聚氨酯的血液相容性评价

血液相容性是生物多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。     

聚乳酸类生物材料的生物相容性研究概述

聚乳酸是广泛应用于生物医学领域的生物材料,随着改性聚乳酸生物材料的大量出现,对其生物相容性的研究越来越成为关注热点。文章概述近年来国内外对聚乳酸类生物材料在细胞相容性、血液相容性和组织相容性等方面所进行的生物相容性研究,汇集被该领域学者普遍采用并接受的技术指标、实验方法和评价体系,论述聚乳酸类生物材料的生物相容性研究中存在的问题,并对该领域的发展趋势与方向进行展望。希望聚乳酸类生物材料的生物相容性评价体系尽快得到完善和发展。     

生物材料血液相容性的表面能量观

前言 对高聚物血液相容性的评价及其抗凝机制的探讨一直是当今生物材料专家们很感兴趣的领域。其中引人关注的是从材料表面能量的角度来考查材料的血液相容性。通常通过测定材料和已知表面张力的液体之间的接触角导出材料的表面张力,从而考查各种表面的能量与血液相容性的相关性。在采用接触角技术确定表     

目前生物医用材料领域的研究热点

<正>1生物材料表面改性改进和发展生物医用材料的血液相容性和组织相容性以及生物材料分子相容性评价新方法研究。今后对材料生物相容性的研究主要集中在以下3个方面:①生物医用材料对组织、器官的     

血小板与生物材料相互作用的研究进展

本文对生物材料血液相容性研究的一个重要方面——血小板与材料的相互作用作了综述。着重介绍了血小板与材料相互作用的评价方法、反应机制及改善生物材料血液相容性的途径的研究进展。     

人工血管材料血液相容性及表面改性

背景:人工血管取于合成材料,是最常用的血管代用品,如何提高血管的通畅性和人工血管材料的相容性是在近年来人工血管研究的重点。目的:综述人工血管材料的生物相容性和血液相容性,归纳近年来国际在生物材料和血液相互作用研究方面出现的一些新方法和视点。方法:由第一作者用计算机检索万方数据库、中国期刊全文数据库和PubMed数据库2001至2014年的文献,检索词分别为"人工血管,生物材料;Biomaterials,Artificial blood vessels"。结果与结论:血液相容性材料的研究虽然历经了很多年,但目前仍然处于探索阶段。血液相容性的影响因素繁多,除血液固有成分外,材料表面界面特征起着决定性作用。目前,材料表面界面特征优化及改性已成为提高其血液相容性的重要途径,但现有的评价体系仍存在一些问题,如敏感指标和有效阳性对照材料的选择及其评价结果量化等。因此良好血液相容性材料的研制及合理、高效血液相容性评价体系的建立依然需要不断努力。     

血小板与生物材料相互作用的研究进展

本对生物材料血液相容性研究的一个重要方面——血小板与材料的相互作用作了综述。着重介绍了血小板与材料相互作用的评价方法、反应机制及改善生物材料血液相容性的途径的研究进展。     

人工材料与人工脏器的生物相容性

目前临床上使用的许多装置都是用金属、玻璃、陶瓷和高分子等材料制作的,现在一般把这些医用材料统称为“生物材料”(Biomaterial)。研究这些材料,首先遇到的问题是如何快速、准确地评价材料的生物相容性,这对于研究新生物材料和加快研究周期将起着重要的作用。但只有少数体外试验能对表面进行很好的表征,并与体内试验结果有相关性。因此,本文结合作者的研究工作,简要介绍生物材料与血液的生物相容性以及生物相容性的评价方法。     

生物材料血液相容性综合评价体系的研究

本文提出由四个体外和半体内试验综合评价生物材料血液相容性的体系,同时用此综合评价体系评价了六种用于心血管系统的聚氨酯材料和一种硅橡胶材料的血液相容性。试验结果表明本文提出的四参数综合评价体系可较真实地评价生物材料对血液的急性反应,并可对生物材料的血液相容性进行粗筛。     

生物材料血液相容性研究进展

本文就材料—血液间相容性的研究进展进行了综述。着重介绍了血液相容性材料、材料—血液间相互作用的生物学基础、血液相容性的评价方法等几方面的内容 ,并对将来生物材料血液相容性的研究方法和从分子水平上设计新型生物材料进行了展望     

血液相容性抗凝血生物医用高分子材料的制备及其机制

背景:由于生物医用材料要接触人体内环境,甚至必须植入生物体内,因此要求具有无毒性、优良的生物相容性、高化学稳定性、合适的物理机械性能以及易加工成型性。 目的：从生物惰性材料、生物活性表面和白蛋白的结构及其在抗凝血上的应用几个方面分析血液相容性抗凝血生物医用高分子材料的制备及其机制。 方法：由第一作者检索1969/2010 PubMed数据及万方数据库有关血液相容性抗凝血生物医用高分子材料的制备及其机制等方面的文献。 结果与结论：目前抗凝血材料的制备基本上只是采用单独的生物惰性表面或生物活性表面,虽然都获得了较好效果,但不能长期保持其生物相容性尤其是血液相容性,如果能将惰性表面与活性表面结合起来,使材料同时具备两者的长处,并能充分利用人体血液中的天然组分白蛋白或许会是抗凝血材料的一个发展趋势。今后希望通过采用高生物惰性的PEU和具有生物活性的白蛋白识别因子cibacron blue复合,合成具有优良性质的活性改性物,并以此对聚氨酯进行改性。     

The use of a library of industrial materials to determine the nature of substrate-dependent performance of primary adherent human cells

We developed a library of industrial materials, which can be applied to any adherent cell type for determining cell-material interactions. Bulk and surface chemistry as well as other material properties were characterized. The library covered broad ranges of various material properties. We applied the library to primary human endothelial and epithelial cells, which play important roles in tissue engineering and biomedical applications. The results revealed that substrate stiffness was the major determinant of cell performance. The ability to grow and differentiate on stiff or more compliant materials was cell type-dependent, but cell performance was consistently best on stiff and smooth materials. These results give new insights into the nature of substrate-dependent performance of primary human cells and are potentially useful for the development of improved biomaterials. The materials of the library can be easily accessed by the scientific community to determine cell-material interactions of any adherent cell type of interest.     

Dynamics of hydrated polyurethane biomaterials: Surface microphase restructuring,protein activity and platelet adhesion

Microphase separation is a central feature of segmented polyurethane biomaterials and contributes to the biological response to these materials. In this study we utilized atomic force microscopy (AFM) to study the dynamic restructuring of three polyurethanes having soft segment chemistries of interest in biomedical applications. For each of the materials we followed the changes in near surface mechanical properties during hydration, as well as fibrinogen activity and platelet adhesion on these surfaces. Both AFM phase imaging and force mode analysis demonstrated that these polyurethane biomaterials underwent reorientation and rearrangement resulting in a net enrichment of hard domains at the surface. Fibrinogen activity and platelet adhesion on the polyurethane surfaces were found to decrease with increasing hydration time. The findings suggest that water-induced enrichment of hydrophilic hard domains at the surface changes the local surface physical and chemical properties in a way that influences the conformation of fibrinogen, changing the availability of the platelet-binding sites in the protein. This work demonstrates that the hydrated polyurethane biomaterial interface is a complex and dynamic environment where the surface chemistry is changing, altering the activity of fibrinogen and affecting blood platelet adhesion.     

Hemocompatibility of high strength oxide ceramic materials: an in vitro study

High strength oxide ceramic materials like alumina and zirconia are frequently used for artificial joints because of their biocompatibility and high wear resistance. Their suitability as materials for implants and biomedical devices with direct blood contact, such as cardiovascular implants or components for blood pumps and dialyzers, has not been confirmed to date. The objective of this study was to investigate whether oxide ceramics show sufficient hemocompatibility. Dense specimens were made out of alumina, zirconia, titanium oxide, and aluminum titanate. Polyvinylchloride and silicone were additionally tested as reference materials. Interactions of human blood with the surfaces were studied by investigating partial thromboplastin time (PTT), thrombin antithrombin III complex (TAT), free plasma hemoglobin concentration, complete blood count, complement factor 5a, and protein adsorption. The results from the PTT and TAT tests clearly indicated higher blood activation by the ceramic materials when compared to the two polymer materials. However, alumina and zirconia showed lower C5a concentrations and less protein adsorption than the reference materials. Our results revealed that oxide ceramic materials alone cannot be used for implants in direct blood contact without modification of the ceramic surface, for example, by made-to-measure inert nanocoatings.     

High molecular weight kininogen adsorption on hemodialysis membranes: influence of pH and relationship with contact phase activation of blood plasma. influence of pre-treatment with poly(ethyleneimine)

Protein adsorption is an essential parameter for the evaluation of the hemocompatibility of biomedical materials. In effect, protein adsorption often generates unfavorable, complex, biochemical reactions and precedes cell adhesion on artificial interfaces. It is therefore necessary to modify the surface in contact with blood in order to minimize the onset of undesirable, biochemical, cascade reactions. Adsorption of high molecular weight kininogen (HK), which participates in the contact phase activation of the endogenous blood coagulation cascade, was evaluated at 37 degrees C. This paper also presents the results of contact phase activation tests carried out in vitro with 1:20 diluted human plasma flowing through minidialyzers containing hollow fibers of synthetic hemodialysis membranes. These tests showed that contact phase activation is strongly dependent on pH around the physiological value (ranging from 7.35 to 7.80) for negatively-charged membranes. The same pH effect was observed on the AN69 membrane as regards HK adsorption from binary labeled solutions of 125I-HK and 131I-Fibrinogen at concentrations corresponding to 1% diluted plasma. It is suggested that the influence of pH could be related to imidazole pKa values in histidine residues of kininogen D5H domain. The same study was also conducted with hemodialysis membranes pre-treated with poly(ethyleneimine). Both HK adsorption and contact phase activation proved to be greatly reduced, irrespective of the pH value (between 7.0 and 7.8). Hence, positively-charged poly(ethyleneimine) adsorbed on the membrane through strong ionic interactions with sulfonate groups of the surface probably constitutes a repelling, water-swollen layer for the kininogen molecule. In addition, the advantages of the high levels of adsorbance of small molecules on the AN69 membrane leading to blood epuration, due to its high porosity and for some of them to its charge density, should not be lost by such a surface treatment.     

血浆蛋白分子在单壁碳纳米管无纺膜表面吸附行为的研究

近年来,碳纳米管的独特表面拓扑结构、化学组成和优异的物理性能已经吸引了众多领域的研究兴趣,以生物医学应用为目标的探索性研究正在迅速形成一个新的方向。我们以血液接触环境下的应用为目标,通过扫描电镜观察、表面元素分析、以及利用酶联免疫分析技术,系统研究了与凝血过程密切相关的纤维蛋白原、白蛋白、免疫球蛋白以及新鲜血浆在单壁碳纳米管无纺膜(SWNT膜)表面的吸附行为。实验结果显示,单壁碳纳米管无纺膜对血浆中的纤维蛋白原分子具有强烈的倾向性吸附,对免疫球蛋白也显示出一定的吸附性,但是,对白蛋白分子却几乎不吸附。血浆蛋白分子在SWNT膜表面的吸附行为与其在其它碳材料表面和其它大多数生物材料表面的吸附行为显著不同。SWNT膜对血浆蛋白分子的独特吸附作用有可能对后续的血液细胞响应产生重要影响。     

Protein adsorption and cellular adhesion and activation on biomedical polymers

The design and development of new biomedical polymers for clinical application in devices, prostheses, and artificial organs requires a basic and fundamental understanding of biological interactions with biomedical polymers. Efforts in our laboratory have been directed towards appreciating the humoral and cellular interactions which govern protein adsorption and cellular adhesion and activation on biomedical polymers. Information and data are presented on protein adsorption from whole human blood, complement activation and receptors, and monocyte/macrophage adhesion and activation with growth factor release. Supported by experimental evidence, concepts regarding protein/polymer, cell/polymer, cell/protein/polymer, and cell/cell interactions as they are related to in vivo events are presented.     

Modification of inflammatory response to implanted biomedical materials in vivo by surface bound superoxide dismutase mimics

The healing response to implanted biomedical materials involves varying degrees and stages of inflammation and healing which in some cases leads to device failure. In this article, we describe synthetic methods and in vivo results of a novel surface treatment for biomedical materials involving covalent conjugation of a low molecular weight superoxide dismutase mimic (SODm), which imparts anti-inflammatory character to the material. SODm investigated in this study are a new class of anti-inflammatory drugs consisting of a Mn(II) complex of a macrocyclic polyamine ring that catalyze the dismutation of superoxide at rates equivalent to that of native enzyme. The SODms were covalently linked to small disks of ultra-high molecular weight polyethylene, poly(etherurethane urea), and tantalum metal at two concentrations and implanted in a subcutaneous rat implant model for 3, 7, 14, and 28 days. Histological examination of the implant tissue performed at 3 and 28 days revealed striking anti-inflammatory effects on both acute and chronic inflammatory responses. At 3 days, the formation of a neutrophil-rich acute inflammatory infiltrate seen in control implants was inhibited for all three materials treated with SODm. At 28 days, foreign body giant cell formation (number of FBGCs per field) and fibrous capsule formation (mean thickness of implant capsule) were also significantly inhibited over untreated control implants. A mechanism based on our current understanding of superoxide as an inflammatory mediator at implanted biomedical materials is proposed.     

Selective Surface Modification in Silicon Microfluidic Channels for Micromanipulation of Biological Macromolecules

Interactions between biological macromolecules and micrometer- and sub-micrometer-scale surface structures are directly influenced by the surface wettability, chemical reactivity and surface charge. Understanding these interactions is crucial for developing integrated microsystems for biological and biomedical processing and analysis. We report development of selective surface modification techniques based on microcontact printing and polyelectrolyte adsorption. These techniques were applied to lithographically patterned silicon microfluidic channels and flat silicon substrates to create surface microstructures with contrasting wetting properties and surface charges. These controls enabled us to devise various techniques for controlled loading and processing of biomaterials in the channels. Solutions containing long chain biological macromolecules DNA and microtubules were directly loaded into the microchannels by using a micromanipulator/microinjector system. Structural arrangements of these linear macromolecules, which were probed by using fluorescence and laser scanning confocal microscopy, were found to be quite different from bulk solutions. As expected, the filamentous molecules were observed to align linearly along the channels, with the degree of alignment dependent on channel width as well as the length of the molecule. This molecular alignment, which is induced by both the surface confinement effect and capillary flow during sample loading, may be used to enhance processing of biological materials in silicon biomedical microdevices. It also opens up the possibility of carrying out direct combinatorial structural characterization of proteins in the microchannels utilizing X-ray diffraction, which so far has not been possible.     

Molecular interactions in collagen and chitosan blends

Molecular interactions between collagen and chitosan (CC) have the potential to produce biocomposites with novel properties. We have characterised the molecular interactions in CC complexes by viscometry, wide angle X-ray scattering and Fourier transform infrared spectroscopy. It was found that CC are miscible at the molecular level and exhibit interactions between the components; X-ray diffraction of CC blends indicate that the collagen helix structure is lost in CC films with increasing chitosan content. Non-linear viscometic behaviour with decreasing chitosan content is interpreted as evidence of a third structural phase formed as a complex of CC. The blending of collagen with chitosan gives the possibility of producing new bespoke materials for potential biomedical applications.