A novel design of bioartificial kidneys with improved cell performance and haemocompatibility

Abstract

Treatment with bioartificial kidneys had beneficial effects in animal experiments and improved survival of critically ill patients with acute kidney injury in a Phase II clinical trial. However, a Phase II b clinical trial failed. This and other results suggested various problems with the current design of bioartificial kidneys. We propose a novel design to improve various properties of device, including haemocompatibility and cell performance. An important feature of the novel design is confinement of the blood to the lumina of the hollow fibre membranes. This avoids exposure of the blood to the non-haemocompatible outer surfaces of hollow fibre membranes, which usually occurs in bioartificial kidneys. We use these outer surfaces as substrate for cell growth. Our results show that commercial hollow fibre membranes can be directly applied in the bioreactor when human primary renal proximal tubular cells are grown in this configuration, and no coatings are required for the formation of robust and functional renal epithelia. Furthermore, we demonstrate that the bioreactor unit produces significant amounts of interleukins. This result helps to understand the immunomodulatory effects of bioartificial kidneys, which have been observed previously. The novel bioartificial kidney design outlined here and the results obtained would be expected to improve the safety and performance of bioartificial kidneys and to contribute to a better understanding of their effects.

Polymeric hollow fiber membranes for bioartificial organs and tissue engineering applications

“…Table presents an overview of some of the most important polymeric materials used to produce HFs, fabrication methods and potential applications in TE and BAO. The polymers are classified based on their origin (natural or synthetic) and on their degradation properties (degradable or non‐degradable).…”

A Non-woven Path: Electrospun Poly(lactic acid) Scaffolds for Kidney Tissue Engineering

“…Biomaterials such as polymer scaffolds have been investigated for kidney tissue engineering in a limited capacity, predominantly through investigation into hollow fibre bioreactors [29] but also as a conduit for renal segments [30]. Synthetic polymers, such as PLGA, have also been combined with natural ECM and have shown to enhance biocompatibility and reduce hydrophobicity of scaffolds compared to PLGA alone [31].…”

Development of an upscaled bioartificial kidney

“…The reasons for this choice were the improved haemocompatibility, the high filtration rates and the high reproducibility and availability of the HFM. More recent work reported newer generations of HFM based on polyarylethersulfone (PAES) from Gambro [94], ethylene vinyl alcohol (EVAL) from Kasei Kuraray Medical [78,80], polyethersulfone (PES) from 3M-Membrana [92]. Since the commercial membranes were available in various materials, several groups even compared them in terms of their ability to support cell adhesion.…”

“…The same group presented a new model of BAK with PTEC seeded on the extraluminal side of the HFM in 2013 [94], [115] and showed improved PTEC performance without using coatings.…”

“…An improved replacement of the renal function -the BAKhistory and perspectives Table 3 highlights the major BAK prototypes -using human PTEC -and their characteristics. [94,99]. The first trials were however performed with MDCK cells, which adhered perfectly without coating on PES/PVP HFM [112].…”