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关于器官芯片作为研究组织屏障的强大临床前模型的综合综述。

A comprehensive review on organ-on-chips as powerful preclinical models to study tissue barriers.

作者信息

Filiz Yagmur, Esposito Alessio, De Maria Carmelo, Vozzi Giovanni, Yesil-Celiktas Ozlem

机构信息

Department of Development and Regeneration, Faculty of Medicine, KU Leuven, 8500 Kortrijk, Belgium.

Research Center E. Piaggio and Department of Information Engineering, University of Pisa, Largo L. Lazzarino 1, Pisa 56126, Italy.

出版信息

Prog Biomed Eng (Bristol). 2024 Sep 16;6(4). doi: 10.1088/2516-1091/ad776c.

DOI:10.1088/2516-1091/ad776c
PMID:39655848
Abstract

In the preclinical stage of drug development, 2D and 3D cell cultures under static conditions followed by animal models are utilized. However, these models are insufficient to recapitulate the complexity of human physiology. With the developing organ-on-chip (OoC) technology in recent years, human physiology and pathophysiology can be modeled better than traditional models. In this review, the need for OoC platforms is discussed and evaluated from both biological and engineering perspectives. The cellular and extracellular matrix components are discussed from a biological perspective, whereas the technical aspects such as the intricate working principles of these systems, the pivotal role played by flow dynamics and sensor integration within OoCs are elucidated from an engineering perspective. Combining these two perspectives, bioengineering applications are critically discussed with a focus on tissue barriers such as blood-brain barrier, ocular barrier, nasal barrier, pulmonary barrier and gastrointestinal barrier, featuring recent examples from the literature. Furthermore, this review offers insights into the practical utility of OoC platforms for modeling tissue barriers, showcasing their potential and drawbacks while providing future projections for innovative technologies.

摘要

在药物研发的临床前阶段,会采用静态条件下的二维和三维细胞培养,随后使用动物模型。然而,这些模型不足以重现人体生理学的复杂性。近年来,随着器官芯片(OoC)技术的发展,相较于传统模型,人体生理学和病理生理学能够得到更好的模拟。在本综述中,将从生物学和工程学角度对器官芯片平台的需求进行讨论和评估。从生物学角度讨论细胞和细胞外基质成分,而从工程学角度阐明这些系统复杂的工作原理、流动动力学和传感器集成在器官芯片中所起的关键作用等技术方面。结合这两个角度,重点围绕血脑屏障、眼屏障、鼻屏障、肺屏障和胃肠道屏障等组织屏障对生物工程应用进行批判性讨论,并列举文献中的最新实例。此外,本综述深入探讨了器官芯片平台在模拟组织屏障方面的实际效用,展示了它们的潜力和缺点,同时对创新技术进行了未来展望。

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