An FDA-Validated, Self-Cleaning Liquid Chromatography–Mass Spectrometry System for Determining Small-Molecule Drugs and Metabolites in Organoid/Organ-on-Chip Medium

Analytical Chemistry, Год журнала: 2024, Номер 96(29), С. 12129 - 12138

Опубликована: Июль 10, 2024

As organoids and organ-on-chip (OoC) systems move toward preclinical clinical applications, there is an increased need for method validation. Using a liquid chromatography-mass spectrometry (LC-MS)-based approach, we developed measuring small-molecule drugs metabolites in the cell medium directly sampled from liver organoids/OoC systems. The LC-MS setup was coupled to automatic filtration filter flush system with online solid-phase extraction (SPE), allowing robust automated sample cleanup/analysis. For matrix, rich in, e.g., protein, salts, amino acids, no preinjection preparation steps (protein precipitation, SPE, etc.) were necessary. approach demonstrated tolbutamide its metabolite, 4-hydroxytolbutamide (4HT). validated analysis of media human stem cell-derived cultured static conditions on microfluidic platform according Food Drug Administration (FDA) guidelines regards selectivity, matrix effects, accuracy, precision, etc. allows hundreds injections without replacing chromatography hardware. In summary, drug/metabolite organoids/OoCs can be performed robustly minimal preparation.

Язык: Английский

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Progress in the Application of Organoids-On-A-Chip in Diseases

Organogenesis, Год журнала: 2024, Номер 20(1)

Опубликована: Авг. 10, 2024

With the rapid development of field life sciences, traditional 2D cell culture and animal models have long been unable to meet urgent needs modern biomedical research new drug development. Establishing a generation experimental is great significance for deeply understanding human health disease processes, developing effective treatment measures. As well known, cycles, high risks, costs are "three mountains" facing drugs today. Organoids organ-on-chips technology can highly simulate reproduce physiological environment complex reactions in

Язык: Английский

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Microfluidic organ-on-chip systems for periodontal research: advances and future directions

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 12

Опубликована: Янв. 7, 2025

Advances in tissue engineering and microfluidic technologies have enabled the development of sophisticated vitro models known as organ-on-a-chip (OoC) or microphysiological systems. These systems enable to potential simulate dynamic interactions between host tissues their microenvironment including microbes, biomaterials, mechanical forces, pharmaceutical, consumer-care products. fluidic are increasingly being utilized investigate host-microbe host-material oral health disease. Of interest is application understanding periodontal disease, a chronic inflammatory condition marked by progressive destruction tissues, gingiva, ligament, alveolar bone. The pathogenesis disease involves complex interplay microbial dysbiosis immune responses, which can lead loss dental support structures contribute systemic conditions such cardiovascular diabetes, bowel This provides comprehensive overview latest developments millifluidic designed emulate interactions. We discuss critical biological considerations designing these platforms, applications studying biofilms, unravel mechanisms therapeutic targets

Язык: Английский

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The utilisation of biliary organoids for biomedical applications

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 12

Опубликована: Янв. 7, 2025

Biliary duct injury, biliary atresia (BA), tract tumors, primary sclerosing cholangitis (PSC), and other diseases are commonly encountered in clinical practice within the digestive system. To gain a better understanding of pathogenesis development these explore more effective treatment methods, organoid technology has recently garnered significant attention. Organoids three-dimensional structures derived from stem/progenitor cells that can faithfully mimic intricate structure physiological function tissues or organs vitro. They provide valuable platform for studying offer novel possibilities repairing regenerating injuries. The main seed used to construct organoids include human epithelial as well pluripotent stem cells. construction involves various techniques such traditional embedding technology, rotary culture hanging drop along with emerging approaches like organ chip (3D) printing four-dimensional (4D) technology. This article comprehensively reviews methods while discussing their applications disease modeling research on mechanisms drug screening tissue/organ repair; it also highlights current challenges suggests future directions regarding which will serve references treating common refractory system practice.

Язык: Английский

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Organoid Ethical Typology: varieties of three‐dimensional stem cell constructs and the many issues they raise in bioethics

Biology of the Cell, Год журнала: 2025, Номер 117(1)

Опубликована: Янв. 1, 2025

Abstract The advancement of and prospects for stem cell research raise a number specific ethical issues. While navigating the landscape is often challenging biology researchers biotechnology innovators, it also difficult public other persons concern (from ethicists to policy‐makers) grasp technicalities burgeoning field that develops in many directions. Organoids are one these new biotechnological constructs currently eliciting rich debate bioethics. In this guide, we argue different types organoids have emerging properties with implications. Going from general particular ones, propose typology organoid technology associated philosophical perspective. We point relevant issues try convey sense uncertainty peculiar ongoing technological objects.

Язык: Английский

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Bioengineering ethics for the age of microphysiological systems

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 13

Опубликована: Март 20, 2025

The development of microphysiological systems (MPS) is pushing ethical standards in biomedical research to a breaking point. This article argues that only perspective drawing from engineering ethics will be able address the new challenges raised by organoids and organs-on-chips. Extending progressively scope moral questioning, we discuss successively following areas: i) individual consent: when cell lines are generated human biomaterial circulated incorporated into biotechnologies whose life cycle far exceed envisioned donors manufacturers, classic notion informed consent becomes almost obsolete, or at least needs revisited. ii) Collective deliberation: MPSs raise many expectations for animal replacement advancement precision regenerative medicine. management these prospects different stakeholders, everyone, itself an challenge interface science society. iii) Consideration novel entities: some complex may endowed with status near future, this have impact on how researchers treat them work them.

Язык: Английский

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From gut to liver: organoids as platforms for next-generation toxicology assessment vehicles for xenobiotics

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Март 26, 2025

Traditional toxicological assessment relied heavily on 2D cell cultures and animal models of study, which were inadequate for the precise prediction human response to chemicals. Researchers have now shifted focus organoids assessment. Organoids are 3D structures produced from stem cells that mimic shape functionality organs a number advantages compared traditional study. They capacity replicate intricate cellular microenvironment in vivo interactions. offer physiologically pertinent platform is useful researchers monitor responses more realistic manner evaluate drug toxicity. Additionally, can be created unique patient, allowing individualized research providing understanding inter-individual heterogeneity responses. Recent developments use gut liver xenobiotics (environmental toxins drugs) reviewed this article. Gut reveal potential damage digestive system how affect nutrient absorption barrier function. Liver primary site detoxification metabolism xenobiotics, usually routed gut. Hence, these linked crucial evaluating chemical or pollutant induced organ toxicity, forecasting their pharmacokinetics. When incorporated into development process, organoid improve accuracy efficiency safety assessments, leading safer effective treatments. We also discuss limitations using organoid-based assays, future prospects, including need standardized protocols overcoming reproducibility issues.

Язык: Английский

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SKOV-3 Cell Aggregates on a Microfluidic Chip with a Thermoresponsive Hydrogel as a Culture Scaffold for DOX Assessment

ACS Omega, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Microfluidic chip technology is very popular in life sciences. Here, ovarian cancer SKOV-3 cell aggregates were formed using thermoresponsive poly(N-isopropylacrylamide-co-acrylic acid) (PNA) hydrogel as a culture scaffold on microfluidic serving an operating platform. A simple was designed and fabricated the three-dimensional (3D) microplatform. Different concentrations of doxorubicin (DOX) fed to obtained via pump. All characterization results indicated that this system could effectively perform 3D drug evaluation certain extent. In addition, by grafting RGD sequence, biocompatibility PNA improved. On one hand, sequence into significantly improve proliferation system; other it led earlier appearance DOX resistance. This versatile model study has potential for further use vitro human physiological models, discovery, toxicology research.

Язык: Английский

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Organoids at the forefront of global health: accelerated research and ethical implications in the cases of Zika and COVID-19

Global Public Health, Год журнала: 2025, Номер 20(1)

Опубликована: Май 6, 2025

Bioengineering technologies are increasingly important in global health research, yet their applications beyond vaccines and diagnostics remain underexplored. Our paper examines the role of organoids - advanced stem cell used to model human organs, such as lungs brains context infectious disease research. Organoids became crucial during Zika COVID-19 outbreaks. These new systems enabled rapid insights into pathogen behaviour. We analyse how urgency Covid-19 accelerated organoid tracing its rise subsequent slowdown. investigation reveals that while experienced a burst activity these emergencies, momentum has waned, with ongoing research predominantly focusing on diseases prevalent Global North. argue uneven acceleration deceleration underscores critical need for equitable integration bioengineering priorities, particularly pandemic preparedness. findings advocate balanced inclusive strategy enhance preparedness address disparities effectively.

Язык: Английский

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Biomedical applications of organoids derived from the digestive system

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Май 30, 2025

The global incidence of digestive system diseases is increasing, posing a significant public health challenge and driving an escalating demand for research into the mechanisms underlying their onset progression. Traditional cell models xenotransplantation animal have been widely used to simulate human diseases, thereby enhancing our understanding disease occurrence, progression, drug resistance. However, these fail fully replicate complex cellular microenvironment spatial structure, are further limited by individual species differences. Organoid technology, as emerging in vitro culture approach, enables precise culturing differentiation stem cells generate highly tissue-specific functionally intact organoids. This technology not only better recapitulates cell-to-cell interactions, extracellular matrix (ECM) microenvironment, organ-specific physiological functions but also more closely mimics state . Moreover, it reduces reliance on experiments, enhances translatability findings, mitigates limitations two-dimensional models, plays pivotal role simulating pathological processes tract. Currently, common techniques constructing organoids include embedding culture, rotating magnetic suspension organ-on-a-chip, three-dimensional (3D), four-dimensional (4D) printing technologies. Seed primarily derived from epithelial pluripotent cells. article reviews construction methods organoids, evaluates applications studying growth development mechanisms, modeling mechanism research, screening, regenerative medicine, precision identifies existing challenges future directions provide valuable reference biomedical research.

Язык: Английский

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