TY - JOUR

T1 - Soluble and immobilized graphene oxide activates complement system differently dependent on surface oxidation state

AU - Wibroe, Peter Popp

AU - Petersen, Søren Vermehren

AU - Bovet, Nicolas Emile

AU - Laursen, Bo Wegge

AU - Moghimi, Seyed Moien

N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.

PY - 2016

Y1 - 2016

N2 - Graphene oxide (GO) is believed to become applicable in biomedical products and medicine, thereby necessitating appropriate safety evaluation dependent on their applications and the route of administration. We have examined the effect of GO form (in solution versus immobilized) and oxidation state on two related elements of innate immunity: the complement system and interleukin-6 (IL-6) release in human blood. In solution, there was a decrease in GO-mediated complement activation with decreasing surface oxygen content (and altered oxygen functionality), whereas with immobilized GO complement response were reversed and increased with decreasing oxygen content. GO solutions, at concentrations below complement activating threshold, did not induce IL-6 release from human blood leukocytes, and further dampened lipopolysaccharide-induced IL-6 release in the whole blood. The latter effect became more profound with GO's having higher oxygen content. This protective role of GO solutions, however, disappeared at higher concentrations above complement-activating threshold. We discuss these results in relation to GO surface structure and properties, and implications for local administration and development of GO-based implantable devices.

AB - Graphene oxide (GO) is believed to become applicable in biomedical products and medicine, thereby necessitating appropriate safety evaluation dependent on their applications and the route of administration. We have examined the effect of GO form (in solution versus immobilized) and oxidation state on two related elements of innate immunity: the complement system and interleukin-6 (IL-6) release in human blood. In solution, there was a decrease in GO-mediated complement activation with decreasing surface oxygen content (and altered oxygen functionality), whereas with immobilized GO complement response were reversed and increased with decreasing oxygen content. GO solutions, at concentrations below complement activating threshold, did not induce IL-6 release from human blood leukocytes, and further dampened lipopolysaccharide-induced IL-6 release in the whole blood. The latter effect became more profound with GO's having higher oxygen content. This protective role of GO solutions, however, disappeared at higher concentrations above complement-activating threshold. We discuss these results in relation to GO surface structure and properties, and implications for local administration and development of GO-based implantable devices.

U2 - 10.1016/j.biomaterials.2015.11.028

DO - 10.1016/j.biomaterials.2015.11.028

M3 - Journal article

C2 - 26646624

VL - 78

SP - 20

EP - 26

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -