Rapid Adsorption of Proinflammatory Cytokines by Graphene Nanoplatelets and Their Composites for Extracorporeal Detoxification

Yishan Zheng,Ganesh Ingavle,Yury Gogotsi,Tochukwu Ozulumba,Nicholas Pescatore,Boris Dyatkin,Susan Sandeman,Sergey Mikhalovsky,Vadym Mochalin

doi:10.1155/2018/6274072

Abstract

Sepsis is a complex clinical syndrome that features excessive release of cytokines and other inflammatory mediators that could lead to organ dysfunction. Despite different treatment and management options, sepsis associated high morbidity and mortality rates remain. This has prompted intensive research into alternative therapeutic approaches such as targeted removal of sepsis related molecules using extracorporeal hemoperfusion. In this study, we explore the use of graphene nanoplatelets (GNP) as low-cost alternative hemosorbents for rapid removal of a broad spectrum of proinflammatory cytokine markers. Firstly, the physical characteristics, cytotoxicity, and cytokine marker adsorption profile of GNP were assessed. The results not only confirmed the surface characteristics of GNP and their ability to rapidly remove cytokine markers, but also indicated a low cytotoxicity towards the hepatic cell line HepG2. GNP were then incorporated into a freestanding flexible GNP-poly(tetrafluoroethylene) film with preserved surface characteristics and cytokine adsorption profile for potential use in hemoperfusion applications.

Highlights

Sepsis is a life-threatening condition caused by the body’s disregulated host response to infection
We explore the use of noncytotoxic graphene nanoplatelets for rapid removal of a broad spectrum of proinflammatory cytokines identified as instigators of sepsis progression and the preparation of a freestanding flexible GNP-poly(tetrafluoroethylene) film (Figures 1(b) and 1(c)) with preserved surface (Figure 1(d)) and cytokine adsorption characteristics for practical use in hemoperfusion applications (Figure 1(e))
Smaller agglomerates of GNP and single nanoplatelets were observed under transmission electron microscopy (TEM) (Figure 2(c)), revealing their multilayer-stacked graphene structure

Summary

Introduction

Sepsis is a life-threatening condition caused by the body’s disregulated host response to infection. Sepsis is the primary cause of death for children and infants [2, 3], and the number of incidences was estimated at over 19 million cases worldwide annually [4]. Sepsis conditions progress as a function of the cytokine cascade, an exaggerated immune response to the incident infection [5]. The exact mechanism of sepsis remains poorly understood, it is believed that high concentrations of proinflammatory cytokines, such as IL-6, IL-8, and TNF-α contribute to the progression of sepsis in patients [6, 7]. Endotoxins have been identified as key substances in sepsis progression, and polymyxin Bimmobilized columns have been designed for the removal of endotoxins through direct hemoperfusion [9].

Methods

Results

Conclusion