Fluorescent Molecular Probe for Imaging Hypoxia in 2D Cell Culture Monolayers and 3D Tumor Spheroids: The Cell Membrane Partition Model for Predicting Probe Distribution in a Spheroid

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Compared to cultured 2D cell monolayers, 3D multicellular spheroids are more realistic tumor models. Nonetheless, remain under-utilized in preclinical research, part, because there is a lack of fluorescence sensors that can noninvasively interrogate all the individual cells within spheroid. This present study describes deep-red fluorogenic molecular probe for microscopic imaging contain high level nitroreductase enzyme activity as biomarker hypoxia. A first-generation version produced "turn-on" monolayer under hypoxic conditions; however, it was not useful spheroid only accumulated peripheral cells. To guide structural optimization process, an intuitive theoretical membrane partition model conceived predict how dosed will distribute The identifies three limiting diffusion pathways determined by probe's properties. lipophilic with affinity rapidly becomes trapped membranes In contrast, very hydrophilic molecule negligible diffuses through intercellular space and rarely enters However, intermediate undergoes sequential out distributes Using predictive tool, second-generation fluorescent prepared smaller structure, optical sectioning using structured illumination or light sheet microscopy revealed roughly even throughout permeation likely be broadly applicable various classes molecules nanoparticles enable distribution

Language: Английский

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オルガノイド (organoid)

The Japanese Journal of SURGICAL METABOLISM and NUTRITION, Journal Year: 2025, Volume and Issue: 59(1), P. 30 - 31

Published: Feb. 15, 2025

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Advances in humanoid organoid-based research on inter-organ communications during cardiac organogenesis and cardiovascular diseases

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 28, 2025

The intimate correlation between cardiovascular diseases and other organ pathologies, such as metabolic kidney diseases, underscores the intricate interactions among these organs. Understanding inter-organ communications is crucial for developing more precise drugs effective treatments systemic diseases. While animal models have traditionally been pivotal in studying interactions, human-induced pluripotent stem cells (hiPSCs) offer distinct advantages when constructing vitro models. Beyond conventional two-dimensional co-culture model, hiPSC-derived humanoid organoids emerged a substantial advancement, capable of replicating essential structural functional attributes internal organs vitro. This breakthrough has spurred development multilineage organoids, assembloids, organoids-on-a-chip technologies, which allow enhanced physiological relevance. These technologies shown great potential mimicking coordinated organogenesis, exploring disease pathogenesis, facilitating drug discovery. As central system, heart serves focal point an extensively studied network interactions. review focuses on advancements challenges organs, presenting comprehensive exploration this cutting-edge approach research.

Language: Английский

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Drug Screening of Primary Human Endometriotic Cells Based on Micro‐Encapsulating Microfluidic Chip

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Abstract Endometriosis (EMs), a significant global health issue, characterized by unclear pathogenesis, nonspecific symptoms, and poor treatment outcomes. The organ‐on‐chip technology has achieved great advances in disease modeling, yet its potential EMs‐related research remains largely untapped. Herein, microfluidic chip platform that integrates primary cell‐laden microcapsules for personalized drug evaluation. Specifically, human ectopic endometrial stromal cells (hESCs) within featuring biocompatible carboxymethyl cellulose (CMC) core stable alginate (ALG) shell using precise electrospray are encapsulated. These integrated into with branched gradient generator multiple cell‐culture chambers, enabling tailored high‐throughput screening. By exposing hESCs‐microcapsules derived from of distinct patient individuals to various drugs on‐chip, inter‐individual variability was revealed, strong correlation clinical This unique combination patient‐specific 3D microenvironments dynamic control represents paradigm shift EMs research. Further integrating omics techniques, capability exploring promising is showcased. results reveal the could deliver dependable screening outcomes, thereby benefiting both scientific inquiries therapies.

Language: Английский

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‘Ship-in-a-Bottle’ Integration of pH-Sensitive 3D Proteinaceous Meshes into Microfluidic Channels

Nanomaterials, Journal Year: 2025, Volume and Issue: 15(2), P. 104 - 104

Published: Jan. 10, 2025

Microfluidic sensors incorporated onto chips allow sensor miniaturization and high-throughput analyses for point-of-care or non-clinical analytical tools. Three-dimensional (3D) printing based on femtosecond laser direct writing (fs-LDW) is useful creating 3D microstructures with high spatial resolution because the structures are printed in space along a designated light path. High-performance biochips can be fabricated using ‘ship-in-a-bottle’ integration technique, which functional microcomponents biomimetic embedded inside closed microchannels fs-LDW. Solutions containing protein biomacromolecules as precursor used to fabricate that retain their native functions. Here, we demonstrate ship-in-a-bottle of pure proteinaceous exhibit pH sensitivity. We mesh gap sizes 10 5 μm. The these gaps changed when exposed physiological buffers ranging from 4 10. size shrunk expanded repeatedly by changing surrounding buffer. Fs-LDW enables construction microscopic meshes dynamic functions such sensing might find applications filtering particles microfluidic channels.

Language: Английский

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Advancements of paper-based microfluidics and organ-on-a-chip models in cosmetics hazards

RSC Advances, Journal Year: 2025, Volume and Issue: 15(13), P. 10319 - 10335

Published: Jan. 1, 2025

Different detection approaches for monitoring adulterants/hazards present in cosmetics using paper-based devices and organ-on-a-chip.

Language: Английский

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Artificial intelligence in preclinical research: enhancing digital twins and organ-on-chip to reduce animal testing

Drug Discovery Today, Journal Year: 2025, Volume and Issue: unknown, P. 104360 - 104360

Published: April 1, 2025

Artificial intelligence (AI) is reshaping preclinical drug research offering innovative alternatives to traditional animal testing. Advanced techniques, including machine learning (ML), deep (DL), AI-powered digital twins (DTs), and AI-enhanced organ-on-a-chip (OoC) platforms, enable precise simulations of complex biological systems. AI plays a critical role in overcoming the limitations DTs OoC, improving their predictive power scalability. These technologies facilitate early-stage, reliable evaluations safety efficacy, addressing ethical concerns, reducing costs, accelerating development while adhering 3Rs principle (Replace, Reduce, Refine). By integrating with these advanced models, can achieve greater accuracy efficiency discovery. This review examines transformative impact research, highlighting its advancements, challenges, steps needed establish as cornerstone efficient

Language: Английский

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Advancing Organ-on-a-Chip Systems: The Role of Scaffold Materials and Coatings in Engineering Cell Microenvironment

Polymers, Journal Year: 2025, Volume and Issue: 17(9), P. 1263 - 1263

Published: May 6, 2025

For organ-on-a-chip (OoC) engineering, the use of biocompatible coatings and materials is not only recommended but essential. Extracellular matrix (ECM) components are commonly used as due to their effects on cell orientation, protein expression, differentiation, adhesion. Among most frequently collagen, fibronectin, Matrigel, according specific type intended OoC application. Additionally, such polydimethylsiloxane (PDMS), thermoplastics, chitosan, alginate serve scaffolding biomechanical properties biocompatibility. Here, we discuss some employed coating techniques, including SAMs, dip coating, spin microcontact printing, 3D bioprinting, each offering advantages drawbacks. Current challenges comprise enhancing biocompatibility, exploring novel materials, improving scalability reproducibility.

Language: Английский

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Emerging Trends in Microfluidic Biomaterials: From Functional Design to Applications

Journal of Functional Biomaterials, Journal Year: 2025, Volume and Issue: 16(5), P. 166 - 166

Published: May 8, 2025

The rapid development of microfluidics has driven innovations in material engineering, particularly through its ability to precisely manipulate fluids and cells at microscopic scales. Microfluidic biomaterials, a cutting-edge interdisciplinary field integrating microfluidic technology with biomaterials science, are revolutionizing biomedical research. This review focuses on the functional design fabrication organ-on-a-chip (OoAC) platforms via 3D bioprinting, explores applications drug delivery, cell culture, tissue evaluates potential systems advancing personalized healthcare. We systematically analyze evolution materials—from silicon glass polymers paper—and highlight advantages bioprinting over traditional methods. Currently, despite significant advances medicine, challenges scalability, stability, clinical translation remain. future will depend combining dynamic design, developing hybrid strategies that combine molds bio-printed structures, using artificial intelligence monitor delivery or response real time. believe collaborations between materials micromachining, medicine accelerate into therapies high-throughput screening tools.

Language: Английский

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Perspectives on organ-on-a-chip technology for natural products evaluation

Food & medicine homology., Journal Year: 2024, Volume and Issue: 1(2), P. 9420013 - 9420013

Published: Aug. 7, 2024

Natural products have always been a treasure trove for clinical drug development and source of inspiration lead compounds in the process new discovery. However, two-dimensional cell cultures animal models traditional model serious limitations generalizing human physiopathology cannot accurately predict real response body to drugs, which brings obstacles challenges evaluation. Organ-on-a-chip (OoC) is an emerging technology based on microfluidic platforms in vitro culture that can mimic physiological environment function organs disease modeling In this review, we explore several major examples how single-OoC systems be used simulate complex outline recent advances organoids natural screening. Finally, summarize future trends OoCs must overcome discovery development. Overall, review highlights OoCs, instead models, open avenues evaluation, therapeutic innovation, vivo embodiment personalized medicine.

Language: Английский

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