A dynamic flow fetal membrane organ-on-a-chip system for modeling the effects of amniotic fluid motion

IF 3 4区医学 Q3 ENGINEERING, BIOMEDICAL

Biomedical Microdevices Pub Date : 2024-07-04 DOI:10.1007/s10544-024-00714-1

Sungjin Kim, Po Yi Lam, Lauren S. Richardson, Ramkumar Menon, Arum Han

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Abstract

Fetal membrane (amniochorion), the innermost lining of the intrauterine cavity, surround the fetus and enclose amniotic fluid. Unlike unidirectional blood flow, amniotic fluid subtly rocks back and forth, and thus, the innermost amnion epithelial cells are continuously exposed to low levels of shear stress from fluid undulation. Here, we tested the impact of fluid motion on amnion epithelial cells (AECs) as a bearer of force impact and their potential vulnerability to cytopathologic changes that can destabilize fetal membrane functions. A previously developed amnion membrane (AM) organ-on-chip (OOC) was utilized but with dynamic flow to culture human fetal amnion membrane cells. The applied flow was modulated to perfuse culture media back and forth for 48 h to mimic fluid motion. A static culture condition was used as a negative control, and oxidative stress (OS) condition was used as a positive control representing pathophysiological changes. The impacts of fluidic motion were evaluated by measuring cell viability, cellular transition, and inflammation. Additionally, scanning electron microscopy (SEM) imaging was performed to observe microvilli formation. The results show that regardless of the applied flow rate, AECs and AMCs maintained their viability, morphology, innate meta-state, and low production of pro-inflammatory cytokines. E-cadherin expression and microvilli formation in the AECs were upregulated in a flow rate-dependent fashion; however, this did not impact cellular morphology or cellular transition or inflammation. OS treatment induced a mesenchymal morphology, significantly higher vimentin to cytokeratin 18 (CK-18) ratio, and pro-inflammatory cytokine production in AECs, whereas AMCs did not respond in any significant manner. Fluid motion and shear stress, if any, did not impact AEC cell function and did not cause inflammation. Thus, when using an amnion membrane OOC model, the inclusion of a dynamic flow environment is not necessary to mimic in utero physiologic cellular conditions of an amnion membrane.

Graphical Abstract

Abstract Image

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用于模拟羊水运动影响的动态流动胎膜片上器官系统。

胎膜（羊膜腔）是宫腔内最内层的衬里，环绕着胎儿并包裹着羊水。与单向血流不同，羊水会微妙地来回摆动，因此最内层的羊膜上皮细胞会持续暴露在羊水摆动产生的低水平剪切应力下。在这里，我们测试了液体运动对羊膜上皮细胞（AECs）的影响，羊膜上皮细胞是受力冲击的承载者，它们可能容易发生细胞病理学变化，从而破坏胎膜功能的稳定性。以前开发的羊膜（AM）片上器官（OOC）被用来培养人类胎儿的羊膜细胞，但采用的是动态流。为了模拟流体运动，在 48 小时的时间里，对所施加的流量进行了调节，以来回灌注培养基。静态培养条件作为阴性对照，氧化应激（OS）条件作为阳性对照，代表病理生理变化。流体运动的影响通过测量细胞活力、细胞转化和炎症来评估。此外，还进行了扫描电子显微镜（SEM）成像，以观察微绒毛的形成。结果表明，无论流速如何，AECs 和 AMCs 都能保持其活力、形态、先天元状态和较低的促炎细胞因子产生量。AECs中E-cadherin的表达和微绒毛的形成随流速而上调，但这并不影响细胞形态、细胞转化或炎症。OS处理会诱导AEC出现间充质形态、波形蛋白与细胞角蛋白18（CK-18）的比率显著升高以及促炎细胞因子的产生，而AMC则没有任何明显的反应。流体运动和剪切应力（如果有的话）不会影响 AEC 细胞的功能，也不会引起炎症。因此，在使用羊膜 OOC 模型时，不需要加入动态流动环境来模拟羊膜在子宫内的生理细胞条件。

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来源期刊

Biomedical Microdevices 工程技术-工程：生物医学

CiteScore

6.90

自引率

3.60%

发文量

审稿时长

6 months

期刊介绍： Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology is an interdisciplinary periodical devoted to all aspects of research in the medical diagnostic and therapeutic applications of Micro-Electro-Mechanical Systems (BioMEMS) and nanotechnology for medicine and biology. General subjects of interest include the design, characterization, testing, modeling and clinical validation of microfabricated systems, and their integration on-chip and in larger functional units. The specific interests of the Journal include systems for neural stimulation and recording, bioseparation technologies such as nanofilters and electrophoretic equipment, miniaturized analytic and DNA identification systems, biosensors, and micro/nanotechnologies for cell and tissue research, tissue engineering, cell transplantation, and the controlled release of drugs and biological molecules. Contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices and nanotechnology are encouraged. A non-exhaustive list of fields of interest includes: nanoparticle synthesis, characterization, and validation of therapeutic or imaging efficacy in animal models; biocompatibility; biochemical modification of microfabricated devices, with reference to non-specific protein adsorption, and the active immobilization and patterning of proteins on micro/nanofabricated surfaces; the dynamics of fluids in micro-and-nano-fabricated channels; the electromechanical and structural response of micro/nanofabricated systems; the interactions of microdevices with cells and tissues, including biocompatibility and biodegradation studies; variations in the characteristics of the systems as a function of the micro/nanofabrication parameters.