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微制造和水凝胶工程在芯片上微器官的研究综述。

A review of microfabrication and hydrogel engineering for micro-organs on chips.

机构信息

Macromolécules et Microsystèmes en Biologie et en Médecine, Institut Curie, UMR 168, Paris 75005, France.

Migration et Invasion Cellulaire, Institut Curie, UMR 144, Paris 75005, France.

出版信息

Biomaterials. 2014 Feb;35(6):1816-32. doi: 10.1016/j.biomaterials.2013.11.021. Epub 2013 Dec 4.

Abstract

This review highlights recent trends towards the development of in vitro multicellular systems with definite architectures, or "organs on chips". First, the chemical composition and mechanical properties of the scaffold have to be consistent with the anatomical environment in vivo. In this perspective, the flourishing interest in hydrogels as cellular substrates has highlighted the main parameters directing cell differentiation that need to be recapitulated in artificial matrix. Another scaffold requirement is to act as a template to guide tissue morphogenesis. Therefore specific microfabrication techniques are required to spatially pattern the environment at microscale. 2D patterning is particularly efficient for organizing planar polarized cell types such as endothelial cells or neurons. However, most organs are characterized by specific sub units organized in three dimensions at the cellular level. The reproduction of such 3D patterns in vitro is necessary for cells to fully differentiate, assemble and coordinate to form a coherent micro-tissue. These physiological microstructures are often integrated in microfluidic devices whose controlled environments provide the cell culture with more life-like conditions than traditional cell culture methods. Such systems have a wide range of applications, for fundamental research, as tools to accelerate drug development and testing, and finally, for regenerative medicine.

摘要

本文综述了近年来向着构建具有特定结构的体外多细胞体系,即“芯片上器官”的发展趋势。首先,支架的化学成分和机械性能必须与体内解剖环境一致。在这方面,水凝胶作为细胞基质的蓬勃发展突出了指导细胞分化的主要参数,这些参数需要在人工基质中重现。支架的另一个要求是作为引导组织形态发生的模板。因此,需要特定的微制造技术在微尺度上对环境进行空间图案化。2D 图案化对于组织平面极化的细胞类型(如内皮细胞或神经元)特别有效。然而,大多数器官的特点是在细胞水平上以三维方式组织的特定亚单位。体外复制这种 3D 图案对于细胞完全分化、组装和协调以形成一个连贯的微组织是必要的。这些生理微结构通常集成在微流控设备中,其受控环境为细胞培养提供了比传统细胞培养方法更接近生理的条件。这些系统具有广泛的应用,包括基础研究、加速药物开发和测试的工具,以及最后用于再生医学。

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