High Blood Compatibility Research Articles

Design of a Thiosemicarbazide-Functionalized Calix[4]arene Ligand and Related Transition Metal Complexes: Synthesis, Characterization, and Biological Studies.

In this study, we synthesized a new thiosemicarbazide-functionalized calix[4]arene L and its Co2+, Ni2+, Cu2+, and Zn2+ transition metal complexes. For characterization several techniques were employed: Fourier-transform infrared (FT-IR), 1H nuclear magnetic resonance (NMR), 13C-NMR, 15N-NMR, correlation spectroscopy (COZY), nuclear Overhauser enhancement spectroscopy (NOESY), electrospray ionization (ESI)–mass spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and elemental analysis. To explore the capability of the thiosemicarbazide function hosted on a calix[4]arene scaffold for growth inhibition of bacteria, fungi, and cancerous tumor cells, a series of biological evaluations were performed. For L, the antimicrobial tests revealed a higher antibacterial activity against gram-positive Bacillus subtilis and a lower activity against gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), whereas the gram-positive Staphylococcus aureus shows resistance. All examined metal derivatives show an enhancement of the antibacterial activity against gram-negative E. coli bacteria, with a more significant improvement for the Ni2+ and Zn2+ complexes. MTT assays showed a considerable in vitro anticancer activity of Co2+, Ni2+, and Cu2+ complexes against Saos-2 bone cancer cell lines. The activity is ascribable to the inorganic ions rather than calixarene ligand. Hemolysis assay results demonstrated that all compounds have high blood compatibility.

Fabrication of chitosan/graphene oxide composite aerogel microspheres with high bilirubin removal performance.

Functional chitosan/graphene oxide (CS/GO) composite aerogel microspheres were fabricated via CO2 supercritical drying, which displayed excellent performance for bilirubin removal. The morphology and chemical structure of CS/GO composite aerogel microspheres were characterized, which illustrated a nanoporous structure with a maximum specific surface area of 174.69 m2/g, and a special pore size distribution at 20-40 nm, also a good mechanical property. Importantly, the composite aerogel microspheres (10% GO) revealed a large adsorption capacity (178.25 mg/g) for bilirubin within 2 h. Dynamic adsorption experiment illustrated that the aerogel microspheres adsorbed much more bilirubin with a shorter equilibrium time of about 30 min. Besides, the adsorption mechanism of bilirubin by the CS/GO composite aerogel microspheres was investigated through the relevant model fitting, including adsorption kinetics and adsorption isotherm, which illustrated that the mechanism included both physical and chemical processes, but chemical adsorption was dominated. Adsorption isotherm indicated that bilirubin adsorption by the microspheres was fitted well with Freundlich isotherm, which ascribed to multilayer adsorption. After five adsorption-desorption cycles, the adsorption capacity still maintains large adsorption capacity. In addition, the hemolysis rate and coagulation time tests presented the good blood compatibility for the adsorbents. Therefore, the CS/GO composite aerogel microspheres with rapid, high adsorption capacity and good blood compatibility might be promising for hyperbilirubinemia treatment.

New membranes based on polyethersulfone – SlipSkin™ polymer blends with low fouling and high blood compatibility

Hemodialysis is an important therapy for treating patients with End Stage Renal Disease (ESRD). These patients visit the hospital 3 times a week and each time their blood is cleansed during 4-hour dialysis sessions using a hollow fiber membrane module; also called artificial kidney. This device mainly achieves removal of small water-soluble toxins and a limited number of middle molecules. To improve the clearance of toxins, especially middle molecules and protein bound toxins, longer treatment via nocturnal dialysis and/or the application of portable/wearable artificial kidney is required. Such therapies require application of membranes with very low fouling and very good blood compatibility. Current membranes often contain hydrophilic additives which could elute during sterilization processes and/or during long-term filtration. In this study, we propose a simple method for developing low fouling blood compatible membranes by blending of polyethersulfone (PES), a material already used for fabrication of dialysis membranes, with small amounts of SlipSkin™ (SS), a blood compatible random copolymer of hydrophilic N-vinylpyrrolidone (NVP) and hydrophobic N-butylmethacrylate (BMA). Our results show that membranes with 2 wt% of SS have high fouling resistance to proteins and middle-size molecules and very good blood compatibility, making these membranes promising for application in dialysis therapy.

Rapid synthesis of SiO2 by ultrasonic-assisted Stober method as controlled and pH-sensitive drug delivery

In this paper, the monodisperse silica nanoparticles were prepared by ultrasonic-assisted Stober method, and it explained that the ultrasonic cavitation effect shortened the reaction time from the original hours to f5 min. The effects of ultrasonic time, ultrasonic power, and stirring speed on the morphology, composition, and specific surface area of silica nanoparticles were investigated by field emission electron microscopy (FE-SEM). The results showed that nanoparticles with the best dispersity and the most uniform morphology were obtained under the optimized conditions (ultrasonic time is 5 min, ultrasonic power is 160 W, and the magnetic stirring speed is 999 rpm). The phase composition of SiO2 was characterized by high-resolution transmission electron microscopy (HR-TEM), X-ray diffraction (XRD), nano-size/zeta potential analyzer, and Fourier transform infrared spectroscopy (FT-IR). It showed that all typical peaks of samples are in line with the SiO2 spectrum, the particle size distribution and zeta potential value of the silica is 615 ± 35.6 nm and 59.87 ± 0.91 mv, respectively, which further verified that the spherical silica nanoparticles with good dispersity can be synthesized in a very short time. Hemolysis test showed that nano-SiO2 had high blood compatibility and biocompatibility when its concentration was less than 1 mg/mL. Doxorubicin (DOX·HCl) was regarded as a drug model to investigate the drug loading capacity of synthesized SiO2; the results showed that the drug loading capacity and encapsulation efficiency reached 42.6 ± 1.2 and 85.2 ± 2.5%, respectively. Furthermore, the drug release experiments fitted well with the Higuichi equation with correlation coefficient (R2) of 0.9984, which further confirmed that the SiO2/DOX drug delivery system has the controlled release property, and it also displayed pH-responsive behavior (at 96 h, the cumulative release of SiO2/DOX in PBS solution with pH 7.4, 6.5, and 5.0 was 48.33, 62.31, and 94.86%, respectively). Therefore, this paper provides the possibility for developing more effective, safer, and more targeted controlled drug carriers.

Simultaneous co-substitution of Sr2+/Fe3+ in hydroxyapatite nanoparticles for potential biomedical applications

In human, strontium (Sr) follows the same physiological pathway as calcium and thus could be used for improving the bioactivity and osteoconductivity of hydroxyapatite (HAp) in bone tissues. Similarly, iron (Fe) can potentially play an important role in bone remodeling due to its magnetic properties. Therefore, the current study was aimed to simultaneously co-substitute Sr2+/Fe3+ in HAp nanoparticles for various potential biomedical applications. The Sr2+/Fe3+ co-substituted HAp nanoparticles were systematically synthesized through sonication-assisted aqueous precipitation method. The as-synthesized nanoparticles were evaluated for different physicochemical and biological properties. X-ray diffraction (XRD) patterns of Sr2+/Fe3+ co-substituted HAp nanoparticles confirmed their phase purity and showed hexagonal-like structure. Scanning electron microscope (SEM) micrographs showed an agglomerated rod-like morphology of HAp nanoparticles which contained pores consisted of small spheroids. The nanoparticles displayed magnetization (Ms) reliance on the loading level of mole % (X = Fe3+) and exhibited tunable porosity and microhardness (Hv) upon heat treatment. The nanoparticles showed less than 5% hemolysis demonstrating high blood compatibility with high in vitro bioactivity performance. The multifunctional properties of synthesized nanoparticles make them a potential candidate for various biomedical applications; including bone grafting and guided bone regeneration, targeted drug delivery, magnetic resonance imaging, and hyperthermia based cancer treatment.

Induction Heating Efficiency of Water-Dispersible Mn0.5Fe2.5O4@YVO4:Eu3+ Magnetic-Luminescent Nanocomposites in an Acceptable ac Magnetic Field: Hemocompatibility and Cytotoxicity Studies.

Not many reports are available on magnetic-luminescent nanocomposites for cancer hyperthermia applications. Further, such nanocomposites on Mn2+-doped iron oxide may be available rather rarely. Studies on the induction heating properties within the threshold magnetic field and frequency factors are still rare. In most cases, magnetic nanoparticles are studied for hyperthermia and lanthanide-doped luminescent nanoparticles for certain biomedical applications. Here, we report on water-dispersible superparamagnetic manganese-doped iron oxide (Mn0.5Fe2.5O4) nanoparticles and a polyethylene glycol6000-coated magnetic-luminescent nanocomposite. The nanocomposite is composed of magnetic Mn0.5Fe2.5O4 (average size 10-20 nm) nanoparticles and red-emitting YVO4:Eu3+ (average size 40-50 nm) nanoparticles. These magnetic nanoparticles and nanocomposites are studied for their induction heating abilities at different acceptable Hf values ( H, strength of alternating magnetic field and f, the operating frequency). The operational Hf values lie in the ranges of 2.15 × 106 to 4.58 × 106 kA m-1 s-1 that are well below the threshold limit of 5 × 106 kA m-1 s-1. A specific absorption rate as high as 132 and 63 W/g, respectively, for Mn0.5Fe2.5O4 and Mn0.5Fe2.5O4@YVO4:Eu3+, can be achieved. The rate of heating and the temperature achieved with time can be tuned with concentrations as well as magnetic constituents in the nanocomposites. Hemocompatibility analysis revealed high blood compatibility with <5% hemolysis. The cytotoxicity analysis in the MCF-7 cell line showed that the cell viability is 74-85% for 0.2-0.5 mg of the magnetic-luminescent nanocomposites. Beyond this concentration, the percentage of cell death is very high. The red-emitting magnetic-luminescent nanocomposites will be useful for in vitro optical imaging and tracking of magnetic nanoparticles. The magnetization analysis showed that the samples have high enough saturation magnetization and low residual magnetization, which is quite suitable for clinical applications. The water dispersibility, hemocompatibility, and cytotoxicity assay in conjunction with their efficient induction heating abilities have shown that these magnetic-luminescent nanocomposites will have potential applications in magnetic fluid hyperthermia and optical imaging.

Current Approaches in Improving Hemocompatibility of Polymeric Membranes for Biomedical Application

Suitable membranes for blood‐contacting medical applications need to be resistant in confrontation with blood proteins and cells, while possessing high blood compatibility and permeability at the same time. Herein, an overview of the recent advances and strategies that have been used to enhance the hemocompatibility of polymeric membranes is provided. The review focuses on two modification strategies: (i) physical modifications and (ii) chemical modifications. It also highlights the current progress in the design of hemocompatible‐functionalized membranes for biomedical applications. Subsequently, the commonly applied biocompatibility tests are also discussed and finally the future perspectives of the application of polymeric membranes in the biomedical field are presented. image

Highly efficient adsorbents based on hierarchically macro/mesoporous carbon monoliths with strong hydrophobicity

Hierarchically porous carbon monoliths (HPCMs) with both ordered hexagonal mesoporosity and three-dimensionally connected macroporosity were synthesized via a simple and time-saving hydrothermal process followed by a nanocasting pathway. These monoliths have high macropore volumes and specific surface areas, strong hydrophobicity, low densities and regular shapes. Importantly, these HPCMs showed excellent performance in cleaning/recycling spilled oils or organic solvents with high adsorption capacity, rate, stability, and reusability, and in adsorbing bilirubin with high adsorption capacity, blood compatibility and durability in plasma as well. The adsorption of oil was based on the dispersion interaction between gasoline molecules and the carbon basal planes of HPCMs, while the isotherm of bilirubin adsorption on the optimized HPCMs and the corresponding kinetic data were found better fitted by Langmuir adsorption model and pseudo-second-order kinetic model, respectively.

Abciximab-Krueppel-like factor 4-plasmid-titanium dioxide coated coronary stent for inhibition of neointimal hyperplasia

Purpose: We developed dual system in delivery of gene and drug for coronary stent. For local gene delivery, denatured polymer coating was used. For drug delivery, titanium dioxide (TiO2) thin film which was non-polymer and had a high blood compatibility was used. In this study, we hypothesized whether dual delivery system of gene and drug for coronary stent was useful in preventing in-stent restenosis (ISR). Methods and results: The coating and modification of TiO2 thin film were manipulated by plasma enhanced chemical vapor deposition (PECVD) method. In vitro study, TiO2-Drug (Abciximab) coating stainless steel (SS) plate catch a larger amount of gWIZ-beta gal (beta-gal) plasmid compared with TiO2-only coating SS plate (2.70±0.32 vs. 7.17±0.38 mg/cm2, p<0.05). Also, the binding plasmid (Krueppel-Like Factor 4, KLF4) was effectively transfected into 293 cells after detachment using plasmid elution buffer. The reverse transfection using direct attachment of pig coronary artery smooth muscles showed the X-gal stain positive cells after 5 days. For analysis of in vivo gene delivery, we used animal models of rat abdominal skin and pig coronary artery. At 5 days after implantation of TiO2-Drug-beta-gal plasmid SS plate in rat abdominal skin, the expression of the beta-gal plasmid was observed. At 5 days after implantation of TiO2-Drug-beta-gal plasmid binding coronary stent in balloon-injured porcine coronary artery restenosis model, X-gal stained linear area was observed. To analyze the inhibitory effect of ISR, we used both TiO2-Abciximab-KLF4-plasmid-cobalt chromium (TAK-CC) and TiO2-only coating CC (T-CC) stent. Four weeks after implantation in porcine coronary artery, in histomorphometric analysis, TAK-CC stent group decreased ISR compared with T-CC group (TAK-CC group: 26.38±10.79% vs. T-CC group: 48.59±20.17%, n=6 in each, p<0.05). Also, both TAK-CC and T-CC stent group did not show the fibrin deposition at Castars' stain and accelerated re-endothelialization indicated by detectable anti-CD31 positive stained cells compared with commercial available paclitaxel-eluting stent. Conclusions: Our study implicate that this novel new system could be useful for coronary stent and other biomedical devices through dual delivery of gene and drug.

Experimental and Analytical Performance Evaluation of Short Circular Hydrodynamic Journal Bearings Used in Rotary Blood Pumps

Rotary blood pumps (RBPs) have demonstrated considerable promise while treating heart failure patients, such that they are being placed at an earlier stage of the disease. These devices may therefore be required to operate for prolonged durations which yields the need for RBPs exhibiting high durability, reliability, and blood compatibility. Noncontacting bearings, utilizing magnetic and/or hydrodynamic suspension techniques, appear to provide a suitable solution to these challenges. Hydrodynamic suspension has the advantage that it does not need feedback control systems. Among various hydrodynamic bearing types, the circular journal bearing has the particular benefit of easy manufacturing. This study presents methods to evaluate the performance of short (length to diameter ratio <1) circular hydrodynamic journal bearings (HJBs) for RBPs. Analytical calculations with specific boundary conditions are presented to predict the rotor's eccentricity under equilibrium states and thus the related performance parameters such as load capacity, power loss, and shear rates. These results and boundary conditions were confirmed experimentally in a specially designed test set-up. The bearing performance was found to correlate to analytical solutions using the full Sommerfeld boundary condition instead of the half Sommerfeld condition conventionally used for such applications. Geometrical and operational parameter variations showed that HJB designs with a short Sommerfeld Number SS >0.02 can provide sufficient fluid film thicknesses and low shear rates. The measurements were further used to evaluate the bearings' stability. The estimation of the stability threshold drawn in relation to a modified stability index and the equilibrium eccentricity of the rotor allows the prediction of stability for short circular HJB designs under full Sommerfeld condition.

Blood Compatibility of Iron-Doped Nanosize Hydroxyapatite and Its Drug Release

Nanosize hydroxyapatite (nHAp) doped with varying levels of Fe(3+) (Fe-nHAp of average size 75 nm) was synthesized by hydrothermal and microwave techniques. The samples were characterized for physiochemical properties by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), inductively coupled plasma optical emission spectrometer (ICP-OES), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), mechanical and dielectric properties. The biological properties like hemocompatibility, antibacterial efficacy, in vitro bioactivity and the cell proliferation of the samples were determined. XRD pattern of the samples were of single phase hydroxyapatite. As the content of Fe(3+) increased, the crystallite size as well as crystallinity decreased along with a morphological change from spherulites to rods. The dielectric constants and Vickers hardness were enhanced on Fe(3+) doping. The VSM studies revealed that the saturation magnetization (M(s)) and retentivity (M(r)) were found to increase for Fe-nHAp. nHAp impregnated with an antibiotic as a new system for drug delivery in the treatment of chronic osteomyelitis was also attempted. The in vitro drug release with an antibiotic amoxicillin and anticancer drug 5-fluorouracil showed sustained release for the lowest concentration of Fe(3+), while with an increase in the content; there was a rapid release of the drug. The hemolytic assay of Fe(3+) doped samples revealed high blood compatibility (<5% hemolysis). The antibacterial activities of the antibiotic impregnated materials were tested against a culture of E. coli, S. epidermidis and S. aureus by agar diffusion test. The in vitro bioactivity test using simulated body fluid (SBF) showed better bone bonding ability by the formation of an apatite layer on the doped samples. The growth of the apatite layer on the samples surface has been confirmed by EDS analysis. The proliferative potential of MG63 cells by MTT assay confirmed the noncytotoxicity of the samples.

Adsorption of Doxorubicin on Poly(methyl methacrylate)–Chitosan–Heparin-Coated Activated Carbon Beads

Extracorporeal filter cartridges, filled with an activated carbon bead (ACB) adsorbent, have been used for removal of overdosed cancer drugs from the blood. Coatings on adsorbent matrices, poly(methyl methacrylate) (PMMA)/activated carbon bead and PMMA/chitosan/heparin/ACB composites, were tested to improve their biocompatibility and blood compatibility. PMMA coating on ACBs was accomplished in a straightforward manner using a PMMA solution in ethyl acetate. A one-step hybrid coating of ACBs with PMMA-anticoagulant heparin required the use of acetone and water co-solvents. Multilayer coatings with three components, PMMA, chitosan, and heparin, involved three steps: PMMA was first coated on ACBs; chitosan was then coated on the PMMA-coated surface; and finally, heparin was covalently attached to the chitosan coating. Surface morphologies were studied by scanning electron microscopy. X-ray photoelectron spectroscopy confirmed the -SO(3)(-) group. Adsorption, of a chemotherapy drug (doxorubicin) from both water and phosphate-buffered saline, by the coated ACBs was examined. The adsorption isotherm curves were fitted using the Freundlich model. The current adsorption system might find potential applications in the removal of high-dose regional chemotherapy drugs while maintaining high efficiency, biocompatibility, and blood compatibility.

Preparation and characterization of heparinized multi-walled carbon nanotubes

The characteristics of heparinized multiwalled carbon nanotubes (MWNTs) were investigated in terms of the activated partial thromboplastin time (APTT) to verify the heparin activity, a carbazole assay was done to measure the content of the immobilized heparin, and the octanol–water partition coefficient was assessed to determine the lipophilicity. Two heparin-immobilized MWNTs were prepared to evaluate their differences. The first preparation method involved polymer-coated MWNTs with heparin indirectly center-point-attached. In the second approach, heparin was directly end-point-attached through its reducing end onto acid-treated MWNTs. The blood compatibility of MWNTs to which heparin was end-point-attached through its reducing end was greatly enhanced compared to that of the MWNTs onto which heparin was center-point-attached. The APTT and carbazole assay results demonstrated that heparinized MWNTs prepared through end-point attachment result in prolonged plasma-based anticoagulant activity. The blood compatibility of MWNTs heparinized by end-point attachment was not decreased up to the fourth pasteurization. Heparinized MWNTs were also studied using octanol–water partition, which should be useful for exploring heparinized MWNTs as drug carriers including delivery systems. The results of octanol/water partition on the design of heparinized MWNTs prepared by end-point attachment with a specific binding can facilitate the design of drug delivery carriers with high blood compatibility.

Blood compatibility of photografted hydrogel coatings

In this work, we have evaluated the haemocompatibility of different surface modifications, intended for biomaterials and bioanalytical applications. Polystyrene slides were coated with thin hydrogel films by self-initiated photografting and photopolymerization (SIPGP) of four different monomers. The hydrogel surface modifications were thoroughly characterized and tested for their protein resistance and ability to resist platelet adhesion and activation of the coagulation system. There was very little protein adsorption from human plasma on the hydrogels prepared from poly(ethylene glycol) methacrylate and 2-hydroxyethyl methacrylate. Platelet adhesion tests performed under both static and flow conditions showed that these coatings also demonstrated very high resistance towards platelet adhesion. A small amount of platelets were found to adhere to hydrogels formed from ethylene glycol methyl ether methacrylate and 2-carboxyethyl methacrylate. The polystyrene substrates themselves facilitated large amounts of platelet adhesion under both static and flow conditions. Utilizing a novel setup for imaging of coagulation, it was confirmed that none of the hydrogel surfaces activated the coagulation system to any great extent. We suggest that this simple fabrication method can be used to produce hydrogel coatings with unusually high blood compatibility, suitable for demanding biomaterials applications.

Preparation of a dual-drug-eluting stent by grafting of ALA with abciximab on a bare metal stent

The preparation of a dual-drug-eluting stent was investigated by grafting α-lipoic acid (ALA) with abciximab on a bare metal stent coated with a polymer layer by plasma polymerization of 1,2-diaminocyclohexane (DACH). The plasma polymerization was carried out at 100 W for 5 min and then at 60 W for 15 min. ALA and abciximab were grafted to the polymer layer after activating in 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide methiodide. The amounts of grafted and released ALA and abciximab were affected by the grafting pattern. When the grafting reaction proceeded in a mixed solution of ALA and abciximab, the amount of grafted ALA was much larger than that of grafted abciximab, and the amount of not only abciximab, but also ALA, released was small. When the grafting reaction was started with the abciximab solution, and the ALA solution was added after a time interval, the amount of grafted abciximab increased and the released amount also increased not only for abciximab, but also for ALA. The released amount of abciximab increases with time while the released amount of ALA decreases with time. Approximately 150 μg of abciximab and 114 μg of ALA were grafted to a stent surface with a smooth and uniform surface morphology, and grafted with 10-min time interval: they were released continuously for 3 weeks in the in vitrodrug-release test. The drug-eluting stent showed high blood compatibility in the in vitroplatelet adhesion test.

Heparin-conjugated polyethylenimine for gene delivery

A major problem when using cationic polymers for gene delivery is that transfection is strongly inhibited by the presence of serum. This shortcoming limits the application of cationic polymers for systematic gene delivery in vivo. Due to the shielding effect of heparin, heparin conjugation to cationic polymers may improve the in vivo gene transfection efficiency. In this study, the transfection efficiency of heparin-conjugated polyethylenimine (HCPEI) with a low molecular weight of 1800 Da was compared to the transfection efficiencies of polyethylenimine with a low molecular weight of 1800 Da (PEI1800), polyethylenimine with a high molecular weight of 25,000 Da (PEI25k), and Lipofectamine ®. The size of the HCPEI/plasmid DNA (pDNA) complex is approximately 250 nm. HCPEI has a proton-buffering effect and HCPEI/pDNA has higher blood compatibility and a lower cytotoxicity than PEI25k/pDNA and Lipofectamine/pDNA. For in vitro transfection of rabbit smooth muscle cells in serum-free medium, the transfection efficiency of HCPEI/pDNA was not significantly different from those of PEI25k/pDNA and Lipofectamine/pDNA. Importantly, in serum-containing medium, the transfection efficiency of HCPEI/pDNA was significantly higher than those of PEI25k/pDNA and Lipofectamine/pDNA. For vascular endothelial growth factor (VEGF) gene transfection to mouse ischemic limbs, HCPEI/pDNA exhibited significantly higher VEGF expression and more extensive neovascularization than PEI/pDNA and Lipofectamine/pDNA. Taken together, heparin conjugation to PEI improves the in vivo gene transfection efficiency of PEI.

Coating of Ti-6Al-4V alloy substrates with TiN/Ti multi-layered films by magnetron sputtering

Coating of Ti-6Al-4V alloy substrates with TiN/Ti multi-layered films by magnetron sputtering in Ar gas atmosphere was examined, aiming at the application of the alloy to artificial heart valves, in order to improve not only the adhesion between the deposited film and the alloy but also the surface smoothness of titanium nitride coatings and thereby to improve the blood compatibility as well as the biocompatibility of the alloy coated with the titanium nitride film. The effects of the thickness of the TiN (titanium nitride) layer on the surface morphology of the film were investigated, in order to develop TiN coatings with higher blood compatibility. The multi-layered films were deposited by sputtering in sequence pure titanium and titanium nitride targets. The thickness of titanium nitride layer was varied from 300 nm to 800 nm, while that of pure titanium was constantly 200 nm. Under visual observation, the obtained multi-layered films looked yellow gold and appeared to be uniform and adhesive, while TiN monolithic films deposited directly onto the alloy substrate under the same sputtering conditions peeled off partly. Therefore it was found that the multi-layered thin films were more adhesive to the alloy than the monolithic films. According to AFM (Atomic Force Microscope) images for both of the films, the surface morphology of each TiN layer observed under the scope of nanometer-scaled area was rough with pits and bumps, while that under the scope of micrometer-scaled area was smooth without such pits and bumps. Furthermore based on the AFM, the surface roughness measured under the area of nanometer scale was found to increase with the increase of the thickness of the TiN layer in the multi-layered film, although that measured under the area of micrometer scale was assumed to be independent of the thickness of the TiN layer.

Thermal property and processability of elastomeric polymer alloy composed of segmented polyurethane and phospholipid polymer.

To develop a thermoplastic elastomer with high blood compatibility, a 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer was blended with the segmented polyurethane (SPU) for preparing the polymer alloy. A tensile strength measurement was carried out to evaluate its mechanical strength. The mechanical strength of the SPU/MPC polymer alloy is the same as that of the original SPU and sufficient for use in medical applications. The thermal properties of the polymer alloy were evaluated by differential scanning calorimetry (DSC). The DSC curves indicated that the MPC polymer blended into the SPU did not affect the hard segment domain of the SPU. The SPU/MPC polymer alloy can be processed by heat treatment at 150 degrees C. Even after heat treatment, the SPU/MPC polymer alloy showed good mechanical properties, and MPC units were observed on the surface. Protein adsorption from human plasma was observed to evaluate the blood compatibility of the polymer alloy. The SPU/MPC polymer alloy suppressed protein adsorption on the surface before and after the heat treatment. Based on these results, it is concluded that the SPU/MPC polymer alloy has an excellent potential for application in various medical devices.

Polymers in nephrology. Characteristics and needs.

Polymers employed as biomaterials in nephrology serve for different applications: they form membranes for dialysis and plasmapheresis, are used as materials for dialyser housings and as a potting mass for capillary membranes, they make up tubing-systems for extracorporeal circuits and - in the form of beads - act as parts of adsorber columns for hemoperfusion or immunoadsorption. However, generally speaking, many polymers have not yet been designed for their final application. To date, many polymers are still taken from the chemist's shelf according to their alleged performance properties or to their sterilisability. When used in medical application, polymers must show a high purity. Uncontrolled leaching of oligomers from the polymer backbone or of additives from or during the manufacturing process must be avoided. Blood and other body fluids are extremely effective in extracting any loosely bound polymers. During long-term application, e.g. in patients suffering from chronic diseases, these effects may lead to an accumulation of these compounds in circulating blood, tissue, or joints. Consequently, polymers should show an excellent biostability and not degrade during their ageing process. The amount of extractable material should be kept low in order to avoid inflammatory reactions. Polymers must have high blood compatibility in terms of minimized cell- and complement activation. Polymers for medical application should at best be able to stand high temperatures in order to survive steam sterilisation. If this is impossible, their release kinetics for residual quantities of sterilizing agents should be fast. Finally, protein adsorption should appear under controlled conditions, otherwise a reduced performance through protein adsorption will take place. Further, the uncontrolled activation of biochemical cascades, such as the coagulation, complement or contact phase cascade, following blood/material contact must be minimized. A final aspect has been recently made responsible for adverse patients reactions, the interaction between polymers and medicinal drugs. This drug/material interaction must be low, at best zero, apart form those situations, where a controlled drug-release is wanted. The chemical variety of polymers for medical application is large. However, all typical requirements cannot be met by one single polymer. Compromises have to be found between properties and application. Polymer selection for application in nephrology has always to be made under the premise of final application.

フレゼニウスポリスルホン透析膜について

Fresenius Polysulfone® has been designed for blood purification only. This membrane has been clinically used since the early 1980's. Especially high flux dialyzers using Fresenius Polysulfone® have high blood compatibility and very good removal of larger molecular weight substances.Fresenius Medical Care started to develop hollow fiber dialyzers using polyamide, however changed the material to polysulfone in 1979. In the early 1980's, the Hemofilter F60 was put on the market.Clinical studies of Fresenius Polysulfone® dialyzers were presented at the High Permeable Membrane Symposium in Bad Homburg in May, 1984. The quality of this superior membrane is highly evaluated and has become the “golden standard” in hemodialysis today.