Cell attachment and proliferation on poly(carbonate urethanes) with various degrees of nanophase separation

In this work, we synthesized six 4,4'-diphenylmethane diisocyanate (MDI)-based poly(carbonate urethanes) (PCU) by using the macrodiol poly(1,6-hexyl, 1,2-ethyl carbonate) diol (MW = 2,017) in different molar ratios to MDI. The bulk and surface properties of cast PCU films were analyzed. The glass transition temperatures measured by dynamic mechanical analysis (DMA) and surface images obtained from atomic force microscopy (AFM) indicated that these PCU had various degrees of nanophase separation that changed with the time and film casting temperatures. The degree of nanophase separation correlated very well with endothelial cell attachment and proliferation on PCU.     

Enhanced biocompatibility in biostable poly(carbonate)urethane

In this work, we synthesized two MDI-based polyurethanes, including a poly(ether)urethane (PEU) and a poly(carbonate)urethane (PCU), by using different soft segments, poly(tetramethylene oxide) and poly(hexyl, ethyl)carbonate diol (M approximately 2,000). We demonstrated that, in addition to the enhanced biostability of PCU over PEU, the biological performances of PCU in vitro were also improved in general. These included, better cellular attachment and proliferation, less platelet activation, as well as reduced monocyte activation. The unusual wide-ranging enhancement in biocompatibility for PCU was believed to be related to the larger micro-phase separation in PCU (approximately 25 nm) that caused distinct protein adsorption on the surface. The total number of adherent monocytes (nonactivated and activated) on the bare sample surfaces, albumin pre-adsorbed sample surfaces, and fibrinogen pre-adsorbed sample surfaces.     

Effect of soft segment length on properties of fluorinated polyurethanes

The effects of soft segment length on the variations in morphology, surface composition, and hydrophilicity have been studied in fluorinated polyurethanes (FPUs) and correlated with their preliminary blood compatibility as evidenced by in vitro platelet adhesion experiments. The fluorinated polyurethanes were obtained using hexamethylene diisocyanate (HDI) and chain extender of 2,2,3,3-tetrafluoro-1,4-butanediol (TF) as the hard segment as well as various soft segments—polytetramethyl oxides (PTMO) with molecular weights of 650, 1000, 1400, and 2000. The increased phase separation in hard-segment domains with lengthening soft segment was observed by FT-IR, which is believed to result in enhanced strength of hydrogen bonds and good hard-segment order arrangement. Thin-film XRD results indicate at least three lateral distances existing between adjacent hard segments in the crystallized hard segment. Their distribution depends strongly on the length of soft segment. Lengthening soft segment promotes the formation of dense arrangement of crystallized hard segments. Compared with the effect of phase separation, surface composition was found to exert a major influence on the preliminary blood compatibility of fluorinated polyurethanes. Increasing fluorine content by decreasing soft segment length promotes reduction in platelet adhesion and activation on polyurethane surfaces.     

Studies on NO releasing from PCU grafted with endogenous NO donors

Films of PCUs grafted with L ‐nitrosocysteine (L ‐CySNO) were successfully prepared in the presence of 3‐aminopropyltriethoxysilane (APTES). The final products (L ‐CySNO‐grafted PCU) were characterized with ATR‐FTIR, SEM, XPS, and tensile strength measurement. Tensile strength of the L ‐CySNO‐grafted PCU was decreased compared to that of non‐grafted PCU. In vitro NO release from the produced films was obtained by using ascorbic acid (Vc) as reducing agent, and the velocity of the released NO was measured by the Griess assay. The effects of temperature, molecular weight of polycarbonate diols (PCN), and thickness of the films on in vitro NO release were investigated in detail. It was found that with the increase of temperature, the velocity of NO release increased, whereas with the increase of molecular weight of polycarbonate diols, the velocity decreased. However, thickness of PCU films has no effect on NO release. The results of cytotoxicity test and hemolytic test indicate that blood compatibility and biocompatibility of the grafted PCU are better than those of the synthesized PCU. Copyright © 2009 John Wiley & Sons, Ltd.     

Influence of brush length of PVP chains immobilized on silicon wafers on their blood compatibility

In this study, the influence of variations in chain length of polyvinylpyrrolidone (PVP) brushes on the blood compatibility of silicon wafer surfaces to which they were chemically attached was studied. Si surfaces were functionalized with various lengths of PVP brush using atom transfer radical polymerization technology and confirmed by elliptical polarized light, atom force microscopy, and X‐ray photoelectron spectroscopy. The blood compatibility of these biointerfaces were systematically investigated by measuring protein adsorption, clotting time, platelet adhesion, contact activation, and complement activation. The results indicate that the hemocompatibility of the surfaces was highly related to PVP brush chain length and hydrophilicity of the surfaces. Our results contribute to rational biointerface design for specific biomedical applications. The results reveal that the PVP brushes with a long chain length have great potential for blood contacting applications due to their reduced protein absorption and cell activation following its contact with blood.     

GRAFTING OF SULFOBETAINE ONTO A POLYURETHANE SURFACE TO IMPROVE BLOOD COMPATIBILITY

On the molecular level, it is believed that polymers containing zwitterionic structures should be compatible withblood. In this work polyurethane films were grafted with sulfobetaine by a three-step procedure. In the first step, the films'surfaces were treated with hexamethylene diisocyanate (HDI) in toluene at 50℃ in the presence of di-n-butyl tin dilaurate(DBTDL) as a catalyst. The extent of the reaction was monitored by ATR-IR spectra; a maximum number of free NCOgroups was obtained after a reaction time of 90 min. In the second step, the hydroxyl groups of N,N-dimethylethylethanolamine (DMEA) were allowed to react in toluene with NCO groups bound on the surface. In the thirdstep, sulfobetaines were formed on the surface through the ring-opening reaction between tertiary amine of DMEA and 1,3-propanesultone (PS). The surfaces of the films were characterized by ATR-IR and XPS showing that the grafted surfaceswere composed of sulfobetaine. The results of the contact angle measurement show that the surface was strongly hydrophilic.The platelet adhesion test demonstrated that the films grafted with sulfobetaine have excellent blood compatibility.     

Platelet and bacterial repellence on sulfonated poly(ethylene glycol)-acrylate copolymer surfaces

Novel poly(ethylene glycol) (PEG) and sulfonated PEG (PEG-SO₃) acrylate copolymers have been prepared and characterized to apply as coating and blending materials for biomedical applications. The modified surfaces using acrylate copolymers demonstrated increased hydrophilicity, possibly due to the hypothesized reorientation of PEG/PEG-SO₃ chains into water phase. All copolymer surfaces demonstrated less platelet adhesion than control. In addition, platelet adhesion on copolymer surfaces decreased as the chain length of PEG and sulfonated PEG in copolymers increases. All copolymer surfaces reduced bacterial adhesion significantly and the adhesion level differs depending on surfaces as well as media. The obtained results attest to the usefulness of these copolymers as a coating or additive material to improve the blood compatibility of blood contacting devices.     

Surface modification of polycarbonate urethane by grafting polyethylene glycol and bivalirudin drug for improving hemocompatibility

As the clinical demand for blood-contacting materials increases, higher requirements are placed on their physicochemical properties, durability and hemocompatibility in vivo. In this work, a multiple functionalized material was developed through a facile modification process. Herein, polycarbonate urethane (PCU) surface was co-modified with polyethylene glycol (PEG) and bivalirudin (BVLD). PCU provides excellent physical and mechanical properties, PEG and BVLD, especially BVLD, enable the surface with outstanding anticoagulant capacity. Specifically, PCU surface was first treated with hexamethylene diisocyanate to introduce active isocyanate groups onto the surface, followed by hydroxy-PEG grafting to improve the hydrophilicity. Finally, BVLD was immobilized on the surface via Michael addition reaction to improve antithrombotic properties. Attenuated total reflection Fourier transforms infrared spectroscopy and UV spectrophotometers were used to confirm the modified surfaces. The hydrophilicity was characterized by static water contact angle measurement, the morphology of the modified surfaces was observed by scanning electron microscopy. Blood compatibility of the modified surfaces was characterized by the hemolysis rate, platelet adhesion assay and cell culture test. The results showed that the BVLD immobilized surface has excellent anticoagulant properties, good fibrin-bound thrombin inhibition, and good resistance against non-specific adhesion of proteins. Hence, the co-modification with PEG and BVLD was proved an encouraging strategy for improving hemocompatibility.     

Inhibitory effect of hydrophilic polymer brushes on surface-induced platelet activation and adhesion

Poly(N,N-dimethylacrylamide) (PDMA) brushes are successfully grown from unplasticized poly(vinyl chloride) (uPVC) by well-controlled surface-initiated atom transfer radical polymerization (SI-ATRP). Molecular weights of the grafted PDMA brushes vary from ≈ 35,000 to 2,170000 Da, while the graft density ranges from 0.08 to 1.13 chains · nm(-2). The polydispersity of the grafted PDMA brushes is controlled within 1.20 to 1.80. Platelet activation (expression of CD62) and adhesion studies reveal that the graft densities of the PDMA brushes play an important role in controlling interfacial properties. PDMA brushes with graft densities between 0.35 and 0.50 chains · nm(-2) induce a significantly reduced platelet activation compared to unmodified uPVC. Moreover, the surface adhesion of platelets on uPVC is significantly reduced by the densely grafted PDMA brushes. PDMA brushes that have high molecular weights lead to a relatively lower platelet activation compared to low-molecular-weight brushes. However, the graft density of the brush is more important than molecular weight in controlling platelet interactions with PVC. PDMA brushes do not produce any significant platelet consumption in platelet rich plasma. Up to a seven-fold decrease in the number of platelets adhered on high graft density brushes is observed compared to the bare PVC surface. Unlike the bare PVC, platelets do not form pseudopodes or change morphology on PDMA brush-coated surfaces.     

Surface Modification of Polyurethanes with Covalent Immobilization of Heparin

Thrombus formation and blood coagulation is a major problem associated with blood contacting products such as catheters, vascular grafts, arteries, artificial hearts and heart valves. An intense research is being conducted towards the synthesis of new hemocompatible materials and modifications of surfaces with biological molecules. In this study, polyurethane (PU) films were synthesized in medical purity from diisocyanate and polyol without using any other ingredients and their surfaces were modified by covalent immobilization of heparin. Two types of heparin, unfractionated (UFH) and low molecular weight heparin (LMWH), were immobilized to investigate their effect on cell adhesion. The surface properties of the modified PUs were examined with ESCA, ATR-FTIR and AFM. ESCA results demonstrated sulfur peaks indicating the presence of heparin and AFM results showed the alteration of surface structure after coating with heparin. Cell adhesion studies were conducted with heparinized whole human blood. The surfaces of the UFH immobilized films resulted in lesser red blood cell adhesion in comparison to LMWH demonstrating strong anti-thrombogenic activity of the latter.     

Inhibition of protein adsorption and cell adhesion on PNIPAAm-grafted polyurethane surface: effect of graft molecular weight

In this work, the effect of molecular weight (MW) of surface grafted poly(N-isopropylacrylamide) (PNIPAAm) on protein adsorption and cell adhesion was investigated systematically. PNIPAAm-grafted polyurethane (PU) surfaces of varying graft MW were prepared via conventional radical polymerization. The MW was controlled by adjusting the monomer concentration. Fibrinogen (Fg) and human serum albumin (HSA) were selected as model proteins and their adsorption from phosphate-buffered saline (PBS, pH 7.4) and blood plasma at 37°C was measured using a radiolabeling method and immunoblot analysis respectively. It was found that in both media, as the MW increased, the adsorption of these two proteins decreased gradually reaching a plateau value at MW above 7.9×10(4). Compared to the unmodified PU, the surface grafted with PNIPAAm of MW 14.6×10(4) reduced the adsorption of Fg and HSA in PBS by 91% and 86%, respectively. Moreover, the surfaces with higher MW PNIPAAm showed minimal adhesion of L929 cells presumably due to the absence of cell-adhesive proteins on the surfaces.     

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.     

聚醚链段长度对氨基聚醚-环氧树脂力学性能的影响

以柔性端氨基聚醚(BATPE)和双酚A环氧树脂(DGEBA)为原料, 制备了无微相分离结构的无定型AB交联热固性树脂. 测试了3种不同聚乙二醇(PEG)链段长度(M_PE)的BATPE-DGEBA环氧树脂固化产物的应力-应变曲线、动态力学温度谱和冲击断面形貌. 结果表明, 在环氧树脂交联网络中引入两端与DGEBA化学连接的PEG链段能避免微相分离结构的生成, 有利于提高DGEBA链段的应变松弛速率. 增加M_PE, 一方面能降低环氧树脂固化产物的玻璃化转变温度和室温下的刚度和拉伸强度, 增加韧性(包括冲击强度和拉伸韧性)、断裂应变和模量损耗因子; 另一方面也能提高固化产物在低温下的储存模量. 优化M_PE可制备出在中低温下同时具有优异的拉伸强度、模量、断裂应变和冲击性能的BATPE-DGEBA环氧树脂.     

Biocompatibility and biostability of a series of poly(carbonate)urethanes

In this work, we synthesized several MDI-based poly(carbonate)urethanes (PCU) by using four different soft segments, including two aliphatic macrodiols (poly(hexyl, ethyl)carbonate diols, MW 2017 and 865, respectively) and two aromatic macrodiols (MW approximately 2000 and 1000, respectively), in different molar ratios to MDI. We demonstrate that these polymers exhibited various degree of micro-phase separation that further influenced their surface protein adsorption, platelet activation as well as cellular attachment and growth. Polyurethanes based on poly(hexyl, ethyl)carbonate diol with MW 2017 in a molar ratio MDI/macrodiol/chain extender of either 3/2/1 or 4/3/1 resulted in greater micro-phase separation as well as superior biocompatibility and biostability.     

铝合金表面改性对有机涂层附着力的影响及腐蚀防护性能研究

利用电化学阻抗（EIS）、扫描微参比技术（SRET）、接触角、粗糙度、附着力、盐雾等测试方法,研究了铝合金阳极氧化与贻贝黏附蛋白（MAP）/CeO₂/硅烷γ-APS（MCA）表面复合修饰的腐蚀防护性能以及对改性聚氨酯涂层附着力和耐蚀性的影响。结果表明,MCA复合膜可抑制铝合金的腐蚀,并具有一定的自修复功能;阳极氧化和MCA表面复合修饰可为铝合金提供有效的早期腐蚀防护作用,且能提高铝合金表面粗糙度和润湿性,显著提升改性聚氨酯涂层在铝合金表面的附着力和耐蚀性,因而结合改性聚氨酯涂层和表面复合修饰可实现对铝合金长期有效的腐蚀防护。     

Surface derivatization strategy for combinatorial analysis of cell response to mixtures of protein domains

We report a robust strategy for conjugating mixtures of two or more protein domains to nonfouling polyurethane surfaces. In our strategy, the carbamate groups of polyurethane are reacted with zirconium alkoxide from the vapor phase to give a surface-bound oxide that serves as a chemical layer that can be used to bond organics to the polymer substrate. A hydroxyalkylphosphonate monolayer was synthesized on this layer, which was then used to covalently bind primary amine groups in protein domains using chloroformate-derived cross-linking. The effectiveness of this synthesis strategy was gauged by using an ELISA to measure competitive, covalent bonding of cell-binding (III(9-10)) and fibronectin-binding (III(1-2)) domains of the cell adhesion protein fibronectin. Cell adhesion, spreading, and fibronectin matrix assembly were examined on surfaces conjugated with single domains, a 1:1 surface mixture of III(1-2) and III(9-10), and a recombinant protein "duplex" containing both domains in one fusion protein. The mixture performed as well as or better than the other surfaces in these assays. Our surface activation strategy is amenable to a wide range of polymer substrates and free amino group-containing protein fragments. As such, this technique may be used to create biologically specific materials through the immobilization of specific protein groups or mixtures thereof on a substrate surface.     

Effect of Aluminum Alloy Surface Modification on Adhesion of the Modified Polyurethane Coating and Its Corrosion Protective Performance北大核心CSCD

The ordinary organic coatings on aluminum alloy usually encounter a problem of low adhesion to the substrate, which results in destruction and failure of the long-term protective performance of the anticorrosion systems. The surface modification of aluminum alloy is able to enhance the adhesion of organic coating on aluminum alloys, and to improve their protective performance. In this work, a combined surface modification of anodic oxidation and mussel adhesion protein/CeO2/3-aminopropyltriethoxysilane composite film (MCA) was developed on the aluminum alloy. The adhesion of modified polyurethane coated on the treated aluminum alloy and its corrosion protective performance were evaluated comprehensively by using contact angle, adhesion strength, electrochemical impedance spectroscopy (EIS), and scanning reference electrode technique (SRET). The measurements of EIS and SRET demonstrated that the MCA composite film on anodic oxidized Al possessed self-healing function and provided effective protection against early corrosion of aluminum alloy. The pull-off test showed that both anodic oxidation treatment and MCA composite film modification were able to increase the adhesion of modified polyurethane coating on aluminum alloy, and their combined action were supposed to remarkably enhance the adhesion strength up to 17.1 MPa. The reason for the improvement of adhesion was that the anodic oxidation treatment and MCA composite film modification could improve the surface roughness of aluminum alloy, and enhance the surface wettability and surface polarity, which is beneficent to enhance the bonding of the modified polyurethane coating to aluminum alloy surface. The EIS results showed that no any corrosion occurred for the modified polyurethane coating on the treated aluminum alloy during 65 d immersion in 3.5wt.% NaCl solution. The impedance value in low frequency range of the modified polyurethane coating always maintained at a high order of magnitude on the aluminum alloy treated by anodic oxidation and MCA composite film modification, showing an excellent protective performance of the coating system. The evaluation of Neutral Salt Spray (NSS) indicated that the modified polyurethane coating on the treated aluminum alloy owned superior corrosion protection performance, and the adhesion strength remained 13.1 MPa and no any corrosion was found at the scratch locations even after 1200 h of salt spray testing. It was concluded that combination of anodic oxidation and MCA composite film were capable of significantly improving the adhesion of modified polyurethane coating on aluminum alloy and providing long-term effective corrosion protection for aluminum alloy. © 2021 Authors. All rights reserved.     

热致相分离技术制备聚氨酯多孔膜的条件控制

采用自制的模具 ,利用热致相分离 (TIPS)的原理制备了聚氨酯 (PU)多孔膜 ,并重点研究了聚合物浓度对多孔膜的表面形貌、孔度大小、孔隙率和透湿率的影响 .在不同的聚合物浓度条件下制备的PU多孔膜的共同特征是底面 (与成膜平台接触面 )光滑平整 ,孔洞尺寸较小 ,为纳米级 ;而表面 (与空气接触的自由面 )的形貌结构较为复杂 ,但都有明显的孔洞出现 ,且孔洞的尺度大于底面 ,在微米级以上 .聚氨酯 1,4 二氧六环 (DO)形成的是上临界共溶温度 (UCST)体系 ,在发生相分离后底面与表面粗化时间的不同是导致形貌结构差异的主要原因 .改变冷台温度或调整DO H2 O的比例也会对PU多孔膜的孔度大小和形貌结构产生明显的影响     

Platelet Adhesion onto Nitinol Surfaces Modified by Microwave Cold-plasma

The macromolecular structures on nitinol surfaces were prepared by ECR microwave cold-plasma of tetraglyme conditions. The surface chemistry was characterized by high resolution ESCA. The results showed that the modified nitinol surfaces were built up mainly of-CH2-CH2-O-linkages and were particularly effective in preventing platelet adhesion.     

Surface grafting of a thermoplastic polyurethane with methacrylic acid by previous plasma surface activation and by ultraviolet irradiation to reduce cell adhesion

The material performance, in a biological environment, is mainly mediated by its surface properties and by the combination of chemical, physical, biological, and mechanical properties required, for a specific application.In this study, the surface of a thermoplastic polyurethane (TPU) material (Elastollan^®1180A50) was activated either by plasma or by ultra-violet (UV) irradiation. After surface activation, methacrylic acid (MAA) was linked to the surface of TPU in order to improve its reactivity and to reduce cell adhesion. Grafted surfaces were evaluated by X-ray photoelectron spectroscopy (XPS), by atomic force microscopy (AFM) and by contact angle measurements. Blood compatibility studies and cell adhesion tests with human bone marrow cells (HBMC) were also performed.If was found that UV grafting method led to better results than the plasma activation method, since cell adhesion was reduced when methacrylic acid was grafted to the TPU surface by UV.