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三维工程心脏体外模型:在三维微生理系统中对心肌细胞的可控排列。

A Three-Dimensional Engineered Cardiac In Vitro Model: Controlled Alignment of Cardiomyocytes in 3D Microphysiological Systems.

机构信息

Microsystems Laboratory-LMIS4, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Faculty of Medicine, Department of Pathology and Immunology, Centre Médical Universitaire (CMU), 1206 Geneva, Switzerland.

出版信息

Cells. 2023 Feb 10;12(4):576. doi: 10.3390/cells12040576.

DOI:10.3390/cells12040576
PMID:36831243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9954012/
Abstract

Cardiomyocyte alignment in myocardium tissue plays a significant role in the physiological, electrical, and mechanical functions of the myocardium. It remains, however, difficult to align cardiac cells in a 3D in vitro heart model. This paper proposes a simple method to align cells using microfabricated Polydimethylsiloxane (PDMS) grooves with large dimensions (of up to 350 µm in width), similar to the dimensions of trabeculae carneae, the smallest functional unit of the myocardium. Two cell groups were used in this work; first, H9c2 cells in combination with Nor10 cells for proof of concept, and second, neonatal cardiac cells to investigate the functionality of the 3D model. This model compared the patterned and nonpatterned 3D constructs, as well as the 2D cell cultures, with and without patterns. In addition to alignment, we assessed the functionality of our proposed 3D model by comparing beating rates between aligned and non-aligned structures. In order to assess the practicality of the model, the 3D aligned structures should be demonstrated to be detachable and alignable. This evaluation is crucial to the use of this 3D functional model in future studies related to drug screening, building blocks for tissue engineering, and as a heart-on-chip by integrating microfluidics.

摘要

心肌组织中心肌细胞的排列对于心肌的生理、电和机械功能起着重要作用。然而,在 3D 体外心脏模型中使心脏细胞排列对齐仍然具有挑战性。本文提出了一种使用微加工的具有大尺寸(高达 350 µm 宽)的聚二甲基硅氧烷(PDMS)槽来对齐细胞的简单方法,这些尺寸类似于心肌的最小功能单元——心肌小梁的尺寸。本工作使用了两组细胞;第一组是 H9c2 细胞与 Nor10 细胞的组合,用于验证概念,第二组是新生心肌细胞,用于研究 3D 模型的功能。该模型比较了有图案和无图案的 3D 结构,以及有和没有图案的 2D 细胞培养物。除了对齐,我们还通过比较对齐和非对齐结构之间的跳动率来评估我们提出的 3D 模型的功能。为了评估模型的实用性,应该展示 3D 对齐结构是可分离和可对齐的。这种评估对于在未来与药物筛选、组织工程构建块以及通过集成微流控技术作为芯片上心脏相关的研究中使用这种 3D 功能模型至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1360/9954012/8a9cbf8f66a5/cells-12-00576-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1360/9954012/01c22ccbabde/cells-12-00576-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1360/9954012/921f003c9e03/cells-12-00576-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1360/9954012/8ee1ee57e62d/cells-12-00576-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1360/9954012/fb076e72702b/cells-12-00576-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1360/9954012/8a9cbf8f66a5/cells-12-00576-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1360/9954012/01c22ccbabde/cells-12-00576-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1360/9954012/921f003c9e03/cells-12-00576-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1360/9954012/8ee1ee57e62d/cells-12-00576-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1360/9954012/fb076e72702b/cells-12-00576-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1360/9954012/8a9cbf8f66a5/cells-12-00576-g005.jpg

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