvascular barrier. The model comprises a multi-layer vertical neural module and vascular module, both of which were connected with a syringe pump. This provides controllable conditions for cell inoculation and nutrient supply, and simultaneously simulates the process of ischemic/hypoxic injury and the process of inflammatory factors in the circulatory system passing through the blood-brain barrier and then acting on the nerve tissue in the brain. The in vitro functionalized neurovascular unit model will be conducive to central nervous system disease research, drug screening, and new drug development.
... The current state of clinically relevant organoid research from reviews As there are few RCTs for clinical outcomes on the way, the systematic reviews identified by our search may provide some overview of ongoing and published studies and detail the clinical prospects of organoid research, as they offer updated summaries of past and currently ongoing organoid research. For example, four publications present results on cancer organoids [Ishiguro et al., 2017;Aberle et al., 2018;Medle et al., 2022;Sisman et al., 2022], seven on organoids derived from healthy tissue [Alves-Lopes and Stukenborg, 2018;Nugraha et al., 2018;De Miguel et al., 2019;Schneemann et al., 2020;Shrestha et al., 2020;Aasen and Vergara, 2020;Samimi et al., 2021], and one discusses the potential of organoids in general to imitate extracellular vesicles [Abdollahi, 2021]. The types of cancer organoids studied are glioma, breast, colon, ovary, prostate, bladder, and gastrointestinal organoids [Ishiguro et al., 2017;Aberle et al., 2018;Medle et al., 2022;Sisman et al., 2022]. ...
... The types of cancer organoids studied are glioma, breast, colon, ovary, prostate, bladder, and gastrointestinal organoids [Ishiguro et al., 2017;Aberle et al., 2018;Medle et al., 2022;Sisman et al., 2022]. Types of healthy organoids include heart, testis, liver, lung, retinal, and thyroid organoids [Alves-Lopes and Stukenborg, 2018;Nugraha et al., 2018;De Miguel et al., 2019;Schneemann et al., 2020;Shrestha et al., 2020;Aasen and Vergara, 2020;Samimi et al., 2021]. Eight of the ten publications are narrative reviews [Ishiguro et al., 2017;Aberle et al., 2018;Alves-Lopes and Stukenborg, 2018;Nugraha et al., 2018;De Miguel et al., 2019;Shrestha et al., 2020;Aasen and Vergara, 2020;Abdollahi, 2021], one is a systematic review [Samimi et al., 2021], and one is a policy article [Schneemann et al., 2020]. ...
... Types of healthy organoids include heart, testis, liver, lung, retinal, and thyroid organoids [Alves-Lopes and Stukenborg, 2018;Nugraha et al., 2018;De Miguel et al., 2019;Schneemann et al., 2020;Shrestha et al., 2020;Aasen and Vergara, 2020;Samimi et al., 2021]. Eight of the ten publications are narrative reviews [Ishiguro et al., 2017;Aberle et al., 2018;Alves-Lopes and Stukenborg, 2018;Nugraha et al., 2018;De Miguel et al., 2019;Shrestha et al., 2020;Aasen and Vergara, 2020;Abdollahi, 2021], one is a systematic review [Samimi et al., 2021], and one is a policy article [Schneemann et al., 2020]. All retrieved reviews report that results are either at an experimental or at a preclinical stage, without any clinical applications at this point in time. ...
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Research on organoids has undergone significant advances during the last decade. However, outcomes from the use of organoids in clinical trials have not yet been documented. Therefore, there is an urgent need to assess the reporting of clinically relevant outcomes from organoid research in the scientific literature. This article presents a systematic review and appraisal of the published literature in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines together with a synopsis of recent relevant reviews. Surprisingly, no randomized controlled trials have reported clinical outcomes with any types of organoids. We found very few ongoing and registered studies that may provide clinically relevant results within this decade. Our screening and interpretation of the literature, including review articles, indicate a focus on technical and pre-clinical aspects of organoid research. This is the first systematic review of clinical trials involving organoids. Few clinical studies are planned or already underway, and, so far, no high-quality evidence relating to clinical outcomes of organoid research has been published. The many promises of organoid research still need to be translated from bench to bed.
... Organ-on-a-Chip microfluidic technologies (Box 3), a sub-discipline within the field of microfluidics, have emerged in the last decades as a platform to replace animal and cell culture models in pre-clinical trials, thus making these trials more reliable and ethical (Beißner, Lorenz and Reichl 2016). Lung-on-a-Chip platforms have been used to investigate lung-related diseases and injuries over the last 15 years (reviewed in Shrestha et al. (2020) and Bennet et al. (2021)). With such microfluidic set-ups, it is possible to reconstruct the three-dimensional (3D) architecture of the lung on a cellular level as well as simulate flow conditions and breathing motion (Huh et al. 2007;Huh 2015). ...
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Fungi, with their enormous diversity, bear essential roles both in nature and our everyday lives. They inhabit a range of ecosystems, such as soil, where they are involved in organic matter degradation and bioremediation processes. More recently, fungi have been recognised as key components of the microbiome in other eukaryotes, such as humans, where they play a fundamental role not only in human pathogenesis, but also likely as commensals. In the food sector, fungi are used either directly or as fermenting agents and are often key players in the biotechnological industry, where they are responsible for the production of both bulk chemicals and antibiotics. Although the macroscopic fruiting bodies are immediately recognisable by most observers, the structure, function and interactions of fungi with other microbes at the microscopic scale still remain largely hidden. Herein, we shed light on new advances in the emerging field of Fungi-on-a-Chip microfluidic technologies for single-cell studies on fungi. We discuss the development and application of microfluidic tools in the fields of medicine and biotechnology, as well as in-depth biological studies having significance for ecology and general natural processes. Finally, a future perspective is provided, highlighting new frontiers in which microfluidic technology can benefit this field.
... Lung organ chips can also solve the shortcomings of animal experiments, such as long cycles, high costs, and ethical problems. They are expected to provide a low-cost alternative for studying human organ physiology and organ diseases as well as advancing toxicology research and drug screening [19,20]. Xu Z. et al. used microfluidic chip technology to conduct an experimental study on the drug sensitivity efficacy of individualized chemotherapy drugs and gefitinib in a 3D cell culture model. ...
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In this study, we used three-dimensional (3D) printing to prepare a template of a microfluidic chip from which a polydimethylsiloxane (PDMS)lung chip was successfully constructed. The upper and lower channels of the chip are separated by a microporous membrane. The upper channel is seeded with lung cancer cells, and the lower channel is seeded with vascular endothelial cells and continuously perfused with cell culture medium. This lung chip can simulate the microenvironment of lung tissue and realize the coculture of two kinds of cells at different levels. We used a two-dimensional (2D) well plate and a 3D lung chip to evaluate the effects of different EGFR-targeting drugs (gefitinib, afatinib, and osimertinib) on tumor cells. The 3D lung chip was superior to the 2D well plate at evaluating the effect of drugs on the NCI-H650, and the results were more consistent with existing clinical data. For primary tumor cells, 3D lung chips have more advantages because they simulate conditions that are more similar to the physiological cell microenvironment. The evaluation of EGFR-targeted drugs on lung chips is of great significance for personalized diagnosis and treatment and pharmacodynamic evaluation.