Elimination of Uremic Toxins by Functionalized Graphene-Based Composite Beads for Direct Hemoperfusion.

Abstract

Conventional absorbents for hemoperfusions suffer from low efficiency and slow absorption with numerous side effects. In this research, we developed cellulose acetate (CA) functionalized graphene oxide (GO) beads (∼1.5-2 mm) that can be used for direct hemoperfusion, aiming at the treatment of kidney dysfunction. The CA-functionalized GO bead facilitates adsorption of toxins with high biocompatibility and high-efficiency of hemoperfusion while maintaining high retention for red blood cell, white blood cells, and platelets. Our in vitro results show that the toxin concentration for creatinine reduced from 0.21 to 0.12 μM (p < 0.005), uric acid from 0.31 to 0.15 mM (p < 0.005), and bilirubin from 0.36 to 0.09 mM (p < 0.005), restoring to normal levels within 2 h. Our in vivo study on rats (Sprague-Dawley, n = 30) showed that the concentration for creatinine reduced from 83.23 to 54.87 μmol L-1 (p < 0.0001) and uric acid from 93.4 to 54.14 μmol L-1 (p < 0.0001), restoring to normal levels within 30 min. Results from molecular dynamics (MD) simulations using free-energy calculations reveal that the presence of CA on GO increases the surface area for adsorption and enhances penetration of toxins in the binding cavities because of the increased electrostatic and van der Waals force (vdW) interactions. These results provide critical insight to fabricate graphene-based beads for hemoperfusion and to have the potential for the treatment of blood-related disease.