Blood Compatibility Properties Research Articles

Bilayered vascular grafts based on silk proteins

A major block in the development of small diameter vascular grafts is achieving suitable blood vessel regeneration while minimizing the risk of thrombosis, intimal hyperplasia, suture retention, and mechanical failure. Silk-based tubular vessels for tissue engineering have been prepared by molding, dipping, electrospinning, or gel spinning, however, further studies are needed to improve the mechanical and blood compatibility properties. In the present study a bilayered vascular graft based on silk fibroin (SF) was developed. The graft was composed of an inner silk fiber-reinforced SF tube containing heparin and a highly porous SF external layer. Compared with previously fabricated SF tubes the fiber-reinforcement provided a comparable or higher mechanical strength, burst pressure, and suture retention strength, as well as mechanical compliance, to saphenous veins for vascular grafts. Heparin release was sustained for at least 1month, affording blood compatibility to the grafts. The outer layer of the grafts prepared through lyophilization had a highly porous structure in which the macropore walls were composed of nanofibers similar to extracellular matrix, which offered an excellent environment for cell growth. In vitro studies showed good cytocompatibility and hemocompatibility.

Development of novel membranes for blood purification therapies based on copolymers of N-vinylpyrrolidone and n-butylmethacrylate.

Developments in membrane based blood purification therapies often come with longer treatment times and therefore longer blood-material contact, which requires long-term membrane biocompatibility. In this study, we develop for the first time membranes for blood purification using the material SlipSkin™, which is a copolymer, made from N-vinylpyrrolidone (NVP) and butylmethacrylate (BMA). Specific attention is focused on understanding the mechanism of pore formation and the tailoring of the membrane mechanical and transport properties to obtain the optimal membrane for blood purification therapies. Polymer composition, solvent type and solvent evaporation time influence membrane morphology and membranes with sieving properties of cascade filters in plasma fractionation applications are developed. The new membranes have very good blood compatibility properties; in fact compared to benchmark flat membranes currently used in the clinic, they have lower platelet adhesion while all other properties (contact activation, thrombogenicity, leukocyte adhesion, hemolysis and complement activation) are also very good and comparable to the benchmarks.

Designing polyethylene glycol (PEG) – plasticized membranes of poly(vinyl alcohol-g-methyl methacrylate) and investigation of water sorption and blood compatibility behaviors

Polyethylene glycol (PEG)-based semi-IPNs have been widely used as hydrogel matrices in tissue engineering applications because of their inherent hydrophilicity and biocompatibility. Today, synthetic scaffolds are being widely used in tissue engineering and allied applications because they offer the ability to precisely control the mechanical properties, morphology, and blood compatibility of the materials. In this regard, an attempt has been made to develop scaffolds membranes by judiciously combining PEG, polyvinyl alcohol, and polymethyl methacrylate. The so prepared hydrogel membranes were undertaken for structural, morphological, and thermal characterization using FTIR, scanning electron microscope (SEM), and DSC techniques, respectively. The hydrogel films were investigated for water sorption capacity under various experimental conditions such as changing chemical composition of the membrane, different pH, and temperature of the swelling media and varying simulated biological fluids. The hydrogel membranes were also studied for their catholicity and in vitro blood compatibility property by following several tests such as blood clot formation, percent haemolysis, and protein adsorption.

Silicon nitride films for the protective functional coating: Blood compatibility and biomechanical property study

Behaviors of silicon nitride films and their relation to blood compatibility and biomechanical have been interesting subjects to researchers. A systematic blood compatibility and biomechanical property investigation on the deposition of silicon-nitride films under varying N2 and CF4 flows was carried out by direct current unbalanced magnetron sputtering techniques. Significant role of surface property, chemical bonding state of silicon nitride film and blood compatibility, mechanical properties for the films were observed. The chemical bonding configurations, surface topography, contact angle and mechanical properties were characterized by means of X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and nano-indentation technique and CSEM pin-on-disk tribometer. Blood compatibility of the films was evaluated by platelet adhesion investigation. The results of the platelet adhesion tests shown that the effect of fluorine and nitrogen-doped revealed an intimate relationship between the ratio of polar component and dispersion component of the surface energy and its hemocompatibility. Si–N–O coating can be a great candidate for developing antithrombogenic surfaces in blood contacting materials. The chemical bonding state made an adjustment in microstructured surfaces, once in the totally wettable configuration, may improve the initial contact between platelet and biomedical materials, due to the appropriate ratio of dispersion component and polar component. To resist wear, biomedical components require coatings that are tough and hard, have low friction, and are bio-inert. The study suggests that by Si–N coating the metal surfaces could be a choice to prolong the life of the sliding pair Co–Cr–Mo alloy/UHMWPE implants.

Superparamagnetic Nanocomposites of Poly(vinyl alcohol‐graft‐acrylonitrile) as Carrier for Magnetically Assisted Release of Ciprofloxacin

AbstractIn the present study also a superparamagnetic nanocomposite of Poly (vinyl‐ alcohol‐g‐acrylonitrile) has been designed by homogeneous impregnation of iron oxide nanoparticles into the graft polymer matrix. The so prepared nanocomposite was characterized by FT‐IR, TEM and XRD techniques and studied for water sorption behavior and magnetization properties. The superparamagnetic nanocomposite was loaded with an antibiotic drug, ciprofloxacin (CFx), and its release behavior was investigated under varying experimental conditions such as chemical composition of the matrix, pH of the release media, applied magnetic field and percent loading of the drug. The drug transport mechanism was also analyzed using Ficks power law. The drug loaded magnetic nanocomposite was also studied for antibacterial and in‐vitro blood compatible properties.

Modification of poly(ether urethane) with fluorinated phosphorylcholine polyurethane for improvement of the blood compatibility

In order to improve the blood compatibility, poly(ether urethane) (PEU) and fluorinated phosphorylcholine polyurethane (P-HFPC) were used to prepare PU/P-HFPC blends by solution mixing. The hemocompatibility in vitro was evaluated with protein adsorption and platelet-rich plasma (PRP) contact tests. It was found that the amount of adsorbed protein on surface was decreased by 87%, and almost no platelet adhesion and activation was observed on the surface of blends when P-HFPC content was above 5 wt %. After adding P-HFPC, the blends basically kept favorable mechanical properties of PEU though the content of P-HFPC rises to 20 wt %. To better understand the relationship between structure and properties, the phase structure and surface property of the blend films were further investigated via differential scanning calorimetry, dynamic mechanical analysis, atomic force microscopy, X-ray photoelectron spectroscopy, and contact angle measurements. The results indicated that the fluorinated phosphorylcholine units could be easily enriched on the surface of blend films due to the phase separation between the PEU and P-HFPC. Therefore, ordinary poly(ether urethane)s can obtain both satisfactory blood compatibility and good mechanical properties just by blending with small amount of P-HFPC.

Chemically induced graft copolymerization of 2-hydroxyethyl methacrylate onto polyurethane surface for improving blood compatibility

To improve hydrophilicity and blood compatibility properties of polyurethane (PU) film, we chemically induced graft copolymerization of 2-hydroxyethyl methacrylate (HEMA) onto the surface of polyurethane film using benzoyl peroxide as an initiator. The effects of grafting temperature, grafting time, monomer and initiator concentrations on the grafting yields were studied. The maximum grafting yield value was obtained 0.0275g/cm2 for HEMA. Characterization of the films was carried out by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), water contact angle measurements. ATR-FTIR data showed that HEMA was successfully grafted onto the PU films surface. Water contact angle measurement demonstrated the grafted films possessed a relatively hydrophilic surface. The blood compatibility of the grafted films was preliminarily evaluated by a platelet-rich plasma adhesion test and hemolysis test. The results of platelet adhesion experiment showed that polyurethane grafted polymerization with monomer of 2-hydroxyethyl methacrylate had good blood compatibility featured by the low platelet adhesion. Hemolysis rate of the PU-g-PHEMA films was dramatically decreased than the ungrafted PU films. This kind of new biomaterials grafted with HEMA monomers might have a potential usage for biomedical applications.

Platelet Adhesion on Silicon Modified Carbon Nanotubes Films

Owing to its high mechanical strength, chemical inertness, low frictional coefficient, high wear and corrosion resistance properties and so on, carbon nanotubes (CNTs) films have emerged as a potential material for biomedical applications. In order to investigate the blood compatibility properties of CNTs films synthesized on the silicon (Si) substrate using thermal chemical vapor deposition, the blood compatibility was evaluated in vitro by the platelet adhesion and the activated partial thromboplastin time (APTT). The experimental results demonstrated that the Si-CNTs films reduced thrombus formation by minimizing the platelet adhesion, activation , aggregation and had a tendency to retard the intrinsic coagulation activities of blood due to a higher APTT compared to Si, lower temperature isotropic pyrolytic carbon (LTIC) and Polydimethylsiloxane (PDMS) materials. Further, we found that hydrophobic surfaces are more prone to direct cellular motility in comparison with hydrophilic surfaces. It is concluded that CNTs films on the Si substrate were effective for improvement of blood compatibility.

Bioactive Supramolecular Hydrogel with Controlled Dual Drug Release Characteristics

Heparin, a powerful anticoagulant used for the prophylaxis of both surgical and medical thrombosis, was covalently incorporated into a supramolecular hydrogel network. For this attempt, heparin was first conjugated with amino-terminated poly(ethylene glycol) methyl ether by carbodiimide chemistry and then used to interact with α-cyclodextrin in aqueous solution. The rheological measurements and X-ray diffraction analyses were used to characterize the hydrogel formation. It was found that the gelation kinetics and hydrogel properties could be modulated by changing the amount of conjugated heparin or α-cyclodextrin. By circular dichroism analyses and in vitro release experiments, resultant hydrogel material was found to have a great potential as an injectable matrix for the encapsulation and sustained release of model protein drug (bovine serum albumin). By in vitro release, blood clotting, and hemolysis experiments, such a supramolecular hydrogel was also confirmed to have a controlled release profile for conjugated heparin and shows good anticoagulant and blood-compatible properties.

Improvement of the Hemocompatibility of PET Surfaces Using Different Sulphated Polysaccharides as Coating Materials

In this study, sulphated polysaccharides were investigated in respect to their blood compatibility properties (hemocompatibility). Pure chitosan was treated with sulphating agents such as SO(3)/pyridine complex and chlorosulfonic acid (HClSO(3)) to obtain 3,6-O-sulfochitosan with low and high concentration of sulfur. These synthetically derived materials and the commercially available sulphated polysaccharides heparin and dextran sulfate, both with high concentrations of sulfur, were coated onto PET foils to act as surfaces with strong antithrombotic activity. This treatment should lead to better blood compatibility properties of PET materials for medical applications. To examine this, the optimized free hemoglobin method was applied to determine the antithrombotic activity of these surfaces. Glass as the standard thrombotic surface and a heparin-coated PET surface as a surface well-known for its strong antithrombotic activity were used as internal references. The experiments showed that dextran sulfate and sulphated chitosan with high concentrations of sulfur demonstrated the same antithrombotic activity as heparin over the whole period of measurement time. In addition, a relationship between the sulfur concentration in these sulphated polysaccharides and their blood compatibility properties can be demonstrated in this article.

Blood compatibility and mechanical properties of oxidized‐chitosan films

AbstractBy dipping chitosan films into saturated NO2–glacial acetic acid solution, the hydromethyl groups on the film surface could be oxidized to carboxyl groups and the blood compatibility of the films improved. Fourier transform infrared (FTIR) spectra indicated the presence of many COOH and COO− groups on the modified membrane surface. Scanning electron microscopy (SEM) showed that the surface of the modified membrane was rough, as compared with the chitosan film, which possessed a smooth surface. In the oxidation process, with increased dipping time of the films in saturated NO2–glacial acetic acid solution, the tensile strength of the films decreased slowly initially, and rapidly 10 h later. The swelling ratio of the modified chitosan film increased obvious noticeably as the degree of oxidation of the film increased. All antithrombosis and hemolysis tests and blood cell morphology observation with SEM revealed that the blood compatibility of modified chitosan membranes is superior to that of chitosan films. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007

Biomedical response of tantalum oxide films deposited by DC reactive unbalanced magnetron sputtering

Tantalum oxide (Ta–O) films have been widely used as dielectric, optoelectronics and high temperature resistance materials. But the biological response of the Ta–O films is rarely studied. In this paper, the biomedical properties of Ta–O films were studied. Tantalum oxide films were deposited on Si(100) and glass substrate at different oxygen-to-argon ratios by DC reactive unbalanced magnetron sputtering. The structure, blood compatibility, surface energy and semiconductor properties were studied. The results showed that the Ta–O films were amorphous and its optical band-gap increased from 3.65 eV to 3.95 eV with increasing oxygen pressure. The surface energy of Ta–O films were about 40–46 mJ/m 2. The low surface energy, and low dispersive energy were the reasons of their better blood compatibility. There were less platelet adhered and aggregated at the Ta–O film which deposited at O 2/Ar ratio 0.4, and it had better antithrombotic properties.

Tissue Compatibility of Interfacial Polyelectrolyte Complexation Fibrous Scaffold: Evaluation of Blood Compatibility and Biocompatibility

Interfacial polyelectrolyte complexation (PEC) fiber has been proposed as a biostructural unit and biological construct for tissue engineering applications, with its ability to incorporate proteins, drug molecules, DNA nanoparticles, and cells. In this study, we evaluated the biocompatibility and blood compatibility of PEC fiber in order to assess its potential for in vivo applications in tissue engineering. Although chitosan-alginate PEC fibrous scaffold was found to be thrombogenic, the blood compatibility of the scaffold could be significantly improved by incorporating a small amount of heparin in the polyelectrolyte solution during fiber formation. The platelet microparticle production and platelet adhesion on the chitosan-alginate-heparin fibrous scaffold were comparable to those on the resting control. In vitro cytotoxicity test showed that the scaffold was not toxic to human mesenchymal stem cells (hMSCs). In the in vivo biocompatibility test in rats, no acute inflammation was observed in the subcutaneously or intramuscularly implanted specimens. Good cell infiltration and vascularization were observed after 2 months of implantations. Enhanced extracellular matrix (ECM) deposition was observed when hMSCs were cultured in the transforming growth factor-beta3 (TGF-beta3)-encapsulated PEC fibrous scaffold in vitro, or when the TGF-beta3-encapsulated PEC was implanted intramuscularly in vivo. The results showed that this versatile PEC fibrous scaffold could be used in various tissue engineering applications for its good biocompatible and blood compatible properties.

In vitro Biological Performances of Phosphorylcholine‐Grafted ePTFE Prostheses through RFGD Plasma Techniques

Arterial prostheses made of microporous Teflon (ePTFE) are currently used in vascular surgery as bypasses for small and medium vessels. However, several clinical complications, such as thrombosis, frequently occur in these prostheses when implanted in humans. In this work, an original strategy was developed to improve the hemocompatibility of ePTFE prostheses, based on glow-discharge surface modification followed by chemical grafting of phosphorylcholine, known for its hemocompatible properties. This procedure leads to a covalent attachment of the molecules, therefore preventing their removal by shear stress induced by blood flow at the implant wall. The improvement of the blood compatibility properties of the modified ePTFE arterial prostheses have been investigated by in vitro tests such as thromboelastography, neutrophil adsorption, platelet aggregation, and cell cultures. These in vitro tests put in evidence that thrombogenicity index, platelet aggregation, and neutrophil adhesion were decreased by the molecule grafted on the prostheses. Moreover, the cell growth on the surface of the PRC-grafted prostheses was greatly enhanced in comparison to the virgin prosthesis. Based on these results, it could be concluded that PRC grafting on ePTFE prostheses permit to improve in vitro hemocompatibility and biocompatibility in comparison with their virgin counterpart.

Clotting times and tensile properties of insoluble silk fibroin films containing heparin

AbstractAlthough many novel approaches for producing small‐caliber arterial grafts have been developed, problems with mechanical properties and blood compatibility have up to now prevented clinical implementation. Blending anticoagulant agents with natural biomaterials having excellent cell attachment and growth properties, and making the release time of anticoagulant agents exceed the time required by endothelial tissue regeneration, might be a novel method to prepare appropriate biomaterials used in small‐diameter arterial grafts. In this article, an insoluble fibroin film, having excellent blood compatibility and mechanical properties, was obtained by blending with heparin. The structural properties of the films were examined through Fourier‐transform infrared attenuated total reflectance (FTIR‐ATR) and X‐ray diffraction (XRD). The results indicated that plentiful β‐sheet crystals existed in fibroin films containing heparin. The tensile strength and elongation at break of film containing heparin were, respectively, 10.3 MPa and 54 % in the wet state, which can satisfy the mechanical requirements of blood‐contacting materials such as small‐diameter tubing. The clot times [activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT)] all exceeded the measurement limit of the clot detection instrument. Even the APTT and TT of film immersed in water for 28 days exceeded the measurement limit of the clot detection instrument. The in vitro culture of endothelial cells on the film was also investigated, and the result indicated that cells can grow to cover all of the available surface area of the film within 8 days. Fibroin films containing heparin could retain blood compatibility for 28 days, which means that this is a promising material for small‐diameter artery applications. Copyright © 2005 Society of Chemical Industry

Correlation between blood compatibility and physical surface properties of titanium-based coatings

Layers of Ti nitride, Ti oxynitrides TiNxOy and Ti oxide were produced by means of metal plasma immersion ion implantation and deposition (MePIIID) from a plasma produced by cathodic arc evaporation of Ti under addition of nitrogen and/or oxygen to the ambient near the substrate. The phase composition and structure of the layers are strongly dependent on the relation of the gases partial pressure. To study the correlation between blood compatibility and physical properties of the coating the thrombocyte adhesion and fibrinogen adsorption on the surface as well as wettability and surface energy were investigated. Thrombocyte adhesion and fibrinogen adsorption are lower for TiNxOy than for TiO2. This correlates with a lower hydrophobicity and higher polar component of the surface energy for TiNxOy.

Surface‐Imprinted Polyurethane Having Affinity Sites for Ampicillin

Affinity sites for an antibacterial drug, ampicillin, were created on the surface of polyurethane using the technique of non-covalent molecular imprinting. This was achieved by polymerizing aminophenylboronic acid in the presence of the ampicillin as a template. The extent of adsorption of the drug by the imprinted surface is nearly five times higher than the non-imprinted surface. The in vitro release studies have shown that the drug is retained for a prolonged period on the imprinted surface while it is rapidly released from the non-imprinted surface. These modified materials were subjected to interactions with two bacterial strains, E. Coli and S. aureus. These species could not adhere to the imprinted surface, further showing the ability of the surface to retain the drug for a prolonged period of time. The non-imprinted surface retained the bacterial strains, reflecting the lack of the drug on the surface. This novel approach seems to be useful for creating surfaces capable of retaining components of interest through non-covalent interactions to impart specific features, such as improved blood compatibility and antibacterial properties. [diagram in text].

Synthesis and adsorption aspect of crosslinked PVA-based blood compatible adsorbents for LDL apheresis

Macroporous poly(vinyl acetate-co-triallyl isocyanurate) beads were prepared with suspension polymerization method. The copolymer beads were transformed into poly(vinyl alcohol-co-triallyl isocyanurate) by ester exchange reaction. Epoxy group was than connected to the surface of poly (vinyl alcohol-co-triallyl isocyanurate) by the reaction of epichlorohydrin with the hydroxyl group of the copolymer. And carboxyl groups were immobilized through 1,6-hexanediamine or triethylenetetramine space arm or directly connected to the hydroxyl group on the copolymer beads. The blood compatibility and adsorption properties for low density lipoprotein (LDL) in human plasma of the resultant macroporous crosslinked PVA-based adsorbents were investigated.

Reduced adhesion of blood cells to biodegradable polymers by introducing phosphorylcholine moieties.

Aliphatic polyesters are believed to be good biocompatible polymers for tissue engineering because of their biodegradability and nontoxicity of the degradated products. However, it is necessary to reduce the nonspecific protein adsorption for the application of biodegradable polymers to drug delivery systems or antiadhesive membranes. We hypothesized that novel biodegradable polymers could be synthesized by introducing phosphorylcholine moieties into aliphatic polyesters. The L-lactide was polymerized in the presence of L-alpha-glycelophosphorylcholine (LGPC) using stannous octate as the catalyst. The molecular weight and crystallinity of poly(L-lactide) (PLLA)-based phospholipid polymers (PLLA-PC) decreased with an increase in the composition of the LGPC unit in the PLLA-PC. The hydrolysis of the PLLA-PC was evaluated by soaking the polymer membranes in a phosphate buffer solution. The rate of weight loss was increased with increasing the LGPC units in PLLA-PC. The surface analysis of the membranes using an X-ray photoelectron microscope showed the composition of phosphorylcoline groups on the surface. The amount of adsorbed protein and adherent blood cell on the polymer surface was decreased with introducing LGPC unit. PLLA-PC is a promising biodegradable polymer having blood compatibility and antiadhesive property.

Surface modification of polypropylene film by radiation‐induced grafting and its blood compatibility

AbstractTo endow blood‐compatible properties onto polypropylene (PP) film, we grafted 2,3‐epoxypropyl methacrylate (EPMA) to PP film with a preirradiation grafting technique and then introduced various functional groups onto the grafted PP film. The EPMA grafting extent was dependent on the absorbed dose, reaction time, and temperature. The reactions of hydroxylation, iminodiacetation, sulfonation, phosphonation, and amination were performed under various conditions to introduce functional groups into the epoxy group of EPMA‐grafted PP films, respectively. We also immobilized heparin on aminated PP film to compare blood compatibility with various functionalized samples. The grafting, functionalization, and heparinization reaction were confirmed by Fourier transform infrared spectroscopy in the attenuated total reflectance mode and electron spectroscopy for chemical analysis. The blood compatibility of various functional groups and heparin‐introduced samples as well as control samples was examined by the determination of platelet adsorption and thrombus formation. For the examination of the blood compatibility of functionalized PP samples, acid citrate dextrose human whole blood and platelet‐rich plasma were used. The amount of the formed thrombus and the adherent platelets on functionalized PP sample surfaces were evaluated by an in vitro method following Imai and Nose's technique and by scanning electron microscopy, respectively. The blood compatibility of various functional‐group‐introduced PP films after grafting was better than that of the PP control. Phosphoric‐acid‐group‐ and heparin‐introduced PP films had especially good blood compatibility. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 1726–1736, 2003