Item Type: | Article |
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Title: | Fabrication of kidney proximal tubule grafts using biofunctionalized electrospun polymer scaffolds |
Creators Name: | Jansen, K., Castilho, M., Aarts, S., Kaminski, M.M., Lienkamp, S.S., Pichler, R., Malda, J., Vermonden, T., 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 |
ISSN: | 1616-5187 |
Publisher: | Wiley |
Volume: | 19 |
Number: | 2 |
Page Range: | e1800412 |
Date: | February 2019 |
Official Publication: | https://doi.org/10.1002/mabi.201800412 |
PubMed: | View item in PubMed |
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