Organs-on-chips technologies – A guide from disease models to opportunities for drug development

Biosensors and Bioelectronics, Год журнала: 2023, Номер 231, С. 115271 - 115271

Опубликована: Март 31, 2023

Current in-vitro 2D cultures and animal models present severe limitations in recapitulating human physiopathology with striking discrepancies estimating drug efficacy side effects when compared to trials. For these reasons, microphysiological systems, organ-on-chip multiorgans microdevices attracted considerable attention as novel tools for high-throughput high-content research achieve an improved understanding of diseases accelerate the development process towards more precise eventually personalized standards. This review takes form a guide on this fast-growing field, providing useful introduction major themes indications further readings. We start analyzing Organs-on-chips (OOC) technologies testing administration routes: (1) oral/rectal route by intestine-on-a-chip, (2) inhalation lung-on-a-chip, (3) transdermal skin-on-a-chip (4) intravenous through vascularization models, considering how drugs penetrate bloodstream are conveyed their targets. Then, we focus OOC (other) specific organs diseases: neurodegenerative brain blood barriers, tumor including vascularization, organoids/spheroids, engineering screening antitumor drugs, liver/kidney chips multiorgan gastrointestinal metabolic assessment biomechanical systems heart, muscles bones structures related diseases. Successively, discuss materials organ chips, microfluidic organs-on-chips, sensor integration real-time monitoring, cell lines chips. (Nano)delivery approaches therapeutics chip also described. Finally, conclude critical discussion current significance/relevance, trends, limitations, challenges future prospects terms revolutionary impact biomedical research, preclinical development.

Язык: Английский

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A gut-on-a-chip incorporating human faecal samples and peristalsis predicts responses to immune checkpoint inhibitors for melanoma

Nature Biomedical Engineering, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

Patient responses to immune checkpoint inhibitors can be influenced by the gastrointestinal microbiome. Mouse models used study microbiome–host crosstalk, yet their utility is constrained substantial anatomical, functional, immunological and microbial differences between mice humans. Here we show that a gut-on-a-chip system mimicking architecture functionality of human intestine including faecal microbiome peristaltic-like movements recapitulates interactions predicts in patients with melanoma. The composed vascular channel seeded microvascular endothelial cells an intestinal organoids derived from induced pluripotent stem cells, two channels separated collagen matrix. By incorporating samples melanoma into performing multiomic analyses, uncovered epithelium-specific biomarkers factors correlate clinical outcomes non-responders has reduced ability buffer cellular stress self-renew. model may help identify prognostic therapeutic targets. A inhibitors.

Язык: Английский

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Advances in Organ-on-a-Chip Materials and Devices

ACS Applied Bio Materials, Год журнала: 2022, Номер 5(8), С. 3576 - 3607

Опубликована: Июль 15, 2022

The organ-on-a-chip (OoC) paves a way for biomedical applications ranging from preclinical to clinical translational precision. current trends in the vitro modeling is reduce complexity of human organ anatomy fundamental cellular microanatomy as an alternative recreating entire cell milieu that allows systematic analysis medicinal absorption compounds, metabolism, and mechanistic investigation. OoC devices accurately represent physiology vitro; however, it vital choose correct chip materials. potential materials include inorganic, elastomeric, thermoplastic, natural, hybrid Despite fact polydimethylsiloxane most commonly utilized polymer microphysiological systems, substitute have been continuously developed its advanced applications. evaluation physiological status can help demonstrate using noninvasive real-time procedures. Therefore, this Review examines used fabricating devices, application-oriented pros cons, possessions device fabrication biocompatibility, well their downstream biochemical surface alteration commercialization. convergence emerging approaches, such materials, artificial intelligence, machine learning, three-dimensional (3D) bioprinting, genomics, perform technology at next generation. Thus, technologies provide easy precise methodologies cost-effective monitoring treatment standardized protocols, even personalized levels. Because inherent utilization integrated employing with approaches will be promising methodology healthcare industry.

Язык: Английский

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Regulatory safety assessment of nanoparticles for the food chain in Europe

Trends in Food Science & Technology, Год журнала: 2023, Номер 134, С. 98 - 111

Опубликована: Фев. 3, 2023

The risk assessment of small particles (including nanoparticles) in products used the food chain EU falls within remit European Food Safety Authority (EFSA) and has been under thorough scientific considerations for over a decade. Now that more experience is gained with evaluating novel foods, contact materials, food/feed additives pesticides, outlines regulatory safety assessments data requirements are established. This paper reviews principles underlying testing particles, referring to two recently published EFSA guidance documents. Examples observations from assessing existing materials provided facilitate wider readership adequate implementation requirements. starting point physicochemical characterisation pristine material, being an engineered nanomaterial, nanostructured material or conventional contains fraction may retain properties at nanoscale. Key parameters threshold values establishing presence techniques methods complex matrices, as well approaches dietary exposure outlined. Where there likelihood remaining after gastrointestinal digestion, hazard identification required special provisions. In particular, certain nano-specific highlighted have be considered during toxicological aim demonstrate consumer Europe.

Язык: Английский

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Revolutionizing drug development: harnessing the potential of organ-on-chip technology for disease modeling and drug discovery

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Апрель 25, 2023

The inefficiency of existing animal models to precisely predict human pharmacological effects is the root reason for drug development failure. Microphysiological system/organ-on-a-chip technology (organ-on-a-chip platform) a microfluidic device cultured with living cells under specific organ shear stress which can faithfully replicate organ-body level pathophysiology. This emerging organ-on-chip platform be remarkable alternative broad range purposes in testing and precision medicine. Here, we review parameters employed using on chip as plot mimic diseases, genetic disorders, toxicity different organs, biomarker identification, discoveries. Additionally, address current challenges that should overcome accepted by regulatory agencies pharmaceutical industries. Moreover, highlight future direction enhancing accelerating discoveries personalized

Язык: Английский

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Gut-on-a-chip for disease models

Journal of Tissue Engineering, Год журнала: 2023, Номер 14

Опубликована: Янв. 1, 2023

The intestinal tract is a vital organ responsible for digestion and absorption in the human body plays an essential role pathogen invasion. Compared with other traditional models, gut-on-a-chip has many unique advantages, thereby, it can be considered as novel model studying functions diseases. Based on chip design, we replicate vivo microenvironment of intestine study effects individual variables experiment. In recent years, been used to several To better mimic microenvironment, structure function are constantly optimised improved. Owing complexity disease mechanism, conjunction chips. this review, summarise well development improvement gut-on-a-chip. Finally, present discuss applications inflammatory bowel (IBD), viral infections phenylketonuria. Further simulation high throughput realisation personalised treatments problems that should solved model.

Язык: Английский

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Assessment of human dermal absorption of flame retardant additives in polyethylene and polypropylene microplastics using 3D human skin equivalent models

Environment International, Год журнала: 2024, Номер 186, С. 108635 - 108635

Опубликована: Апрель 1, 2024

To overcome ethical and technical challenges impeding the study of human dermal uptake chemical additives present in microplastics (MPs), we employed 3D skin equivalent (3D-HSE) models to provide first insights into bioavailability polybrominated diphenyl ether (PBDEs) MPs; evaluated different factors influencing percutaneous absorption PBDEs under real-life exposure scenario. were bioavailable varying degrees (up 8 % dose) permeation was evident, albeit at low levels (≤0.1 dose). While polymer type influenced release from studied MPs skin, less important driving PBDEs. The absorbed fraction strongly correlated (r

Язык: Английский

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Dermal bioavailability of perfluoroalkyl substances using in vitro 3D human skin equivalent models

Environment International, Год журнала: 2024, Номер 188, С. 108772 - 108772

Опубликована: Май 23, 2024

Perfluoroalkyl substances (PFAS) have been identified in various products that come contact with human skin, ranging from school uniforms to personal care products. Despite this, knowledge on dermal uptake of PFAS is lacking. Thus, the absorption 17 was assessed, for first time, using vitro 3D-human skin equivalent models exposed 500 ng/cm

Язык: Английский

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Unraveling the mystery of efficacy in Chinese medicine formula: New approaches and technologies for research on pharmacodynamic substances

Arabian Journal of Chemistry, Год журнала: 2022, Номер 15(11), С. 104302 - 104302

Опубликована: Сен. 27, 2022

Traditional Chinese medicine (TCM) is the key to unlock treasures of civilization. TCM and its compound play a beneficial role in medical activities cure diseases, especially major public health events such as novel coronavirus epidemics across globe. The chemical composition formula complex diverse, but their effective substances resemble "mystery boxes". Revealing active ingredients mechanisms action has become focal point difficulty research for herbalists. Although existing methods are numerous constantly updated iteratively, there remain lack prospective reviews. Hence, this paper provides comprehensive account new approaches technologies based on previous studies with an vitro vivo perspective. In addition, bottlenecks also revealed. Especially, we look ahead perspectives, applications future development. This work reviews perspectives open horizons research. Consequently, herbal compounding pharmaceutical study should carry essence while pursuing innovations field.

Язык: Английский

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Basement membrane properties and their recapitulation in organ-on-chip applications

Materials Today Bio, Год журнала: 2022, Номер 15, С. 100301 - 100301

Опубликована: Май 23, 2022

Drug discovery and toxicology is a complex process that involves considerable basic research preclinical evaluation. These depend highly on animal testing which often fails to predict human trial outcomes due species differences. Coupled with ethical concerns around testing, this leads high demand for improved in vitro cell culture platforms. Current efforts, regard, however, are facing challenge provide physiologically relevant organ models reliable assessment of the physiological responses body drug compounds toxins. The latest development models, organ-on-chips (OOCs), seek introduce more realistic function. OOCs use commercial porous polymeric membranes as barrier membrane challenging poor replication architectures. Better recapitulation native basement (BM) characteristics desirable modelling physical (e.g. intestine, skin lung) metabolic liver) models. In review, relevance mechanical properties system behaviour elucidated. Key parameters replicating BM also described. This review provides information future focusing BM-mimicking substrates core structure.

Язык: Английский

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