Towards a novel carbon device for the treatment of sepsis

Sepsis is a systemic inflammatory response to infection in which the balance of pro- andanti-inflammatory mediators, which normally isolate and eliminate infection, is disrupted[1]. Gram negative sepsis is initiated by bacterial endotoxin release which activatesmacrophages and circulating monocytes to release TNF and IL-1β followed by IL-6 andother inflammatory cytokines [2]. As the disease progresses, an unregulatedinflammatory response results in, tissue injury, haematological dysfunction and organdysfunction. Severe sepsis, involving organ hypoperfusion may be further complicatedby hypotension that is unresponsive to adequate fluid replacement, resulting in septicshock and finally death [3].Despite improvements in anti-microbial and supportive therapies, sepsis remains asignificant cause of morbidity and mortality in ICUs worldwide [4]. The complexity ofprocesses mediating the progression of sepsis suggests that an extracorporeal devicecombining blood filtration with adsorption of a wide range of toxins, and inflammatorymediators offers the most comprehensive treatment strategy. However, no such deviceexists at present. A novel, uncoated, polymer pyrolysed synthetic carbon device isproposed which combines the superior adsorption properties of uncoated activatedcarbons with the capacity to manipulate porous structure for controlled adsorption oftarget plasma proteins and polypeptides [5]. Preliminary haemocompatibility andadsorptive capacity was assessed using a carbon matrix prototype

Mathematical model of oxygen transfer rate in the fibre-in-fibre bioartificial liver (fif- bal)

This article discusses the mathematical model of oxygen transfer rate in the fibre-in-fibre bioartificial liver (fif- bal

Bioartificial liver : review of science requirements and technology

Social development in health services is concerned as a global issue. More than nine million people die due to internal organ failure and one percent of this number is due to liver disease. In 1990, more than 27,000 deaths in the USA were caused by liver failure. From the numerous reviews on liver failure and associated support therapies, there is increasing interest in this field throughout the world. Although Liver Transplantation (LT) has become standard procedure for hepatic failure patients, a number of issues still need to be addressed which make LT a very challenging field. One alternative way for liver failure therapy is a bioartificial liver (BAL) (hepatocytes cells device). The optimal BAL should be able to supply the required oxygen and sufficient nutrients. This paper focuses on how sustainable developments in science and technology were used for illness fighting. Current developments in hybrid artificial liver systems and their design parameters were used in this paper as examples. In addition, our new theory of Fibre-in-Fibre BAL device is also reviewed as an alternative to provide the support of daily and social life of human beings

Oxygen transfer in a convection-enhanced hollow fiber bioartificial liver

A mathematical model was developed to predict oxygen transport in a hollow fiber bioartificial liver device. The model parameters were taken from the HepatAssist 2000 device, a plasma perfused hollow fiber cartridge with primary hepatocytes seeded in the extracapillary space. Cellular oxygen uptake was based on Michaelis-Menten kinetics. Oxygen transport due to the convective flow of plasma into the extracapillary space was considered. The effect of modulating several important parameters was investigated, namely, the Michaelis-Menten constant Vm (the maximum oxygen consumption per unit volume of the cell mass), the oxygen partial pressure, the flow rate of the plasma at device inlet, and the permeability of the cell mass contained in the extracapillary space. A computer implementation of the model was used to assess whether a given number of cells could be maintained within such a device. The results suggest that a substantial proportion of the hepatocytes are exposed to hypoxic conditions under which metabolism may be impaired

Evaluation of toxicity of modified PVC materials using a human monocyte cell line

Paper detailing an evaluation of toxicity of modified PVC materials using a human monocyte cell line

The interaction of plasticised PVC materials with u937 human monocyte cell line and human platelets

Paper focusing on the interaction of plasticised PVC materials with u937 human monocyte cell line and human platelets

Characterization of the distribution of matter in hybird liver support devices where cells are cultured in a 3-D membrane network or on flat substrata

Bioreactors for liver assist tested on small animal models are generally scaled-up to treat humans by increasing their size to host a given liver cell mass. In this process, liver cell function in different culture devices is often established based on the metabolite concentration difference between the bioreactor inlet and outlet irrespective of how matter distributes in the bioreactor. In this paper, we report our investigation aimed at establishing whether bioreactor design and operating conditions influence the distribution of matter in two bioreactors proposed for liver assist. We investigated a clinical-scale bioreactor where liver cells are cultured around a three-dimensional network of hollow fiber membranes and a laboratory-scale bioreactor with cells adherent on collagen-coated flat substrata. The distribution of matter was characterized under different operating modes and conditions in terms of the bioreactor residence time distribution evaluated by means of tracer experiments and modeled as a cascade of N stirred tanks with the same volume. Under conditions recommended by the manufacturers, matter distributed uniformly in the clinical-scale bioreactor as a result of the intense backmixing (N=1) whereas axial mixing was negligible in the laboratory-scale bioreactor (N=8). Switching from recycle to single-pass operation definitely reduced axial mixing in the clinical-scale bioreactor (N=2). Increasing feed flow rate significantly enhanced axial mixing in the laboratory-scale bioreactor (N=4). The effects of design, operating mode and conditions on matter distribution in bioreactors for liver cell culture suggest that characterization of the distribution of matter is a necessary step in the scale-up of bioreactors for liver assist and when function of liver cells cultured in different bioreactors is evaluated and compared

In vitro investigation of the blood response to medical grade PVC and the effect of heparin on the blood response

This paper reports the results of an investigation into the blood response of polymers in vitro, using non-anticoagulated and heparinised blood and plasma. The materials studied were regenerated cellulose, (Cuprophan), an acrylonitrile-allyl sulphonate copolymer (AN69S), and medical grade polyvinyl chloride plasticised with di-2-ethyl-hexyl-phthalate (PVC/DEHP). Blood-material or plasma-material contact was achieved using a parallel plate flow cell, and C3a generation and FXII-like activity measured. The results of the study with non-anticoagulated human blood show that PVC/DEHP is a high complement activator. C3a concentration in the blood was higher after contact with PVC/DEHP than after contact with regenerated cellulose. The introduction of heparin in the blood induced complex alterations in the blood response. C3a generation could be elevated, decreased, or remain the same, depending on the material. The FXII-like activity on the surface of the PVC/DEHP after contact with plasma was also higher than the other two polymers. The introduction of heparin could increase or decrease FXII-like activity, depending on material. The patterns of response obtained with non-anticoagulated blood in vitro for AN69S and Cuprophan bore a strong resemblance with patterns of response obtained in the clinic, whereas those obtained with heparinised blood in vitro did not