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Biomedical subjects

Y Missirlis

Publications and source records attributed to Y Missirlis.

13 recordsLinked to original sources
PubMed2005

Development of polymer membranes with improved haemocompatibility for biohybrid organ technology.

Biomedical technology has opened up possibilities of treating the failure of internal organs like kidney and liver by artificial organ therapy. Most of these techniques are based on polymer membranes, which allow the removal of excess of water, salts and toxins from the circulation. However, haemodialysis for the replacement of kidney function results in an increased morbidity and mortality of patients after long-term application. Conventional therapy, such as haemofiltration for the treatment of acute liver failure does not improve significantly the survival rate of patients. Biohybrid organ support as a combination of the artificial organ therapy with the functional activity of immobilised cells seems to be a solution of the problem. Membranes applied in these devices have to face both tissue cells and blood. Organ cells in biohybrid organs have to make intimate contact with the surface of membrane but must also develop close cell-cell-connections as a prerequisite for their survival and high functional activity. Blood to be detoxified will contact the other side of membrane and may not become activated by the synthetic material. New polymer membranes based on acrylonitrile were developed to address these requirements by tailoring the composition of copolymers and to be applied in a specific hollow fibre bioreactor with an outer fibre for blood contact, and an inner fibre for tissue contact or vice versa.

Animals↗
PubMed2002

Polyetherimide: a new membrane-forming polymer for biomedical applications.

Membranes for biohybrid organs such as the biohybrid liver support system have to face 2 different environments, namely blood and tissue cells. Accordingly, the respective membrane surfaces must have optimal properties in terms of biocompatibility for blood or tissue. Flat membranes prepared by a phase inversion process from polyetherimide were modified by binding of tris-(hydroxymethyl)-aminomethane to obtain a surface with hydroxyl groups by binding of polyethylene imine to attach a hydrophilic macromolecule with amine groups useful as a spacer for later bonding of further ligands and by attachment of heparin. The binding of the different ligands was successful as monitored by different physicochemical methods. The blood response of plain polyetherimide was comparable to that of polyacrylonitrile, and it could be further improved by the binding of heparin. The tissue compatibility of polyetherimide and its different modifications was compared with commercial cell culture substrate membranes (Millicell) and found to be comparable for polyetherimide and even better after the modification with tris-(hydroxymethyl)-aminomethane. In conclusion, polyetherimide seems to be an interesting material for the production of membranes for application in biohybrid organ systems.

Complement Activation↗
PubMed2001

Impairment of erythrocyte viscoelasticity is correlated with levels of glycosylated haemoglobin in diabetic patients.

Erythrocytes from diabetic patients exhibit impaired viscoelastic properties when estimated by various methods. We determined erythrocyte filterability through 5-microm pores, in 51 patients with non-insulin-dependent diabetes mellitus, 18 healthy controls, 15 patients with homozygous beta-thalassemia and 15 with beta-thalassemia traits. The filtration measurements were made with a Hemorheometer, which uses the "initial flow rate" principle. To determine the Index of Rigidity (IR) of the red blood cells, we measured the passage time of white blood cell-free erythrocyte suspensions, 8% per volume, through the filter. Diabetic patients had significantly increased IR in comparison to healthy controls and to patients with beta-thalassemia trait, but not at the level found in patients with homozygous beta-thalassemia. In diabetic patients, a strong correlation between IR and the percentage of glycosylated haemoglobin was found (r=0.737, P < 0.0001), and a weaker one with serum unconjugated bilirubin (r=0.363, P=0.0097) and serum total lipids (r=0.321, P=0.0286). Patients with severe retinopathy also had significantly increased IR, in comparison to those with or without mild retinopathy. Anaemic diabetic patients, especially those with the anaemia of chronic disease, also had significantly increased IR in comparison to non-anaemic diabetics. No correlation between IR, MCV, MCH, MCHC, RDW, RBC morphology, serum LDH or the presence of erythrocyte inclusions after incubation with nitrous sodium solution was found. Our findings suggest that glycosylation of skeletal proteins probably contributes significantly to the increased membrane rigidity of diabetic erythrocytes.

Diabetes Mellitus, Type 2↗
PubMed2000

Deformability and filterability of white blood cell subpopulations. Evaluation of these parameters in the cell line HL-60 and in type II diabetes mellitus.

The rheological properties of human leukocytes (WBCs) have been studied using the micropipette aspiration and the filtration technique. Partial micropipette (i.d. 2.8-4.5 microm) aspiration of individual leukocytes under constant aspiration pressure of 8 mm H20 and measurement of the aspirated length as a function of time (creep experiments) according to the Evans model have been carried out and the apparent viscosity mu(app) was estimated. In the filtration experiments, using the Hemorheometer, the Index Rigidity of Leukocytes, ILR, was also estimated. The apparent viscosity mu(app) of normal PMN and MNC was significantly different p < 0.05), while the LYM and PMN had no statistical difference (p < 0.5). The leukocytes of the cell line HL-60 were more rigid than the normal PMN (p < 0.01), while the PMN from patients with type II diabetes mellitus were more rigid than the normal PMN (p < 0.005). The results of IRL showed similar differences among all of the leukocyte subpopulations. Comparison of these findings suggests a possible relationship between ILR and mu(app) which in this case is: ILR = 598 + 0.54 mu(app) (r = 0.986, p-value 0.0003).

Adult↗
PubMed1998

Resorbable continuous-fibre reinforced polymers for osteosynthesis.

Four institutes from three countries in the European Union have collaborated under the BRITE-EURAM framework programme for the development of processing technologies for resorbable osteosynthesis devices. The devices should be continuous-fibre reinforced, and the technology should offer the possibility of orienting the fibres in the main trajectories. Poly-L-lactide and poly-L-DL-lactides have been synthesized for reinforcement fibres and matrix material, respectively. Melt-spun P-L-LA fibres of a strength of 800 MPa have been embedded in an amorphous P-L-DL-LA 70 : 30 matrix by compression moulding. Ethyleneoxide sterilized samples have been tested in vitro and in vivo. A satisfying bending modulus has been reached (6 GPa). Yet with 50% strength retention after ten weeks, fast degradation occurred that could be related to residual monomers. By this fast degradation 70% resorption after one year could be observed in the non-functional animal studies in rabbits. There was only a mild inflammatory reaction, which confirmed the good biocompatibility of the materials even during the resorption period. Further effort has to concentrate on the reduction of initial monomer content. The great advantage of the processing method to orient fibres in the device will be utilized in prototype samples, e.g. an osteosynthesis plate with fixation holes.

Journal Article↗
PubMed1998

Augmentation of anterior transvertebral screws using threaded teflon anchoring.

This is a biomechanical study to investigate the effect of augmentation of single anterior transvertebral screws. Two subsequent experiments (pullout and caudal loading) were performed in 78 porcine vertebral bodies of equal bone mineral density using 6.5-mm transvertebral screws augmented or not with specially designed Teflon anchoring. Three different types of 35- and 45-mm unaugmented screws (Kaneda, TSRH, and Zielke) were inserted at 90 degrees laterally in the vertebral body and were tested for pullout force. The pullout load to loosen the three different unaugmented screws did not significantly differ. The pullout force to loosen the 35- and 45-mm Zielke screws was 507 +/- 22 and 860 +/- 50 N, respectively. The corresponding pullout load to loosen the construct Zielke screw-Teflon anchoring was 1,005 +/- 148 N and 1,306 +/- 135 N for the 35- and 45-mm screws, respectively. When comparing the pullout force needed for unaugmented versus the augmented Zielke screw of the same length, there was a statistically significant (p < 0.0001) difference. During the caudal loading test, the unaugmented 45-mm Zielke screw showed that a uniform slope up to the yield point occurred at 0.35 +/- 0.12 mm of displacement, with an average tilting force for the tested screw of 1,362 +/- 151 N, when the screw became loose. The caudal loading test for the augmented Zielke screw was interrupted at 2,000 N because the load applied exceeded the load capacity of the testing machine, and thus no loosening occurred. The findings of this in vitro study showed that the Teflon anchoring provides superior anchorage and stability of single transvertebral Zielke screws. However, further biomechanical and clinical studies are required before using this device or its modification.

Animals↗
PubMed1997

Model experimental system for investigation of heart valve calcification in vitro.

A model system was developed for the in vitro quantitative investigation of the calcification process occurring in heart valves. The process of heart valve calcification consists of the formation of calcium phosphates at the heart valve-biological fluid interface. Calcium phosphate deposits may consist of more than one calcium phosphate mineral phase, differing with respect to their physical and chemical properties. The kinetics of the formation of hydroxyapatite, the model inorganic compound for the calcified deposits, was precisely monitored in a reactor containing supersaturated calcium phosphate solutions in which the heart valves were immersed after being treated with glutaraldehyde and mounted on special racks. The precipitation process, accompanied with proton release in the solution, was monitored by a pair of glass-saturated calomel electrodes. Upon initiation of the formation of calcium phosphate deposits, the supersaturation in the working solution was reestablished through the addition of titrant solutions made with the appropriate concentration to compensate for the ions precipitated. With this methodology, not only the rates were measured very precisely but also the nucleation capability of the various substrates could be evaluated. Moreover, it was possible to identify the formation of intermediate calcium phosphate phases formed during the calcification process. Valves previously treated with glutaraldehyde were shown to nucleate octacalcium phosphate, which at lower supersaturations converted to the thermodynamically more stable hydroxyapatite. The rates measured were found to depend on the solution supersaturation, while the apparent order of the precipitation process was found to be 1.

Animals↗
PubMed1997

Soft tissue and cancellous bone reaction to the implantation of novel biodegradable pins and plates in rabbits.

Biodegradable implants for osteosynthesis have had insufficient strength and a fast degradation rate. We produced a polymer based lactide to increase the molecular weight and strength of the implant and delay the degradation rate. This novel fiber-reinforced material in the form of plates and pins was tested in vitro for mechanical performance and in vivo in a neutral mechanical environment to assess biocompatibility. 21 rabbits with implants in the tibia and femoral condyles were killed at 1, 6, 12 months after implantation. Only a mild foreign-body reaction was observed and the implant was encapsulated by a thin 0.8-1.6 mm layer of connective tissue. Only a few lymphocytes and giant cells were detected in the early stages, dense fibroblasts in the middle stage, and giant cells clearing material particles in the late stage. In conclusion, the novel fiber-reinforced polymer based on polylactides was found mechanically superior to former degradable implants and biocompatible, showing no late inflammatory tissue response.

Biodegradation, Environmental↗
PubMed1994

The effect of shear rate on the adhesion/activation of human platelets in flow through a closed-loop polymeric tubular system.

Three polymers, produced as reference materials of a European Communities program, namely PE, PP, and PVC, in tubular form, were comparatively evaluated for their hemocompatibility. In particular, the following parameters: platelet retention index, beta-thromboglobulin (beta-TG) release from activated platelets, and expression of the platelet protein GMP 140 (PADGEM) were measured as a function of time for whole anticoagulated human blood flowing in a closed-loop system under two different shear rates of 2000 and 500 s-1. Data up to 20 min (afterwards there was hemolysis) showed a fluctuating platelet retention index as time increased for PE and PVC and an increasing value for PP. Platelet aggregation and dislodgment from the surface could not be differentiated. Activation of platelets as expressed with beta-TG release were higher for both PE and PP in both shear rates in comparison to PVC which elicited a higher response at the high shear rate. Finally, PADGEM estimations seem to indicate a more stable platelet retention layer for PP than PE or PVC.

Humans↗
PubMed1994

The viscosity of red blood cell membranes in patients with beta-thalassaemia.

The purpose of this work was to study the viscoelastic behaviour of the red blood cell membrane (RBCM) in cells from patients with beta-thalassaemia and to investigate whether the precipitated haemoglobin, which is one of the main features of thalassaemic syndromes, influences the membrane viscosity. RBCM viscosities were determined using the micropipet aspiration method. A negative pressure of about 50 Pa was applied in steps at the membrane surface so as to cause partial aspiration of the cell and the entry process was analyzed automatically by a TV-line analyzer. This analysis enabled estimation of the characteristic times (tau 1, tau 2) and corresponding values of the viscosity (eta 1, eta 2). Results were as follows: eta 1 = (1.87 +/- 0.55) microNs/m and eta 2 = (51.42 +/- 20) microNs/m for erythrocytes from normal donors; eta 1 = (3.97 +/- 0.98) microNs/m and eta 2 = (110.40 +/- 35) microNs/m for erythrocytes from patients. Inclusions (Heinz Bodies) were produced artificially in normal cells and the characteristic times (tau 1, tau 2) and corresponding viscosities (eta 1, eta 2) derived in the same manner. For three types of RBC containing increasing numbers of inclusions, the values were: eta 1 = (3.26 +/- 1.70) microNs/m and eta 2 = (77.33 +/- 46.96) microNs/m; eta 1 = (4.21 +/- 1.49) microNs/m and eta 2 = (129.60 +/- 47.90) microNs/m; eta 1 = (7.93 +/- 2.62) microNs/m and eta 2 = (206.60 +/- 93.19) microNs/m. It is concluded that the association of inclusion bodies with the membrane, either in disease or through artificial production, increases the membrane viscosity.

Adult↗
PubMed1991

An approach to the optimization of preparation of bioprosthetic heart valves.

The stress and strain states of the valve leaflets during fixation with glutaraldehyde affect their final mechanical parameters. Comparative studies of the stress-strain relationships of aortic valve leaflet strips from fresh, statically and dynamically fixed porcine and human valves were made. Static pressures of 5 mmHg, 16 mmHg, and 95 mmHg result in stress-strain relationships which are in a region between that of fresh porcine and fresh human leaflet strips in the circumferential direction, while they are far from that of fresh porcine tissue (larger strains) in the radial direction. Leaflet strips, fixed under dynamic loading between zero and a predefined maximum load, set at an early post-transition state, give parameters not significantly different from those of human valves.

Adolescent↗
PubMed1991

Erythrocyte membrane deformability in patients with thalassemia syndromes.

The purpose of this study was to measure the erythrocyte membrane's elasticity in patients with thalassemia syndromes. These syndromes have been well investigated regarding the problems associated with the hemoglobin solution. A few studies dealing with the whole cells' flexibility have also been published. However, there are extremely few studies regarding the elastic behaviour of the membrane of these cells which plays a significant role in the viability of these erythrocytes especially when they transverse the small capillaries of the spleen. The micropipette aspiration method was used for this purpose. Cells from patients with thalassemia syndromes were aspirated into micropipettes of internal diameter of 1.2-1.6 microns. The slope of the curve relating the length of the aspirated tongue to the negative pressure was measured to give the elastic shear modulus. This modulus was compared with the one of the normal cells. Inclusions (Heinz bodies) were produced artificially in normal cells and their elastic shear modulus was also measured. The results show that the elastic shear modulus measured in homozygous beta-thalassemia was 33% higher than the normal one. The elastic shear modulus in cells with artificial Heinz bodies was also higher than the normal one and its value increased with the number of the inclusion Heinz bodies. The elastic shear modulus in heterozygous beta-thalassemia was slightly higher than the normal one. The apparent stiffening of the membrane of the homozygous cells might be partially due to the "constraining effect" of the inclusions to the membrane's ability to deform freely.

Elasticity↗