Blood Compatibility Of Poly Research Articles

Blood compatibility of poly(propylene glycol diester) and its water structure observed by differential scanning calorimetry and 2H-nuclear magnetic resonance spectroscopy

Recently, we applied solution 2H-nuclear magnetic resonance spectroscopy (2H NMR) to analyze the water (deuterium oxide, D2O) structure in several biopolymers at ambient temperature. We established that polymers with good blood compatibility (i.e. poly(2-methoxyethyl acrylate) (PMEA)) have water observed at high magnetic fields (upfield) compared with bulk water. Polymers containing poly(propylene glycol) (PPG) or poly(propylene oxide) (PPO) exhibit good compatibility; however, the reason for this remains unclear. In addition, reports on the blood compatibility of PPO/PPG are limited. Therefore, PPG diester (PPGest) was prepared as a model polymer, and its blood compatibility and water structure were investigated. PPGest exhibited excellent blood compatibility. The water in PPGest was observed upfield by 2H NMR, and it was defined as non-freezing water via differential scanning calorimetry. Based on these observations, the relationship between the blood compatibility and water structure of PPGest is discussed by comparing with those of PMEA, and the reason for the good performance of PPG/PPO-based polymers is discussed.

Hemocompatibility of pseudozwitterionic polymer brushes with a systematic well-defined charge-bias control

In this study, a pseudozwitterionic surface bearing positively and negatively mixed charged moieties was developed as a potential hemocompatible material for biomedical applications. In this work, hemocompatility of pseudozwitterionic surface prepared from copolymerization of negatively charged 3-sulfopropyl methacrylate (SA) and positively charged [2-(methacryloyloxy)ethyl] trimethylammonium (TMA) was delineated. Mixed charge distribution in the prepared poly(TMA-co-SA)-grafted surface can be controlled by regulating TMA and SA monomer ratios via surface-initiated atom transfer radical polymerization. The effects of grafting composition and charge bias variations on blood compatibility of poly(TMA-co-SA)-grafted surface were reported. The protein adsorption on different poly(TMA-co-SA)-grafted surfaces from human plasma protein (fibrinogen, HSA, and γ-globulin) solutions was evaluated using an enzyme-linked immunosorbent assay. Blood platelet adhesion and time measurements on plasma clotting were conducted to determine the platelet activation on the grafted surface. It was found that the protein resistance and anti-blood cell adhesion of prepared surface can be precisely controlled by controlling the charge balance of TMA/SA compositions. In addition, different charge bias variations on the poly(TMA-co-SA)-grafted surface would induce electrostatic interactions between plasma proteins and prepared surfaces which lead to adsorptions of interfacial protein and blood cells, plasma clotting, and blood cell hemolysis. Results from this study suggest that the hemocompatility of mixed charged poly(TMA-co-SA)-grafted surface depends on the charge bias level. This provides a great potential for designing biomaterial with unique surface chemical structure which could be used in contact with human blood.

Surface modification of poly(ether ether ketone) with methacryloyl-functionalized phospholipid polymers via self-initiation graft polymerization

To improve blood compatibility of poly(ether ether ketone) (PEEK), surface modification with methacryloyl-functionalized phospholipid polymers was performed through self-initiation graft polymerization. The copolymers (PMA) of 2-methacryloyloxyethyl phosphorylcholine (MPC) and 2-aminoethyl methacrylate hydrochloride were synthesized by conventional free radical polymerization. The PMA was then immobilized with pentafluorophenyl methacrylate to obtain methacryloyl-functionalized MPC polymers (PMAMA). The degree of substitution of the methacryloyl group into the copolymer was nearly completed. The PMAMA was dissolved in 1-butanol and the solution was dropped on PEEK. UV light (350 ± 50 nm) was subsequently irradiated on PEEK for various periods. Elemental analysis of the PEEK surface was performed by X-ray photoelectron spectroscopy and phosphorus and nitrogen signals due to the MPC units on PEEK were observed. The surface wettability of PEEK was also improved by immobilization of PMAMA. Plasma protein adsorption was effectively reduced on the PMAMA-immobilized surface regardless of the type of protein. Furthermore, PMAMA immobilization was also useful in reducing platelet adhesion on PEEK. In conclusion, methacryloyl-functionalized MPC polymers could be immobilized on PEEK by simple photo-irradiation, resulting in significant improvement in blood compatibility.

Zwitterionic Sulfobetaine-Grafted Poly(vinylidene fluoride) Membrane with Highly Effective Blood Compatibility via Atmospheric Plasma-Induced Surface Copolymerization

Development of nonfouling membranes to prevent nonspecific protein adsorption and platelet adhesion is critical for many biomedical applications. It is always a challenge to control the surface graft copolymerization of a highly polar monomer from the highly hydrophobic surface of a fluoropolymer membrane. In this work, the blood compatibility of poly(vinylidene fluoride) (PVDF) membranes with surface-grafted electrically neutral zwitterionic poly(sulfobetaine methacrylate) (PSBMA), from atmospheric plasma-induced surface copolymerization, was studied. The effect of surface composition and graft morphology, electrical neutrality, hydrophilicity and hydration capability on blood compatibility of the membranes were determined. Blood compatibility of the zwitterionic PVDF membranes was systematically evaluated by plasma protein adsorption, platelet adhesion, plasma-clotting time, and blood cell hemolysis. It was found that the nonfouling nature and hydration capability of grafted PSBMA polymers can be effectively controlled by regulating the grafting coverage and charge balance of the PSBMA layer on the PVDF membrane surface. Even a slight charge bias in the grafted zwitterionic PSBMA layer can induce electrostatic interactions between proteins and the membrane surfaces, leading to surface protein adsorption, platelet activation, plasma clotting and blood cell hemolysis. Thus, the optimized PSBMA surface graft layer in overall charge neutrality has a high hydration capability and the best antifouling, anticoagulant, and antihemolytic activities when comes into contact with human blood.

Lipid-like Diblock Copolymer as an Additive for Improving the Blood Compatibility of Poly(lactide-co-glycolide)

To optimize the blood biocompatibility of poly(lactide-coglycolide) (PLGA), lipid-like diblock copolymer poly(DL-lactide)-block-poly(2-methacryloyloxyethyl phosphorylcholine) (PLA-b-PMPC) was employed as a surface-modifying additive. The blends of PLGA and PLA-b-PMPC coated poly(ethylene terephthalate) membranes were prepared by dip-coating. ATR-FTIR spectroscopy showed the incorporation of phosphorylcoline groups in the blends and contact angle results indicated that the hydrophilicity of the blends improved with increasing PLA-b-PMPC content. The plasma recalcification time of polymer coating was prolonged and the amount of adherent platelets on coating surface was decreased by introducing PLA-b-PMPC. The adhesion of polymer coating on the gold electrode of quartz crystal microbalance was monitored and PLGA containing PLA-b-PMPC additives showed excellent polymer—metal adhesion. These results show that the blends of PLGA and lipid-like PLA-b-PMPC could be used as high performance biodegradable polymer coatings for blood contact medical devices.

Study on the Water Structure and Blood Compatibility of Poly(acryloylmorpholine-r-butyl methacrylate)

We have been studying the blood compatibility of polymeric materials from the viewpoint of their water structure, and have proposed that freezable water interacting with polymer molecules plays an important role in determining that compatibility. As we found that water-soluble poly(acryloylmorpholine) interacted with water, resulting in the formation of 'bound water', we newly prepared water-non-soluble poly(acryloylmorpholine-r-butyl methacrylate) (denoted as ACMO co-polymer) with various composition ratios. In addition, the properties of a co-polymer based on N,N-diethylacrylamide (DEA co-polymer), where DEA has a similar chemical structure to ACMO, except that DEA has no ether oxygen, were compared with that of the ACMO co-polymer. Contact angle and DSC analysis revealed that an increase in the content of an N-substituted acrylamide unit in the co-polymers enhanced the hydrophilicity of the polymer and that the hydrophilicity of the ACMO co-polymer was stronger than that of the DEA co-polymer. As for the water structure, it was found that the ACMO co-polymer had a lot of bound water compared to the DEA co-polymer. The difference in these properties between the ACMO and DEA co-polymers was due to the ether oxygen of the morpholine group. At the same time, in vitro blood compatibility tests showed that the ACMO co-polymer exhibited a much better performance than the DEA co-polymer. The water structure and blood compatibility is discussed in detail.

Characterization, biodegradability and blood compatibility of poly[(R)‐3‐hydroxybutyrate] based poly(ester‐urethane)s

Poly(ester-urethane)s (PUs) were synthesized using hexamethylene diisocyanate (HDI) or toluene diisocyanate (TDI) to join short chains (M(n) = 2000) of poly(R-3-hydroxybutyrate) (PHB) diols and poly(epsilon-caprolactone) (PCL) diols with different feed ratios under different reaction conditions. The multiblock copolymers were characterized by nuclear magnetic resonance spectrometer (NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), thermogravimetric analyses (TGA), X-ray diffraction (XRD), and scanning electron microscope (SEM). XRD spectra and second DSC heat thermograms of the multiblock copolymers revealed that the crystallization of both PHB and PCL segments was mutually restricted, and, especially, the PCL segment limited the cold crystallization of the PHB segment. The SEM of platelet adhesion experiments showed that the hemocompatibility was affected to some extent by the chain flexibility of the polymers. Hydrolysis studies demonstrated that the hydrolytic degradation of PUs was generated from the scission of their ester bonds or/and urethane bonds. Simultaneously, the rate of ester bond scission was determined to some extent by the crystallization degree, which was further affected by the configuration of polymer chains. These highly elastic multiblock copolymers combining hemocompatibility and biodegradability may be developed into blood contact implant materials for biomedical applications.

Surface characterization and blood compatibility of poly(ethylene terephthalate) modified by plasma surface grafting

Poly(ethlene terephthalate) (PET) used in artificial heart valve sewing rings were treated by argon plasma discharge and grafted by different molecular water-soluble polymer—polyethylene glycols (PEG). The surface properties of the plasma treated and grafted films were determined by contact angle measurement, X-ray photoelectron spectroscopy (XPS), and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). The contact angle of water decreased from 83.5° to 38.7° and the interfacial energy diminished from 30.7 to 6.3 mN/m. The ratio of oxygen to carbon increased from 0.15 to 0.25. All the results revealed that PEG chains were successfully grafted onto the surface of the PET films. The interaction between the surface-modified PETs and blood components was investigated to evaluate the blood compatibility of the samples. Activated partial thromboplastin time (APTT) of the PET-PEG was significantly longer than that of the untreated PET. Scanning electron microscopy (SEM) and optical microscopy indicated that adhered, aggregated and morphologically changed platelets were significantly reduced by grafting PEG chains onto the PET films. The in vitro blood compatibility tests suggested that the blood compatibility of PET grafted with PEG was related to the molecular weight of PEG. The best blood compatibility was achieved when the grafted molecular weight of PEG was 6000. The hemocompatibility improvement can be explained by the low interfacial free energy, sterically hindered effects of PEG chains, and maintaining of the normal conformation.

Acrylonitrile-based copolymer membranes containing reactive groups: effects of surface-immobilized poly(ethylene glycol)s on anti-fouling properties and blood compatibility

The anti-fouling properties and blood compatibility of poly(acrylonitrile- co -maleic acid) (PANCMA) membranes were improved by the immobilization of poly(ethylene glycol)s (PEG) on membrane surface. It was found that the reactive carboxyl groups on PANCMA membrane surface could be conveniently conversed into anhydride groups and then esterified with PEG. Chemical and morphological changes as well as biocompatibility on membrane surface were analyzed by Fourier transform infrared spectroscopy, elemental analysis, scanning electron microscopy, water contact angle, protein adsorption, and platelet adhesion. Results revealed that, with the immobilization of PEG, the hydrophilicity and blood compatibility of the acrylonitrile-based copolymer membranes were improved obviously. The molecular weight of PEG had an obvious influence on the properties of the PEG-immobilized membranes. Permeation behaviors for the studied membranes were investigated by water and bovine serum albumin (BSA) filtration experiments. Compared with the original PANCMA membrane, the membrane immobilized with PEG 400 ( M w =400 g/mol) showed a three-fold increase in a BSA solution flux, a 40.4% reduction in total fouling, and a 57.9% decrease in BSA adsorption.

Biodegradation and biocompatibility of polyorganophosphazene.

We investigated biodegradation and biocompatibility of poly(organophosphazenes). We prepared poly(organophosphazenes) having different side chain groups. The blood compatibility of poly(organophosphazenes) containing fluorinated side groups, poly(bis[trifluoroethoxy]phosphazene) (PbFP) and poly([trifluoroethoxy][ethyl glycinate]phosphazene) (PFGP), without heparinization were evaluated in vitro. The deformation and aggregation of platelets adhered on PbFP and PFGP were not observed and they suppressed platelet activation. Additionally, PbFP and PFGP showed a higher degradation rate, despite their high hydrophobic nature. We found that the high mobility of water in PbFP and PFGP was one of the important factors facilitating their degradation. Their polymer structures were formed in a more open nature, indicating that water easily attacked the backbone of the phosphorus and nitrogen atoms in the poly(organophosphazene). On the other hand, the proliferation of HeLa cells cultured on poly(organophosphazene) was reduced compared with that on the control tissue culture polystyrene.

Interaction of blood components with heparin-immobilized polyurethanes prepared by plasma glow discharge

The blood compatibility of poly(ethylene oxide) (PEO)-grafted and heparin (Hep) immobilized polyurethanes was investigated using in vitro plasma recalcification time (PRT), activated partial thromboplastin time (APTT), platelet adhesion and activation, and peripheral blood mononuclear cell (PBMC) adhesion and activation. In the experiment with plasma proteins, the PRT of the polyurethane (PU) surface was prolonged by PEO grafting and further prolonged by heparin immobilization. The APTT was prolonged on PU-Hep, suggesting the binding of immobilized heparin to antithrombin III. The percentage of platelet adhesion on PU was not much different from that on acrylic acid- and PEO-grafted PUs (PU-C, PU-6, PU-33), yet was substantially decreased by heparin immobilization (PU-6-Hep, PU-33-Hep). The release of serotonin from adhering platelets was slightly suppressed on PEO-grafted PUs yet significantly suppressed on heparin-immobilized PUs. In the PBMC experiments, the adhesion and activation of the cells were significantly suppressed on heparin-immobilized PUs, and the amount of interleukin-6 (IL-6) released from PBMCs stimulated with surface-modified PUs decreased with a decrease in PBMC adhesion.

The in vitro blood compatibility of poly(ethylene oxide)-grafted polyurethane/polystyrene interpenetrating polymer networks

Poly(ethylene oxide) (PEO)-grafted polyurethane (PU)/polystyrene (PS) interpenetrating polymer networks (IPNs) were synthesized. The effects of the mobile pendant PEO chains with their microphase separated structure on blood-compatibility were investigated. The morphology of both the fracture surface as well as the top surface indicate that the size of the dispersed domains of the PS-rich phase decreased as the grafting with the PEO was increased. The swelling ratio also decreased as the grafting with the PEO was increased. However, the dynamic contact angle and the interfacial energy between IPN surface and water decreased, due to the structural reorganization of the pendant PEO chains. PU/PS IPNs have an excellent mechanical property as compared with PU homopolymers. The adsorption of bovine plasma fibrinogen (BPF) onto the PU/PS IPNs and PU homopolymers was effectively suppressed by the PEO-grafting. In the platelet adhesion test, the amount of platelets adsorbed, activated, and/or coagulated upon the PEO-grafted PU/PS IPNs were reduced when compared to the ungrafted PU homopolymers.

Adsorption of proteins onto poly(ether urethane) with a phosphorylcholine moiety and influence of preadsorbed phospholipid.

In a previous report we demonstrated that the blood compatibility of poly(ether urethane) (PEU) was improved by grafting phosphorylcholine (PC) groups on the surface. The improved blood compatibility was indicated by decreased platelet adsorption/activation and reduced thrombin formation at the polymer surface in experiments in which the surfaces were contacted with platelet-rich plasma in vitro. In the present study, we investigated the effect of grafted PC groups at a PEU surface on protein and phospholipid adsorption. Adsorption of human fibrinogen (Fg), human serum albumin (Alb), human high-molecular-weight kininogen (HMWK), and dioleoyl phosphatidylcholine (DOPC) vesicles was measured by ellipsometry. For this purpose, thin PEU films were cast on silicon wafers. The polymer film was photochemically modified with a PC-containing aryl azide. The presence of PC groups on the polymer surface was demonstrated by ESCA (Electron Spectroscopy for Chemical Analysis). The hydrophilicity of the polymer surface increased by the surface modification, as indicated by a decrease of the contact angle from 59 degrees before to 43 degrees after modification. Our data show that the presence of PC groups has little effect on the adsorption of proteins to a PEU surface. The highest adsorption was observed for Fg (0.49 microgram/cm2 on PC-modified PEU and 0.50 microgram/cm2 on PEU), followed by HMWK (0.28 microgram/cm2 on both PC-modified PEU and PEU), and Alb (0.16 microgram/cm2 on PC-modified PEU and 0.18 microgram/cm2 on PEU). Protein adsorption was further studied on a "biomembrane-like" DOPC bilayer formed on hydrophilic silicon. We found no protein adsorption on this DOPC bilayer. The adsorption of small unilamellar DOPC vesicles on the polymer surfaces amounted to about 0.06 microgram/cm2 (corresponding to circa 30% of monolayer coverage) and was similar for PC-modified PEU and PEU. Despite this partial surface coverage, preadsorbed DOPC on the polymer surface diminished the subsequent adsorption of proteins considerably. These results show that the mere presence of phosphorylcholine groups on a PEU surface is insufficient to suppress protein adsorption. The highly ordered structure of natural phospholipid bilayers seems to be required to suppress protein adsorption effectively.

Synthesis and Blood-Compatibility of Poly(ethylene-g-γ-benzyl-L-glutamate)

A novel graft copolymer consisting of commercial chlorosulfonated polyethylene and γ-benzyl-L-glutamate was synthesized. The graft yield was over 70% at a mild reaction condition while we did not observe any crosslinking reaction. Polypeptide units were grafted into sulfonyl groups of the polyethylene. They formed an α-helical conformation as evidence by FT-IR, circular dichroism spectra, and wide angle X-ray diffraction patterns. The mechanical properties of copolymers showed that the Young’s modulus and the yield stress increased with peptide content in the polyethylene. The dynamic mechanical property showed that the side chain mobility was increasing due to incoporation of the peptide units.These affected the blood compatibility performance. The clotting time of the GP-4 and GP-5 samples was about 51 minutes. The platelet adhesion performance for the GP-4 and GP-5 samples was less than 5% as investigated by Coulter counter. Fibrin networks were not observed on the surface of GP-4 and GP-5 examined by SEM pictures.