LARGELY IMPROVED BLOOD COMPATIBILITY OF POLYURETHANE BY BLENDING WITH FLUORINATED PHOSPHATIDYLCHOLINE POLYURETHANE

The improvement of biocompatibility of polyurethanes was investigated.The results demonstrate that the blood compatibility of polyurethanes can be further improved by just simply mixing with the fluorinated phosphatidylcholine poly(carbonate urethane)s(FPCPCUs).The solution blending was done by mixing poly(ether urethane)(PEU)with FPCPCU in different compositions.An increased blood compatibility of the blend films was observed with the increase of FPCPCU content,and when FPCPCU content reached to 40 wt%(40F...

Facile Conjugation of Heparin onto Titanium Surfaces via Dopamine Inspired Coatings for Improving Blood Compatibility

Immobilization of heparin on biomaterials surface has been proven to be an effective strategy for preventing thrombus formation. However, the procedures of most immobilization methods（physical adsorption, covalent linkage, electrostatic interaction） are complicated and time-consuming. In the present study, heparin with various concentrations immobilized on a titanium（Ti） substrate via polydopamine layer for improving blood compatibility was investigated. Water contact angle measurement showed that the immobilization of heparin resulted in an increase of the hydrophilicity. X-ray photoelectron spectroscopy（XPS） and Toluidine Blue O（TBO） tests displayed that the heparin molecules were successfully immobilized on Ti surface. The evaluations of blood compatibility（hemolysis rate, APTT, platelet adhesion and activation, fibrinogen conformational change） showed that the immobilization of heparin decreased hemolysis rate, prolonged blood coagulation time, reduced platelets adhesion and activation, and induced less fibrinogen conformational change. Moreover, a significant inhibition of blood coagulation and platelet adhesion was obtained when the heparin concentration was higher than 5 mg/mL, indicating that only with a certain surface densities could heparin perform its anticoagulant properties well. The results suggest that the immobilization of heparin via polydopamine layer can confer excellent antithrombotic properties, and the heparin immobilization method via polydopamine layer provides an alternative approach for other biomolecules immobilization on biomaterials surface. Thus it is envisaged that this method will be potentially useful for the surface modifi cation of blood-contacting biomaterials.

Microwave-assisted Immobilization of Heparin onto Polyurethane Surface for Improving Blood Compatibility

Heparin was covalently immobilized onto polyurethane surface via a PEG spacer by a microwave-assisted approach to improve blood compatibility. Firstly, amino-terminated poly（ethylene glycol） （APEG） was rapidly grafted onto PU surface within 20 rain by a two-step method involving microwave-assisted MDI-functionalization and subsequent microwave-assisted APEG coupling. Then, heparin was eovalently immobilized through an amide linkage by the direct coupling of the carboxylic acid of heparin with the amino group of APEG on PU surface using carbodiimide coupling reaction. The surface structure and properties were characterized by X-ray photoelectron spectroscopy （XPS）, atomic force microscopy （AFM） and water contact angle measurements. The results revealed that hepadn-immobilized PU surface had slightly increased roughness and significantly improved hydrophilicity in comparison to the original PU surface. The anticoagulant activity of films was evaluated by whole blood clotting time （CT） and prothrombin time （PT）. Complement activation was assessed by detecting complement fragment 3a concentrations of serum exposed to the films. The results revealed that the microwave-assisted heparin-immobilized PU films had excellent antithrombogenicity and suppressed complement activation, indicating improved blood compatibility.

SYNTHETIC STUDIES ON BLOOD COMPATIBLE BIOMATERIALS 13:A NOVEL SEGMENTED POLYURETHANE CONTAINING PHOSPHORYLCHOLINE STRUCTURE:SYNTHESIS,CHARACTERIZATION AND BLOOD COMPATIBILITY EVALUATION

A new phosphorylcholine, (6-hydroxy) hexyl-2-(trimethylammonio) ethyl phosphate (HTEP), was synthesized andcharasterized. Segmented polyurethane (SPU) containing phosphorylcholine structure was synthesized based ondiphenylmethane diisocyanate (MDI), soft segment polytetramethylene glycol (PTMG) and HTEP, with 1,4-butanediol (BD)as a chain extender. The existence of phosphorylcholine structure on the surface of SPU was revealed by attenuated totalreflectance Fourier transform infrard spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and water contactangle measurements. The blood compatibilities of the polymers were evaluated by hemolytic testing and a platelet-richplasma (PRP) adhesion experiment, which was viewed by scanning electron microscopy (SEM) with polyurethane as areference. The novel segmented polyurethane containing phosphorylcholine structure showed improved blood compatibility.

Surface Characterization and in Vitro Blood Compatibility of Poly (Ethylene Terephthalate) Immobilized with Hirudin

Poly （ethylene terephthalate）（dacron, PET） films were exposed under argon plasma glow discharge with different glows and induced polymerization of acrylic acid（AA） in order to in- troduce carboxylic acid group onto PET （PET-AA） assisted by ultraviolet radiation（UV）. Hirudin- immobilized PET （PET-HRD） films were prepared by the grafting of PET-AA, followed by chem- ical reaction with hirudin. The surface structure of the treated PET was determined by X-ray photoelectron spectroscopy （XPS）. The wettability, surface free energy, and interface free energy of the films were investigated by contact angle measurement. The blood compatibility of the films was assessed by platelet-adhesion test and fibrinogen conformational change measurements to eval- uate the viability of the materials in biomedical engineering. Measurement by scanning electron microscopy （SEM） revealed that the amounts of adhered, aggregated and morphologically changed platelets were reduced on the hirudin-immobilized PET films. Enzyme-linked-immunoassay mea- surements that disclosed fibrinogen conformational changes showed results consistent with the platelets＇ behavior.

In vitro Blood Compatibility of Polyethylene Terephthalate with Covalently Bounded Hirudin on Surface

Polyethylene terephthalate （PET,Dacron） was modified by surface immobilization of hirudin with glutaraldehyde（GA） as coupling reagent to improve the blood compatibility.Hirudin-immobilized PETs were characterized by X-ray photoelectron spectroscopy （XPS） and contact angle measurements.The blood compatibility of the PETs was evaluated by platelet adhesion evaluation and fibrinogen conformational change measurements in vitro.The results showed the decrease of platelet adhesion and activation on hirudin-immobilized PET with increasing of glutaraldehyde concentration.Fibrinogen experiment showed that fibrinogen adherence and conformational changes of PET-HRD were less than those of untreated PET,which made the materials difficult to form thrombus.The proper reason of blood compatibility improvement was low interface tension between hirudin-immobilized PETs and blood,as well as blood proteins,and low ratio of dispersive/polar component of the surface energy（γsd/γsp） and high hydrophilicity.

In vitro Cyto and Blood Compatibility of Titanium Containing Diamond-Like Carbon Prepared by Hybrid Sputtering Method

In recent years, diamond-like carbon films （DLC） have been given more attention in research in the biomedical industry due to their potential application as surface coating on biomedical materials such as metals and polymer substrates. There are many ways to prepare metal containing DLC films deposited on polymeric film substrates, such as coatings from car- bonaceous precursors and some means that incorporate other elements. In this study, we in- vestigated both the surface and biocompatible properties of titanium containing DLC （Ti-DLC） films. The Ti-DLC films were prepared on the surface of poly （ethylene terephthalate） （PET） film as a function of the deposition power level using reactive sputtering technique. The films＇ hydrophilicity was studied by contact angle and surface energy tests. Their surface morphology was studied by scanning electron microscopy （SEM） and atomic force microscopy （AFM）. Their elemental chemical composition was analyzed using energy dispersive X-spectra （EDX） and X-ray photoelectron spectroscopy （XPS）. Their blood and cell compatibility was studied by in vitro tests, including tests on platelet adhesion, thrombus formation, whole blood clotting time and osteoblast cell compatibility. Significant changes in the morphological and chemical composition of the Ti-DLC films were observed and found to be a function of the deposition level. These morphological and chemical changes reduced the interfacial tension between Ti-DLC and blood proteins as well as resisted the adhesion and activation of platelets on the surface of the Ti-DLC films. The cell compatibility results exhibited significant growth of osteoblast cells on the surface of Ti incorporated DLC film compared with that of DLC film surface.

Blood Compatibility of Nano-Hydroxyapatite Dispersed Using Various Agents

Nano-hydroxyapatite (nHAP),dispersed with three kinds of dispersants (heparin sodium,polyacrylic sodium and wa-ter),reacted with red blood cell,Bel-7402 tumor cell,to compare their dispersing efficiency against nHAP from one another. The blood compatibility of nHAP is also determined by blood solubil-ity experiment so that the capability of different dispersant dis-persing against nHAP of different concentration and the relation between nHAP and blood compatibility have been determined. The inhibiting function of Bel-7402 against tumor cells is deter-mined with the MTT staining method. The study result shows that heparin sodium has the best dispersing efficiency for nHAP with-out the phenomenon of hemolysis.

Study on Blood Compatibility of Carbon-Nitride Film Synthesized by Ion Beam Enhanced Deposition

In this paper, blood compatibility of carbonnitride film synthesized by ion beam enhanced deposition is studied. Clotting time measurement, platelet adhesion test and surface energy determination were performed to evaluate the interaction between blood and material. The results show that carbonnitride film has better blood compatibility than titanium, and may be promising in biomaterial filed.

CHARACTERIZATION OF AMPHIPHILIC AND MICROPHASE SEPARATED GRAFT COPOLYMERS Ⅱ SURFACE CHARACTERIZATION AND IN VITRO BLOOD-COMPATIBILITY ASSESSMENT OF POLYSTYRENE-GRAFT-ω-STEARYLPOLY (ETHYLENE OXIDE)

This paper reported the research results concerning the surface characterization ofpolystyrene-graft-w-stearyl poly(ethylene oxide) (PS-g-SPEO) by means of XPS,contactangle measurement and TEM, and its in vitro blood compatibility assessment by measuringthe plasma recalcification time (RT) and partial thromboplastin time (PTT). The XPSresults demonstrated that the surface and bulk composition of the PS-g-SPEO graftcopolymers differ remarkably from each other,and that SPEO component was constantlyenriched at the copolymer/air interface. Contact angle studies indicated that the surfacewater wettability can be adjusted effectively by changing the composition of the copolymer.PS-g-SPEO graft copolymers can undergo microphase separation as clearly illustrated byTEM photographs. The relationship between the surface properties of PS-g-SPEO graftcopolymer and its blood compatibility was also discussed.

Surface Modification of Silk Fibroin Films with Zwitterionic Phosphobetaine to Improve the Hemocompatibility

Zwitterionic phosphobetaine bearing a hydroxyl and a zwitterionic group,8-hydroxy-2-octyl phosphorylcholine（HOPC）,was synthesized and constructed to the surface of silk fibroin（SF） films in order to improve the hemocompatibility of fibroin films by a an isocyanate head group.The surface characteristics of the modified films were measured by attenuated total reflection Fourier transform infrared spectroscopy（ATR-FTIR） and electron spectroscopy for chemical analysis（ESCA）,displaying the successful immobilization of Zwitterionic phosphobetaine on the surface of these fibroin films.Moreover,the further platelet adhesion test in platelets rich plasma（PRP） of human beings showed the zwitterionic phosphobetaine led mainly to good nonthrombogenicity.The experimental results indicated a reasonable approach to improve the blood compatibility of fibroin films.

SYNTHETIC STUDIES ON BLOOD COMPATIBLE BIOMATERIALSⅡ. SYNTHESIS OF POLY(ETHYLENEGLYCOL MONOMETHYLLTHER ) METHACRYLATE AND ANTITHROMBOGENICITY OF ITS COPOLYMERS

Poly （ethyleneglycol monomethylether） methacrylate （PEGMM）was synthesized by means of the reaction of methacrylyl chloride with sodium monomethylpolyethyleneglycoxide and was characterized by FTIR,;H-NMR,and ultraviolet spectrometries. A series of poly （vinyl alcohol）-graft-PEGMM （PVA-g-PEGMM ）and methyl methacrylate-PEGMM copolymer （PMMA-PEGMM） were prepared and tested for antithrombogenicity in vitro. The results indicate that the antithrombogenicity of the copolymers basically increases with the increasing of the DP of polyoxyethylene （POE） chain and tends to a plateau after the DP around 114,i.e. the long chain structure of POE is favourable to the antithrombogenicityof its copolymers ;moreover, the extent of the improvement ofantithrombogenicity also relates to the PEGMM content of the copolymers and the kind of the matrix that the POE chains are located on. These results are consistent with the anticipation of the hypothesis of maintaining proteins normal conformations for blood compatible bioraaterials.

SYNTHETIC STUDIES ON BLOOD COMPATIBLE BIOMATERIALS Ⅲ. SYNTHESIS, CHARAC-TERIZATION AND ANTITHROMBOGENICITY OF DIMETHYLDIPHEN YLPOLYSILOXANE/POLY (OXYTETRAM ETHYLENE)-POLYUREA SEGMENTED COPOLYMERS

A novel class of segmented copolymers, dimethyldiphenylpolysiloxane/poly (oxytetramethylene)-polyurea (PSPEU), was synthesized from α , ω-bis (γ-aminopropyl) dimethyldiphenylpolysiloxane (APMPS), which was prepared by means of basic ring-opening copolymerization of octamethylcyclotetrasiloxane, hexaphenylcyclotrisiloxane and 1, 3-bis (γ-aminopropyl) tetramethyl disiloxane. The relationships between the diphenylsiloxy contents and the properties of APMPS, including refractive index, glass transition temperature, solubility parameter as well as thermal stability, were investigated; meanwhile, the thermal stability, dynamic mechanical properties, mechanical properiesas well as the antithrombogenicity in vitro of the PSPEU were also revealed.

SYNTHETI C STUDIES ON BLOOD COMPATIBLE BIOMATERIALS Ⅳ. SYNTHESIS, CHARACTERIZATION AND ANTITHROMBOGENICITY OF POLY-[N, N'( p,p-OXYDIPHENYLENE)] PYROMELLI-TIMIDE-POLYDIMETHYLDIPHENYLSILOXANE SEGMENTED COPOLYMER

A novel class of aromatic polyimide-silicone segmented copolymer was synthesized with α, ω-bis (γ-aminopropyl) polydimethyldiphenylsiloxane (APMPS) as a silicone segment precursor, from which the segmented polyamic acid-b-silicone intermediate could be prepared simply with DMF as solvent. The segmented copolymer displays microphase separation and exhibits improved antithrombogenicity, which depends mainly upon both the content level and the DP of the silicone segment. Thermal stability and mechanical property of the copolymer are between that of the aromatic polyimide and the silicone, and also relate to both the content level and the DP of the silicone segment.

Nickel-free Stainless Steel for Medical Applications

BIOSS4 steel is essentially a nickel-free austenitic stainless steel developed by the Institute of Metal Research, Chinese Academy of Sciences, in response to nickel allergy problems associated with nickel-containing stainless steels that are widely used in medical applications. The high nitrogen content of this steel effectively maintains the austenitic stability and also contributes to the high levels of corrosion resistance and strength. BIOSS4 steel possesses a good combination of high strength and toughness, better corrosion resistance, and better blood compatibility, in comparison with the medical 316L stainless steel. Potential applications of BIOSS4 steel can include medical implantation material and orthodontic or orthopedic devices, as well as jewelries and other decorations.

Preparation of antifouling ultrafiltration membranes from copolymers of polysulfone and zwitterionic poly(arylene ether sulfone)s

The past few decades have witnessed rapid gains in our demands of antifouling membranes such as water purification membranes and hemodialysis membranes.A variety of methodologies have been proposed for improving the antifouling performance and the hemocompatibility of the membranes.In this study,a series of copolymers(PSF-PESSB)containing polysulfone(PSF)and poly(arylene ether sulfone)bearing pendant zwitterionic sulfobetaine groups(PESSB)were prepared via one-pot polycondensation.Subsequently,the ultrafiltration(UF)membranes were prepared from different zwitterion-containing copolymers.The prepared membranes showed high thermal stability and mechanical properties.Besides,it also displayed attractive antifouling performance and blood compatibility.Compared with the original PSF membrane,the amount of protein absorption on the modified membrane was reduced;the flux recovery ratio and the resistance to blood cells were significantly improved.The results of this work suggest that PSF-PESSB membranes are expected to be applied in blood purification.The introduction of zwitterion-containing polymers to membranes paves ways for developing advanced hemodialysis technologies for crucial process.

Preparation and Adsorption Properties of PAM Based Adsorbents for Plasma Lipoproteins

Crosslinked macroporous polyacrylamide (PAM) was prepared with inverse phase suspension polymerization technique. After treatment with hydrazine, the polymer was functionalized with chloroacetic acid, trifluoroacetic acid diethylenetriaminepentaacetic acid (DEPAA), and maleic acid, respectively, and PAM based adsorbents bearing carboxyl functional groups for low density lipoprotein (LDL) apheresis use were obtained. The blood compatibility and the adsorption properties for plasma lipoproteins of PAM based adsorbents were investigated.

Layer-by-layer deposition of bioactive layers on magnesium alloy stent materials to improve corrosion resistance and biocompatibility

Magnesium alloy is considered as one of the ideal cardiovascular stent materials owing to its good mechanical properties and biodegradability.However,the in vivo rapid degradation rate and the insufficient biocompatibility restrict its clinical applications.In this study,the magnesium alloy(AZ31B)was modified by combining the surface chemical treatment and in-situ self-assembly of 16-phosphonyl-hexadecanoic acid,followed by the immobilization of chitosan-functionalized graphene oxide(GOCS).Heparin(Hep)and GOCS were alternatively immobilized on the GOCS-modified surface through layer by layer(LBL)to construct the GOCS/Hep bioactive multilayer coating,and the corrosion resistance and biocompatibility were extensively explored.The results showed that the GOCS/Hep bioactive multilayer coating can endow magnesium alloys with an excellent in vitro corrosion resistance.The GOCS/Hep multilayer coating can significantly reduce the hemolysis rate and the platelet adhesion and activation,resulting in an excellent blood compatibility.In addition,the multilayer coating can not only enhance the adhesion and proliferation of the endothelial cells,but also promote the vascular endothelial growth factor(VEGF)and nitric oxide(NO)expression of the attached endothelial cells on the surfaces.Therefore,the method of the present study can be used to simultaneously control the corrosion resistance and improve the biocompatibility of the magnesium alloys,which is expected to promote the application of magnesium alloys in biomaterials or medical devices,especially cardiovascular stent.