光屏障:体外调节内皮屏障的光遗传学平台。

IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS
Sharon Fleischer, Martin Liberman, Max Summers, Vanessa Li, Trevor R. Nash and Gordana Vunjak-Novakovic*, 
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引用次数: 0

摘要

器官芯片平台已经成为药物筛选和机制研究的有前途的人体组织模型,为传统的动物模型提供了替代方案。将血管结构整合到这些平台中,对于创建生理上忠实于单个器官的模型和研究器官间的串扰至关重要。然而,大多数体外培养的血管结构不能解释器官特异性内皮通透性或其在疾病反应中的调节。在这里,我们提出了optoBarrier,一个光遗传器官芯片平台,旨在通过光刺激调节内皮屏障的通透性。通过光激活工程光遗传内皮细胞中的RhoA信号,我们证明了应力纤维的形成,血管内皮钙粘蛋白(VE-cadherin)的破坏和屏障通透性的增加。我们进一步表明,在响应光时,渗透率以可逆和剂量依赖的方式可调。因此,我们提出optoBarrier提供了一种用户定义的、可控的、简单的方法来操纵内皮细胞的渗透性,用于体外研究人类血管系统。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

OptoBarrier: An Optogenetic Platform for Modulating Endothelial Barriers In Vitro

OptoBarrier: An Optogenetic Platform for Modulating Endothelial Barriers In Vitro

Organ-on-a-chip platforms have emerged as promising human tissue models for drug screening and mechanistic studies, offering alternatives to traditional animal models. Integration of vascular structures into these platforms is pivotal for creating physiologically faithful models of individual organs and studying interorgan crosstalk. However, most vascular structures grown in vitro do not account for organ-specific endothelial permeability or its modulation in response to disease. Here, we present optoBarrier, an optogenetic organ-on-a-chip platform designed to modulate endothelial barrier permeability through light stimulation. By optically activating RhoA signaling in engineered optogenetic endothelial cells, we demonstrate the formation of stress fibers, disruption of vascular endothelial cadherin (VE-cadherin) and increased barrier permeability. We further show that permeability is tunable in a reversible and dose-dependent manner in response to light. We therefore propose that optoBarrier offers a user-defined, controlled and simple method to manipulate endothelial permeability for in vitro studies of human vasculature.

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来源期刊
ACS Biomaterials Science & Engineering
ACS Biomaterials Science & Engineering Materials Science-Biomaterials
CiteScore
10.30
自引率
3.40%
发文量
413
期刊介绍: ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics: Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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