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用于制备用于内皮屏障研究的载细胞中空纤维的微流控方法。

Microfluidic approach for the fabrication of cell-laden hollow fibers for endothelial barrier research.

作者信息

Nguyen Thi Phuong Thuy, Tran Buu Minh, Lee Nae Yoon

机构信息

Department of BioNano Technology, College of BioNano Technology, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, 13120, Republic of Korea.

出版信息

J Mater Chem B. 2018 Oct 14;6(38):6057-6066. doi: 10.1039/c8tb02031k. Epub 2018 Sep 24.

Abstract

This study reports an advanced approach to effectively generate hollow fibers in a triple-flow polydimethylsiloxane (PDMS) microfluidic device based on the gelation of alginate induced with CaCl inside a coaxial flow system. Two PDMS replicas with a semi-cylindrical microchannel were assembled to obtain a complete microchannel with a circular cross-section, which allowed the formation of mild and continuous coaxial flows for the fabrication of hollow fibers without employing complex glass microcapillaries. Mineral oil was introduced into the central flow to serve as an inert space inside the Ca-alginate wall. This was used to maintain the consistent formation of the hollow core of the microfiber and to easily transport fluid through the lumen structure in subsequent applications. The hollow fibers exhibited characteristics such as flexibility while showing robust mechanical strength, high permeability, and biocompatibility, and were used as scaffolds for the attachment and proliferation of human umbilical vein endothelial cells (HUVECs) to mimic a blood vessel. The fully covered HUVEC fibers were further integrated into a neurovascular system and co-cultured with astrocytes forming an on-chip blood brain barrier (BBB) platform. The use of this neurovascular model for drug testing will pave the way for developing or synthesizing a new drug that can cross the BBB in the human brain.

摘要

本研究报告了一种先进的方法,该方法基于在同轴流动系统中用氯化钙诱导海藻酸盐凝胶化,在三流聚二甲基硅氧烷(PDMS)微流控装置中有效地生成中空纤维。将两个带有半圆柱形微通道的PDMS复制品组装在一起,以获得具有圆形横截面的完整微通道,这允许形成温和且连续的同轴流,用于制造中空纤维,而无需使用复杂的玻璃微毛细管。将矿物油引入中心流中,以作为海藻酸钙壁内的惰性空间。这用于维持微纤维中空芯的一致形成,并在后续应用中便于通过管腔结构输送流体。中空纤维表现出柔韧性等特性,同时具有强大的机械强度、高渗透性和生物相容性,并被用作人脐静脉内皮细胞(HUVECs)附着和增殖的支架,以模拟血管。完全覆盖HUVEC的纤维进一步整合到神经血管系统中,并与星形胶质细胞共培养,形成片上血脑屏障(BBB)平台。使用这种神经血管模型进行药物测试将为开发或合成一种能够穿过人脑中血脑屏障的新药铺平道路。

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