Carbon Nanotube/Conducting Polymer Hybrid Nanofibers as Novel Organic Bioelectronic Interfaces for Efficient Removal of Protein-Bound Uremic Toxins

ACS Appl Mater Interfaces. 2019 Nov 27;11(47):43843-43856. doi: 10.1021/acsami.9b14351. Epub 2019 Nov 12.

Abstract

Protein-bound uremic toxins (PBUTs) can cause noxious effects in patients suffering from renal failure as a result of inhibiting the transport of proteins and inducing their structural modification. They are difficult to remove through standard hemodialysis (HD) treatment. Herein, we report an organic bioelectronic HD device system for the effective removal of PBUTs through electrically triggered dissociation of protein-toxin complexes. To prepare this system, we employed electrospinning to fabricate electrically conductive quaternary composite nanofiber mats-comprising multiwalled carbon nanotubes (MWCNTs), poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS), poly(ethylene oxide) (PEO), and (3-glycidyloxypropyl)trimethoxysilane (GOPS)-on conventional polyethersulfone (PES) dialysis membranes. These composite nanofiber platforms exhibited (i) long-term water resistance (due to cross-linking among PSS, PEO, and GOPS), (ii) high adhesion strength on the PES membrane (due to GOPS functioning as an adhesion promoter), (iii) enhanced electrical properties [due to the MWCNTs and PEDOT:PSS promoting effective electrical stimulation (ES) operation in devices containing bioelectronic interfaces (BEI)], and (iv) good anticoagulant ability and negligible hemolysis of red blood cells. We employed this organic BEI electronic system as a novel single-membrane HD device to study the removal efficiency of four kinds of uremic toxins [p-cresol (PC), indoxyl sulfate, and hippuric acid as PBUTs; creatinine as a non-PBUT] as well as the effects of ES on lowering the protein binding ratio. Our organic BEI devices provided a high rate of removal of PC with low protein loss after 4 h of a simulated dialysis process. It also functioned with low complement activation, low contact activation levels, and lower amounts of platelet adsorption, suggesting great suitability for use in developing next-generation bioelectronic medicines for HD.

Keywords: bioelectronic interfaces (BEIs); hemodialysis (HD); multiwalled carbon nanotubes (MWCNTs); poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS); protein-bound uremic toxins (PBUTs).

MeSH terms

  • Adsorption
  • Cresols / blood
  • Cresols / chemistry
  • Electronics / instrumentation
  • Hippurates / blood
  • Hippurates / chemistry
  • Humans
  • Indican / blood
  • Indican / chemistry
  • Nanotubes, Carbon / chemistry*
  • Polymers / chemistry
  • Proteins / chemistry*
  • Renal Dialysis / instrumentation*
  • Toxins, Biological / blood
  • Toxins, Biological / chemistry*
  • Uremia / blood
  • Uremia / therapy*

Substances

  • Cresols
  • Hippurates
  • Nanotubes, Carbon
  • Polymers
  • Proteins
  • Toxins, Biological
  • 4-cresol
  • Indican
  • hippuric acid