改性壳聚糖吸附Cu(Ⅱ)及其生物活性研究

壳聚糖具有特殊的生物活性和生理调节机能,其分子的重复单元中富含氨基和羟基,对Cu(Ⅱ)具有良好的络合能力.壳聚糖分子结构的规整性和分子间氢键的存在使其难溶于多数溶剂,对壳聚糖进行改性以增强溶解性和对Cu(Ⅱ)的吸附能力是壳聚糖研究的热点.文章综述了目前壳聚糖的理化改性和对Cu(Ⅱ)的吸附研究,对吸附过程的影响因素做了总结,对壳聚糖吸附体内Cu(Ⅱ)生物学活性的应用作了展望.     

壳聚糖吸附胆固醇的研究

血清中胆固醇水平高是冠心病等疾病的重要原因。在当前吸附法治疗高脂血症的推广应用中,所用吸附剂不是价格过于昂贵就是性能不稳定,很难应用于临床。本文试图以具有优良血液相容性和吸附性的壳聚糖用作胆固醇吸附剂。 通过 Ｈａｃｋｍａｎ法制备了壳聚精,并研磨成 ７５～１５０μｍ的粉末,加入血清中吸附,用酶氧化法测量吸附量。 实验中发现壳聚糖对胆固醇的吸附与壳聚糖脱乙酸化程度、分子量有密切关系,实验结果表明：随壳聚糖脱乙酸化度提高,壳聚糖对胆固醇吸附量也提高,当壳聚糖分子量为５３～５４万时,吸附量达到最大值,吸附量还跟壳聚糖形态有关,壳聚精粉末粒径越小越利于吸附。     

壳聚糖的血液相容性

壳聚糖是一种天然的氨基多糖,作为一种海洋生物活性物质被广泛地应用于生物医学工 程领域。从血小板、红细胞、白细胞、凝血因子以及补体系统等方面对壳聚糖与血液中各成分的 作用进行了探讨,认为壳聚糖的止血作用是通过激活外源性血液凝固途径和补体系统旁路途径 实现的。在此基础上介绍了几种提高壳聚糖材料血液相容性的方法及相应的抗凝血机理,包括 磺酸化、酰化、表面修饰等。     

壳聚糖及其衍生物在生物医药中的应用与研究进展

随着科学、医疗技术的不断发展,自然界中很多有用的化学物质都被提炼出来,并广泛运用于生物、医疗、美容、化学等方面,壳聚糖就是其中的一种,壳聚糖具有天然高分子的生物官能性和相容性、血液相容性、安全性、微生物降解性,这些特性使得其被各行各业广泛关注并应用。本文系统地介绍了壳聚糖极其衍生物发展史、性质、以及其生物医药中的具体应用。     

壳聚糖减肥降脂作用的研究进展

肥胖是当今普遍存在的健康问题,与其伴随的心脏病、高血压、高血脂、中风和糖尿病等疾病已经严重影响了人们的生活质量.壳聚糖由于对脂肪、胆汁酸和胆固醇有着良好的吸附作用.已被广泛应用于减肥降脂.将壳聚糖与其他具有减肥降脂作用的活性物质共同使用亦可提高其时油脂的吸附能力和减肥效果,还可以通过对壳聚糖进行改性使用其衍生物来提高吸附油脂的效率.而且虽然市场上已有壳聚糖降脂产品热销,但其降脂作用机理目前还不是很清楚.本文综述了不同种类壳聚糖减肥降脂的作用效果和作用机制.还提出将壳聚糖制备成纳米粒以提高其减肥降脂作用的新观点.     

功能化多孔聚氨酯薄膜的制备及其生物医学应用

聚氨酯(PU)因其具有良好的生物相容性、优异的力学性能、耐磨损及易加工成型等优点,广泛应用于生物医学领域,将其加以修饰改性制备多孔结构聚氨酯,有望成为组织工程支架领域的热门材料。本文中,笔者通过热致相分离法制备多孔PU薄膜,利用肝素对多孔PU薄膜进行改性;通过血液实验证明肝素改性前后多孔PU薄膜血液相容性差异;并采用血管内皮生长因子(VEGF)对薄膜进行修饰。傅里叶红外光谱、电子光谱测试和扫描电子显微镜等分析结果表明肝素改性成功。与改性前相比,修饰肝素可以赋予多孔PU薄膜优异的抗粘附特性,有效延长薄膜的体外凝血时间,降低溶血率,避免红细胞形态学异常现象和凝集现象,同时避免补体激活和血小板激活现象。因此,肝素修饰的多孔PU薄膜展示了良好的生物相容性。此外,实验结果表明:VEGF对薄膜进行修饰,可以有效提高生物活性涂层的细胞活性,促进细胞增殖。     

碳纤维/碳纳米管增强磷酸钙生物复合材料的血液相容性研究

目的：探讨以碳长纤维模拟骨组织中的胶原纤维束,碳纳米管弥散分布在骨水泥基质中所制备的仿生复合材料的血液相容性。方法：采用血小板静态浸渍黏附、聚集实验法,通过扫描电镜（SEM）观察复合材料表面、粗糙断面及气孔内的血栓形成情况,对其血液相容性进行研究。结果：以两种碳材料为增强相制备的复合材料与血液接触后,在材料光滑的表面、粗糙的断面及气孔内、以及碳纤维与碳纳米管的表面,由于纤维蛋白原的吸附量较少使血小板难以黏附、聚集,因此,在材料表面未能形成白血栓。结论：以碳纤维和碳纳米管为增强相制备的骨水泥生物复合材料具有良好的血液相容性。     

去细胞牛颈静脉构建组织工程右心带瓣管道生物相容性实验

目的:检测去细胞处理牛颈静脉的生物相容性.方法:去细胞处理牛颈静脉,与新鲜牛颈静脉分别于兔皮下包埋,术后2,4,12周取材,HE染色;进行血浆蛋白吸附和血小板粘附实验,检测血液相容性.结果:包埋早期有炎性细胞浸润,后期炎性细胞消失,以成纤维细胞为主.去细胞牛颈静脉与新鲜牛颈静脉血浆蛋白吸附和血小板粘附无显著差异.结论:去细胞牛颈静脉有良好的生物相容性.     

壳聚糖及其衍生物抗肿瘤作用研究进展

壳聚糖为天然多糖甲壳素脱除部分乙酰基的产物,是自然界存在的唯一碱性多糖,无毒,可生物降解,具有免疫功能和良好的生物相容性。近年发现,壳聚糖具有抗肿瘤作用,却因其难溶于水及中性溶剂而影响其应用,壳聚糖衍生物改善了壳聚糖的这个缺点,也具有更广泛的药理作用。本文对壳聚糖及其壳聚糖衍生物在抗肿瘤方面的研究情况做了综述。     

纳米结构Ti/TiN涂层对NiTi合金生物相容性的影响

目的：评价纳米结构Ti/TiN涂层对镍钛形状记忆合金（含镍50.6at%）生物相容性的影响,为生物医用纳米结构Ti/TiN涂层表面改性的NiTi合金材料生物安全性提供依据。方法：不影响基体的形状记忆性或超弹性效应的前提下,采用真空过滤电弧离子镀技术,在NiTi合金表面沉积一层纳米结构Ti/TiN涂层,分别对表面改性前和改性后的NiTi合金样品进行体外细胞毒性实验、溶血实验和血小板粘附实验,探索纳米结构Ti/TiN涂层对NiTi合金生物相容性的影响。结果：表面具有纳米结构Ti/TiN涂层的NiTi合金无细胞毒性,H9C2（2-1）细胞相容性优于涂层前,细胞形态典型,粘附数量明显大于涂层前。纳米结构Ti/TiN涂层有改善NiTi合金的血液相容性作用,其溶血率从2.1%降至涂层改性后的1.2%,同时,血小板黏附量和聚集程度小于处理前的NiTi合金。结论：纳米Ti/TiN涂层能够显著改善NiTi合金的生物相容性。     

Resolution of enantiomers by HPLC on tris(4-alkoxyphenylcarbamate)s of cellulose and amylose

Ten phenylcarbamate derivatives of cellulose and amylose having alkoxy groups such as ethoxy, isopropoxy, and isobutoxy at 4-position, and methyl groups at 3- and 5-positions and methoxy group at 4-position were synthesized and their chiral recognition abilities as stationary phases for high-performance liquid chromatography were investigated and compared to those with tris(4-methoxyphenylcarbamate)s of cellulose and amylose. In 4-alkoxy derivatives of cellulose, chiral recognition ability increased as the bulkiness of 4-alkoxy groups increased. 4-Isopropoxy and 4-isobutoxy derivatives showed high chiral recognition. On the other hand, chiral discrimination of amylose 4-alkoxy derivatives scarcely depended on the bulkiness of the alkoxy group, and 4-methoxy and 4-isopropoxy derivatives showed high chiral recognition. 3,5-Dimethyl-4-methoxyphenylcarbamates of cellulose and amylose possessed higher chiral recognition ability than the corresponding 4-methoxy derivatives. © 1993 Wiley-Liss, Inc.     

聚氨酯／液晶（PU／EBBA）复合膜的血液相容性研究

以聚氨酯弹性体为基质材料,与液晶化合物EBBA共混后,由溶剂蒸发法浇铸成膜。偏光显微镜观察证实了复合膜中液晶相的存在。用动态凝血实验、血小板粘附实验和扫描电镜观察的方法研究了复合膜中液晶含量对材料抗凝血性能的影响。结果表明,只有当液晶含量达到30%（wt）时,复合膜的血液相容性随着液晶含量的增加有明显改善,同时发现复合膜表面吸附的血小板随着液晶含量的增加而明显减少。     

Preparation and characterization of novel chitosan/gelatin membranes using chitosan hydrogel

Chitin and chitosan are novel biomaterials. The novel chitosan/gelatin membranes were prepared using the suspension of chitosan hydrogel mixed with gelatin. The prepared chitosan/gelatin membranes were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), mechanical, swelling, and thermal studies. The morphology of these chitosan/gelatin membranes was found to be very smooth and homogeneous. The XRD studies showed that the chitosan/gelatin membranes have good compatibility and interaction between the chitosan and gelatin. The stress and elongation of chitosan/gelatin membranes on wet condition showed excellent when the mixture ratio of gelatin was 0.50. The prepared chitosan/gelatin membranes showed good swelling, mechanical and thermal properties. Cell adhesion studies were also carried out using human MG-63 osteoblast-like cells. The cells incubated with chitosan/gelatin membranes for 24 h were capable of forming cell adhesion. Thus the prepared chitosan/gelatin membranes are bioactive and are suitable for cell adhesion suggesting that these membranes can be used for tissue-engineering applications. Therefore, these novel chitosan/gelatin membranes are useful for biomedical applications.     

Synthesis of anionic poly(ethylene glycol) derivative for chitosan surface modification in blood-contacting applications

To improve blood compatibility, chitosan surface was modified by the complexa-tion-interpenetration method using an anionic derivative of poly(ethylene glycol) (PEG). Methoxypoly(ethylene glycol) sulfonate (MPEG sulfonate)-modified chitosan was prepared by allowing the base polymer to swell in an acidic medium, followed by polyelectrolyte complexation and interpenetration of MPEG sulfonate with the chitosan matrix. Addition of a strong base collapsed the base polymer to permanently immobilize the modifying agent on the surface. Electron spectroscopy for chemical analysis (ESCA) confirmed the presence of MPEG sulfonate on chitosan and the high resolution Cls peak showed an increase in -C—O- which is indicative of the ethylene oxide residues. The number of adherent platelets and the extent of platelet activation was significantly reduced on MPEG sulfonate-modified chitosan. Compared to an average of more than 66 fully activated platelets on unmodified chitosan surface, only 3.0 contact-adherent platelets were present on MPEG sulfonate-modified chitosan. Plasma recalcification time, a measure of the intrinsic coagulation reaction, was about 11.5 min in contact with modified chitosan. The results of this study show that chitosan surface can be modified by the complexation-interpenetration method with anionic PEG derivative. Surface-immobilized MPEG sulfonate was effective in preventing plasma protein adsorption and platelet adhesion and activation by the steric repulsion mechanism.     

Synthesis and HPLC chiral recognition of regioselectively carbamoylated cellulose derivatives

Four regioselective-carbamoylated cellulose derivatives having two different substituents at 2-, 3-, and 6-position were prepared and evaluated as chiral stationary phases (CSPs) for high-performance liquid chromatography. Investigations showed that the nature and arrangement of the substituents significantly influenced the chiral recognition abilities of the heterosubstituted cellulose derivatives and each derivative exhibited characteristic enantioseparation. Some racemates were better resolved on these derivatives than the corresponding homogeneously substituted cellulose derivatives including a commercial CSP, Chiralcel OD. Racemic compounds shown in this study were most effectively discriminated on cellulose 2,3-(3-chloro-4-methylphenylcarbamate)-6-(3,5-dimethylphenylcarbamate) and 2,3-(3,5-dimethylphenylcarbamate)-6-(3-chloro-4-methylphenylcarbamate).     

Covalent immobilization of chitosan and heparin on PLGA surface

Chitosan and heparin were covalently immobilized onto a poly(lactic acid-co-glycolic acid) (PLGA) surface using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC), N-hydroxysuccinimide (NHS) in a 2-morpholinoethane sulfonic acid (MES) buffer system. The properties of the modified PLGA surface and the control were investigated by water contact angle measurement and electron spectroscopy for chemical analysis (ESCA). The water contact angle of the modified film was greatly decreased and the element content on the surface of the films changed correspondingly. Platelet adhesion assay showed that blood compatibility of the chitosan/heparin modified film was improved while hepatocyte culture indicated that the cell compatibility of the modified film was enhanced.     

Improved blood biocompatibility of composite film of chitosan/carbon nanotubes complex

Single-walled carbon nanotubes are novel molecular-scale wires having excellent anti-adhesion properties with regard to platelets. On the other hand, chitosan is a partially de-acetylated derivative of chitin that has a critical role in cell attachment and growth. The aim of this study was to investigate how carbon nanotubes improve the blood biocompatibility of chitosan film. We prepared composite films with various concentrations of chitosan/carbon nanotubes (CS/CNTs) (1.3–6.3 wt%). The sample surfaces were characterized by Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and contact angle measurements. The surface characterization revealed that the surface of the CS/CNTs composite film became more hydrophobic with increasing amounts of CNTs. Cell attachment tests using bovine aortic endothelial cells (BAECs) indicated that CS/CNTs composite films retained their cell adhesion ability. The blood compatibility of the CS/CNTs composite films was evaluated using the blood platelet adhesion and activation tests in vitro. Platelet adhesion results confirmed that platelet adhesion and the formation of a platelet network were inhibited on composite films with higher concentrations of CNTs (5.1 wt%). Our experimental results show that the novel composite film containing CS/CNTs possesses two paradoxical characteristics, namely, good adherence of endothelial cells and minimum adherence and activation of platelets, making this film a promising antithrombogenic material for use in the biomedical field.     

Poly(N-isopropylacrylamide) surface-grafted chitosan membranes as a new substrate for cell sheet engineering and manipulation

The immobilization of poly(N-isopropylacrylamide) (PNIPAAm) on chitosan membranes was performed in order to render membranes with thermo-responsive surface properties. The aim was to create membranes suitable for cell culture and in which confluent cell sheets can be recovered by simply lowering the temperature. The chitosan membranes were immersed in a solution of the monomer that was polymerized via radical initiation. The composition of the polymerization reaction solvent, which was a mixture of a chitosan non-solvent (isopropanol) and a solvent (water), provided a tight control over the chitosan membranes swelling capability. The different swelling ratio, obtained at different solvent composition of the reaction mixture, drives simultaneously the monomer solubility and diffusion into the polymeric matrix, the polymerization reaction rate, as well as the eventual chain transfer to the side substituents of the pyranosyl groups of chitosan. A combined analysis of the modified membranes chemistry by proton nuclear magnetic resonance ((1)H-NMR), Fourier transform spectroscopy with attenuated total reflection (FTIR-ATR) and X-ray photoelectron spectroscopy (XPS) showed that it was possible to control the chitosan modification yield and depth in the solvent composition range between 75% and 100% of isopropanol. Plasma treatment was also applied to the original chitosan membranes in order to improve cell adhesion and proliferation. Chitosan membranes, which had been previously subjected to oxygen plasma treatment, were then modified by means of the previously described methodology. A human fetal lung fibroblast cell line was cultured until confluence on the plasma-treated thermo-responsive chitosan membranes and cell sheets were harvested lowering the temperature.     

Synthesis and antimicrobial activity of a water-soluble chitosan derivative with a fiber-reactive group

A novel fiber-reactive chitosan derivative was synthesized in two steps from a chitosan of low molecular weight and low degree of acetylation. First, a water-soluble chitosan derivative, N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC), was prepared by introducing quaternary ammonium salt groups on the amino groups of chitosan. This derivative was further modified by introducing functional (acrylamidomethyl) groups, which can form covalent bonds with cellulose under alkaline conditions, on the primary alcohol groups (C-6) of the chitosan backbone. The fiber-reactive chitosan derivative, O-acrylamidomethyl-HTCC (NMA-HTCC), showed complete bacterial reduction within 20 min at the concentration of 10ppm, when contacted with Staphylococcus aureus and Escherichia coli (1.5-2.5 x 10(5) colony forming units per milliliter [CFU/mL]).     

Enantioseparation using urea- and imide-bearing chitosan phenylcarbamate derivatives as chiral stationary phases for high-performance liquid chromatography

Completely deacetylated chitosan was prepared by the treatment of commercial chitosan with 50% aqueous NaOH, and then derivatized into several new chitosan phenylcarbamate derivatives having a urea and an imide moiety at the 2-position of the glucosamine ring by the reaction with isocyanate and phthalic anhydride/isocyanate, respectively. The chitosan derivatives were coated on macroporous silica gel and evaluated as chiral stationary phases (CSPs) for high-performance liquid chromatography. The chiral recognition ability of the chitosan derivative was improved using the completely deacetylated chitosan. Among the novel chitosan derivatives, the 3,5-dimethyl-, 3,5-dichloro-, and 3,4-dichlorophenylcarbamate derivatives were found to possess relatively high chiral resolution abilities. The CSPs based on the chitosan phenylcarbamate-urea and -imide derivatives were stable in the presence of chloroform and ethyl acetate as a component of the eluents, and some racemates were better resolved by such eluents. The dichlorophenylcarbamate-imide derivatives showed a high chiral recognition for metal acetylacetonate complexes. The enantiomerization of Al(acac)3 was performed on the chitosan 3,5-dichlorophenylcarbamate-imide derivative CSP and the resulting chromatogram showed a 26% (+)-isomer enrichment.