A Fibrin-Based Tissue-Engineered Renal Proximal Tubule for Bioartificial Kidney Devices: Development, Characterization and In Vitro Transport Study

Abstract

A bioartificial renal proximal tubule is successfully engineered as a first step towards a bioartificial kidney for improved renal substitution therapy. To engineer the tubule, a tunable hollow fiber membrane with an exterior skin layer that provides immunoprotection for the cells from extracapillary blood flow and a coarse inner surface that facilitates a hydrogel coating for cell attachment was embedded in a “lab-on-a-chip” model for the small-scale exploratory testing under flow conditions. Fibrin was coated onto the inner surface of the hollow fiber, and human renal proximal tubule epithelial cells were then seeded. Using this model, we successfully cultured a confluent monolayer, as ascertained by immunofluorescence staining for ZO-1 tight junctions and other proximal tubule markers, scanning electron microscopy, and FITC-inulin recovery studies. Furthermore, the inulin studies, combined with the creatinine and glucose transport profiles, suggested that the confluent monolayer exhibits functional transport capabilities. The novel approaches here may eventually improve current renal substitution technology for renal failure patients.