肝素涂层插管生物相容性评价

对肝素涂层插管和未涂层插管设计了抗凝血、血栓形成观察以及溶血、细胞毒性、炎性和免疫反应等多种试验，从多角度综合对肝素涂层插管材料进行生物相容性评价。通过活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、纤维蛋白原降解产物(FIB)、凝血酶时间(TT)、血小板活化因子、纤维蛋白吸附等试验，测定样品的体外抗凝血性，然后通过半体内血栓形成试验，模拟插管在动物体内的使用环境和过程，观察样品引起血栓形成的状况。同时，通过溶血试验和细胞毒性试验以及炎症反应、补体激活、免疫球蛋白等检测，进一步对样品进行血液相容性评价。结果显示，肝素涂层实验组APTT和TT得到有效延长，而其他体外抗凝指标未见显著变化；在动物半体内模型试验和检测中，肝素涂层实验组6 h血栓形成的各项指标均低于未涂层对照组，表明肝素涂层通过抑制内源性凝血途径达到了预期的抗凝效果；而溶血率、细胞毒性、炎症反应、补体激活、免疫球蛋白等方面的试验结果与未涂层对照组无差异，表明肝素涂层对材料的血液相容性无不良影响。结果表明，肝素涂层显著提高了动静脉插管的体内外抗凝血性，具有良好的生物相容性，可提高临床应用的安全性。     

基于肝素和硫酸软骨素的两种纳米颗粒改性表面对生物相容性影响的研究

本研究合成了基于肝素和硫酸软骨素的两种纳米颗粒,用于316L不锈钢表面的生物功能改性。通过激光粒度分析仪、傅立叶变换红外光谱(FTIR)、原子力显微镜(AFM)、水接触角等对纳米颗粒的性质及颗粒固定前后表面的理化性质进行表征。通过体外血液相容性评价和内皮细胞相容性评价对两种纳米颗粒改性表面的生物相容性进行对比研究。结果表明,两种纳米颗粒均能有效降低材料表面血小板的粘附和聚集行为,但肝素纳米颗粒对内皮细胞的生长增殖表现出抑制作用,而硫酸软骨素纳米颗粒改性表面则具有促进内皮再生的潜能。     

肝素化单壁碳纳米管的制备、表征及生物相容性

背景:碳纳米管具有独特的结构和理化性质,在药物载体、生物传感器及生物材料等领域应用前景广阔,但其疏水性强,易缠绕聚集,并且具有一定的细胞毒性,致生物相容性差。目的:制备肝素化单壁碳纳米管,探讨表面肝素化对碳纳米管水溶性及生物相容性的影响。方法:采用共价接枝的方法制备肝素化单壁碳纳米管,通过红外光谱进行表征;考察肝素化单壁碳纳米管在水溶液中的分散情况和稳定性;硫酸咔唑显色测定单壁碳纳米管表面的肝素多糖接枝量;测定抗Ⅹa因子活性和活化部分凝血酶时间研究肝素化单壁碳纳米管的血液相容性,用MTT法研究10,20,40 mg/L肝素化单壁碳纳米管浸提液与小鼠骨髓干细胞的相容性。结果与结论:肝素被成功接枝到单壁碳纳米管表面,肝素接枝量为257.53 mg/g;肝素化单壁碳纳米管在水溶液中分散良好,具有很好的悬浮稳定性;肝素化单壁碳纳米管抗Ⅹa因子活性为36.53 U/mg,具有明显的抗栓活性,能显著延长绵羊血浆活化部分凝血活酶时间,表现出显著的抗凝活性;肝素化单壁碳纳米管细胞毒性低,并对细胞增殖具有一定的促进作用。表明肝素化不仅能提高碳纳米管在水溶液中的分散性和稳定性,而且赋予其良好的血液相容性和细胞相容性。     

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     

含氟聚醚聚氨酯与聚醚聚氨酯共混的表面结构及血液相容性的研究

为了获得一种高氟聚氨酯表面 ,进一步改善聚醚聚氨酯的生物相容性和生物稳定性 ,将侧链含氟聚氨酯与聚醚聚氨酯共混而实现这一目的。通过 XPS、AFM、接触角和血小板黏附对含氟聚醚聚氨酯和聚醚聚氨酯共混物表面结构和血液相容性进行研究发现 ,在聚醚聚氨酯共混入极少量的氟 (0 .342 wt% )就能具有与含氟聚醚聚氨酯相同的表面结构和良好的血液相容性 ,而且共混物表面的强疏水性和对血小板的黏附与体系中混入的含氟聚醚聚氨酯的量无关 ,与表面 CF3的含量有关     

新型醛基化海藻酸钠抗凝血涂层物制备及性能评价

应用醛基化海藻酸钠交联涂层体外循环管路,并对涂层管路的血液相容性和生物相容性等性能进行研究和评价。将多醛基的氧化海藻酸钠(OSA),固定到体外循环聚氯乙烯(PVC)管路表面,评价其血液相容性和生物相容性等指标,并与空白对照组(PVCC)和进口产品美敦力肝素涂层组(PVCM)比较。结果表明,OSA涂层物有效固定在PVC管道表面,且OSA涂层管路(PVCS)具有良好的抗凝血性能,仅次于PVCM(P<0.05),显著优于PVCC(P<0.05);PVCS蛋白粘附率显著低于PVCC(P<0.05)和PVCM(P<0.05);PVCS血小板粘附量显著低于PVCC(P<0.05),与PVCM相比无显著差异(P>0.05)。PVCS与PVCM脱落率相比,有着相似的趋势。OSA涂层体外循环管路,具有良好的抗凝血性能、优越的生物相容性和较好的稳定性。     

海藻酸钠交联肝素涂层在体外循环及人工心肺支持装置管路中的应用

背景：目前国内体外循环心脏手术使用的非肝素涂层管路和插管对血液破坏大、炎性反应重,影响心脏手术后患者的恢复和生存。 目的：采用生物医用高分子材料研制新型体外循环管道肝素涂层技术,并对其稳定性及抗凝血性能进行研究。 方法：利用CaCl₂将活化医用聚氯乙烯体外循环管道内表面修饰形成Ca2+膜,并与海藻酸钠和肝素交联;其中Ca²⁺与海藻酸钠、肝素钠中的Na+反应,从而使线型聚合物分子发生交联,形成化学交联海藻酸钠-肝素复合物的网状结构,实现生物型材料肝素化涂层。 结果与结论：CaCl₂修饰活化医用聚氯乙烯体外循环管道并与海藻酸钠和肝素交联反应,形成生物型高分子材料肝素化涂层管道,试验证明肝素化涂层管道具有良好的血液相容性、稳定性、抗凝血性能,可满足体外循环中短期转流的要求。     

碳纳米管/聚氨酯复合材料的制备及生物相容性评价

目的 制备和评价碳纳米管/聚氨酯复合材料的生物相容性。方法 通过溶胶-凝胶方法制备碳纳米管/聚氨酯复合材料,对其力学性能进行测试;根据ISO10993指南,选取溶血实验、动态凝血实验、血小板黏附实验、血小板活化实验、细胞毒性实验和材料局部植入方法对复合材料的生物相容性进行评价。结果 复合材料无明显细胞毒性,并表现出比聚氨酯材料更好的抗溶血性能、动态凝血性能、抑制血小板黏附性能以及组织相容性。结论 碳纳米管－聚氨酯复合材料具有优良的生物相容性,可以作为制备组织工程细胞生长支架、人工血管、药物载体的基础材料。     

血液接触面的抗凝技术——肝素涂抹

在人造物质和材料表面,移植上有活性的肝素以达到抗凝作用的技术即肝素涂抹技术(HCS)。HCS技术可在不进行全身肝素化情况下防止血液凝集和血液与高分子材料接触,达到抗凝效果,可减少体外循环术中肝素用量及其副作用。本文介绍了HCS的工艺技术、HCS的生物相容性及其临床应用。目前HCS用品价格昂贵,妨碍其推广。     

五种国产医用嵌段聚醚聚氨酯的细胞毒性评价

国内最近研制成功的医用嵌段聚醚聚氨酯(SPEU)是一类用于人工心脏,血管及其辅助装置的抗凝血材料,经两种细胞培养细胞毒性试验方法评价证明具有优良的生物相容性。实验结果报告如下。     

肝素化胶原/壳聚糖多孔支架的制备及其血管化的研究

本研究旨在构建一种能快速血管化的人工真皮替代物。用冻干法制备了胶原／壳聚糖多孔支架，并对其进行肝素化，观察此支架的结构特征、亲水性、体外降解性和组织相容性，同时将血管生成素引入到此支架，对复合有血管生成素的肝素化支架的体内血管化进行了初步研究。结果表明，肝素化胶原／壳聚糖多孔支架具有合适的三维多孔结构、良好的吸水性和较理想的酶解稳定性，体内实验表明，此支架具有良好的组织相容性，血管生成素可加快支架的血管化。     

Negative cilia concept for thromboresistance: synergistic effect of PEO and sulfonate groups grafted onto polyurethanes

In order to investigate the interaction between various sulfonated polyurethanes (PUs) and blood, a commercial PU surface was chemically modified by poly(ethylene oxide) (PEO), dodecanediol(DDO), and propane sultone to give hydrophilic, hydrophobic, and negative sulfonated surfaces, respectively. The blood compatibility of modified PUs was evaluated by an in vitro platelet adhesion test, activated partial thromboplastin time (APTT), and prothrombin time (PT) measurements as well as an ex vivo rabbit A-A shunt method. In the platelet adhesion test, the hydrophilic PEO grafted PUs showed less platelet adhesion than untreated PU and hydrophobic DDO grafted PU. Sulfonated PU-PEO exhibited a lower degree of adhesion and shape change of platelet. The APTT and PT, especially APTT, of the sulfonated PUs were extended, whereas those of PU-PEO and PU-DDO did not show any significant change compared with untreated PU. Meanwhile, in the ex vivo experiment, hydrophilic PEO grafted PUs showed longer occlusion times than untreated PU or hydrophobic DDO grafted PU. In addition, the incorporation of SO3 groups at the end of PU-DDO and PU-PEO, particularly PU-PEO-SO3, exhibited an enormous prolongation in occlusion time, indicating a synergistic effect of the hydrophilic PEO and the negative SO3 groups on thromboresistance. These occlusion times corresponded well to in vitro evaluation results: the less adhesion and shape change of platelet and the longer APTT and PT, the more extended the ex vivo occlusion time.     

Interaction of blood components with heparin-immobilized polyurethanes prepared by plasma glow discharge

The blood compatibility of poly(ethylene oxide) (PEO)-grafted and heparin (Hep) immobilized polyurethanes was investigated using in vitro plasma recalcification time (PRT), activated partial thromboplastin time (APTT), platelet adhesion and activation, and peripheral blood mononuclear cell (PBMC) adhesion and activation. In the experiment with plasma proteins, the PRT of the polyurethane (PU) surface was prolonged by PEO grafting and further prolonged by heparin immobilization. The APTT was prolonged on PU-Hep, suggesting the binding of immobilized heparin to antithrombin III. The percentage of platelet adhesion on PU was not much different from that on acrylic acid- and PEO-grafted PUs (PU-C, PU-6, PU-33), yet was substantially decreased by heparin immobilization (PU-6-Hep, PU-33-Hep). The release of serotonin from adhering platelets was slightly suppressed on PEO-grafted PUs yet significantly suppressed on heparin-immobilized PUs. In the PBMC experiments, the adhesion and activation of the cells were significantly suppressed on heparin-immobilized PUs, and the amount of interleukin-6 (IL-6) released from PBMCs stimulated with surface-modified PUs decreased with a decrease in PBMC adhesion.     

Synthesis and characterization of heparinized polyurethanes using plasma glow discharge

Polyurethanes (PU) were synthesized from 4,4'-diphenylmethane diisocyanate and polytetramethylene glycol, and subsequently with ethylene diamine as a chain extender. The PU film was exposed to oxygen plasma glow discharge to produce peroxides on the surfaces. These peroxides were then used as catalysts for the copolymerization of acrylic acid (AA) and methyl acrylate (MA) in order to prepare carboxyl group-introduced PU (PU-C). Heparin-immobilized PU was prepared using the coupling reaction of PU-C with polyethylene oxide (PEO) followed by the reaction of grafted PEO with heparin. The surface-modified PUs were then characterized by attenuated total reflection Fourier transform infrared spectroscopy, electron spectroscopy for chemical analysis (ESCA), and a contact angle goniometer. The concentration of carboxylic acid groups on the PU surfaces could be controlled within the range of 0.47-1.68 micromol cm(-2) by the copolymerization of AA and MA. The amounts of heparin coupled to terminus amino groups on PU-6 and PU-33 were 1.30 and 1.16 microg cm(-2), respectively. The water contact angle of the PU was decreased by AA grafting, and further decreased by PEO grafting and heparin immobilization, showing an increased hydrophilicity of the modified PUs. A 3% loss from the originally bound heparin appeared within several hours and thereafter almost no heparin was released when heparin-immobilized PUs were immersed in a physiological solution for 100 h, indicating the covalent immobilization of heparin on the surfaces.     

Interaction of blood components with heparin-immobilized polyurethanes prepared by plasma glow discharge

The blood compatibility of poly(ethylene oxide) (PEO)-grafted and heparin (Hep) immobilized polyurethanes was investigated using in vitro plasma recalcification time (PRT), activated partial thromboplastin time (APTT), platelet adhesion and activation, and peripheral blood mononuclear cell (PBMC) adhesion and activation. In the experiment with plasma proteins, the PRT of the polyurethane (PU) surface was prolonged by PEO grafting and further prolonged by heparin immobilization. The APTT was prolonged on PU-Hep, suggesting the binding of immobilized heparin to antithrombin III. The percentage of platelet adhesion on PU was not much different from that on acrylic acid- and PEO-grafted PUs (PU-C, PU-6, PU-33), yet was substantially decreased by heparin immobilization (PU-6-Hep, PU-33-Hep). The release of serotonin from adhering platelets was slightly suppressed on PEO-grafted PUs yet significantly suppressed on heparin-immobilized PUs. In the PBMC experiments, the adhesion and activation of the cells were significantly suppressed on heparin-immobilized PUs, and the amount of interleukin-6 (IL-6) released from PBMCs stimulated with surface-modified PUs decreased with a decrease in PBMC adhesion.     

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。     

Microbial degradation,cytotoxicity and antibacterial activity of polyurethanes based on modified castor oil and polycaprolactone

The objective of this study was to assess the effects of type of polyol and concentration of polycaprolactone (PCL) in polyurethanes (PUs) on microbial degradability, cytotoxicity, biological properties and antibacterial activity to establish whether these materials may have biomedical applications. Chemically modified and unmodified castor oil, PCL and isophorone diisocyanate in a 1:1 ratio of NCO/OH were used. PUs were characterized by stress/strain fracture tests and hardness (ASTM D 676-59). Hydrophilic character was determined by contact angle trials and morphology was evaluated by scanning electron microscopy. Degradability with Escherichia coli and Pseudomonas aeruginosa was evaluated by measuring variations in the weight of the polymers. Cytotoxicity was evaluated using the ISO 10993-5 (MTT) method with mouse embryonic fibroblasts L-929 (ATCC® CCL-1) in direct contact with the PUs and with NIH/3T3 cells (ATCC® CRL-1658) in indirect contact with the PUs. Antimicrobial activity against E. coli and P. aeruginosa was determined. PUs derived from castor oil modified (P0 and P1) have higher mechanical properties than PUs obtained from castor oil unmodified (CO). The viability of L-929 mouse fibroblasts in contact with polymers was greater than 70%. An assessment of NIH/3T3 cells in indirect contact with PUs revealed no-toxic degradation products. Finally, the antibacterial effect of the PUs decreased by 77% for E. coli and 56% for P. aeruginosa after 24 h. These results indicate that PUs synthesized with PCL have biocidal activity against Gram-negative bacteria and do not induce cytotoxic responses, indicating the potential use of these materials in the biomedical field.     

Molecular mechanical analysis of polymer conformation, 2. Relation between chain conformation and birefringence of stretched non-crystalline polyurethanes with various substituent groups

The relationship between birefringence and polymer structure was studied both by theoretical and experimental analyses of a series of non-crystalline polyurethanes (PU) with different side groups. The most probable steric structures of PUs were estimated by molecular mechanical calculation (MM2) of their oligomeric model compounds, and their birefringence was theoretically calculated on the structural data obtained. In addition, some of the PUs were practically synthesized and melt-spun into thin fibers, which were drawn to a maximum draw ratio to measure the values of birefringence. The comparison of the measured and estimated values revealed that the present estimation method is effective for simulating the chain conformations and the birefringence of fully or partially extended polymer chains, which ought to be formed by drawing and melt-flow of glassy materials. Of particular interest was that phenyl-substituted PUs exhibit an unexpectedly larger birefringence than methyl-substituted PUs. This fact was reasonably explained by the angular rotation of the highly polarizable phenyl group, which is energetically easily allowed and influences strongly the value of birefringence.     

In vitro interactions of biomedical polyurethanes with macrophages and bacterial cells

Three commercial medical-grade polyurethanes (PUs), a poly-ether-urethane (Pellethane), and two poly-carbonate-urethanes, the one aromatic (Bionate) and the other aliphatic (Chronoflex), were tested for macrophages and bacterial cells adhesion, in the presence or absence of adhesive plasma proteins. All the experiments were carried out on PUs films obtained by solvent casting. The wettability of these films was analysed by measuring static contact angles against water. The ability of the selected PUs to adsorb human fibronectin (Fn) and fibrinogen (Fbg) was checked by ELISA with biotin-labelled proteins. All PUs were able to adsorb Fn and Fbg (Fn > Fbg). Fn adsorption was in the order: Pellethane > Chronoflex > Bionate, the highest Fbg adsorption being detected onto Bionate (Bionate > Chronoflex > Pellethane). The human macrophagic line J111, and the two main bacterial strains responsible for infection in humans (Staphylococcus aureus Newman and Staphylococcus epidermidis 14852) were incubated in turn with the three PUs, uncoated or coated with plasma proteins. No macrophage or bacterial adhesion was observed onto uncoated PUs. PUs coated with plasma, Fn or Fbg promoted bacterial adhesion (S. aureus > S. epidermidis), whereas macrophage adhered more onto PUs coated with Fn or plasma. The coating with Fbg did not promote cell adhesion. Pellethane showed the highest macrophage activation (i.e. spreading), followed, in the order, by Bionate and Chronoflex.     

Synthesis,Characterization and Cell Compatibility of Novel Poly(ester urethane)s Based on Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) and Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) Prepared by Melting Polymerization

Novel tailor-made poly(ester urethane)s (PUs) based on microbial polyesters poly(3-hydroxybutyrate-co-4hydroxybutyrate) (P3HB4HB) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) were synthesized by melting polymerization (MP) using 1,6-hexamethylene diisocyanate (HDI) as a coupling agent. A comprehensive characterization using ¹H-NMR, Fourier transform infrared spectroscopy (FT-IR), gel-permeation chromatography (GPC), differential scanning calorimetry (DSC), mechanical properties, static water contact angles, cell proliferation using smooth muscle cells from rabbit aorta (RaSMCs) and immortalized human keratinocytes (HaCat), and blood coagulation behavior were conducted on the synthesized PUs films. DSC showed that PU samples had a low degree of crystallinity at room temperature and became fully amorphous after a melt-quenched process. The series of tailor-made PUs based on different mass ratios of P3HB4HB and PHBHHx revealed a ductile and flexile mechanical property especially for PHBHHx-rich PU, or a hydrophobic property for 4HB-rich PU. A 4 days incubation experiment showed that all PU films had a better cell proliferation than poly(lactic acid) (PLA), polyhydroxybutyrate (PHB), P3HB4HB and PHBHHx. RaSMCs cultured on PU films had a quiescent contractile phenotype, indicating that they were fully functional. HaCat incubated on tailor-made PU films showed a proliferation approximately equal to tissue-culture plates (TCPs). Blood coagulation behavior tests revealed a strong platelet adhesion and a short coagulation time on PU films. This study demonstrated potential medical applications for P3HB4HB and PHBHHx based polyurethane as a hydrophobic wound-healing and hemostatic materials.