Fabrication of Kidney Proximal Tubule Grafts Using Biofunctionalized Electrospun Polymer Scaffolds

Katja Jansen, Miguel Castilho, Sanne Aarts, Michael M. Kaminski, Soeren S. Lienkamp, Roman Pichler, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde Masereeuw (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

The increasing prevalence of end-stage renal disease and persistent shortage of donor organs call for alternative therapies for kidney patients. Dialysis remains an inferior treatment as clearance of large and protein-bound waste products depends on active tubular secretion. Biofabricated tissues could make a valuable contribution, but kidneys are highly intricate and multifunctional organs. Depending on the therapeutic objective, suitable cell sources and scaffolds must be selected. This study provides a proof-of-concept for stand-alone kidney tubule grafts with suitable mechanical properties for future implantation purposes. Porous tubular nanofiber scaffolds are fabricated by electrospinning 12%, 16%, and 20% poly-ε-caprolactone (PCL) v/w (chloroform and dimethylformamide, 1:3) around 0.7 mm needle templates. The resulting scaffolds consist of 92%, 69%, and 54% nanofibers compared to microfibers, respectively. After biofunctionalization with L-3,4-dihydroxyphenylalanine and collagen IV, 10 × 10 6 proximal tubule cells per mL are injected and cultured until experimental readout. A human-derived cell model can bridge all fiber-to-fiber distances to form a monolayer, whereas small-sized murine cells form monolayers on dense nanofiber meshes only. Fabricated constructs remain viable for at least 3 weeks and maintain functionality as shown by inhibitor-sensitive transport activity, which suggests clearance capacity for both negatively and positively charged solutes.

Original languageEnglish
Article number1800412
Number of pages9
JournalMacromolecular Bioscience
Volume19
Issue number2
DOIs
Publication statusPublished - Feb 2019

Keywords

  • polycaprolactone
  • regenerative medicine
  • renal replacement therapy
  • renal transport
  • tissue engineering
  • Biocompatible Materials/therapeutic use
  • Tissue Engineering/methods
  • Cell Proliferation
  • Lactones/chemistry
  • Epithelial Cells/cytology
  • Humans
  • Caproates/chemistry
  • Cells, Cultured
  • Kidney Failure, Chronic/surgery
  • Tissue Scaffolds
  • Kidney Tubules, Proximal/cytology
  • Transplants/growth & development
  • Polymers

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