A glomerulus chip with spherically twisted cell-laden hollow fibers as glomerular capillary tufts

Abstract

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 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.

Physiological Replication of the Human Glomerulus Using a Triple Culture Microphysiological System

“…[22,42] There was a wide range of concentrations used in this type of assay, and no "gold standard" had been established. Some researchers use higher concentrations, [13,16,67,68] , while others employ the same concentration as we do. [7,15,22] Even some leading experts in this field have adjusted their concentrations over time.…”

Tailoring biomaterials for biomimetic organs-on-chips

“…Inspired by the anatomical structure of glomeruli, Dai et al spherically twisted the hollow fiber bundles and implanted them into Bowman's capsules, followed by successively seeding podocytes and endotheliocytes on the outer and inner side of fibers. 214 Based on the bionic structure design of biomaterials and fluidic culture microenvironment, the glomerulus chip demonstrated the favorable viability and metabolic function of cells, together with the selective barrier and filtration regulation functions of glomerular capillaries.…”

“…In addition, Roye et al constructed glomerular injury model in a glomerulus chip by introducing Adriamycin to destroy the tissue integrality of ECs and podocytes. 214 Employing Pseudorabies virus as an inducible factor in a distal tubule-on-a-chip, Wang et al developed a kidney disease model to study the potential pathogenesis of virus-induced renal dysfunctions. 249 They found that virus infection caused the disorder of Na transporters, injury of reabsorption barrier, transformation of microvilli, as well as abnormalities of serum electrolyte.…”