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 freeenergy 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.

Aptasensors Based on Graphene Field-Effect Transistors for Arsenite Detection

“…The CHARMM36 force field was used, including the particle-mesh Edwald electrostatics, the temperature was rescaled from 0 to 300 K, a pressure of 101.3 kPA was maintained by the Langevin thermostat and a Langevin piston barostat, and a 1 fs time step was used. With all the charges, LJ parameters were assigned in accordance with the CGenFF parameterization and were implemented according to all the required parameters, as discussed in the previously published research . The adaptive biasing force method, using the Colvar module, was applied for the calculation of free energy estimation and potential of mean force calculations, as published previously.…”

“…With all the charges, LJ parameters were assigned in accordance with the CGenFF parameterization and were implemented according to all the required parameters, as discussed in the previously published research. 43 The adaptive biasing force method, using the Colvar module, 44 was applied for the calculation of free energy estimation and potential of mean force calculations, as published previously. Statistical calculations and image rendering over the trajectories were done using VMD.…”

Bilirubin Removal by Polymeric Adsorbents for Hyperbilirubinemia Therapy

“…In addition to carbon nanotubes, graphene, as a new carbonaceous material, also has extensive adsorption capacity for various toxins. Tyagi et al developed cellulose acetate (CA) functionalized graphene oxide (GO) beads for direct hemoperfusion, [73] aiming at the treatment of kidney dysfunction, which adsorb creatinine, uric acid and even bilirubin. Regretfully, these cellulosebased studies did not study the interaction between adsorbents and proteins, such as protein adsorption, complement activation and contact activation.…”

Synthesis of an IRMOF-1@SiO2 Core–Shell and Amino-Functionalization with APTES for the Adsorption of Urea and Creatinine Using a Fixed-Bed Column Study

“…3,4 Hemodialysis is beneficial to people with decreased renal function to prevent the accumulation of waste products in their bodies and to remove uremic toxicity. 5 However, some small uremic toxins such as urea (UR) and creatinine (CR) cannot be entirely removed by hemodialysis (the elimination rate of UR and CR from the body was approximately 75% and 66%, respectively) 6 which causes numerous uremic syndromes. Executing dialysis requires a huge amount of pure water (150−300 L).…”

“…Chronic kidney disease is a lifestyle-dependent illness and is recently increasing due to dietary preferences for oily and junk foods in some cultures and sedentary lifestyles. , This could lead to significant health issues and conceivably cause extreme mortality rates. Malfunctions of the kidney may progress, and chronic renal failure might appear in individuals. , Hemodialysis is beneficial to people with decreased renal function to prevent the accumulation of waste products in their bodies and to remove uremic toxicity . However, some small uremic toxins such as urea (UR) and creatinine (CR) cannot be entirely removed by hemodialysis (the elimination rate of UR and CR from the body was approximately 75% and 66%, respectively) which causes numerous uremic syndromes.…”