Biocompatibility: the need for a systems approach.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D Falkenhagen.
Explore the source record for details and available documents.
Seven different types of dialysers were investigated in five dialysis centres in four countries with respect to behaviour of white blood cells and the complement system. The results of this controlled crossover study demonstrated significant differences in the dialysers. Those containing cuprammonium cellulose (G10-3N and G120 M) showed the greatest changes in white blood cell count, including monocytes and neutrophils, as well as the greatest complement activation. With regard to lymphocytes the subpopulation of low-mobility cells, which were predominantly the B-cells, showed the greatest mobility with dialysers containing cuprammonium cellulose. The PAN copolymer- and PMMA-containing dialysers Filtral and T 150 clearly caused the least changes in white blood cells and complement factors. Dialysers containing cellulose acetate and polysulphone membranes (Duo-Flux Artificial Kidney, CD 4000, and F 60) produced only a moderate decrease of WBC, monocyte, neutrophil, and lymphocyte counts, and this result corresponded to a relatively small change in complement factors.
The biocompatibility and solute permeability characteristics of a high-permeability modified cellulose membrane (Hemophan-HP) (He-HP) were compared with those of two synthetic membranes (poly(ethylene-co-vinyl alcohol) (EVAL) and poly(acrylonitrile-co-sodium methallyl sulphonate) (AN69)) and Cuprophan in a multicentre, four-way cross-over clinical trial. Cuprophan membranes caused significant complement activation, leukopenia, and granulocyte elastase release. He-HP membranes demonstrated a lesser effect, which was similar to that observed for the EVAL membrane, although less than that seen with the AN69 membrane. A similar order for the four membranes was seen for their effect on platelets. Cuprophan membranes provided superior small-molecule removal to the other three membranes. In contrast, Cuprophan was essentially impermeable to beta 2-microglobulin, whereas He-HP, EVAL, and AN69 allowed the removal of 60-90 mg of beta 2-microglobulin per treatment. However, a decrease in the plasma concentration of beta 2-microglobulin was observed only with the AN69 membrane, most probably as a result of the ability of that membrane to adsorb proteins. Our results demonstrate that high-permeability membranes of comparable biocompatibility to some synthetic membranes can be fabricated from cellulose derivatives.
The neutralization of bacterial endotoxins (ET) is still an unsolved problem in therapeutic medicine. The efficacy of anti-endotoxin antibodies or receptor antagonists and other substances interfering with the endotoxin-induced pathomechanisms is dependent on an intact cellular degradation system of the host. However, the phagocytosis function of that system seems to be impaired regularly in patients with intense or long-lasting endotoxemia or septic shock and in patients undergoing hemodialysis. Extracorporeal adsorption of ET might well be an effective support in the anti-ET therapy by lowering the amount of circulating ET and thus relieving the defense system of the body. In this work a new ET-adsorbent based on macroporous cellulosic beads with immobilized polyethylenimine (PEI) was tested for its ET-removal capacity in vitro. A test solution with 100 ng/ml ET from Escherichia coli 055:B5 was recirculated in a system containing the adsorbent beads. Polymyxin B immobilized to the same carrier was used for comparison. PEI as well as polymyxin B showed complete removal of ET from plasma and water as was measured by the Limulus Amebocyte Lysate (LAL) test (Chromogenix). The biocompatibility of the PEI absorber was superior to that of polymyxin B. The results indicate that the PEI absorber is of high efficacy and possibly of interest for the treatment of endotoxemia.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
As the quality of water in dialysis fluid varies considerably, and, in view of the fact that endotoxin or active derivates can cause acute and chronic side effects in patients under hemodialysis treatment, the dialysis fluid must be sterile and endotoxin-free. The predialyzer fluid in 20 hemodialysis patients was investigated. The bacterial loading was between 5/ml and 12,000/ml, the endotoxin concentration was high and extremely variable. Therefore we introduced the ultrafiltration of the dialysis fluid by a polyamide hollow fiber membrane before entering the dialyzer. All samples were free of bacteria, and the concentration of endotoxin was lower than the detectable limit. With this procedure we can obtain sterile dialysis fluid, which is endotoxin free. Our preliminary results showed that Interleukin-1 in the patients was significantly (p less than 0.005) lower under ultrafiltration of the dialysis fluid than without ultrafiltration.
Methods for the detection of positive or negative charges on the surface of biomaterials/membranes and inside a membrane are important for the characterisation of such materials. We tested different dyes and optimized staining procedures. Under standardized conditions negatively charged membranes were stained with cationic triarylmethane compounds such as crystal violet and positively charged membranes with the anionic anthraquinone dye anthralan blue B. There was no staining of uncharged cellulose membranes. The applicability of these methods was demonstrated on membranes coated to varying degrees with charged compounds such as heparin, these changes in charge being detectible quantitatively by photometry. The distribution of charges inside a membrane was detected by optical sectioning across the stained (FITC labelled poly-L-lysine) membrane using confocal laser scanning microscopy (LSM). LSM offers a completely new application possibility in biomaterial and biocompatibility research.
Leukocyte (PMN) functional capacity has been investigated through evaluation of phagocytosis of opsonised yeast cells in a radiometric test system. The PMN of dialysis patients (DP) had a slightly lower ability to ingest opsonised yeast cells in comparison with normal persons (NP), suggesting that an intrinsic cellular defect may exist. Under the influence of six membranes (cellulose acetate, regenerated cellulose, modified cellulose, cuprophane, polysulphone, and polymethylmethacrylate) the phagocytosis index decreased significantly between 10 and 17% in NP and between 13 and 23% in DP. There is a clear correlation with the membrane surface area. These results are not explained by the number of dead leukocytes (4-6.5% in DP and also in NP independently of membrane contact). The direct membrane effect could be responsible for the diminished phagocytic activity of leukocytes in NP and DP. Aqueous extracts of membranes alone resulted in no change of the phagocytic ability of PMN. Extracellular or 'uraemic factors' were excluded by the test procedure. The killing rate of yeast cells by PMN in NP and DP was not influenced in any of the membranes tested.
Endotoxins are not only important for inducing pyrogenic reactions during haemodialysis but also for the stimulation of different blood cells. This is followed by the release of interleukin-1 and other powerful biological active substances, resulting in a broad spectrum of biological activities. Permeation of LPS (endotoxins) through dialysis and haemofiltration membranes is of great importance. Using a quantitative turbidimetric method based on the LAL (limulus amoebocyte lysate) test LPS concentrations were measured in a closed in vitro system for 11 different dialysers and haemofilters. To assess the passage of endotoxin through the membrane, permeation was measured from the dialysate to the blood side as well as from the blood compartment to the dialysate side.
Explore the source record for details and available documents.
Blood compatibility is determined by interactions at the blood-material interface that depend on the material surface chemical structure. Through selective modifications of the chemically reactive hydroxyl groups of cellulose, the aim was to improve the biocompatibility of cellulose membranes. The number of potentially reactive hydroxyl groups on the cellulose membrane surface were reduced through isocyanate cross-links or through the introduction of hydrophilic, hydrophobic, or ionic functionalities by graft copolymerization. To assess blood compatibility, levels of C3a desArg were determined in plasma after membrane contact. Using the electrophoretic mobility test, the release of cytokines were measured after in-vitro incubation of mononuclear cells with membranes. Adsorption of 131J-human fibrinogen was additionally investigated. With respect to the biocompatibility parameters selected, the modified cellulose membranes show improved in-vitro blood compatibility in comparison to unmodified cellulose membranes.
Considering the plasma colloid osmotic pressure (COP) as a possible parameter for the monitoring of dialysis treatment compatibility, a characteristic time course was found. The COP and the total protein concentration very often do not increase significantly during the first treatment hour in spite of ultrafiltration. An increase in the plasma sodium concentration, which was higher than expected, was found to be the reason for a plasma dilution effect. This can be explained by a transcapillary sodium transfer coefficient which is not infinitely high as assumed in single-pool sodium modelling. From a 2-pool model considering the plasma volume as a separate pool and including capillary filtration time courses for plasma sodium, total protein concentration and COP could be calculated, which was very similar to the measured curves.
Explore the source record for details and available documents.
Due to their partial permeability and their good mechanical properties, the symplex capsules are technically suited for an application in extracorporal detoxification. By this newly developed procedure the activity of encapsulated enzymes is considerably increased; thus, application for extracorporal detoxification seems to be advisable.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Rat liver microsomes were microencapsulated in a pure aqueous medium by means of a new technique. The wall of the microcapsules consists of a semipermeable simplex membrane which is stabilized mainly by electrostatic interactions between a polymeric polyanion (sodium cellulose sulphate) and a polymeric polycation (polydimethyldiallylammonium chloride). The metabolic as well as the mechanic parameters of the microcapsules could be markedly improved by separating the metabolic (liver microsomes) from the membrane component (sodium cellulose sulphate) in such a way that two distinct compartments are formed during the preparation of the microcapsules.