医用聚碳酸酯的涂层修饰及生物相容性研究

目的 研制低分子肝素钠(LMWH)涂层和多醛基氧化海藻酸钠(OSA)涂层的聚碳酸酯,并对其生物相容性进行评价.方法 利用化学接枝改性方法制备涂层材料,进行表征并验证涂层稳定性;通过接触角测定、体外血清蛋白、血小板黏附试验、体外凝血试验等进行生物相容性评价.结果 分析红外光谱,发现涂层后材料出现与涂层物相关的吸收峰变化,定量结果显示材料表面涂层量稳定.与未涂层材料相比,涂层材料表面与水的接触角减小,血清蛋白、血小板黏附量显著减少,凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)显著延长,其差异有统计学意义(P＜0.05).与LMWH涂层材料相比,OSA涂层材料抗凝效果略差,但其蛋白黏附量、表面接触角小于LMWH涂层,差异具有统计学意义(P＜0.05).结论 应用化学接枝改性方法制备LMWH、OSA涂层的聚碳酸酯,其涂层稳定,生物相容性显著改善.     

医用聚氨酯生物相容性研究新进展

聚氨酯因有良好的生物相容性和机械性能，而被广泛用于生物医学领域，但聚氨酯长期植入人体内，也会引起机体的炎症反应，使材料发生老化降解现象。因而要进一步提高医用聚氨酯的生物相容性，使其与机体生理环境更加相容，不诱发或少诱发炎症反应，就要使材料表面更加生物化，可以维持蛋白的正常构象。本文综述了以仿生化为基础提高医用聚氨酯生物相容性的两种主要途径－表面内皮细胞化及仿生物膜结构（表面膦脂化），并总结了其实施方法及存在的问题。     

生物医用脂肪族聚氨酯的合成、表征及血液相容性研究

采用一步法合成以4，4’—甲烷二环巳基二异氰酸酯(HMDI)、扩链剂1，4—丁二醇(BDO)为硬段，聚四氢呋喃醚(PTMG)为软段的脂肪族聚氨酯。并对所合成材料进行了傅立叶变换红外光谱分析、力学性能测试、水接触角测试、溶血实验及体外静态血小板粘附实验。结果表明，本论文合成的聚氨酯断裂强度可达30MPa以上，可与芳香族聚氨酯材料相比拟，而其断裂伸长率、断裂永久形变、亲水性能较之更好，具有理想的机械力学性能。溶血实验和体外静态血小板粘附实验显示该材料具有优良的血液相容性。该材料在生物医学领域，尤其是介入诊疗和医用薄膜产品方面有极大的应用潜力，是一种有着巨大应用前景的生物医用材料。     

聚碳酸酯型聚氨酯的体外降解研究

本研究聚碳酸酯型聚氨酯(PCU),在预氧化处理后(5%H2O2/0.05M CoCl2溶液),再用酶(番木瓜蛋白酶,20U/ml的溶液)水解处理后的表面形态及分子结构变化,同时与聚醚聚氨酯(PEU)和氟碳化合物封端的聚碳酸酯型聚氨酯(PCUF)材料作对比。通过扫描电镜(SEM),光电子能谱(XPS)和分子量(GPC)表征材料表面降解情况和分子结构变化。结果证实了材料的抗氧化性能直接影响材料的整体降解情况,结果显示PCU抗氧化性能优良,所以它的整体抗降解能力比抗氧化能力较低的PEU强,而且在PCU中引入氟碳化合物,其抗降解能力会更强。     

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。     

物理交联型生物医用聚氨酯水凝胶的合成研究

我们采用碳酸亚乙酯(E thy lene carbonate)与乙醇胺(E thano lam ine)反应合成得到含有氨基甲酸酯结构的新型小分子二醇扩链剂双羟乙基氨基甲酸酯(B is-hydroxy lethy l carbom ate(EC-AE))。用一步法通过扩链剂EC-AE和1,4-bu taned io l合成了聚氨酯聚合物PUA 25和PU B 25,对其结构用红外光谱分析(FT-IR)、差动扫描量热法分析(DSC)进行了表征,其结果表明:PUA 25微相分离程度比PU B 25的低,即PUA 25的硬段之间形成氢键的数量较PU B 25的少,相混和程度大。并以PUA 25和PU B 25为原料,对其形成的物理交联水凝胶进行了研究,发现PUA 25能够制备物理交联型水凝胶,且该水凝胶随着冷却-加热-冷却过程的重复而出现“凝胶-溶液-凝胶”的循环转变,证明了相容性程度较高的聚氨酯易形成水凝胶。     

多嵌段聚氨酯材料的表面结构与生物相容性

人工心脏隔膜用的聚氨酯材料至少应具有抗凝和耐挠曲的性能。通常提高聚氨酯的耐挠曲性多从调整其本体结构来考虑。由于聚氨酯的本体结构与表面结构不同,在挠曲过程中本体的相分离变化会影响表面软段的取向行为。因此为了知道挠曲对聚氨酯抗血凝性能的影响,作者从1983年起通过自制的耐疲劳试验代,利用XPS,FT-ATR-IR,WAXD,SAXS,SALS和血小板粘附试验等方法,测得在疲劳过程中聚氨酯表面的微相分离程度下降,聚醚软段含量减少,并导致其抗凝血性能下降。这样作者便把聚氨酯在反复变形过程中的本体形态,表面结构和生物相容性间的关系联系起来了。     

两亲聚氨酯弹性体一羟基磷灰石生物复合材料

以聚己二酸乙二酯和聚乙二醇合成的两亲聚氨酯弹性体与羟基磷灰石通过凝胶法制备生物复合材料     

肝素化聚氨酯表面修饰材料的研究

通过两步溶液聚合法合成了阳离子化聚氨酯 (PU) ,再与肝素结合 ,得到肝素化聚氨酯。使用红外光谱法、X射线光电子能谱仪 (ESCA)测定法、比浊法等分析手段对离子化前后以及肝素化前后结构特点的变化进行了表征 ,同时还用全血凝固时间 (CT)、活化部分凝血致活酶时间 (APTT)、成纤维细胞增殖试验等方法对其进行了生物相容性试验。结果表明阳离子化聚氨酯对肝素具有较强的吸附能力 ,能形成稳定的肝素化聚氨酯 ,具有较好的生物相容性 ,是一种理想的生物医用材料。     

两亲聚氨酯弹性体一羟基磷灰石生物复合材料(PUHA)的研究(Ⅰ)——PUHA的制备及力学功能

以聚己二酸乙二酯和聚乙二醇合成的两亲聚氨酯弹性体与羟基磷灰石通过凝胶法制备生物复合材料 ( PUHA)。研究了 HA含量、亲 /疏水软段比例、合成条件等因素对 PUHA力学性能的影响。结果表明 :当 HA含量为 30 % ,亲疏水软段比例为 4 0 /60时 ,PUHA的综合力学性能最好     

Synthesis of Functional Sugar‐Based Polyurethanes

Three new polyurethanes (PUs) with multiple pendant allyl groups were synthesized from L ‐arabinitol as versatile materials for the preparation of tailor‐made PUs with varying degrees of functionalization. Their allyl functional groups can take part in thiol‐ene reactions to obtain greatly diverse materials. Thus, six new highly functional PUs were prepared by click chemistry to give polymers with NHBoc [NH‐CO‐OC(CH₃)₃], amino, carboxylic, and 1,2‐dihydroxyethyl side groups. The thermal stability of the novel PUs was investigated by thermogravimetric analysis and differential scanning calorimetry. This strategy provides a simple and versatile platform for the design of new materials whose functionality can be easily modified to anchor diverse biologically active molecules.     

Synthesis and Hemocompatibilities of Cellulose‐Containing Segmented Polyurethanes

Novel segmented polyurethanes (SPUs) have been synthesized using hydrolyzed cellulose triacetate (HCTA) and 1,4‐butanediol (BD) as diol component. By altering the molar ratio of HCTA to diphenylmethane diisocyanate (MDI), a series of polymers having poly(butadiene) (PBD) diol soft segments and varying content of HCTA was prepared. Then the polymers were further deacetylated with NaOCH₃/CH₃OH. Viscosity measurements showed the polymers had the viscosity behavior of common polyelectrolytes. Attenuated total reflectance‐Fourier transform infrared spectroscopy (ATR‐FTIR) and water contact angle measurements revealed that the cellulose is oriented on the surface of these materials. The hemocompatibility in vitro was evaluated with platelet‐rich plasma (PRP) contact tests and viewed by scanning electron microscopy (SEM) using commercial BioSpan® and cellulose‐free SPU as control samples. Platelet adhesion to cellulose‐containing SPUs was inhibited by 30–75% compared with cellulose‐free polyurethanes. Cell spreading was observed on the control SPUs but not on any of the other surfaces. The incorporation of cellulose into the SPUs backbone effectively reduced platelet adhesion and thus potentially could result in better hemocompatibility.     

以PEG和PTMG为混合软段的聚氨酯的合成、表征及血液相容性研究

我们用4,4'-二苯基甲烷二异氰酸酯(MDI),扩链剂1,4-丁二醇(BDO)为硬段,聚乙二醇(PEG)与聚四氢呋喃醚二元醇(PTMG)为混合软段,在不同PEG、PTMG配比下,采用二步法,合成了一系列聚醚聚氨酯(PU)。对所合成的材料进行了傅立叶变换红外光谱、力学性能测试、水接触角、吸水率、溶血试验和静态血小板粘附试验。结果表明,本研究成功合成了机械强度高、亲水性好、血液相容性良好的新型混合软段的聚氨酯,是一种有着巨大应用前景的生物医用材料。     

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。     

Synthesis and Properties of Segmented Polyurethanes with Triptycene Units in the Soft Segment

Segmented polyurethanes based on poly(tetramethylene glycol) soft segments (SS) containing aromatic units are synthesized. Hydroquinone bis(2‐hydroxyethyl) ether and 4,4′‐methylenebis(phenyl isocyanate) are used as the chain extender and the diisocyanate, respectively. Effects of incorporation of hydroquinone (HQ) and triptycene hydroquinone into the soft segments on the morphology and properties of the undeformed segmented polyurethanes are investigated. Differential scanning calorimetry and dynamic mechanical analysis indicate that the incorporation of triptycene units leads to an increased glass transition temperature (T_g) and an elimination of the crystallization of soft segments. The tensile analysis shows there is no strain hardening for the polymer films with triptycene‐containing soft segments. Wide‐angle x‐ray diffraction demonstrates that the absence of strain hardening in triptycene‐containing segmented polyurethane likely arises from the suppressed strain induced crystallization. In contrast, the less bulky HQ units show little effect on either thermally or strain induced crystallization of the soft segments. Morphology studies, including small angle x‐ray scattering on the compression molded films and atomic force microscopy on the solvent cast film, reveal that polyurethanes with HQ and triptycene containing soft segments maintain distinct microphase separated morphology.

     

Synthesis of Novel Polyurethanes and Polyureas by Polyaddition Reactions of Dianhydrohexitol Configurated Diisocyanates

The 2,5‐diamino compounds of the three isomeric 1,4 : 3,6‐dianhydrohexitols with D ‐gluco‐ ( 1 ), D ‐manno‐ ( 2 ) and L ‐ido ( 3 ) configuration were efficiently transformed into the corresponding diisocyanates 7 , 8 and 10 as well as the L ‐ido diisothiocyanate 9 by a hot phosgenation procedure. Catalytic homogenous polyaddition procedures yielded various novel carbohydrate‐derived polyurethanes and polyureas. The polymers were characterized using IR and ¹H/ ¹³C NMR spectroscopy, viscosimetry and DSC. Number‐average molecular weights were obtained from gel‐permeation chromatography to be M̄_n 8 900–20 600 g/mol.     

Polyurethanes based on dihydroxamic acids. Synthesis, chemical characterization, and biological activity

A series of segmented polyurethanes based on polyethylene oxide/polycaprolactone diol, isophorone diisocyanate, and dihydroxamic acids were synthesized and characterized. Biocompatibility and antitumoral activity were in vivo tested on Wistar male rats and Wistar rats affected with Walker 256 carcinosarcoma, respectively. The effect of dihydroxamic acid structure on the biological properties was determined. A better antitumoral response of the polyurethanes containing aliphatic dihydroxamic segment compared with those which resulted using terephthaloyl dihydroxamic acid was evidenced. With increasing polymer chain polyethylene oxide content the antitumoral activity was also enhanced. Some attempts on the in vitro biodegradation of above polyurethanes were also performed.     

Polyurethanes based on dihydroxamic acids. Synthesis,chemical characterization,and biological activity

A series of segmented polyurethanes based on polyethylene oxide/polycaprolactone diol, isophorone diisocyanate, and dihydroxamic acids were synthesized and characterized. Biocompatibility and antitumoral activity were in vivo tested on Wistar male rats and Wistar rats affected with Walker 256 carcinosarcoma, respectively. The effect of dihydroxamic acid structure on the biological properties was determined. A better antitumoral response of the polyurethanes containing aliphatic dihydroxamic segment compared with those which resulted using terephtaloyl dihydroxamic acid was evidenced. With increasing polymer chain polyethylene oxide content the antitumoral activity was also enhanced. Some attempts on the in vitro biodegradation of above polyurethanes were also performed.     

Molecular Design,Synthesis and Properties of Novel Polyurethanes Containing Tetracyanocyclopropyl Groups as Piezoelectric Chromophores

Summary: 1‐(2′,2′,3′,3′‐Tetracyanocyclopropyl)‐3,4‐di‐2′‐hydroxyethoxybenzene (4) was prepared by the reaction of bromomalononitrile with 3,4‐di‐(2′‐hydroxyethoxy)benzylidenemalononitrile (3). The dipole moment of diol 4, calculated by the ASED‐MO method, was 4.01 D. Diol 4 was condensed with 2,4‐toluenediisocyanate and 3,3′‐dimethoxy‐4,4′‐biphenylenediisocyanate to yield polyurethanes 5 and 6 containing tetracyanocyclopropane functionalities in the side‐group. The resulting polymers 5 and 6 were soluble in common organic solvents and the inherent viscosities were in the range of 0.25–0.30 dL · g^?1. Solution‐cast films showed a thermal stability up to 280 °C with glass‐transition temperatures of 163–167 °C. The approximate lengths of aligned piezoelectric chromophores estimated from AFM images of poled polymer films were about 4 nm. Piezoelectric coefficients (d₃₁) of the poled polymer films 5 and 6 were around 2.2–2.4 pC · N^?1. These polymers showed good temporal and long‐term thermal stability due to the hydrogen bonding of the urethane linkage.

Structure of one of the obtained polymers.