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h-FIBER:用于肾小球滤过屏障研究的微流控拓扑中空纤维

h-FIBER: Microfluidic Topographical Hollow Fiber for Studies of Glomerular Filtration Barrier.

作者信息

Xie Ruoxiao, Korolj Anastasia, Liu Chuan, Song Xin, Lu Rick Xing Ze, Zhang Boyang, Ramachandran Arun, Liang Qionglin, Radisic Milica

机构信息

MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Beijing Key Lab of Microanalytical Methods & Instrumentation, Department of Chemistry, Centre for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, P. R. China.

Institute for Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario M5S 3G9, Canada.

出版信息

ACS Cent Sci. 2020 Jun 24;6(6):903-912. doi: 10.1021/acscentsci.9b01097. Epub 2020 May 13.

Abstract

Kidney-on-a-chip devices may revolutionize the discovery of new therapies. However, fabricating a 3D glomerulus remains a challenge, due to a requirement for a microscale soft material with complex topography to support cell culture in a native configuration. Here, we describe the use of microfluidic spinning to recapitulate complex concave and convex topographies over multiple length scales, required for biofabrication of a biomimetic 3D glomerulus. We produced a microfluidic extruded topographic hollow fiber (h-FIBER), consisting of a vessel-like perfusable tubular channel for endothelial cell cultivation, and a glomerulus-like knot with microconvex topography on its surface for podocyte cultivation. Meter long h-FIBERs were produced in microfluidics within minutes, followed by chemically induced inflation for generation of topographical cues on the 3D scaffold surface. The h-FIBERs were assembled into a hot-embossed plastic 96-well plate. Long-term perfusion, podocyte barrier formation, endothelialization, and permeability tests were easily performed by a standard pipetting technique on the platform. Following long-term culture (1 month), a functional filtration barrier, measured by the transfer of albumin from the blood vessel side to the ultrafiltrate side, suggested the establishment of an engineered glomerulus.

摘要

芯片肾脏装置可能会彻底改变新疗法的发现。然而,制造三维肾小球仍然是一个挑战,因为需要一种具有复杂地形的微尺度软材料来支持细胞在天然构型中的培养。在这里,我们描述了使用微流体纺丝来重现生物制造仿生三维肾小球所需的多个长度尺度上的复杂凹凸地形。我们制造了一种微流体挤出的地形中空纤维(h-FIBER),它由一个用于内皮细胞培养的类似血管的可灌注管状通道,以及一个表面具有微凸地形的类似肾小球的结组成,用于足细胞培养。在微流体中几分钟内就能制造出米长的h-FIBER,随后通过化学诱导膨胀在三维支架表面生成地形线索。将h-FIBER组装到热压塑料96孔板中。通过标准移液技术在该平台上可以轻松进行长期灌注、足细胞屏障形成、内皮化和通透性测试。经过长期培养(1个月),通过白蛋白从血管侧转移到超滤液侧来测量的功能性滤过屏障表明已构建出工程化肾小球。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e7b/7318083/e3535170cf5b/oc9b01097_0001.jpg

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