基于纤维技术的用于构建人工近端小管的肾脏生物学驱动的宏观和微观设计策略。

Renal Biology Driven Macro- and Microscale Design Strategies for Creating an Artificial Proximal Tubule Using Fiber-Based Technologies.

机构信息

Department of Nephrology and Hypertension, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.

Department of Orthopaedics, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.

出版信息

ACS Biomater Sci Eng. 2021 Oct 11;7(10):4679-4693. doi: 10.1021/acsbiomaterials.1c00408. Epub 2021 Sep 7.

Abstract

Chronic kidney disease affects one in six people worldwide. Due to the scarcity of donor kidneys and the complications associated with hemodialysis (HD), a cell-based bioartificial kidney (BAK) device is desired. One of the shortcomings of HD is the lack of active transport of solutes that would normally be performed by membrane transporters in kidney epithelial cells. Specifically, proximal tubule (PT) epithelial cells play a major role in the active transport of metabolic waste products. Therefore, a BAK containing an artificial PT to actively transport solutes between the blood and the filtrate could provide major therapeutic advances. Creating such an artificial PT requires a biocompatible tubular structure which supports the adhesion and function of PT-specific epithelial cells. Ideally, this scaffold should structurally replicate the natural PT basement membrane which consists mainly of collagen fibers. Fiber-based technologies such as electrospinning are therefore especially promising for PT scaffold manufacturing. This review discusses the use of electrospinning technologies to generate an artificial PT scaffold for / cellularization. We offer a comparison of currently available electrospinning technologies and outline the desired scaffold properties required to serve as a PT scaffold. Discussed also are the potential technologies that may converge in the future, enabling the effective and biomimetic incorporation of synthetic PTs in to BAK devices and beyond.

摘要

慢性肾脏病影响全球六分之一的人。由于供体肾脏的稀缺以及与血液透析(HD)相关的并发症,人们希望有一种基于细胞的生物人工肾(BAK)设备。HD 的一个缺点是缺乏溶质的主动转运,而这些溶质通常是由肾上皮细胞中的膜转运蛋白来完成的。具体来说,近端肾小管(PT)上皮细胞在代谢废物的主动转运中起着主要作用。因此,包含人工 PT 的 BAK 可以在血液和滤液之间主动转运溶质,从而提供重大的治疗进展。创建这样的人工 PT 需要一个生物相容性的管状结构,该结构支持 PT 特异性上皮细胞的粘附和功能。理想情况下,这种支架应在结构上复制主要由胶原纤维组成的天然 PT 基底膜。因此,基于纤维的技术,如静电纺丝,对于 PT 支架制造特别有前途。这篇综述讨论了使用静电纺丝技术来生成用于 / 细胞化的人工 PT 支架。我们比较了现有的静电纺丝技术,并概述了作为 PT 支架所需的理想支架特性。还讨论了未来可能会融合的潜在技术,从而能够有效地仿生地将合成的 PT 纳入 BAK 设备及其他设备中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2094/8512683/f6a66a071183/ab1c00408_0004.jpg

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