介入用聚氨酯材料的血液相容性研究

介入导管优良的血液相容性是确保血管内介入技术安全可靠进行的重要因素，我们对自己合成的四种介入导管用聚氨酯材料的血液相容性进行了评价，包括溶血试验、血小板黏试验、动态凝血时间试验和动态血栓形成实验。结果表明，其中的H50-100和H60-100具有优良的血液相容性，完全可以用作介入导管材料。此外，还讨论了聚氨酯结构与血液相容性的关系。     

胆红素吸附柱的血液相容性

背景：胆红素吸附柱在临床上用于清除患者体内高浓度的胆红素,在使用过程中与血液有大面积长时间的接触,对其血液相容性的评价具有重要意义。 目的：评价一个树脂类胆红素吸附柱的血液相容性。 方法：将待测胆红素吸附柱及对照已经上市胆红素吸附柱中的树脂微粒置于硅化玻璃管中,以空硅化玻璃管作为空白对照。向3组硅化玻璃管中加入人新鲜血浆,于37 ℃隔水培养箱的旋转培养器上以30 r/min的速率旋转,3 min后吸取出血浆,用于凝血酶原时间、活化部分凝血活酶时间、纤维蛋白原含量及总补体活性CH50的检测,实验重复3次。 结果与结论：与空白对照组比较,对照组与实验组凝血酶原时间、活化部分凝血活酶时间延长,纤维蛋白原含量减少,CH50减小,但随着树脂微粒与新鲜血浆接触次数的增多,这种变化越来越小。与对照组比较,实验组凝血酶原时间、活化部分凝血活酶时间、纤维蛋白原含量的3次检测数值更接近于空白对照组;实验组CH50在3次检测中先大于对照组,再与对照组相当,最后小于对照组。表明：①随着与新鲜血浆接触次数的增多,树脂微粒的血液相容性得到改善。②待测胆红素吸附柱中树脂微粒对凝血系统的影响小于对照,对补体系统的影响在预吸附过程中小于对照,但其相容性的改善慢于对照。     

聚谷氨酸苄酯/聚乙二醇嵌段共聚物膜的血液相容性研究

使用凝血时间实验、血小板的黏附和变形实验、血浆蛋白的吸附实验来评价聚谷氨酸苄酯 /聚乙二醇(PBL G/PEG)嵌段共聚物膜的血液相容性 ,PEG嵌段的引入对共聚物血液相容性的影响。结果表明 ,均聚物的血液相容性优于玻璃和硅油 ,共聚物的血液相容性优于均聚物 ,且随着 PEG含量增加 ,其血液相容性更好。     

血液透析器中空纤维体外血液相容性的评价

背景:血液透析器中的中空纤维与肾透析患者的血液有大面积长时间的接触,对其进行血液相容性评价尤为重要。目的:通过对一种透析器中空纤维血液相容性的2次评价,拟初步建立透析器体外血液相容性评价的方法。方法:将样品透析器中的中空纤维截为3cm长,取100根置于硅化玻璃管中,作为一个样品。两次评价试验中,选用不同的已经上市的血液透析器的中空纤维作为对照,对照中空纤维取与样品中空纤维相近表面积的数量,同样处理。每个硅化玻璃管中加入新鲜全血1.2mL,放在置于37℃隔水培养箱的略倾斜的旋转培养器上,以30r/min的速率旋转。30min后取各硅化玻璃管中的全血,用于血细胞分析、凝血分析及血清总补体的检测。结果与结论:与两个对照透析器中空纤维相比,样品透析器中空纤维在不同指标上显示出一定差异,但样品透析器对纤维蛋白原和血小板的巨大消耗作用在2次试验中均有充分体现,且与对照参数差值的绝对值相对于对照参数的百分比远大于15%,可以认为样品透析器中空纤维与对照透析器中空纤维之间血液相容性的差异不被接受,说明实验中所使用的体外血液相容性评价方法具有很好的重现性。     

医用Ta5+掺杂TiO2生物薄膜材料的合成与性能研究

利用射频控溅射技术合成Ta^5 掺杂的TiO2薄膜材料。采用X射线衍射（XRD）和电子能谱（XPS）等技术对薄膜的成分和结构进行了分析,并利用动态凝血时间测定法和血小板粘附试验研究了薄膜的血液相容性,同时对薄膜的硬度、耐磨性等力学特性进行了研究和评价。结果表明,Ta^5 掺杂的TiO2薄膜不仅具有良好的血液相容性,同时还具有较优的力学耐久性能。     

PGLA牙周再生片的细胞相容性研究

研究聚乙交酯-丙交酯(PGLA)牙周再生片及其降解产物的细胞相容性。采用不同浸提温度、不同授提时间和不同授提比例对PGLA牙周再生片材料的细胞增殖情况进行实验研究I同时用材料在2、4、6、8、10周时的体外障解液与培养细胞接触，观察不同降解周期其降解产物对培养细胞的毒性作用。结果表明。浸提比例为0．1g／ml时，37℃下其畏提时间长短对材料的细胞毒性无明显影响l授提比例为O．1cm^2／ml时，随着浸提温度的升高(50℃或70℃)，材料出现了轻度对细胞毒性反应；浸提比例为O．5cm^2／ml时，37℃浸提72h可引起细胞增殖率下降;浸提比例为6cm^2／ml时，即使是37℃、24h，也出现了一定程度的细胞毒性。材料浸泡2、4周，其降解产物对细胞无明显的毒性作用，材料浸泡后6周起，降解液对细胞相对增殖率作用明显降低。由此提示：在体外评价试验中，试样表面积(重量)／浸提介质的比例大小、浸提温度高低、浸提时间长短以及降解产物在浸提介质中的积聚等因素都可能在一定程度上影响细胞生长。该PGLA牙周再生片具有良好的细胞相容性。本研究既为PGLA牙周再生片材料的临床应用提供科学依据，又为生物降解类材料的生物安全性评价提供新的研究思路和实验手段     

可吸收羟基磷灰石／聚DL—乳酸复合骨折内固定材料的生物 …

可吸收骨折内固定材料要求具有良好的生物相容性。对自行研制的可吸收羟基磷灰石／聚ＤＬ－乳酸（ＨＡ／＝ＰＤＬＬＡ）复全骨折内固定材料进行了一系列生物相容性实验,包括Ａｍｅｓ实验,微核实验、急性和亚急性毒性实验、溶血实验、凝血试验和肌肉、骨内长期植入实验。结果表明,ＨＡ／ＰＤＬＬＡ材料无毒,无致突变性,不引起民血和凝血,结论：ＨＡ／ＰＤＬＬＡ复全材料具有很好的生物相容性。     

可吸收羟基磷灰石/聚DL-乳酸复合骨折内固定材料的生物相容性研究

可吸收骨折内固定材料要求具有良好的生物相容性。对自行研制的可吸收羟基磷灰石／聚ＤＬ乳酸（ＨＡ／ＰＤＬＬＡ）复合骨折内固定材料进行了一系列生物相容性实验,包括Ａｍ ｅｓ 实验、微核实验、急性和亚急性毒性实验、溶血实验、凝血试验和肌肉、骨内长期植入实验。结果表明,ＨＡ／ＰＤＬＬＡ 材料无毒,无致突变性,不引起溶血和凝血。结论：ＨＡ／ＰＤＬＬＡ 复合材料具有很好的生物相容性。     

单宁酸后处理牛颈静脉血管的血液相容性研究

评价经单宁酸后处理的牛颈静脉带瓣血管的血液相容性,探讨其在心血管外科中的应用前景。带瓣牛颈静脉经常规戊二醛处理后,再以单宁酸溶液进行后处理,然后进行体外动态凝血实验,血小板黏附性能实验,D-二聚体测定和补体激活实验进行血液相容性评价,与传统的戊二醛处理的带瓣牛颈静脉作平行对照。结果表明：（1）单宁酸处理后的带瓣牛颈静脉抗凝血性能优于对照组;（2）单宁酸处理后带瓣牛颈静脉血小板黏附比对照组明显减轻且变形小;（3）D-二聚体含量各组均在正常范围内,单宁酸处理前后无显著性差异（P〉0.05）;（4）补体激活实验中单宁酸处理后的带瓣牛颈静脉组补体C3a水平明显低于对照组（P〈0.05）。经单宁酸处理后带瓣牛静脉体外血液相容性得到改善,显示了在临床上应用的可能性。     

组织因子途径抑制因子和生物材料血液相容性关系的体 …

本文试就组织因子途径抑制因子（Ｔｉｓｓｕｅ ｆａｃｔｏｒ ｐａｔｈｗａｙ ｉｎｈｉｂｉｔｏｒ,ＴＦＰＩ）和生物材料血液相容性之间的关系进行了初步的探讨。本研究通过基因重组的方法制备了人重组ＴＦＰＩ,将其涂于医用聚乙烯和聚氯乙烯薄膜材料表面,观察ＴＦＰＩ涂层对接触血液的凝血时间、血液中组织因子及凝血因子Ｘａ活性的影响。结果显示：１．实验组（ＴＦＰＩ处理）的材料表面与血液接触后其凝血时间比对照组（未经     

Plasma-deposited tetraglyme surfaces greatly reduce total blood protein adsorption, contact activation, platelet adhesion, platelet procoagulant activity, and in vitro thrombus deposition

The ability of tetraethylene glycol dimethyl ether (tetraglyme) plasma deposited coatings exhibiting ultralow fibrinogen adsorption to reduce blood activation was studied with six in vitro methods, namely fibrinogen and von Willebrand's factor adsorption, total protein adsorption, clotting time in recalcified plasma, platelet adhesion and procoagulant activity, and whole blood thrombosis in a disturbed flow catheter model. Surface plasmon resonance results showed that tetraglyme surfaces strongly resisted the adsorption of all proteins from human plasma. The clotting time in the presence of tetraglyme surfaces was lengthened compared with controls, indicating a lower activation of the intrinsic coagulation cascade. Platelet adhesion and thrombin generation by adherent platelets were greatly reduced on tetraglyme-coated materials, compared with uncoated and Biospan-coated glass slides. In the in vitro disturbed blood flow model, tetraglyme plasma coated catheters had 50% less thrombus than did the uncoated catheters. Tetraglyme-coated materials thus had greatly reduced blood interactions as measured with all six methods. The improved blood compatibility of plasma-deposited tetraglyme is thus not only due to their reduced platelet adhesion and activation, but also to a generalized reduction in blood interactions.     

Poly(O-acyl hydroxy L-proline) (II) wetting characteristics and blood clotting on surfaces of poly O-acetyl, butyryl, hexanoyl, dodecanoyl, and benzoyl hydroxy L-proline

Poly O-acetyl, butyryl, hexanoyl, dodecanoyl, and benzoyl hydroxy L-proline (poly[O-acyl Hyp]s) were evaluated as materials for blood contact by means of contact angle and blood clotting time measurements. Critical surface tensions obtained from Zisman plots for all materials were 22-29 dyn/cm, suggesting that these materials may exhibit good blood compatibility. Dispersion and nondispersion force contributions to the surface tension were gamma ds = 1.4, gamma ns = 49.3 dyn/cm, (11.0, 16.2), (19.8, 3.8), (21.2, 4.6) and (14.1, 10.8) for the poly(O-Acetyl, Butyryl, Hexanoyl, Dodecanoyl and Benzoyl Hyp) surfaces, respectively. The materials showed remarkable wetting differences that were dependent on the type of acyl group attached to Hyp. The values of the dispersion and nondispersion components of the surface tension for poly(O-hexanoyl Hyp) and poly(O-dodecanoyl hyp) were very close to those obtained for glutaraldehyde-treated umbilical cord vessels. The blood clotting times on the respective polymer surfaces, obtained by using the kinetic method, were normalized to those of control glass and siliconized glass surfaces. All the poly(O-acyl Hyp)s surfaces showed longer clotting times than those of the poly(L-proline) and glass surfaces. The surfaces of those polymers having longer aliphatic or aromatic acyl groups had longer clotting times than those of the polymers with relatively shorter groups.     

Hemocompatibility evaluation of poly(glycerol-sebacate) in vitro for vascular tissue engineering

Poly(glycerol-sebacate) (PGS) is an elastomeric biodegradable polyester that could potentially be used to engineer blood vessels in vivo. However, its blood-material interactions are unknown. The objectives of this study were to: (a) fabricate PGS-based biphasic tubular scaffolds and (b) assess the blood compatibility of PGS in vitro in order to get some insight into its potential use in vivo. PGS was incorporated into biphasic scaffolds by dip-coating glass rods with PGS pre-polymer. The thrombogenicity (platelet adhesion and aggregation) and inflammatory potential (IL-1beta and TNFalpha expression) of PGS were evaluated using fresh human blood and a human monocyte cell line (THP-1). The activation of the clotting system was assessed via measurement of tissue factor expression on THP-1 cells, plasma recalcification times, and whole blood clotting times. Glass, tissue culture plastic (TCP), poly(l-lactide-co-glycolide) (PLGA), and expanded polytetrafluorethylene (ePTFE) were used as reference materials. Biphasic scaffolds with PGS as the blood-contacting surface were successfully fabricated. Relative to glass (100%), platelet attachment on ePTFE, PLGA and PGS was 61%, 100%, and 28%, respectively. PGS elicited a significantly lower release of IL-1beta and TNFalpha from THP-1 cells than ePTFE and PLGA. Similarly, relative to all reference materials, tissue factor expression by THP-1 cells was decreased when exposed to PGS. Plasma recalcification and whole blood clotting profiles of PGS were comparable to or better than those of the reference polymers tested.     

Experimental hypercalcaemia and whole blood clotting

Experimental hypercalcaemia was induced in rats by (1) transplantation of the solid Walker 256 tumour, and (2) intraperitoneal injections of calcium gluconate. Whole blood clotting was studied by means of thromboelastography and whole blood clotting times in polystyrene and glass test tubes. At serum calcium levels between 10.3 and 11.5 m-equiv/l a slight delay in clot formation was found which was reversible by the addition of EDTA to whole blood. Acute, calcium-gluconate-induced hypercalcaemia, however, leads to a significant shortening of the clotting time in the polystyrene tube and to a lesser degree in the glass tube. Maximal factor XII activation in vitro with ellagic acid levels the difference of clotting times again. From these experiments it is concluded that acute hypercalcaemia induces a hypercoagulable state, possibly by partial contact activation, and thus may favour thrombus formation in vivo.     

Measurement of the rate of thrombin production in human plasma in contact with different materials.

Thrombin production in plasma in contact with various materials was consistent with a first-order autocatalytic model (d[T]/dt = kp[T]; [T] = thrombin concentration, t = time, kp = thrombin production rate constant) since the initial portion of a semilogarithmic plot of thrombin concentration against time was linear. Thrombin concentration was measured in clotting plasma (phospholipid enhanced or platelet-rich plasma) using a fluorogenic substrate (BMCA) by aliquot sampling at various intervals or more conveniently by monitoring cumulative fluorescence. The latter was generated by the action, on BMCA incubated in the clotting plasma, of the thrombin as it was generated. The thrombin concentration was determined from the first derivative of the S-shaped cumulative fluorescence curve. kp was greater for glass (7.92 x 10(-3) cm/s) than for the other materials (polypropylene, polystyrene, polyethylene and PVA; kp approximately 3.1 x 10(-3) cm/s) in plasma with cephalin without flow. A kp for heparin-PVA could not be determined since the thrombin concentration was too low to be quantified. A larger difference between polyethylene and PVA was noted with platelet-rich plasma without flow while lower values (1.0 x 10(-3) cm/s) were noted in a flow system but at a higher surface to volume ratio. The first-order rate constant can be used in simple models relating production of thrombin at a wall of a tube to its mass transfer away from the wall in flowing blood. One such model predicts that the concentration of thrombin at the wall should become infinite at the point in the tube when the mass transfer coefficient equals kp. According to this model, kp on the order of 10(-4) cm/s would be a useful target for a nonthrombogenic material.     

mPEG-PLGA-mPEG纳米粒的体外降解规律的研究

通过开环共聚方法合成了具有不同组份的丙交酯 /乙交酯 /聚乙二醇 (LA/GA/PEG)共聚物 (PLGA PEG ,PELGA) ,并进一步偶联制得三嵌段共聚物 (mPEG PLGA mPEG ,简称PELGE)。采用超声乳化—溶剂蒸发法 (O/W )制备PELGE纳米粒 ,用紫外分光光度法测定乳酸含量的方法研究了PELGA、PELGE纳米粒体外降解规律 ,体外降解实验表明 :共聚物分子量增加 ,降解减慢 ;共聚物中GA含量增加 ,即LA/GA比例减小 ,降解加快 ;PEG含量增加 ,降解加快 ;LA/GA和PEG含量相同的PELGE比PELGA的降解速度快。证明了可通过改变LA/GA的比例或PEG的含量来调节聚合物的降解速率。     

A new haemocompatible phospholipid polyurethane based on hydrogenated poly(isoprene) soft segment

A new haemocompatible phospholipid polyurethane based on hydrogenated poly(isoprene) glycol (HPIP) and 4,4'-methylenediphenyl diisocyanate (MDI) was synthesized using 2-[bis(2-hydroxyethyl)methylammonio]ethylstearylphosphate (BESP) and 1,4-butanediol (BD) as chain extender. The bulk and surface characteristics of this material was investigated by differential scanning calorimetry (DSC), dynamic viscoelasticity and tensile property measurements, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and contact angle measurement. This polymer possessed a hydrophobic surface revealed by contact angle measurement. The haemocompatibility of this polyurethane was evaluated by platelet rich plasma (PRP) contacting studies and scanning electron microscopy (SEM) observation using medical grade poly(vinyl chloride) (PVC) as the reference.The results show that this new polyurethane had relatively lower platelet adhesion and limited shape change for the attached platelets compared to PVC. The clotting time of the materials in contact with platelet poor plasma (PPP) was 99, 75, and 62 s and in contact with PRP was more than 240, 100, and 86 s for new polyurethane, PVC, and glass, respectively. This new phospholipid polyurethane is expected to have wide applications as coating or structural material for blood-contacting medical equipment due to its outstanding haemocompatibility and excellent mechanical strength.     

Effect of blood collection tube types on the measurement of human epidermal growth factor

We observed significant differences in measured human epidermal growth factor (hEGF) levels for the same individual's serum/plasma samples between different tube types (glass, polystyrene, plastic with clot activator, plastic without clot activator, plastic with EDTA, polypropylene tubes). For all individuals, hEGF levels in plasma were found to be below the detection limit. The discrepancy of the hEGF levels in serum and plasma was attributed to the platelet derived EGF by analyzing platelet lyzate with size exclusion chromotography and demonstrating the immunoreactivity of the fractions corresponding to the pre-proEGF and/or proEGF elution time. Besides, samples of females showed much higher EGF levels than those of males in certain test tube types. As a conclusion, all blood samples should be taken and stored in the same type of test tubes in order to make precise measurements for hEGF. And, the measured hEGF level in blood is susceptible to changes with blood clotting.     

热解碳人工心脏瓣膜材料表面改性研究

对氮离子注入热解碳及在热解碳表面离子束增强沉积钛氧化物薄膜进行了研究,采用Ｘ光电子能谱仪,俄歇电子能谱仪测定了表面改性层的成价和价态,用四探针方法测定了表面电阻率,用接触角方法测定了材料表面能,用动态凝血时间及血小板粘附评价了表面改性层的血液相容性。研究表明,热解碳经表面Ｎ离子注入后有碳氧化合物形成,其血液相容性有所改善,而采用离子束增强沉积合成ＴｉＯ２－ｘ薄膜则使热解碳备注相 容性获得了显著改善