2-甲基丙烯酰羟乙基磷酰胆碱聚合膜的研究现状及应用前景

2-甲基丙烯酰羟乙基磷酰胆碱(2-methacryloyloxyethyl phosphorylcholine,MPC)聚合膜是由MPC与其它乙烯基化合物聚合而得的具有优良血液渗透性和生物相容性的生物医学材料。该聚合膜侧链上含有类似细胞膜结构的磷脂极性基团,这在其良好的血液和组织相容性上起了重要作用。MPC聚合膜能有效抑制蛋白吸附和血小板黏附作用,能有效抑制凝血作用,它不仅是人造器官的主要材料来源,还可对生物医学设备进行表面修饰以增加其血液相容性和生物相容性。因而,MPC聚合膜被广泛应用于血液透析、人造器官、膜充氧器和一次性临床设备等生物医学领域。MPC聚合膜在血液相容性上很具发展空间,但关于它的很多研究工作还都处于初期或中级阶段,本文介绍了MPC聚合膜的研究现状及应用前景。     

磷脂聚合物接枝纤维素的血液相容性

血液透析需要明显的超过滤特性、溶质的渗透性、机械强度和血液相容性。由于纤维素膜的广泛应用,虽然认为其具有效好的渗透性和机械强度,但作为血液透析还需要改进血液相容性,在透析时需要灌入肝素抗凝剂减少血液的凝固。另外纤维素膜产生补体的激活是由于表面与补体蛋白的相互作用。Akizawa等研究了去补体活性的纤维素膜,通过水溶性聚合物与材料表面起反应,得到去补体活化的纤维素。目前作者发现含有磷脂极性基团2-甲基丙烯酸氧乙基磷酰胆硷(MPC)与亲水单体共聚显示了明显的血液相容性,当     

类细胞膜仿生药物缓释涂层冠脉支架材料的研究

由单体2-(甲基丙烯酰氧基)乙基-2-(三甲基氨基)乙基磷酸酯(MPC)、甲基丙烯酸十八酯(SMA)、甲基丙烯酸羟丙酯(HPMA)和甲基丙烯酸(三甲氧)硅基丙酯(TSMA)合成了一种新型类细胞膜涂层材料。接触角显示聚合物/水界面向更加亲水方向转化。这种类细胞膜能防止血小板黏附,显著延长复钙化时间。将雷帕霉素作为模型药物植被药物涂层支架,动物实验表明,这种涂层支架能有效预防再狭窄的发生。     

培养在不同可湿性和带电的甲基丙烯酸酯表面人内皮细胞的粘连

曾报导不同类型的哺乳动物对具有聚合物特性的各种表面粘附和增生与表面可湿性及带电相同,常常用系列甲基丙烯酸酯和共聚物作血小板,纤维母细胞及上皮细胞粘连的研究。而作者在本文中介绍了人内皮细胞(HEC)对甲基丙烯酸酯复合聚合物粘附的研究,这种复合聚合物包括聚羟乙基甲基丙烯酸酯(PHEMA),聚甲基丙烯酸甲酯(PMMA)。HEMA与MMA共聚物及HEMA或MMA与甲基丙烯酸(MAA)或三甲基氨乙基甲基丙烯酸酯(TMAEA-HCl),将其材料涂层于玻璃或硅化玻     

001 聚氨酯表面接枝左旋-丙交酯以改善细胞粘附性

[英]/Hsu Shan-Hui… //Biomaterials. - 2000, 21(4).-359～367 聚氨酯具有良好的生物相容性和力学性能,在心血管材料及其它生物医用材料领域得到广泛应用,但其表面的细胞粘附性较差,本文研究了运用等离子体引发表面接枝方法改善聚氨酯表面的细胞粘附性.市售聚氨酯溶于四氢呋喃铸成膜,用氩等离子体处理后在空气中放置一定时间,浸入溶有左旋丙交酯的甲苯中,脱气封管在70℃反应5h,得到表面接枝左旋丙交酯的PU膜.接触角测量显示等离子体处理后水接触角由73°下降到36.,接枝使接触角略有上升,但仍比未处理聚氨酯及聚左旋乳酸表面亲水性好.只用等离子体处理而未进行表面接枝的聚氨酯膜接触角会逐渐升高,原因是表面亲水基团的重新分布.表面接枝后即无此现象.ESCA分析显示处理后表面基团发生变化,O/C比上升,有新的表面基团形成,且结构也不同与本体聚合的聚左旋乳酸.经过如此表面接枝处理的聚氨酯膜对成纤维细胞的粘附性较未处理聚氨酯膜有了成倍增长,也优于仅用等离子体处理的聚氨酯膜,对上皮细胞的粘附情形也类似.SEM观察显示粘附在接枝处理后的聚氨酯膜表面的细胞更为伸展.而血小板在接枝处理过的聚氨酯膜表面的粘附量及活性明显下降.总之,运用等离子体引发聚氨酯表面接枝左旋丙交酯获得了更好的血液相容性,具有潜在的广泛应用前景. (陈晓东摘朴东旭校)     

纤维素透析膜血液相容性的改进在纤维素膜的表面接枝2—甲基丙烯酰乙氧基磷酸胆碱

作为血液透析膜纤维素膜的血液相容性不能令人满意。本文提出将2-甲基丙烯酰乙氧基磷酸胆碱(MPC)接枝到纤维素膜表面,以改善其血液相容性。接枝反应以MPC为单体,铈离子(Ce~(4+))为引发剂,反应混合物经除氧后于40℃反应一小时得产物。体系中微量氧的存在会严重影响反应的进行。产物的X-射线光电子能谱(xps)和付里叶变换红外光谱(FT-IR)证明了MPC接枝到膜表面的事实。反应混合物中〔MPC〕、〔Ce~4〕的改变对接枝反     

似肝素聚氨酯尿素的合成与非血栓形成

在合成血液相容性材料中,最主要的是肝素化作用。肝素是一种天然聚阴离子多糖,能涂层或固定于材料表面。本文作者曾经合成新的聚醚聚氨酯尿素,研究了肝素化聚醚聚氨酯作为体外抗血栓性、蛋白吸附、血小板粘附、成纤维细胞附着和体内抗血栓性。结果表明了肝素释放对材料的非血栓形成性及肝素化聚合物抑制凝血系统活性和血小板活化。许多作者采用了磺酸盐基团合成聚合物来提高材料的血液相容性。在本文的研究中,作者发现采用功能基因进入聚氨酯尿素中,获得非血     

血小板膜糖蛋白Ⅳ的基础与临床

血小板膜糖蛋白Ⅳ(GP Ⅳ)与溶酶体结合膜蛋白(LIMP Ⅱ)同属于一类新基因家族。近年,血小板膜GP Ⅳ的cDNA克隆成功,使人们对它的分子结构和基因结构特征有了清楚的认识。血小板膜GP Ⅳ主要参与血小板的粘附、聚集和信号传导功能,而血小板膜GP Ⅳ的质或量异常,可能与某些疾病的发生、发展有一定的关系。     

大鼠烧伤后血小板免疫粘附功能的变化

用血小板免疫粘附补体致敏酵母菌凝集试验,对烧伤在血小板免疫粘附功能方面的影响进行了研究。对烧伤前及烧伤后24小时、48小时大白鼠的血小板进行了试验。烧伤后24小时和48小时血小板免疫粘附功能明显增强(P<0.01)。本文对血小板免疫粘附功能与 DIC 和烧伤早期致死性的关系进行了讨论。     

一种新型生物人工肝膜材料体外激活血小板的实验

目的：体外研究一种新型生物人工肝反应器材料-丙稀酰胺接枝改性聚丙烯膜（PP-g-AAm）对血小板的激活，并评价其血液相容性。方法： 模拟体内条件将PP-g-AAm膜和对照组未改性的聚丙烯（PP）膜与富含血小板血浆（PRP）接触后，用ELISA法检测血浆中β－血小板球蛋白（β-TG）的表达， 用流式细胞术检测血小板活化标志CD62P和CD63的表达，用扫描电镜检测两种膜上血小板粘附情况。 结果： 两种膜材料接触PRP 30 min后，血浆β-TG的表达均高于空白对照组（P<0.01, P<0.05），两材料组之间差异显著（P<0.05）； PP-g-AAm膜激活血小板表达CD62P、CD63的百分率都明显少于PP膜（P<0.05， P<0.01）；两种膜材料接触PRP 1 h后，扫描电镜观察材料表面粘附的血小板都有明显变形，但PP-g-AAm膜表面粘附的血小板明显少于PP膜。结论： PP-g-AAm膜对血小板的激活明显少于PP膜，具有较好的血液相容性。     

Nano-scale surface modification of a segmented polyurethane with a phospholipid polymer

Nano-scale modification of a segmented polyurethane (SPU) with cross-linked 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer was performed to obtain a biocompatible elastomer. To control the domain size and the depth of the modified layer, various compositions of monomers, including MPC, 2-ethylhexyl methacrylate (EHMA), and glycerol 1,3-diglycerolate diacrylate, were examined. SPU film was immersed in the monomer solution and visible light irradiation was applied to initiate polymerization to the SPU film that was held by mica to condense MPC units at the surface. The surfaces of the obtained film were analyzed by X-ray photoelectron spectroscopy and water contact angle measurement. The surface density of MPC units changed with the monomer concentration, and the density was the highest when the ratio between MPC and EHMA was 7:3. In modified SPU films, 6- to 25-nm MPC unit-enriched domains were observed and the density of these domains gradually decreased with depth. The sizes of the domains depended on the MPC composition in the monomer solution. The mechanical properties of the modified films as evaluated by tensile strength measurement under wet conditions were not significantly different from those of SPU. With increase in the existence of MPC unit-enriched domains on the MEG film surface, platelet adhesion and activation were remarkably reduced compared to the SPU film. This nano-scale surface modification may be a useful technique for applying elastic polymer biomaterials.     

Synthesis,Characterization and Biomedical Properties of UV-Cured Polyurethane Acrylates Containing a Phosphorylcholine Structure

Abstract

In order to develop a simple, economical and rapid approach to incorporate 2-methacryloyloxyethyl phosphorylcholine (MPC) with other monomers without any solvent, we prepared a series of ultraviolet cured poly(urethane acrylate) (PUA) membranes containing different MPC content. Their chemical structure and surface properties were investigated by FT-IR, XPS, water swelling ratio and water contact angle measurement, while the biocompatibilities were evaluated through fibrinogen adsorptions, platelet adhesion and plasma recalcification time determination. The results demonstrate that the phosphorylcholine (PC) groups were successfully introduced into the PUA system by the UV-curing approach and the all PC-containing membranes showed better biocompatibility than those without PC moiety. The UV-curing method is potentially to be applied in the coating of medical devices which require biocompatibility and manufacturing efficiency.     

Modification of polysulfone with phospholipid polymer for improvement of the blood compatibility. Part 2. Protein adsorption and platelet adhesion.

Protein adsorption and platelet adhesion from human plasma on polysulfone (PSf) membranes modified with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer were studied. The modification was carried out by blending of the MPC polymer in the PSf. The amount of protein adsorbed on the PSf/MPC polymer blend membrane was significantly decreased with an increase in the composition of the blended MPC polymer. The distribution of the specific proteins adsorbed on the membrane surface was also determined by a gold-colloid immunoassay. Albumin, gamma-globulin and fibrinogen were observed on every membrane surface after contact with plasma. However, in the case of the blended membrane, the density of the adsorbed proteins decreased compared with that of original PSf membrane. That is, the MPC polymer blended in the membrane could function as a protein-adsorption-resistant additive. The number of platelets adhered on the PSf membrane was reduced, and change in the morphology of adherent platelets was also suppressed by the modification with the MPC polymer. Therefore, the PSf/MPC polymer blend membrane had improved blood compatibility compared with the PSf membrane.     

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.     

Physical properties and blood compatibility of surface-modified segmented polyurethane by semi-interpenetrating polymer networks with a phospholipid polymer

Segmented polyurethanes, (SPU)s, are widely used in the biomedical fields because of their excellent mechanical property. However, when blood is in contact with the SPU, non-specific biofouling on the SPU occurs which reduces its mechanical property. To obtain novel blood compatible elastomers, the surface of the SPU was modified with 2-methacryloyloxyethyl phosphorylcholine (MPC) by forming a semi-interpenetrating polymer network (semi-IPN). The SPU film modified by MPC polymer with the semi-IPN (MS-IPN film) was prepared by visible light irradiation of the SPU film in which the monomers were diffused. X-ray photoelectron spectroscopy confirmed that the MPC units were exposed on the MS-IPN film surface. The mechanical properties of the MS-IPN film characterized by tensile testing were similar to those of the SPU film. Platelet adhesion on MS-IPN films was also investigated before and after stress loading to determine the effects of the surface modification on the blood compatibility. Many platelets did adhere on the SPU film before and after stress loading. On the other hand, the MS-IPN film prevented platelet adhesion even after repeated stress loading.     

Methacrylate polymer layers bearing poly(ethylene oxide) and phosphorylcholine side chains as non-fouling surfaces: in vitro interactions with plasma proteins and platelets

Two methacrylate monomers, oligo(ethylene glycol) methyl ether methacrylate (OEGMA; MW = 300 g mol⁻¹, poly(ethylene glycol) (PEG) side chains of average length n = 4.5) and 2-methacryloyloxyethyl phosphorylcholine (MPC; MW = 295 g mol⁻¹), were grafted from silicon wafer surfaces via surface-initiated atom transfer radical polymerization. The grafted surfaces were used as model PEG and phosphorylcholine surface systems to allow comparison of the effectiveness of these two motifs in the prevention of plasma protein adsorption and platelet adhesion. It was found that at high graft density fibrinogen adsorption from plasma on the poly(MPC) and poly(OEGMA) surfaces for a given graft chain length was comparable and extremely low. At low graft density, poly(OEGMA) was slightly more effective than poly(MPC) in resisting fibrinogen adsorption from plasma. Flowing whole blood experiments showed that at low graft density the poly(OEGMA) surfaces were more resistant to fibrinogen adsorption and platelet adhesion than the poly(MPC) surfaces. At high graft density, both the poly(MPC) and poly(OEGMA) surfaces were highly resistant to fibrinogen and platelets. Immunoblots of proteins eluted from the surfaces after contact with human plasma were probed with antibodies against a range of proteins, including the contact phase clotting factors, fibrinogen, albumin, complement C3, IgG, vitronectin and apolipoprotein A-I. The blot responses were weak on the poly(MPC) and poly(OEGMA) surfaces at low graft density and zero at high graft density, again indicating strongly protein resistant properties for these surfaces. Since the side chains of the poly(OEGMA) are about 50% greater in size than those of poly(MPC), the difference in protein resistance between the poly(MPC) and poly(OEGMA) surfaces at low graft density may be due to the difference in surface coverage of the two graft types.     

Chemical modification of silk fibroin with 2-methacryloyloxyethyl phosphorylcholine. II. Graft-polymerization onto fabric through 2-methacryloyloxyethyl isocyanate and interaction between fabric and platelets

2-Methacryloyloxyethyl phosphorylcholine (MPC) was grafted onto silk fabric in a two-step heterogeneous system through the vinyl bonds of 2-methacryloyloxyethyl isocyanate (MOI) modified on the fabric. First, habutae silk fabric was modified with the MOI monomer in anhydrous dimethyl sulfoxide using di-n-butyltin (IV) dilaurate and hydroquinone at 35 degrees C. The saturated weight gain of modified MOI monomer on the fabric was 7.3 wt% versus the original silk. Second, graft polymerization with MPC onto the MOI modified silk was conducted using 2,2'-azo bis[2-(2-imidazolin-2-yl)propane dihydrochloride] (VA-044) as an azo polymerization initiator. The weight of the grafted MPC eventually gained was about 26.0 wt%. The MOI-modified and MPC-grafted silk fabrics were analyzed by Fourier transform infrared (FT-IR) spectroscopy. To confirm the improved biocompatibility of the silk fabric, platelet adhesion was preliminarily tested measuring lactate dehydrogenase. The number of platelets adhering to polyMPC-grafted silk fabric decreased by about one tenth compared to original and MOI-modified silk after 60 min of contact with human platelet-rich plasma (1.0 x 10(6) platelets cm(-2)).     

Tuned Surface and Mechanical Properties of Polymeric Film Prepared by Random Copolymers Consisting of Methacrylate‐POSS and 2‐(Methacryloyloxy)ethyl Phosphorylcholine

Poly(2‐(methacryloyloxy)ethyl phosphorylcholine) (PMPC) is known as a biocompatible polymers. Copolymerization of 2‐(methacryloyloxy)ethyl phosphorylcholine (MPC) and hydrophobic monomers is a general approach that gives bioinert functions to solid materials via the surface coating. However, due to the amorphous nature and super hydrophilicity of the MPC‐based copolymers, both the surface and the mechanical properties are not controlled for biomedical applications. Here, the modulated mechanical property and the surface wettability of the MPC‐based copolymers are shown by using a polyhedral oligomeric silsesquioxane (POSS) methacrylate. MPC is copolymerized with POSS methacrylates bearing different vertex groups of ethyl (C₂H₅), hexayl (C₆H₁₃), and octayl (C₈H₁₇) via radical polymerization. It is found that only the C₂H₅‐POSS induces the increased mechanical strength, low surface wettability, and cellular attachment, suggesting that the C₂H₅‐POSS moiety restricts the motion of PMPC chain. The finding is anticipated to be tuned for both surface and bulk functions of PMPC for biomedical applications.     

Surface tethering of phosphorylcholine groups onto poly(dimethylsiloxane) through swelling--deswelling methods with phospholipids moiety containing ABA-type block copolymers

The surface modification of poly(dimethylsiloxane) (PDMS) substrates by using ABA-type block copolymers comprising poly(2-methacryloyloxyethyl phosphorylcholine (MPC)) (PMPC) and PDMS segments was investigated. The hydrophobic interaction between the swelling-deswelling nature of PDMS and PDMS segments in block copolymers was the main mechanism for surface modification. Block copolymers with various compositions were synthesized by using the atom transfer radical polymerization (ATRP) method. The kinetic plots revealed that polymerization could be initiated by PDMS macroinitiators and it proceeds in a well-controlled manner; therefore, the compositions of the block copolymers were controllable. The obtained block copolymers were dissolved in a chloroform/ethanol mixed solvent. The surface of the PDMS substrate was modified using block copolymers by the swelling-deswelling method. Static contact angle and X-ray photoelectron spectroscopy (XPS) measurements revealed that the hydrophobic surface of the PDMS substrate was converted to a hydrophilic surface because of modification by surface-tethered PMPC segments. Protein adsorption test and L929 cell adhesion test were carried out for evaluating the biocompatibility. As observed, the amount of adsorbed proteins and cell adhesion were drastically reduced as compared to those in the non-treated PDMS substrate. We conclude that this procedure is effective in fabricating biocompatible surfaces on PDMS substrates.