肝素化聚氨酯表面血小板粘附研究

作者通过表面活化点放大和引入侧链间隔来增加聚氨酯（ＰＵ）表面共价结合的肝素量与生物活性，用固－液接触角分析所得样品表面性质，同时进行肝素浓度测定及血小板粘附实验，结果证明，与肝素直接接枝到ＰＵ表面相比，本文方法表面接枝肝素量和生物活性均得到较大提高，其血小板粘附程度大为降低。     

肝素化牛心包膜对VEGF165控释的体外研究

通过交联的去细胞牛心包膜进行肝素化表面改性,提高对血管内皮细胞生长因子(VEGF)的控释能力及对内皮细胞(ECs)的促增殖能力.采用3种方式进行肝素改性,即共价键合肝素、离子结合肝素以及共价-离子联合负载肝素.评估肝素化基质对VEGF控释及促ECs粘附和增殖的影响.结果表明,共价键合肝素,结合VEGF稳定性强;而离子结合肝素,结合VEGF量可任意调节,且表面易于ECs粘附;共价-离子联合负载肝素,将两种方法的优点相结合,取长补短,使这种方式肝素改性的牛心包具有良好的VEGF控释能力和促ECs增殖能力.     

不同硬段含量嵌段聚醚氨酯的合成、性能及莫膜上丙烯酰胺的接枝聚合

本文报告以4，4′—二苯甲烷二异氰酸酯、聚四氢呋喃—环氧丙烷共聚醚（Mn=2300），1，4—丁二醇为原料，用两步溶液聚合法合成了四种不同硬段含量的嵌段聚醚氨酯并测定了性能。四种聚醚氨酯的硬段含量分别为29％，46％，63％与78％。测定的性能有动态力学性能、物理—机械性能以及抗凝血性能。并用铈盐引发丙烯酰胺在这四种聚合物的膜上进行了接枝聚合。研究了硬段含量对聚醚氨酯的性能与接枝能力的影响。     

类肝素化抗凝血材料的研究—PVA,PET及PEU的磺化反应及血液？…

通过研究ＰＶＡ,ＰＥＴ接枝纤维及ＰＥＵ树脂磺化反应前后的物理机械性能和化学结构的变化不初步探讨生物材料的类肝素化反应,结果表明该类材料直接磺化容易,但要求有适当的磺化度才能保持材料原有物理机械性能。血小板吸附实验表明ＰＶＡ,ＰＥＴ接枝纤维及ＰＥＵ树脂磺化后对血小板的吸附明显减少,表现出类似肝素的抗凝血活性。     

共价-离子结合肝素改性对牛心包膜抗凝血性能的影响

目的在碳化二亚胺交联的去细胞牛心包膜上采用3种方式进行肝素改性,即共价键合肝素、离子结合肝素以及共价-离子联合负载肝素,比较这3种肝素化方式对牛心包膜抗凝血性能的影响,并筛选出最佳肝素化方式。方法通过溶血试验、血小板黏附实验、体外凝血测试以及复钙时间测定观察3种方式肝素化的基质抗凝血性能和血栓形成情况,以评价其血液相容性。结果综合上述4项检测的结果,共价-离子联合负载肝素改性的抗凝血性能优于共价键合肝素、离子结合肝素这2种单独负载肝素方式,溶血率〈5％,电镜照片无血小板黏附,体外生理盐水浸泡15d后,仍保持良好的抗凝血活性。结论共价-离子联合负载肝素,将离子结合肝素活性好、共价键合肝素稳定性强的优点结合起来,取长补短,使这种方式肝素改性的牛心包具有良好的血液相容性。     

类肝素化抗凝血材料的研究——PVA，PET及PEU的磺化反应及血液相容性

通过研究ＰＶＡ,ＰＥＴ 接枝纤维及ＰＥＵ 树脂磺化反应前后的物理机械性能和化学结构的变化来初步探讨生物材料的类肝素化反应,结果表明该类材料直接磺化容易,但要求有适当的磺化度才能保持材料原有物理机械性能。血小板吸附实验表明ＰＶＡ,ＰＥＴ 接枝纤维及ＰＥＵ 树脂磺化后对血小板的吸附明显减少,表现出类似肝素的抗凝血活性。     

犬体内动态接触生物材料对血清补体及免疫球蛋白影响

醋酸纤维素（ＣＡ）、聚醚砜（ＰＥＳ） 及聚氨酯Ⅱ型（ＰＵⅡ）３ 种生物材料按常规方法分别涂层于聚氯乙烯（ＰＶＣ） 管壁内,经烘干处理后直接与犬体内血液循环接触,根据材料与血液接触不同时间取血,分离血清测定总补体溶血活性（ＣＨ５０） 及免疫球蛋白含量,结果表明,ＣＡ 材料血液接触后,随时间的延长ＣＨ５０ 值明显降低,０ ｍｉｎ 为５８ ．３ ±８ ．３ ,１２０ ｍｉｎ 时为３８ ．６ ±１８ ．６ ,接触前后比较显示明显差异（ Ｐ＜ ０ ．０１） ,而ＰＥＳ和ＰＵⅡ材料接触前后比较在个别时间点稍有降低,但经统计学分析无明显差异。     

78例缺血性脑卒中病人光量子血疗治疗前后SSEP变化及疗效分析

对７８例缺血性卒中患者采用ＵＢＩＯ治疗，并在治疗前后进行ＳＳＥＰ测定。结果发现ＵＢＩＯ治疗有效率为６７．９％。治疗前后的ＳＳＥＰ与临床体征变化显著相关。ＣＴ上脑梗塞灶周围有半暗区者ＵＢＩＯ治疗效果好。ＳＳＥＰ可作为其疗效评定的客观指标。     

黄芪多糖对嗜中性粒细胞与内皮细胞粘附及粘附分子的影响

目的：通过研究黄芪多糖对嗜中性粒细胞与血管内皮细胞粘附及粘附分子的影响,探讨黄芪多糖对炎症反应的作用及其机制。方法：以黄芪多糖或黄芪多糖加ＩＬ－１ＴＮＦ处理人嗜中性粒细胞或人脐静脉内皮细胞（ＨＵＶＥＣ）后,用蛋白染料染色法研究药物对嗜中性粒细胞与内皮细胞粘附的作用,用细胞ＥＬＩＳＡ法、ＡＰＡＡＰ免疫细胞化学染色法研究药物对ＨＵＶＥＣ表面ＩＣＡＭ－１及嗜中性粒细胞表面ＣＤ１８表达的影响。结果：黄芪多糖（４０μｇｍＬ－１ｍｇｍＬ）作用于ＨＵＶＥＣ,能促进ＨＵＶＥＣ与嗜中性粒细胞粘附,并与ＩＬ－…     

生物材料改性对人涎腺细胞生长的影响

目的：利用SO2等离子体对聚乳酸和聚醚酯膜进行表面改性，研究人类涎腺细胞系HSG细胞在生物材料上的生长。方法：材料的表面性质通过表面接触角和X射线光电子能谱(XPS)进行表征。细胞形态与生长情况则通过倒置显微镜观察和MTT检测来评估。结果：用SO2等离子体改性后，膜表面接枝上磺酸基团。亲水性明显增强；在几种材料中。用S02等离子体改性后的聚醚酯膜更适合HSG细胞的粘附生长。结论：用SO2等离子体改性后的聚醚酯材料可能用于人造涎腺的支架材料。     

Novel Poly(urethane-aminoamides): an in vitro study of the interaction with heparin

In order to obtain heparin-binding polyurethanes, tertiary amino-groups have been introduced in the polymer backbone by attributing a key-role to the chain extender, i.e. substituting butanediol, commonly used in polyurethane synthesis, with a tailor-made diamino-diamide-diol. In this work a poly(ether-urethane-aminoamide) (PEU/PIME/al) was obtained with poly(oxytetramethylene) glycol 2000, 1,6-hexamethylene-diisocyanate and the new chain extender, in the molar ratio 1 :2 : 1. The heparin binding capacity of PEU/PIME/al was evaluated with ¹²⁵I labelled heparin, using for comparison the analogous polymer obtained with a diamide-diol (i.e. the poly(ether-urethane-amide) PEU/PIBLO/al), and two commercially available biomedical polyurethanes (Pellethane 2363 and Corethane). pH and ionic strength dependence of the heparin uptake were investigated by treating all the polyurethanes with solutions of ¹²⁵I heparin into buffers from pH 4 to 9 or NaCl molarity from 0.0 to 1.0. The stability of the interaction with bound heparin was investigated by sequential washing treatments (PBS, 1 N NaOH, 2% SDS solution), then analysing the residual radioactivity on the materials. Results indicated that the heparin binding of PEU/PIME/al is significantly higher and more stable than that of the other polyurethanes, with a time-dependent kinetic. The interaction with heparin appears to be prevalently ionic, with the contribution of other electrostatic and hydrophobic interactions. Activated partial thromboplastin time (APTT), performed on human plasma with polyurethane-coated, heparinized test tubes, indicated that bound heparin maintains its biological activity after the adsorption.     

Interaction of poly(sodium vinyl sulfonate) and its surface graft with antithrombin III

Poly(sodium vinyl sulfonate) (PVS) was found to be 1/14 times as active as heparin in inducing the conformational change and activation of antithrombin III. The conformational change of antithrombin III was investigated in terms of the intrinsic fluorescence of tryptophan residue, the extrinsic fluorescence using 1,6-diphenyl-1,3,5-hexatriene as fluorescent probe, and Fourier-transform infrared spectroscopy. It was evident in the experiment using 2,4,6-trinitrobenzene sulfonate that PVS elicited the activity of antithrombin III by interacting with amino groups of the protein as does heparin. Sodium vinyl sulfonate was graft-polymerized onto polyetherurethane (PEU) film that was treated with glow discharge in advance. PVS-grafted PEU film adsorbed antithrombin III easily and, like ungrafted PVS, induced conformational change and activation of antithrombin III. However, the mechanism of interaction of the PVS graft with antithrombin III did not seem to be completely the same as that of ungrafted PVS in solution.     

Novel poly(urethane-aminoamides): an in vitro study of the interaction with heparin

In order to obtain heparin-binding polyurethanes, tertiary amino-groups have been introduced in the polymer backbone by attributing a key-role to the chain extender, i.e. substituting butanediol, commonly used in polyurethane synthesis, with a tailor-made diamino-diamide-diol. In this work a poly(ether-urethane-aminoamide) (PEU/PIME/al) was obtained with poly(oxytetramethylene) glycol 2000, 1,6-hexamethylene-diisocyanate and the new chain extender, in the molar ratio 1:2:1. The heparin binding capacity of PEU/PIME/al was evaluated with 125I labelled heparin, using for comparison the analogous polymer obtained with a diamide-diol (i.e. the poly(ether-urethane-amide) PEU/PIBLO/al), and two commercially available biomedical polyurethanes (Pellethane 2363 and Corethane). pH and ionic strength dependence of the heparin uptake were investigated by treating all the polyurethanes with solutions of 125I heparin into buffers from pH 4 to 9 or NaCl molarity from 0.0 to 1.0. The stability of the interaction with bound heparin was investigated by sequential washing treatments (PBS, 1 N NaOH, 2% SDS solution), then analysing the residual radioactivity on the materials. Results indicated that the heparin binding of PEU/PIME/al is significantly higher and more stable than that of the other polyurethanes, with a time-dependent kinetic. The interaction with heparin appears to be prevalently ionic, with the contribution of other electrostatic and hydrophobic interactions. Activated partial thromboplastin time (APTT), performed on human plasma with polyurethane-coated, heparinized test tubes, indicated that bound heparin maintains its biological activity after the adsorption.     

Does surface chemistry affect thrombogenicity of surface modified polymers?

With some exceptions, surface chemistry had little effect on platelet and leukocyte activation, and cell deposition, by scanning electron microscopy after blood exposure and clotting times among a group of 12 unmodified and plasma modified tubings. All materials activated platelets and leukocytes to detectable levels, although some materials increased the value of one activation parameter but not another. Unmodified materials [polyethylene (PE), Pellethane (PEU), latex, nylon, and Silastic] and modified materials (H(2)O plasma treated PE and PEU, CF(4) plasma treated PE, fluorinated PEU, NH(4) plasma treated PEU, polyethylene imine treated PEU, and heparin treated PEU) were characterised by XPS and contact angle. The objective of this project was to define a series of assays for the evaluation of hemocompatibility of cardiovascular devices with a view to clarify the specific requirements of ISO-10993-4, and to define an appropriate screening program for new blood contacting biomaterials. PE, PE--CF(4), PE--H(2)0, PEU--F, latex, and PEU-heparin were the exceptions to the general observations, although each behaved differently. PE proved to be least reactive, whereas PE-CF(4) was most reactive by several assays. Platelet microparticle formation (determined by flow cytometry), PTT, postblood exposure SEM, total SC5b-9, C3a, and platelet and leukocyte loss (cell counts) were able to distinguish differences among these materials, and often, but not always, showed expected correlations.     

A comparative evaluation of the biostability of a poly (ether urethane) in the intraocular, intramuscular, and subcutaneous environments.

A transparent poly (ether urethane) (PEU) was considered for use as a foldable intraocular lens material. The PEU was found to possess excellent mechanical, optical, and surface characteristics for this application. In vitro hydrolytic and ultraviolet aging studies suggested the PEU to be tolerant to conditions simulating 3-10 years of normal intraocular exposure. Different behavior was obtained, however, from intraocular and subcutaneous implantation of the PEU. After 6 months of intraocular exposure in the feline model, prototype PEU lenses had lost most or all of their optical resolving power. SEM analysis demonstrated scattered pitting and cracking on the lens surfaces. Degradation was found to be more extreme after as little as 30 days of subcutaneous exposure in rabbits. Severe pitting over the entire surface of implanted flat PEU specimens was observed by SEM. Macroscopic examination showed the samples to be frosty in appearance. It was postulated that the subcutaneous implant environment provides an accelerated in vivo model for materials intended for intraocular use. A minimum acceleration of 6-10x was estimated on a preliminary basis. The PEU studied here was found to be unsuitable for use as a foldable intraocular lens material.     

Biodegradation of polyether polyurethane inner insulation in bipolar pacemaker leads

Several bipolar coaxial pacemaker leads, composed of an outer silicone rubber insulation and an inner polyether polyurethane (PEU) insulation, which were explanted due to clinical evidence of electrical dysfunction, were analyzed in this study. Optical microscopy (OM) and scanning electron microscopy (SEM) were used to determine the cause of failure. Attenuated total reflectance-Fourier transform infrared microscopy (ATR-FTIR) was used to analyze the PEU insulation for chemical degradation. In all leads, the silicone rubber outer insulation showed no signs of physical damage. Physical damage to the inner PEU insulation was the source of electrical dysfunction. Cracks through the PEU compromised the insulation between the inner and outer conductor coils in the lead. It was observed with SEM that these cracks originated on the outer surface of the inner insulation and progressed inward. ATR-FTIR analysis showed that the PEU had chemically degraded via oxidation of the ether soft segment. Furthermore, it was revealed that chemical degradation was more advanced on the outer surface of the PEU. It was hypothesized that hydrogen peroxide permeated through the outer silicone insulation and decomposed into hydroxyl radicals that caused the chemical degradation of PEU. The metal in the outer conductor coil catalyzed the decomposition of the hydrogen peroxide. Chemical degradation of the PEU could also have been catalyzed by metal ions created from the corrosion of the metal in the outer conductor coil by hydrogen peroxide. Physical damage probably occurred in regions of the leads that were subjected to a higher hydrogen peroxide concentration from inflammatory cells and high degrees and rates of strain due to intercorporeal movement, including, but not limited to, cardiac movement. Chemical degradation and physical damage probably had a synergistic affect on failure of the insulation, in that as chemical degradation proceeded, the polymer surface became brittle and more susceptible to physical damage. As physical damage proceeded, cracks propagated into the unaffected bulk, exposing it to oxidants.     

The effect of gas plasma modification on platelet and contact phase activation processes

Medical-grade polytetrafluoroethylene (PTFE), polydimethylsiloxane (PDMS), polyetherurethane (PEU) and ultrahigh molecular weight polyethylene (UHMWPE) were plasma treated with O2, Ar, N2 and NH3. Their surface properties were characterised using X-ray photoelectron spectroscopy (XPS), static secondary ion mass spectroscopy (SSIMS), atomic force microscopy (AFM) and dynamic contact angle (DCA) analysis. Platelet adhesion, aggregation, activation and release of microparticles were determined after contact with whole blood in a cone and plate viscometer. Activation of the coagulation system was quantified in a static environment using a partial thromboplastin time (PTT) assay. The chemical compositions of the untreated surfaces were found to be very similar to those of the bulk material except for PEU, whose surface was comprised almost entirely of soft ether segments. For all materials, the different plasma treatments resulted in moderate etching with the incorporation of functional groups and removal of side groups: defluorination, dehydrogenation, cleavage of methyl side groups and soft segments for PTFE, UHMWPE, PDMS and PEU, respectively. Consequently, plasma treatment resulted in increased wettability in all cases. Blood contact with the virgin materials resulted in activation of platelets and the clotting cascade. Plasma treatment resulted in a significant reduction in platelet adhesion for all materials and all treatments. In the case of PTFE and PEU, the activation status of these cells was also reduced. Plasma treatment of all materials reduced fluid-phase CD62P expression. Platelet aggregate size correlated well with degree of aggregate formation, but many treatments increased the degree of aggregation, as was the case for microparticle shedding. There was no correlation between CD62P expression, aggregate formation and platelet microparticle (PMP) shedding. It is concluded that despite incorporation of the same chemical groups, the pattern of response to blood in vitro is not the same across different polymers.     

Surface modification of a segmented polyetherurethane using a low-powered gas plasma and its influence on the activation of the coagulation system

A medical grade segmented polyetherurethane (PEU) was treated with a low-powered gas plasma using O₂, Ar, N₂ and NH₃ as the treatment gases. Changes in the surface functional group chemistry were studied using X-ray photoelectron spectroscopy. The wettability of the surfaces was examined using dynamic contact angle measurements and the surface morphology was evaluated using atomic force microscopy. The influence of the surface modification to the polyurethane on the blood response to the polyetherurethane was investigated by measuring changes in the activation of the contact phase activation of the intrinsic coagulation cascade. The data demonstrate that the plasma treatment process caused surface modifications to the PEU that in all cases increased the polar nature of the surfaces. O₂ and Ar plasmas resulted in the incorporation of oxygen-containing groups that remained present following storage in an aqueous environment. N₂ and NH₃ plasmas resulted in the incorporation of nitrogen-containing groups but these were replaced with oxygen-containing groups following storage in the aqueous environment. In all plasma treatments there was a lowering of contact phase activation compared to the untreated surface, the N₂ and NH₃ treatments dramatically so.     

Variations between Biomer lots. I. Significant differences in the surface chemistry of two lots of a commercial poly(ether urethane).

We have studied the surface chemistry of two lots of Biomer (BSP067 and BSUA001), a widely used commercial poly(ether urethane) (PEU). Although transmission infrared adsorption studies revealed no differences in the bulk chemistry of the two lots, the surface chemistry, as seen by x-ray photoelectron spectroscopy (XPS) and static secondary ion mass spectrometry (SIMS), was different. Lot BSP067 showed soft-segment enrichment at the surface, which is typical of PEU. Lot BSUA001 showed no evidence of either hard- or soft-segment PEU components at the surface. The surface of this lot was completely covered with a nonextractable additive identified as poly(diisopropyl amino ethyl methacrylate). Small amounts of a low-molecular-weight antioxidant were observed at the surface of both samples. Because the biological response to polymers is dependent on surface structure, these results are of considerable importance to biomaterials research.