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Fabrication of kidney proximal tubule grafts using biofunctionalized electrospun polymer scaffolds

Item Type:Article
Title:Fabrication of kidney proximal tubule grafts using biofunctionalized electrospun polymer scaffolds
Creators Name:Jansen, K. and Castilho, M. and Aarts, S. and Kaminski, M.M. and Lienkamp, S.S. and Pichler, R. and Malda, J. and Vermonden, T. and Jansen, J. and Masereeuw, R.
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.
Keywords:Polycaprolactone, Regenerative Medicine, Renal Replacement Therapy, Renal Transport, Tissue Engineering
Source:Macromolecular Bioscience
Page Range:e1800412
Date:February 2019
Official Publication:https://doi.org/10.1002/mabi.201800412
PubMed:View item in PubMed

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