Department of Electronic Engineering and Information Science, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, People's Republic of China.
Biofabrication. 2023 Apr 12;15(3). doi: 10.1088/1758-5090/acc35d.
Glomerulus-on-a-chip, as a promising alternative for drug nephrotoxicity evaluation, is attracting increasing attention. For glomerulus-on-a-chip, the more biomimetic the chip is, the more convincing the application of the chip is. In this study, we proposed a hollow fiber-based biomimetic glomerulus chip that can regulate filtration in response to blood pressure and hormone levels. On the chip developed here, bundles of hollow fibers were spherically twisted and embedded in designed Bowman's capsules to form spherical glomerular capillary tufts, with podocytes and endotheliocytes cultured on the outer and inner surfaces of the hollow fibers, respectively. We evaluated the morphology of cells, the viability of cells, and the metabolic function of cells in terms of glucose consumption and urea synthesis by comparing the results obtained under fluidic and static conditions, confirmed the barrier function of the endotheliocyte-fiber membrane-podocyte structure by monitoring the diffusion of fluorescein isothiocyanate (FITC)-labeled inulin, albumin and IgG, and, for the first time, achieved on-chip filtration regulation in response to the hormone atrial natriuretic peptide. In addition, the application of the chip in the evaluation of drug nephrotoxicity was also preliminarily demonstrated. This work offers insights into the design of a more physiologically similar glomerulus on a microfluidic chip.
肾小球芯片作为药物肾毒性评价的一种有前途的替代方法，正越来越受到关注。对于肾小球芯片来说，芯片的仿生程度越高，其应用就越有说服力。在本研究中，我们提出了一种基于中空纤维的仿生肾小球芯片，该芯片可以根据血压和激素水平调节过滤。在我们开发的这种芯片上，将一束中空纤维球形扭曲并嵌入设计的鲍曼氏囊内，形成球形肾小球毛细血管丛，分别在中空纤维的外表面和内表面培养足细胞和内皮细胞。我们通过比较在流动和静态条件下获得的结果，从细胞形态、细胞活力以及葡萄糖消耗和尿素合成的代谢功能等方面进行了评估，通过监测荧光素异硫氰酸酯（FITC）标记的内毒素、白蛋白和 IgG 的扩散，证实了内皮细胞-纤维膜-足细胞结构的屏障功能，并且首次实现了对激素心房利钠肽的芯片过滤调节。此外，还初步展示了该芯片在药物肾毒性评价中的应用。这项工作为在微流控芯片上设计更接近生理的肾小球提供了思路。
