Activation-dependent adsorption of cytokines and toxins related to liver failure to carbon beads.

In the course of severe pathological conditions, such as acute liver failure and sepsis, toxic metabolites and mediators of inflammation are released into the patient's circulation. One option for the supportive treatment of these conditions is plasmapheresis, in which plasma, after being separated from the cellular components of the blood, is cleansed by adsorption of harmful molecules on polymers or activated carbon. In this work, the adsorption characteristics of activated carbon beads with levels of activation ranging from 0 to 86% were assessed for both hydrophobic compounds accumulating in liver failure (bilirubin, cholic acid, phenol and tryptophan) and cytokines (tumor necrosis factor α and interleukin-6). Progressive activation resulted in significant gradual reduction of both bulk density and mean particle size, in an increase in the specific surface area, and to changes in pore size distribution with progressive broadening of micropores. These structural changes went hand in hand with enhanced adsorption of small adsorbates, such as IL-6 and cholic acid and, to a lesser extent, also of large molecules, such as TNF-α.

The in vitro adsorption of cytokines by polymer-pyrolysed carbon.

This study investigated a range of phenol-formaldehyde-aniline-based pyrolysed carbon matrices and their component materials, for their ability to adsorb a range of inflammatory cytokines crucial to the progression of sepsis. The efficiency of adsorption of the target molecules from human plasma was assessed and compared to that of Adsorba 300C, a commercially available cellulose-coated activated charcoal. Results indicate that a number of the primary carbon/resin materials demonstrate efficient adsorption of the cytokines studied here (TNF, IL-6 and IL-8), comparable to other adsorbents under clinical investigation. Our findings also illustrate that these adsorbent capabilities are retained when the primary particles are combined to form a pyrolysed carbon matrix. This capability will enable the engineering of the carbon matrix porosity allowing a blend of carbonised particle combinations to be tailored for maximum adsorption of inflammatory cytokines. The present findings support further investigation of this carbon material as a combined carbon-based filtration/adsorbent device for direct blood purification.

Assessing the in vitro biocompatibility of a novel carbon device for the treatment of sepsis.

The aim of the present study was to conduct a preliminary investigation into the blood biocompatibility of a novel, uncoated carbon for use in a filtration/adsorption device for the treatment of sepsis. Carbon well prototypes were manufactured from phenol-formaldehyde-aniline-based pyrolysed carbons using monolithic polymer technology. Inflammatory blood cell and plasma protein mediation of the inflammatory response were evaluated using the novel carbon prototypes and compared with dialyser membrane and tissue culture plate controls. Assays determining monocyte and granulocyte adhesion, platelet adhesion and activation, granulocyte activation and complement activation were performed. Preliminary findings suggest an adsorptive but passivating carbon surface. Moderate levels of monocyte and granulocytes adhesion were seen in conjunction with adsorption of plasma proteins to the carbon surface. Activation of granulocyte and adherent platelets was not detected and the complement cascade was not activated by the carbons, indicating a surface compatible with blood contact. The results support the further development of the proposed carbon-based device for the treatment of sepsis.