3D Printed Tubulointerstitium Chip as an In Vitro Testing Platform

Macromolecular Bioscience, vol. 24, pp. e2300440

Abstract

Chronic kidney disease (CKD) ranks as the twelfth leading cause of death worldwide with limited treatment options. The development of in vitro models replicating defined segments of the kidney functional units, the nephrons, in a physiologically relevant and reproducible manner can facilitate drug testing. The aim of this study was to produce an in vitro organ-on-a-chip platform with extrusion-based three-dimensional (3D) printing. The manufacturing of the tubular platform was produced by printing sacrificial fibers with varying diameters, providing a suitable structure for cell adhesion and proliferation. The chip platform was seeded with primary murine tubular epithelial cells and human umbilical vein endothelial cells. The effect of channel geometry, its reproducibility, coatings for cell adhesion, and specific cell markers were investigated. The developed chip presents single and dual channels, mimicking segments of a renal tubule and the capillary network, together with an extracellular matrix gel analogue placed in the middle of the two channels, envisioning the renal tubulointerstitium in vitro. The 3D printed platform enables perfusable circular cross-section channels with fully automated, rapid, and reproducible manufacturing processes at low costs. This kidney tubulointerstitium on-a-chip provides the first step toward the production of more complex in vitro models for drug testing.

Authors 6

1. Gabriele Addario

   Maastricht University

   Affiliation as printed

   Maastricht University MERLN Institute for Technology‐Inspired Regenerative Medicine Complex Tissue Regeneration Department Maastricht 6229 ER The Netherlands

   Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine, Complex Tissue regeneration Department, Maastricht, 6229 ER The Netherlands

2. Daphne Eussen

   Maastricht University

   Affiliation as printed

   Maastricht University MERLN Institute for Technology‐Inspired Regenerative Medicine Complex Tissue Regeneration Department Maastricht 6229 ER The Netherlands

   Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine, Complex Tissue regeneration Department, Maastricht, 6229 ER The Netherlands

3. Sonja Djudjaj Aachen Institute of Pathology

   RWTH Aachen University

   Affiliation as printed

   Institute of Pathology RWTH University of Aachen 52074 Aachen Germany

   Institute of Pathology RWTH University of Aachen 52074 Aachen Germany

4. Peter Boor Aachen Division of Nephrology Electron Microscopy Facility Institute of Pathology

   RWTH Aachen University

   Affiliation as printed

   Division of Nephrology RWTH University of Aachen 52074 Aachen Germany

   Electron Microscopy Facility RWTH University of Aachen 52074 Aachen Germany

   Institute of Pathology RWTH University of Aachen 52074 Aachen Germany

   Division of Nephrology RWTH University of Aachen 52074 Aachen Germany

   Electron Microscopy Facility RWTH University of Aachen 52074 Aachen Germany

   Institute of Pathology RWTH University of Aachen 52074 Aachen Germany

5. Lorenzo Moroni

   Maastricht University

   Affiliation as printed

   Maastricht University MERLN Institute for Technology‐Inspired Regenerative Medicine Complex Tissue Regeneration Department Maastricht 6229 ER The Netherlands

   Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine, Complex Tissue regeneration Department, Maastricht, 6229 ER The Netherlands

6. Carlos Mota corresponding

   Maastricht University

   Affiliation as printed

   Maastricht University MERLN Institute for Technology‐Inspired Regenerative Medicine Complex Tissue Regeneration Department Maastricht 6229 ER The Netherlands

   Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine, Complex Tissue regeneration Department, Maastricht, 6229 ER The Netherlands