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Schematic illustration of a microfluidic brain-on-a-chip device. human induced pluripotent stem cells (hiPSC)-based can be produced from adult somatic cells using a nanoliposome-based-clustered regularly interspaced palindromic repeats (CRISPR) system. The hiPSCs can differentiate into many cell types such as (A)) astrocytes (ASTs), (B) neurons, and (C) oligodendrocytes. Co-culture of theses neural cells (A, B, and C) in a microfluidic brain-on-a-chip device can be used to evaluate the molecular, cellular, and structural connections between neural cells such as ASTs, neurons, and oligodendrocytes for NDDs researches
Source publication
Neurodegenerative diseases (NDDs) include more than 600 types of nervous system disorders in humans that impact tens of millions of people worldwide. Estimates by the World Health Organization (WHO) suggest NDDs will increase by nearly 50% by 2030. Hence, development of advanced models for research on NDDs is needed to explore new therapeutic strat...
Citations
... OoCS ought to provide incentives for continued investment in research and development (R&D) to stakeholders [81] . Organizations recognize the limitations of toxicology data from animal studies and encourage the development of methods to enhance candidate selection and decision-making [82] . Significant Table 3 Organ-on-a-chip analytical techniques and their shortcomings [39] Organ on a chip analytical technique Considerations and shortcomings Reference ...
Introduction
Approximately 50 million people worldwide have epilepsy, with many not achieving seizure freedom. Organ-on-chip technology, which mimics organ-level physiology, could revolutionize drug development for epilepsy by replacing animal models in preclinical studies. Our goal is to determine if customized micro-physiological systems can lead to tailored drug treatments for epileptic patients.
Materials and methods
A comprehensive literature search was conducted utilizing various databases, including PubMed, Ebscohost, Medline, and the National Library of Medicine, using a predetermined search strategy. We focused on articles that addressed the role of personalized micro-physiological systems in individual drug responses and articles that discussed different types of epilepsy, diagnosis, and current treatment options. Additionally, articles that explored the components and design considerations of micro-physiological systems were reviewed to identify challenges and opportunities in drug development for challenging epilepsy cases.
Results
The micro-physiological system offers a more accurate and cost-effective alternative to traditional models for assessing drug effects, toxicities, and disease mechanisms. Nevertheless, designing patient-specific models presents critical considerations, including the integration of analytical biosensors and patient-derived cells, while addressing regulatory, material, and biological complexities. Material selection, standardization, integration of vascular systems, cost efficiency, real-time monitoring, and ethical considerations are also crucial to the successful use of this technology in drug development.
Conclusion
The future of organ-on-chip technology holds great promise, with the potential to integrate artificial intelligence and machine learning for personalized treatment for epileptic patients.
... The researchers showcase the platform's usefulness in neuroscience research by demonstrating how it may be used to test therapeutic interventions and investigate the evolution of diseases. 133 ■ MICROFLUIDIC ORGAN-ON-A-CHIP SYSTEM: ...
Pulmonary diseases like asthma, chronic obstructive pulmonary disorder, lung fibrosis, and lung cancer pose a significant burden to global human health. Many of these complications arise as a result of exposure to particulate matter (PM), which has been examined in several preclinical and clinical trials for its effect on several respiratory diseases. Particulate matter of size less than 2.5 μm (PM2.5) has been known to inflict unforeseen repercussions, although data from epidemiological studies to back this are pending. Conventionally utilized two-dimensional (2D) cell culture and preclinical animal models have provided insufficient benefits in emulating the in vivo physiological and pathological pulmonary conditions. Three-dimensional (3D) structural models, including organ-on-a-chip models, have experienced a developmental upsurge in recent times. Lung-on-a-chip models have the potential to simulate the specific features of the lungs. With the advancement of technology, an emerging and advanced technique termed microfluidic organ-on-a-chip has been developed with the aim of identifying the complexity of the respiratory cellular microenvironment of the body. In the present Review, the role of lung-on-a-chip modeling in reproducing pulmonary complications has been explored, with a specific emphasis on PM2.5-induced pulmonary complications.
... Microfluidic devices in combination with 3D culture techniques are advancing further, enabling the modeling of fluid flow (such as blood or its substitute) as well as mimicking physical actions (such as heart contractions). Multiple layers of different cell types can be created on chips, and signal transmission between them can be facilitated using a porous structure [13]. ...
Animal cell cultures have found applications in various fields, from basic to advanced research. This includes studying the fundamentals of cell biology, mechanisms of the cell cycle, specialized cell functions, cell-cell and cell-matrix interactions, toxicity testing for the study of new drugs, gene therapy for replacing non-functional genes with functional cells, characterization of cancer cells, understanding the role of various chemical substances, viruses, and radiation in cancer cells, vaccine production, monoclonal antibodies, and pharmaceuticals. Additionally, the cultivation of viruses for use in vaccine production, such as for diseases like rabies, hepatitis B, and measles, is another important application of animal cell cultures. Aim. The purpose of this study was to analyze the literature data on the use of animal cell lines in genetic engineering, therapy, xenotransplantation, biopharmaceuticals, the food industry, and research. Methods. An analytical review of literature data was conducted using the information analysis of Medline (PubMed), Web of Science and Scopus databases, Google Scholar, the Cochrane Central Register of Controlled Trials (CENTRAL), and other sources up to the inclusive year 2023 using the keywords: “animal cell lines”, “immunobiological preparations”, “xenotransplantation”, “biopharmaceuticals”, “genetic engineering”. Results. An analysis of research related to the use of animal cells in the biopharmaceutical industry was carried out, and considerations regarding the prospects for their use in various research and production technologies were outlined. Conclusion. The technology of cultivating animal cells has become a fundamental tool in the development of research in the field of biotechnological sciences. The ability to culture animal cells in vitro has allowed the development of innovative methods, such as iPSC and organ-on-a-chip models, which have provided valuable information about disease mechanisms and potential therapeutic targets. Although there are some challenges with the use of animal cells related to variability in differentiation efficiency and concerns about safety and efficacy, further studies are needed to optimize protocols and overcome these limitations. Overall, animal cell culture technology remains an important component of modern biomedical research and has the potential to revolutionize the field of regenerative medicine.
... [1] The most studied among them are Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), which affect millions of people worldwide. It has been estimated that, in the past 15 years, the percentage of people affected by these diseases increased from 20% to 30% [2] and, according to the World Health Organization, the incidence will keep rising, reaching more than double by 2050 [3] and likely becoming the second-most prevalent cause of death. Their prevalence is increasing due to, in part, the extension of lifespan. ...
The alteration in the neural circuits of both central and peripheral nervous systems is closely related to the onset of neurodegenerative disorders (NDDs). Despite significant research efforts, the knowledge regarding NDD pathological processes, and the development of efficacious drugs are still limited due to the inability to access and reproduce the components of the nervous system and its intricate microenvironment. 2D culture systems are too simplistic to accurately represent the more complex and dynamic situation of cells in vivo and have therefore been surpassed by 3D systems. However, both models suffer from various limitations that can be overcome by employing two innovative technologies: organ‐on‐chip and 3D printing. In this review, an overview of the advantages and shortcomings of both microfluidic platforms and extracellular matrix‐like biomaterials will be given. Then, the combination of microfluidics and hydrogels as a new synergistic approach to study neural disorders by analyzing the latest advances in 3D brain‐on‐chip for neurodegenerative research will be explored.
... Neurospheroids are widely employed to construct neural system-on-a-chip for both CNS and PNS [90,92]. However, the modeling of neural system-on-a-chip devices is different for researches of CNS and PNS. ...
Neural tissues react to injuries through the orchestration of cellular reprogramming, generating specialized cells and activating gene expression that helps with tissue remodeling and homeostasis. Simplified biomimetic models are encouraged to amplify the physiological and morphological changes during neural regeneration at cellular and molecular levels. Recent years have witnessed growing interest in lab-on-a-chip technologies for the fabrication of neural interfaces. Neural system-on-a-chip devices are promising in vitro microphysiological platforms that replicate the key structural and functional characteristics of neural tissues. Microfluidics and microelectrode arrays (MEAs) are two fundamental techniques that are leveraged to address the need for microfabricated neural devices. In this review, we explore the innovative fabrication, mechano-physiological parameters, spatiotemporal control of neural cell cultures and chip-based neurogenesis. Although the high variability in different constructs, and the restriction in experimental and analytical access limit the real-life applications of microphysiological models, neural system-on-a-chip devices have gained considerable translatability for modelling neuropathies, drug screening and personalized therapy.
... Hydrogels are extremely porous networks of hydrophilic polymer chains that allow diffusion of small molecules and bioparticles [75,77]. Hydrogels offer biocompatibility, low cytotoxicity, biodegradability, controllable pore size, high permeability, and compatibility with aqueous environments [77,78]. Doxorubicin is used as a powerful chemotherapy drug for cancer treatment. ...
The platform of microfluidics offers a precise control and manipulation over fluids at a small scale and therefore has gained much attention in recent times. This topic is currently applied to automation and high-throughput analysis in several areas, including extraction of DNA, RNA and proteins, gene identification, gene assembly, cloning, single-cell analysis, organs grown on chips, PCR, drug screening, toxicity testing and drug delivery. Conventional methods used for drug delivery are sometimes non-targeted leading to loss of administered drugs and reduced drug effectiveness. Recent advances in microfluidics allow precise dose-dependent delivery of a drug to a targeted location. Several microfluidics designs have been implemented to improve the precision of treatment in clinics. This review highlights currently available tools in microfluidics, designs for drug carriers, delivery methods, robotics and artificial intelligence in the field of microfluidics.
... A major shortcoming of conventional in vitro models (e.g., monolayer cell cultures) is their inability to recapitulate the human brain or spinal cord physiology with regard to the varied cell types [138], complex cell-cell interactions [139], mechanical properties [140], and dynamic fluidic conditions [141]. Micro-3D cell culture systems such as organ-on-a-chip (OOAC) devices and stem-cell-derived organoids have been used as more physiologically relevant models to overcome these problems of the 2D setting, albeit with major deficits in their capacity to factor in the effects of systemic blood circulation, immune regulation, and neural modulation. ...
Central nervous system (CNS) repair after injury or disease remains an unresolved problem in neurobiology research and an unmet medical need. Directly reprogramming or converting astrocytes to neurons (AtN) in adult animals has been investigated as a potential strategy to facilitate brain and spinal cord recovery and advance fundamental biology. Conceptually, AtN strategies rely on forced expression or repression of lineage-specific transcription factors to make endogenous astrocytes become “induced neurons” (iNs), presumably without re-entering any pluripotent or multipotent states. The AtN-derived cells have been reported to manifest certain neuronal functions in vivo. However, this approach has raised many new questions and alternative explanations regarding the biological features of the end products (e.g., iNs versus neuron-like cells, neural functional changes, etc.), developmental biology underpinnings, and neurobiological essentials. For this paper per se, we proposed to draw an unconventional distinction between direct cell conversion and direct cell reprogramming, relative to somatic nuclear transfer, based on the experimental methods utilized to initiate the transformation process, aiming to promote a more in-depth mechanistic exploration. Moreover, we have summarized the current tactics employed for AtN induction, comparisons between the bench endeavors concerning outcome tangibility, and discussion of the issues of published AtN protocols. Lastly, the urgency to clearly define/devise the theoretical frameworks, cell biological bases, and bench specifics to experimentally validate primary data of AtN studies was highlighted.
... The use of hydrogels as starting materials for MF devices poses issues in terms of device integrity. Because of the structural resemblance of hydrogels to the extracellular matrix [59][60][61], applications have been developed in which this material is employed to simulate physiological tissues in so-called "biomicrofluidic" devices [62,63]. Table 1 highlights the prevalent ways of producing microfluidic devices based on the constituting materials that discussed in session 3. ...
... Table 2 reports a practical comparison between 3D printing and the most commonly used traditional procedures for the production of MF devices. Restrictions related to mechanical properties [62,63] Until recently, MF chips were manufactured using methods that necessitate a cleanroom environment and several post-production procedures. The novel feature of 3DP is the tightly integrated fabrication of an item from design software, which allows models to be quickly modified and repeated, resulting in an empirically informed recurrent design optimization loop. ...
Nanomedicine has grown tremendously in recent years as a responsive strategy to find novel therapies for treating challenging pathological conditions. As a result, there is an urgent need to develop novel formulations capable of providing adequate therapeutic treatment while overcoming the limitations of traditional protocols. Lately, microfluidic technology (MF) and additive manufacturing (AM) have both acquired popularity, bringing numerous benefits to a wide range of life science applications. There have been numerous benefits and drawbacks of MF and AM as distinct techniques, with case studies showing how the careful optimization of operational parameters enables them to overcome existing limitations. Therefore, the focus of this review was to highlight the potential of the synergy between MF and AM, emphasizing the significant benefits that this collaboration could entail. The combination of the techniques ensures the full customization of MF-based systems while remaining cost-effective and less time-consuming compared to classical approaches. Furthermore, MF and AM enable highly sustainable procedures suitable for industrial scale-out, leading to one of the most promising innovations of the near future.
... Hydrogel has become one of the matrix materials of microfluidic chips (Liu M. et al., 2017;Yang F. et al., 2018;Jing et al., 2019;Mofazzal Jahromi et al., 2019;Nielsen et al., 2020), which usually have a hydrophilic porous structure, and its porous structure is filled with water molecules, allowing biomacromolecules to pass through (Lee et al., 2014;Chen et al., 2016;Liu M. et al., 2017;Chen et al., 2017;Xu et al., 2019;Huang et al., 2020;Vera et al., 2021). ...
Microfluidic chip technology is a technology platform that integrates basic operation units such as processing, separation, reaction and detection into microchannel chip to realize low consumption, fast and efficient analysis of samples. It has the characteristics of small volume need of samples and reagents, fast analysis, low cost, automation, portability, high throughout, and good compatibility with other techniques. In this review, the concept, preparation materials and fabrication technology of microfluidic chip are described. The applications of microfluidic chip in immunoassay, including fluorescent, chemiluminescent, surface-enhanced Raman spectroscopy (SERS), and electrochemical immunoassay are reviewed. Look into the future, the development of microfluidic chips lies in point-of-care testing and high throughput equipment, and there are still some challenges in the design and the integration of microfluidic chips, as well as the analysis of actual sample by microfluidic chips.
... [3][4][5][6][7][8] OOC is a microfluidic-based platform that bridges between 2D cell culture and animal models, mimicking the critical aspects of human physiology. Since the development of the first mechanically actuatable lung-on-a-chip device in 2010, 9 there has been a plethora of work on OOC for different organs, such as the intestine, 10,11 brain, 12,13 blood-brain-barrier, 14,15 and multi-organ system. 16,17 In this review, we will focus on liver-on-a-chip (LOC), which is a sub-group of OOC. ...
... LOC has attracted increasing attention over the years, with recent developments aimed at recapitulating the in vivo tissue structure, functions, biochemical cues, and microenvironment of the liver, which conventional 2D culturing has failed to achieve. [6][7][8][9][10][11][12][13][14][15][16][17][18] lOC allows the study of drug metabolism in models relevant to human physiology and offers an alternative approach to animal models. 19,20 Although animal studies are still required during drug development to assess drug efficacy and toxicity before human trials, increasing evidence has suggested that animal models may not sufficiently reflect human physiological conditions, and numerous failed trials are becoming an increasing source of concern. ...
The liver is the largest internal organ in the human body with largest mass of glandular tissue. Modeling the liver has been challenging due to its variety of major functions, including processing nutrients and vitamins, detoxification, and regulating body metabolism. The intrinsic shortfalls of conventional two-dimensional (2D) cell culture methods for studying pharmacokinetics in parenchymal cells (hepatocytes) have contributed to suboptimal outcomes in clinical trials and drug development. This prompts the development of highly automated, biomimetic liver-on-a-chip (LOC) devices to simulate native liver structure and function, with the aid of recent progress in microfluidics. LOC offers a cost-effective and accurate model for pharmacokinetics, pharmacodynamics, and toxicity studies. This review provides a critical update on recent developments in designing LOCs and fabrication strategies. We highlight biomimetic design approaches for LOCs, including mimicking liver structure and function, and their diverse applications in areas such as drug screening, toxicity assessment, and real-time biosensing. We capture the newest ideas in the field to advance the field of LOCs and address current challenges.
