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注塑微流控芯片上受人类眼部血管生成启发的血管模型。

Human Ocular Angiogenesis-Inspired Vascular Models on an Injection-Molded Microfluidic Chip.

机构信息

Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul, 08826, Republic of Korea.

Program for Bioengineering, Seoul National University, Seoul, 08826, Republic of Korea.

出版信息

Adv Healthc Mater. 2019 Aug;8(15):e1900328. doi: 10.1002/adhm.201900328. Epub 2019 Jun 14.

DOI:10.1002/adhm.201900328
PMID:31199057
Abstract

Angiogenic sprouting, which is the growth of new blood vessels from pre-existing vessels, is orchestrated by cues from the cellular microenvironment, such as spatially controlled gradients of angiogenic factors. However, current in vitro models are less scalable for in-depth studies of angiogenesis. In this study, a plastic-based microfluidic chip is developed to reconstruct in vitro 3D vascular networks. The main disadvantages of the preexisting system are identified, namely, the low productivity and difficulty of experiments, and a breakthrough is suggested while minimizing disadvantages. The selection of plastic materials contributes to the productivity and usability of in vitro devices. By adopting this material, this chip offers simple fluid patterning, facilitating the construction of a cell-culture microenvironment. Compared with previous systems, the chip, which can form both inward and outwardly radial vascular sprouting, demonstrates the growth of functional, morphologically integral microvessels. The developed angiogenic model yields dose-dependent results for antiangiogenic drug screening. This model may contribute significantly not only to vascular studies under normal and pathological conditions, but also to fundamental research on the ocular neovascularization. Furthermore, it can be applied as a tool for more practical, extended preclinical research, providing an alternative to animal experiments.

摘要

血管生成芽生是指新血管从预先存在的血管中生长,由细胞微环境中的信号调控,如血管生成因子的空间控制梯度。然而,目前的体外模型对于血管生成的深入研究的可扩展性较差。在这项研究中,开发了一种基于塑料的微流控芯片来重建体外 3D 血管网络。确定了现有系统的主要缺点,即低产量和实验难度,并在最小化缺点的同时提出了突破。塑料材料的选择有助于提高体外设备的产量和可用性。通过采用这种材料,该芯片可以进行简单的流体图案设计,便于构建细胞培养微环境。与以前的系统相比,该芯片可以形成内向和外向的径向血管芽生,展示了功能性、形态完整的微血管的生长。所开发的血管生成模型可用于进行抗血管生成药物筛选的剂量依赖性研究。该模型不仅可以为正常和病理条件下的血管研究做出重要贡献,还可以为眼部新生血管的基础研究做出贡献。此外,它可以作为一种更实用、扩展的临床前研究的工具,为动物实验提供替代方案。

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