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在微流控装置中诱导趋化性和贴壁趋化性信号用于三维体外分析。

Inducing chemotactic and haptotactic cues in microfluidic devices for three-dimensional in vitro assays.

机构信息

Multiscale in Mechanical and Biological Engineering, Aragon Institute of Engineering Research, University of Zaragoza , Zaragoza, Spain.

出版信息

Biomicrofluidics. 2014 Dec 11;8(6):064122. doi: 10.1063/1.4903948. eCollection 2014 Nov.

DOI:10.1063/1.4903948
PMID:25587374
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4265035/
Abstract

Microfluidic devices allow for the production of physiologically relevant cellular microenvironments by including biomimetic hydrogels and generating controlled chemical gradients. During transport, the biomolecules interact in distinct ways with the fibrillar networks: as purely diffusive factors in the soluble fluid or bound to the matrix proteins. These two main mechanisms may regulate distinct cell responses in order to guide their directional migration: caused by the substrate-bound chemoattractant gradient (haptotaxis) or by the gradient established within the soluble fluid (chemotaxis). In this work 3D diffusion experiments, in combination with ELISA assays, are performed using microfluidic platforms in order to quantify the distribution of PDGF-BB and TGF-β1 across collagen and fibrin gels. Furthermore, to gain a deeper understanding of the fundamental processes, the experiments are reproduced by computer simulations based on a reaction-diffusion transport model. This model yields an accurate prediction of the experimental results, confirming that diffusion and binding phenomena are established within the microdevice.

摘要

微流控设备通过包含仿生水凝胶和生成受控化学梯度来实现生理相关的细胞微环境。在运输过程中,生物分子以不同的方式与纤维状网络相互作用:作为可溶性流体中的纯扩散因子或与基质蛋白结合。这两种主要机制可能调节不同的细胞反应,以指导它们的定向迁移:由基质结合趋化因子梯度(趋触性)引起或由可溶性流体中建立的梯度引起(趋化性)。在这项工作中,使用微流控平台进行了 3D 扩散实验,结合 ELISA 测定,以定量测定 PDGF-BB 和 TGF-β1 在胶原蛋白和纤维蛋白凝胶中的分布。此外,为了更深入地了解基本过程,实验通过基于反应-扩散输运模型的计算机模拟进行了再现。该模型对实验结果进行了准确预测,证实了扩散和结合现象在微器件内建立。

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