TiO2-x薄膜与热解碳血液相容性的对比研究

本文用血小板粘附试验证实了TiO2 x薄膜具有优于热解碳的血液相容性 ;并通过对材料表面 (界面 )能参数与血浆蛋白吸附关系的分析 ,阐述了两种材料表面蛋白质的不同吸附行为是导致其血液相容性差异的重要原因。     

TiO2-x薄膜与热解碳血液相容性的对比研究

本文用血小板粘附试验证实了TiO2-x薄膜具有优于热解碳的血液相容性;并通过对材料表面(界面)能参数与血浆蛋白吸附关系的分析,阐述了两种材料表面蛋白质的不同吸附行为是导致其血液相容性差异的重要原因.     

用于心血管医疗装置的聚合物材料表面构建与生物相容性研究Ⅱ-心血管医疗装置聚合物的表面构建与生物反应行为

背景:用于心血管医疗的生物材料在血液接触性条件下必须具有抗血栓性、对抗生物降解性与抗感染性。目的:研制用于心血管组织工程的新型植(介)入型聚合物材料(表面),从聚合物生物材料的表面构建与生物反应行为方面考察各种相应改性表面的生物相容性、血液相容性和细胞相容性。方法:检索1984至2013年PubMed数据库及万方数据库,英文检索词为"Biocompatibility,Blood compatibility,Biomedical Materials,Biomedical polymer materials",中文检索词为"生物相容性材料;血液相容性材料;生物医用材料;医用高分子材料"。结果与结论:通过对蛋白质吸附、细胞黏附中的生物识别、凝血与纤溶过程中的酶催化作用"瀑布模型",以及生物材料表面构建与蛋白质表面吸附行为4个方面的归纳分析,研制用于心血管组织工程的新型植(介)入型聚合物材料(表面)关键在于对聚合物生物材料生物功能性表面的构建,以及对其相应生物相容性与内皮细胞相容性的研究。通过对聚合物生物材料种类与应用及其心血管医疗器件和可植入性软组织替代物的深入研究可以发现,表面与本体的差别将体现在从表面向本体延伸的很多层分子上,而两种主要因素决定了其包括本体/表面差异及表面相分离在内的本体/表面行为,即表面能和分子运动性。如果考虑到对本体-表面组成差异的理解,还必须追加附加决定因素,即各组分的结晶行为。     

生物材料与血液相互作用过程的研究进展

血液相容性是制约生物材料在血液环境中应用的一个关键因素。材料的血液相容性主要取决于材料与血液之间一系列的相互作用过程。近年来,随着对蛋白质结构检测手段的增加,以及分子生物学技术的发展,对材料与血液的相互作用过程的研究也逐步深入到分子结构水平。国际上越来越多地应用分子生物学的方法,从多角度分析材料表面结构和组成对血液中蛋白质分子和细胞功能与结构的影响。本文主要归纳了近年来国际上在生物材料与血液相互作用研究方面出现的一些新的视点和方法,并对它们的特点以及发展趋势进行了探讨。     

白蛋白固定的聚氨酯材料的血液相容性

与血液接触的医用材料用白蛋白进行表面处理后,可抑制血小板粘附、激活以及继而产生的血栓形成。尽管已被吸附的白蛋白能够改善材料的血液相容性,但当材料表面的白蛋白层与循环血液接触时,仍能迅速地发生能吸附作用。在本文中,作者将人血清白蛋白固定在聚氨酯(Pu)材料表面上,以研究其血液相容性及血液-材料相互作用方法的延伸效应。先用HMDI处理Pu材料表面,然后将白蛋白与Pu-HMDI接触,以便把白蛋白固定在Pu表面(P-u-Alb)。Pu-Alb材料表面具有富里叶衰减全反射红外光谱、电子能谱、扫描电镜以及动态接触角等方面的特征。通过蛋白质吸附、血小板粘附等体外试验,     

类肝素化高分子表面:通过不溶聚合物的官能团化抑制凝血和补体激活

在低的流动条件下,或当接触表面积与血液容量之比较高时,血液与异种表面接触所发生的情况是由所谓的“血液相容性”所决定的。常规情况下,除了我们自身健康的内皮细胞,我们的血液与任何表面都不相容。对于一个人工表面,血液不相容性至少要考虑两个方面:凝血过程和     

聚氨酯的血液相容性评价

血液相容性是生物材料研究领域里最受关注的问题之一。血液相容性是一个涉及血液和生物医学材料表面作用的复杂现象 ,影响因素繁多。对材料的血液相容性的测试和评价同样是一个复杂问题 ,涉及到多学科、多领域的技术和方法。本文以聚氨酯为例 ,对生物材料血液相容性的概念、生物医学材料表面和血液的相互作用以及评价方法作一综述     

用于心血管医疗装置的聚合物表面构建与生物相容性研究Ⅲ——聚合物生物材料表面的凝血及抗凝血涂层改性（英文）

背景:用于心血管医疗的生物材料在血液接触性条件下必须具有抗血栓性、对抗生物降解性与抗感染性。目的:研制用于心血管组织工程的新型植(介)入型聚合物材料(表面),从聚合物生物材料表面的凝血及抗凝血涂层改性方面考察各种相应改性表面的生物相容性、血液相容性和细胞相容性。方法:检索1983至2014年PubMed数据库及万方数据库。英文检索词为"biocompatibility,blood compatibility,biomedical materials,biomedical polymer materials",中文检索词为"生物相容性材料;血液相容性材料;生物医用材料;医用高分子材料"。排除与研究目的相关性差及内容陈旧、重复的文献,保留与生物医用高分子材料的血液相容性研究,进行归纳总结。结果与结论:通过对血液与植入物间的相互作用和生物材料表面的抗凝血涂层改性两个方面的归纳分析,从聚合物生物材料表面的凝血及抗凝血涂层改性方面考察了各种相应改性表面的生物相容性、血液相容性和细胞相容性。研制用于心血管组织工程的新型植(介)入型聚合物材料(表面)关键在于对聚合物生物材料表面的凝血及抗凝血涂层改性以及对其相应生物相容性与内皮细胞相容性的研究。通过对心血管医疗用聚合物生物材料的种类与应用及其心血管医疗器件和可植入性软组织替代物的深入研究可以发现表面与本体的差别则将体现在从表面向本体延伸的很多层分子上,而2种主要因素决定了其包括本体/表面差异及表面相分离在内的本体/表面行为,即表面能和分子运动性。如果考虑到对本体-表面的组成差异的理解,则还必须追加另以附加决定因素,即各组分的结晶行为。     

改进生物材料表面血液相容性的现代技术

改进医用装置的血液相容性有两种基本途径,即研制具备所需血液相容性的新材料和对装置的血液接触表面进行改性。由于研制一种既具有要求的机械性能,同时又有良好的表面血液相容性材料通常十分困难,因此,通过表面改性获得血液相容性装置是一种更为实用的技术。这些技术可分为三种基本类型:首先是增加表面亲水性,降低表面与血液成分的相互作用。其中在表面接枝聚氧化乙烯是一种广为应用的方法,应引起特别注意;其次,对聚合物表面进行伪饰,使其不被血液视为异     

渗透性聚氨酯聚合物亲水性对组织反应的影响

键段聚氨酯已用于生物医学装置,因为它们具有明显的物理机械特性及相对较好的生物相容性。聚氨酯材料表面改性提高血液相容性,主要与表面电荷、表面能、地形和疏—亲水性平衡等因素有关。认为亲—疏水性比率最好可提高血液相容性,     

类金刚石薄膜血液相容性与蛋白吸附的关系研究

以金刚石薄膜 ( DF)和石墨为参比材料 ,采用放射性同位素 1 2 5I标记技术 ,研究了人血白蛋白 ( HSA)、纤维蛋白原 ( HFG)和免疫球蛋白 ( Ig G)在类金刚石薄膜 ( DL C)表面单一蛋白的等温吸附和二元蛋白体系的竞争吸附。结果显示 :( 1)随着蛋白浓度的增加 ,三种蛋白在三种材料表面的吸附量增加 ,并趋于吸附平衡 ;( 2 )石墨对三种蛋白的吸附量远高于 DL C和 DF;( 3 ) DL C对 HSA的吸附活性高于 DF,而 DF、石墨对 HFG、Ig G的吸附活性则明显高于 DL C;( 4) DL C对三种蛋白的吸附能力相差不大 ,而 DF和石墨对 HFG、Ig G的吸附量则显著高于 HSA;( 5 )三种蛋白在 DF和石墨表面的相对竞争吸附能力为 HFG>Ig G>HSA,而对于 DL C,这一顺序则为 HFG≈ HSA>Ig G,HFG对 HSA没有表现出明显的竞争吸附优势。这些结果表明 :DL C对三种血浆蛋白的吸附是非特异性的 ,而DF和石墨则不同程度地优先吸附 HFG和 Ig G,从而在分子水平上阐释了 DL C血液相容性好于 DF和石墨的内在原因     

Fibrinogen adsorption, platelet adhesion and activation on mixed hydroxyl-/methyl-terminated self-assembled monolayers

The effect of surface wettability on fibrinogen adsorption, platelet adhesion and platelet activation was investigated using self-assembled monolayers (SAMs) containing different ratios of longer chain methyl- and shorter chain hydroxyl-terminated alkanethiols (C15CH3 vs. C11OH) on gold. Protein adsorption studies were performed using radiolabeled human fibrinogen (HFG). Platelet adhesion and activation studies with and without pre-adsorbed fibrinogen, albumin and plasma were assessed using scanning electron microscopy (SEM) and a glutaraldehyde-induced fluorescence technique (GIFT). Results demonstrated a linear decrease of HFG adsorption with the increase of OH groups on the monolayer (increase of the hydrophilicity). Platelet adhesion and activation also decrease with increase of hydrophilicity of surface. Concerning SAMs pre-immersed in proteins, fibrinogen adsorption was related with high platelet adhesion and activation. The passivant effect of albumin on platelet adhesion and activation was only demonstrated on SAMs contained C11OH. When all the blood proteins are present (plasma) platelet adhesion was almost absent on SAMs with 65% and 100% C11OH. This could be explained by the higher albumin affinity of the SAMs with 65% C11OH and the lower total protein adsorption associated with SAMs with 100% C11OH.     

Improvement of blood compatibility on polysulfone-polyvinylpyrrolidone blend films as a model membrane of dialyzer by physical adsorption of recombinant soluble human thrombomodulin (ART-123)

ART-123 is a recombinant soluble human thrombomodulin (hTM) with potent anticoagulant activity, and is available for developing antithrombogenic surfaces by immobilization. We focused on improving blood compatibility on the dialyzer surface by the physical adsorption of ART-123 as a safe yet simple method without using chemical reagents. The physical adsorption mechanism and anticoagulant activities of adsorbed hTM on the surface of a polysulfone (PSF) membrane containing polyvinylpyrrolidone (PVP) as a model dialyzer were investigated in detail. The PVP content of the PSF-PVP films was saturated at 20 wt% after immersion in Tris-HCl buffer, even with the addition of over 20 wt% PVP. The surface morphology of the PSF-PVP films was strongly influenced by the PVP content, because PVP covered the outermost surface of the PSF-PVP films. The adsorption speed of hTM slowed dramatically with increasing PVP content up to 10 wt%, but the maximum adsorption amount of hTM onto the PSF-PVP film surface was almost the same, regardless of the PVP content. The PSF-PVP film with the physically adsorbed hTM showed higher protein C activity as compared to the PSF film, it showed excellent blood compatibility due to the protein C activity and the inhibition properties of platelet adhesion. The physical adsorption of hTM can be useful as a safe yet simple method to improve the blood compatibility of a dialyzer surface.     

类金刚石薄膜成分变化对蛋白吸附的影响

采用全方位离子注入离子束增强沉积工艺制备类金刚石薄膜 (DL C) ,再将 DL C进行有氧和低压氩气保护条件下的热处理 ,分别得到富石墨相 DL C和富金刚石相 DL C。通过 X光电子能谱分析了三种 DL C的碳相组成 ,用放射性同位素 1 2 5I标记法 ,测定了恒温条件下人血白蛋白 (HSA)、纤维蛋白原 (HFG)和免疫球蛋白 (Ig G)在 3种 DL C材料表面的吸附量。结果 ,经两种不同的热处理工艺 ,DL C中石墨相和金刚石相分别增加了一倍左右 ;随着石墨、金刚石等杂质相的增加 ,DL C对 HSA的吸附能力下降 ,对 HFG和 Ig G的吸附能力显著提高 ,同时蛋白吸附特性也由原来对 3种蛋白的非特异性吸附 ,转变为对 HFG和 Ig G的优先吸附。这一结果表明 ,石墨和金刚石等杂质相将严重影响 DL C的蛋白吸附性能 ,并进而对 DL C的血液相容性产生负面影响。文中还对石墨和金刚石相的转化生成机理进行了探讨     

Improvement of Blood Compatibility on Polysulfone–Polyvinylpyrrolidone Blend Films as a Model Membrane of Dialyzer by Physical Adsorption of Recombinant Soluble Human Thrombomodulin (ART-123)

ART-123 is a recombinant soluble human thrombomodulin (hTM) with potent anticoagulant activity, and is available for developing antithrombogenic surfaces by immobilization. We focused on improving blood compatibility on the dialyzer surface by the physical adsorption of ART-123 as a safe yet simple method without using chemical reagents. The physical adsorption mechanism and anticoagulant activities of adsorbed hTM on the surface of a polysulfone (PSF) membrane containing polyvinylpyrrolidone (PVP) as a model dialyzer were investigated in detail. The PVP content of the PSF–PVP films was saturated at 20 wt% after immersion in Tris-HCl buffer, even with the addition of over 20 wt% PVP. The surface morphology of the PSF–PVP films was strongly influenced by the PVP content, because PVP covered the outermost surface of the PSF–PVP films. The adsorption speed of hTM slowed dramatically with increasing PVP content up to 10 wt%, but the maximum adsorption amount of hTM onto the PSF–PVP film surface was almost the same, regardless of the PVP content. The PSF–PVP film with the physically adsorbed hTM showed higher protein C activity as compared to the PSF film, it showed excellent blood compatibility due to the protein C activity and the inhibition properties of platelet adhesion. The physical adsorption of hTM can be useful as a safe yet simple method to improve the blood compatibility of a dialyzer surface.     

In vitro studies of platelet adhesion, activation, and protein adsorption on curcumin-eluting biodegradable stent materials

A major complication of coronary stenting is in-stent restenosis (ISR) due to thrombus formation. We hypothesized that locally released curcumin from coronary stent surface would inhibit ISR due to thrombus formation because of antithrombosis of curcumin. In the present work, curcumin-eluting polylactic acid-co-glycolic acid (PLGA) films were fabricated and their properties in vitro were investigated. The in vitro platelet adhesion and activation, as well as protein adsorption on curcumin-loading PLGA films were investigated to evaluate the blood compatibility of curcumin-eluting films. The structure of curcumin-eluting PLGA film and control was examined by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy indicating that the peaks of curcumin did not shift in curcumin-eluting films. The results of contact angle and surface free energy indicated that loading curcumin in PLGA would make PLGA become more hydrophilic, which contributed to the increase of polar fraction of surface free energy. With the increase of curcumin in films, platelets adhering to the curcumin-eluting films decreased significantly. The number of activation platelets decreased after incorporating curcumin in PLGA films. Loading curcumin in PLGA film can markedly reduce the fibrinogen adsorption. All results indicated that incorporating curcumin in PLGA film can improve the blood compatibility of PLGA films. It can be used to fabricate drug-eluting stent to prevent thrombosis formation.     

类金刚石薄膜蛋白吸附与碳相成分关系的定量分析研究

运用灰色系统理论中的 T型关联度分析方法 ,对类金刚石 (DL C)薄膜、富石墨相 DL C薄膜和富金刚石相 DL C薄膜三种 DL C薄膜进行了碳相成分对其白蛋白 (HSA)、纤维蛋白原 (HFG)、免疫球蛋白 (Ig G)三种血浆蛋白吸附量影响的定量分析研究。合理地解释了三种材料蛋白吸附量随碳相成分变化的实验结果 ,并得出如下重要的分析结论 :(1)石墨和 C- H相对 HSA的吸附影响较大 ,随着二者的增加 ,HSA的吸附量下降 ;(2 )与 HFG吸附有较强关联的碳相成分是 DL C相和 C- O相 ,前者呈负相关 ,后者为正相关 ;(3)各碳相成分对 Ig G的吸附均有性质不尽相同的影响 ,但程度有限 ,且彼此间相差不大 ;(4 ) DL C碳相具有增强 HSA吸附、抑制 HFG、Ig G吸附的双重功效 ,其对 DL C薄膜血液相容性的影响远较其它碳相成分更为重要。     

Competitive protein adsorption on biomaterial surface studied with reflectometric interference spectroscopy

Reflectometry interference spectroscopy (RIfS) is known as a highly sensitive and robust technique for direct, label-free detection of the interaction of biomacromolecules in real time and in situ. The aim of the present study was to investigate the competitive protein adsorption on the surface of fluorocarbon end-capped poly(carbonate) urethane (PCUF) and polystyrene (PS) based on the RIfS method. The surface energy and microstructures of PCUF and PS were characterized by contact angle measurement and atomic force microscopy. Interfacial energies between these surfaces and the proteins were then calculated. The protein adsorption experiments were carried out with both single solution and ternary solutions composed of albumin, fibrinogen and immunoglobulin-G (IgG). The results of surface characterization showed that PCUF was more hydrophilic than PS with a smaller surface energy, and micro-phases separation of PCUF was observed. RIfS analysis results revealed that more albumins, less fibrinogen and IgG were detected on the PCUF surface compared with PS after simplex and competitive protein adsorption, which indicated that PCUF had a preferential adsorption for albumin. The special morphology, smaller surface energy and calculated interfacial energies between PCUF and proteins may be responsible for the better blood compatibility of PCUF compared to PS. The results suggest that RIfS could serve as a novel, effective method for studying the competitive protein adsorption on biomaterial surfaces.     

Crosslinked polyether/polysiloxane networks for blood-interfacing applications

The interaction of blood with new artificial surfaces is an area of continual medical interest. In this study, a series of polyether/polysiloxane networks were synthesized, characterized in terms of both bulk and surface compositions, and evaluated for blood compatibility. The crosslinked networks were produced by reacting the epoxy groups of polyglycidoxy propyl methyl siloxane (PGPMS) with the hydroxyl end groups of polypropylene glycol (PPG). Blood compatibility was evaluated using an in vitro platelet retention test and fibrinogen adsorption experiments from human plasma and buffered saline. The PPG/PGPMS networks exhibit low fibrinogen adsorption and low platelet activation. Such properties make the networks potentially attractive as materials for blood-interfacing applications.     

Influence of silicon concentration on the haemocompatibility of amorphous carbon

Amorphous carbon (a-C) has good blood compatibility and has been proposed as a coating material for blood contacting devices such as heart pumps and stents. In this study, unhydrogenated a-C films with different silicon concentrations were synthesized by magnetron sputtering, and the corresponding evolution of the surface energy and compatibility with blood were analysed. The incorporation of silicon not only decreased the sp(2)-hybridized carbon bonding configurations, but the static evaluation of the films incubated in human platelet-rich plasma also showed a decrease in platelet adhesion. Bonding structure and surface energy were determined to be factors contributing to the improved haemocompatibility.