Experimental evaluation and theoretical modeling of oxygen transfer rate for the newly developed hollow fiber bioreactor with three compartments.

Bioartificial liver support provides a bridge to transplantation which is at present the only proven specific treatment for acute liver failure. In this paper, a novel multi-coaxial hollow fiber bioreactor so-called "Fibre-in-Fibre FIF Bioartificial liver device" with three compartments is experimentally and mathematically studied. The mathematical model in this paper is an extension of Krogh cylinder model for hollow fibre devices by including one more zone for oxygen transfer, i.e. oxygenation compartment. Three simultaneous linear differential equations were derived for pressure in plasma and cell compartments and flow rate in cell compartment. To validate the model, Oxygen Transfer Rate and hydrostatic pressure experimental measurements for different flow rates, 17-400 ml/min, and different number of hollow fibres pairs are used. Several important parameters of the Michaelis-Menten was investigated, namely, constant Vmax (the maximum oxygen consumption per unit volume of the cell mass), the oxygen partial pressure, the flow rate of the perfusate at device inlet. The results showed that the oxygenation compartment should easily secure Oxygen to the cells in compartment B.

The effect of betacyclodextrin and hydroxypropyl betacyclodextrin incorporation into plasticized poly(vinyl chloride) on its compatibility with human U937 cells.

Di (2-ethyl hexyl) phthalate (DEHP) is one of the main plasticizers used in poly(vinyl chloride) (PVC) medical devices and is currently the only one listed for use in the European Pharmacopoeia Monograph. It leaches out of PVC when the material is in contact with lipophilic media, for example, blood and certain nutritional feeds. Consequently, concerns have been expressed since in certain animal species, DEHP has been shown to exhibit both carcinogenic and reproductive toxic effects. Incorporation of beta cyclodextrin (BCD) and hydroxypropyl betacyclodectrin (HPBCD) into plasticized materials has been reported to decrease the leaching of DEHP. We have investigated whether this results in improved in vitro biocompatibility by measuring the responses of U937 cells to plasticized PVC in the presence and absence of added BCD or HPBCD. Growth and viability of the U937 cells, as well as tumor necrosis factor-α (TNF-α) production in contact with these materials revealed no significant difference between unmodified plasticized PVC materials and those containing BCD or HPBCD. Lipopolysaccharide (LPS) was used to elicit TNF-α production, and the response of cells to LPS in the presence of the PVC materials was evaluated. When PVC was modified by addition of HPBCD there was a significant reduction in the TNF-α production in response to LPS. Modification of plasticized PVC biomaterials by adding cyclodextrins did not significantly improve their biocompatibility. However, the HPBCD modified plasticized PVC materials caused a reduction in the production in TNF-α induced by LPS which may have implications for the inflammatory potential of these biomaterials.

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.