肝素化壳聚糖/大豆蛋白质复合材料的制备及其抗凝血功能研究
|
摘要
抗凝血材料是生物材料的重要组成部分,被广泛应用于与人体血液和组织相接触的医疗器械或组织工程化材料上,例如人工心脏瓣膜、血液透析系统、体外循环系统、血管栓塞剂、心脏起搏器、人工血管、血管支架、介入导管、外科手术线等；这类与血液直接接触的材料不仅要求具有组织相容性,不会对生物体组织引起炎症,而且要求具有血液相容性,能够抗血栓,不会在材料表面发生凝血现象,还要求具有与人体组织相似的弹性、延展性及良好的耐疲劳性等生物力学性能。因此,研制一种无需注射抗凝剂、抗血栓作用强而致凝作用弱、生物相容性和力学性能俱佳的医用抗凝血生物材料具有重要的理论意义和应用价值。
肝素作为临床上最常用的抗凝剂,其主要给药途径为静脉注射,存在全身用药、用量大、易引起出血、血小板减少、过敏等副作用,而肝素化生物材料是减少这些副作用最有效的途径,肝素化材料也是最主要的抗凝血材料。本论文拟以醋酸为主要溶剂体系,以壳聚糖和大豆蛋白质这两种具有良好生物相容性和生物降解性的天然高分子为主要原料,制备不同组成和结构的壳聚糖/大豆蛋白质复合材料；利用肝素分子与蛋白质、壳聚糖分子间的物理和化学作用,将肝素结合到材料上,制备肝素化生物材料。通过不同的肝素化工艺来控制肝素在材料上的分布和结合程度。通过体外和体内实验,系统评价肝素化生物材料的血液和组织相容性及其抗凝血功能,揭示影响其性能和功能的规律,以期获得新型肝素化生物材料。本工作的主要内容包括以下几个方面：
(1)壳聚糖/大豆蛋白质复合膜的制备及其生物学性能评价：以壳聚糖和大豆蛋白质为原料,以醋酸水溶液为溶剂,通过共混和流延法制备了一系列壳聚糖/大豆蛋白质复合膜。通过扫描电镜观察、红外光谱分析、x-射线衍射分析、水接触角测试、力学性能测试、体外细胞培养及动物体内埋植实验等方法研究了不同组成的壳聚糖/大豆蛋白质复合膜的结构与性能。结果表明,随着复合膜中大豆蛋白质含量的增加,复合膜的结晶度降低,亲水性增加。在大豆蛋白质含量为10%时力学性能最高。大豆蛋白质的存在,具有促进细胞增殖,提高细胞相容性、组织相容性和生物降解性的作用。因此,可以通过调节大豆蛋白质的含量来调控复合材料的微观结构、力学性能和生物学性能。
(2)表面肝素化壳聚糖/大豆蛋白质复合膜的制备及抗凝血功能研究：以EDC为交联剂,将肝素接枝到壳聚糖/大豆蛋白质复合膜表面,获得表面肝素化壳聚糖/大豆蛋白质复合膜。通过甲苯胺蓝法、红外光谱分析、静态水接触角测试、力学性能测试等方法评价了表面肝素化壳聚糖/大豆蛋白质复合膜的结构和物理化学性能；通过体外细胞培养和抗凝血试验评价了表面肝素化复合材料的细胞相容性和血液相容性。结果表明,经表面肝素化的壳聚糖/大豆蛋白质复合膜的亲水性能明显提高,但力学性能有所降低,表面肝素密度在0.59～1.12μg/cm2之间；体外细胞培养实验结果显示,肝素化壳聚糖/大豆蛋白质复合膜能促进细胞粘附和生长,具有良好的细胞相容性；抗凝血试验结果显示,表面肝素化显著地减少了血小板的粘附,显著延长了复钙时间(表面肝素化组338 s-352s,未肝素化组112s-201 s1,抑制了血栓的形成,而且几乎没有溶血发生,表现出较好的血液相容性。
(3)共混法制备肝素化壳聚糖/大豆蛋白质复合膜及其抗凝血性能：采用共混法制备了一系列交联型(EDC为交联剂)和未交联型肝素化壳聚糖/大豆蛋白质复合膜。通过甲苯胺蓝法、红外光谱分析、静态水接触角测试、力学性能测试等方法评价了肝素化壳聚糖/大豆蛋白质复合膜的结构和物理化学性能；通过体外细胞培养和抗凝血试验评价了肝素化复合材料的细胞相容性和血液相容性。结果表明,交联型肝素化复合膜比未交联型以及表面肝素化复合膜的肝素结合量大(交联型组1.24～2.47μg/cm2；未交联型组0.67～1.29μg/cm2；表面肝素化组0.59～1.12μg/cm2),具有更好的力学性能,其亲水性能也较好；体外细胞培养实验结果显示,交联型肝素化壳聚糖/大豆蛋白质复合膜能促进细胞生长和增殖,具有良好的细胞相容性；抗凝血试验结果显示,交联型肝素化有效地减少了血小板的粘附,显著延长了复钙时间((交联型组903s-1179 s；未交联型组292s-306 s；表面肝素化组338 s-352s,未肝素化组112s-201 s),抑制了血栓的形成,而且几乎没有溶血发生,表现出良好的血液相容性。
(4)壳聚糖/大豆蛋白质复合海绵的制备及其生物学性能评价：采用冷冻干燥法制备了一系列壳聚糖/大豆蛋白质复合海绵。通过红外光谱分析、X-衍射分析及扫描电镜观察等方法研究大豆蛋白质含量对复合海绵结构与性能的影响；通过体外细胞培养实验和体内植入实验综合评价了壳聚糖/大豆蛋白质复合海绵的生物相容性和生物降解性。结果表明,这种复合海绵材料具有三维多孔结构。体外细胞培养实验显示,复合海绵材料中所含的大豆蛋白质能为细胞生长提供营养成分,促进细胞在复合海绵表面及内部粘附和生长,提高细胞的增殖活性。动物体内埋植实验结果表明,壳聚糖/大豆蛋白质复合海绵材料具有良好的组织相容性和降解性,大豆蛋白质促进其降解,多孔结构有利于组织进入也促进其降解。因此复合海绵的降解速度快于相对应的复合膜。由此,壳聚糖/大豆蛋白质复合海绵具有良好的生物相容性和降解性,具有作为组织工程支架材料的潜力。
(5)壳聚糖涂层纤维素/大豆蛋白质复合膜的制备及其细胞相容性和血液相容性研究：以氢氧化钠/尿素溶液为共溶剂,制备一系列纤维素/大豆蛋白质复合膜,然后将较低分子量壳聚糖(50000 Da)涂层在纤维素/大豆蛋白质复合膜表面。经红外光谱分析、X-射线衍射分析、扫描电镜观察、水接触角测试以及力学性能检测等评价壳聚糖涂层对于复合材料的结构和性能的影响；通过体外细胞培养和抗凝血试验评价了壳聚糖涂层复合材料的细胞相容性和血液相容性。结果表明,壳聚糖涂层粘附在多孔的原始纤维素/大豆蛋白质复合膜表面,并且形成了一层光滑平整的表面。力学性能测试表明,壳聚糖涂层增强了复合膜的力学性能,尤其是湿态条件下的力学性能。细胞培养实验和MTT测试结果显示,壳聚糖涂层改变了纤维素/大豆蛋白质复合膜的组分和微观结构,并且减缓了大豆蛋白质在细胞培养介质中的释放速度,能够促进细胞在复合膜表面粘附,提高了细胞增殖活性。血液相容性评价结果表明,壳聚糖涂层有效地减少了血小板的粘附,延长了复钙时间,降低了溶血率。因此,壳聚糖表面涂层是提高和改善纤维素/大豆蛋白质复合膜力学性能、细胞相容性以及血液相容性的一种简便而行之有效的方法。
综上所述,本工作制备了不同系列的壳聚糖/大豆蛋白质复合膜、肝素化壳聚糖/大豆蛋白质复合膜以及壳聚糖/大豆蛋白质复合海绵,通过高分子化学与物理方法表征了各类复合膜与复合海绵的结构与理化性能,通过体外细胞培养和体内植入实验综合评价了复合膜和复合海绵的细胞相容性与组织相容性,通过抗凝血实验评价了其血液相容性,从而获得了具有良好细胞相容性、组织相容性和抗凝血功能的壳聚糖/大豆蛋白质复合材料,为其应用提供了理论依据和实验数据。
Anticoagulant material, an important part of biological materials, which has been widely used as medical device and tissue engeering materials contacted with blood, such as artificial heart valve, hemodialysis system, extracorporeal circulation system, blood vessels embolic agents, heart pacemakers, artificial vascular, stents, interventional catheter, surgical line. The materials which directly contact with blood should have not only histocompatibility without inflammation, but also have good blood compatibility such as antithrombotic, without clotting phenomenon. In addition, it is required that the materials'mechanical properties such as elasticity and ductility are similar with human tissue and favorable fatiguedurability. Therefore, it is importantly to develop biomedical anticoagulant materials which have strong antithrombotic ability, good biocompatibility and mechanical properties without injecting anticoagulants as a substitutes.
Heparin is the most commonly clinlic anticoagulation drug. The mostly delivery method is intravenous injection. However, it caused some side-effects such as dosage, bleeding, thrombocytopenia, allergies. Heparinization is one of the most effective ways that reduce the side effects which direct injection of heparin caused. And heparinized materials are the uppermost anticogulant materials.
In this work, acetic acid was used as the co-solvent and two kinds of natural polymers, chitosan and soy protein, were used as main raw materials to prepare chitosan/soy protein composites with different composition and structure. The heparinized biomaterials were prepared with the physical or chemical interaction between heparin molecules and protein molecules, as well as chitosan molecules. The distribution and binding degree of heparin ware controlled by different heparinization technologies. The biological characteristics of the chitosan/soy protein composites including blood compability and histocompatibility were systematically evaluated by in vitro testing and in vivo animal experiments. Meanwhile, the factors affected on the properties and function of the new heparinized biomaterials were revealed. The main contents are as following:
(1) Preparation and characterization of chitosan/soy protein composite membrane materials:A series of chitosan/soy protein composite membrane was prepared by blending and casting using chitosan and soy protein isolate (SPI) as the raw materials and acetic acid aqueous solution as co-solvent. The effects of SPI content on the structure and properties of the final chitosan/soy protein composite membranes were investigated by scanning electron microscope (SEM), Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), water contact angle, tensile testing, in vitro cell culture and in vivo implantation experiments. The results revealed that the crystallinity decreased and the hydrophilicity of the composite membranes increased with the increase of SPI content. It was found that the mechanical properties of chitosan/soy protein composite membranes were excellent when SPI content was 10%. SPI had obvious promoted cell proliferation and improved cytocompatibility, tissue compatibility and biodegradability of the membranes. Therefore, it could regulate the microstructure, mechanical properties and biological properties of the materials by adjusting SPI content.
(2) Preparation, characterization and hemocompability evaluation of surface-heparinized chitosan/soy protein composite membranes:Using EDC as cross-linker, heparin was grafted on to the surface of chitosan/soy protein composite membranes for hepariniztion. The structure and properties of the surface-heparinized chitosan/soy protein composite membranes were investigated by assay with toluidine blue, attenuated total reflection-fourier transforms infrared spectrometry, water contact angle test and tensile testing; The cytocompability and hemocompability of surface-heparinzed chitosan/soy protein composite membranes in vitro cell culture and anticoagulation experiments. The results revealed that the hydrophilicity of chitosan/soy protein composite membranes were remarkably improved by suface-grafting of heparin, but the mechanical properties decreased and the content of immobiled-heparin was 0.59～1.12μg/cm2. Moreover, the heparinized membranes could improve of growth of L929 cells and showed good cytocompability. Surface-heparinization could effectively reduce platelet adhesion, extend the plasma recalcification time (surface-heparinization groups 338 s～352 s, non-heparinization groups 112 s～201 s), curb thrombosis and reduce the hemolysis rate. It indicated that the surface-heparinized membranes have good blood compatibility.
(3) Preparation, characterization and hemocompability evaluation of heparinized chitosan/soy protein composite membranes:A series of heparinized chitosan/soy protein composite membranes were prepared by blending, with or without cross-linking. The structure and properties of the heparinized chitosan/soy protein composite membranes were investigated by assay with toluidine blue, Attenuated total reflection-Fourier transforms infrared spectrometry, water contact angle test and tensile testing; The cytocompability and hemocompability of the heparinized chitosan/soy protein composite membranes were evaluated by in vitro cell culture and anticoagulation experiments. The results revealed that the amount of immobilized-heparin of the cross-linking heparinized chitosan/soy protein composite membranes was higher than that on the non-crosslinking heparinized and surface-heparinized chitosan/soy protein composite membranes (crosslinking heparinized groups 1.24～2.47μg/cm, non-crosslinking heparinized groups 0.67-1.29μg/cm2, surface-heparinization groups 0.59～1.12μg/cm2). The cross-linking heparinized membranes were more hydrophilic than the non-crosslinking heparinized membranes, and showed the mechanical properties than he non-crosslinking heparinized and surface-heparinized membranes. Moreover, the cross-linking heparinized membranes could improve the proliferation of L929 cells, and showed good cytocompability. Cross-linking heparinization can effectively reduce platelet adhesion, extended the plasma recalcification time (crosslinking heparinized groups 903 s～1179 s, non-crosslinking heparinized groups 292 s～306 s, surface-heparinization groups 338 s～352 s, non-heparinization groups 112 s～201 s), curb thrombosis and reduce the hemolysis rate. The cross-linking heparinized membranes showed better blood compatibility than the non-crosslinking heparinized membranes and surface-heparinized membranes.
(4) The chitosan/soy protein sponges were fabricated in order to enhance the biodegradability of chitosan-based composites. A series of chitosan/soy protein isolate sponges were prepared by freeze-drying process. The effects of soy protein content on the structure and properties of the sponges were investigated by FT-IR, XRD and SEM. The biocompatibility and biodegradability of chitosan/soy protein sponges were evaluated by in vitro cell culture and in vivo implantation experiments. The results showed that the chitosan/soy protein sponges exhibited uniform three-dimensional porous structure, and the pore structure of the chitosan/SPI sponges can keep well with an increase in soy protein content. The in vitro cell culture process showed that the incorporation of soy protein isolate in the composite sponges could provide nutrients for cell growth, which was beneficial to the cell's growth and spread on the sponges, as well as to the enhancement of cell viability during cell culture. The sponges implanted into rats showed good biocompatibility and biodegradability. The biodegradation rate of the chitosan/soy protein sponges was higher than the corresponding membranes, which is due to the incorporation of SPI, the three-dimensional porous structure. Therefore, chitosan/soy protein sponges may be used as cell scaffolds with good biodegradability and biodegradability.
(5) Preparation and characterization of chitosan-coated cellulose/soy protein composite membrane with improved physical properties and hemocompability:A series of cellulose/soy protein membranes was prepared using NaOH/urea solution as co-solvent, then chitosan (50000Da) was coated on the surface of cellulose/soy protein membranes. The original cellulose/soy protein composite membrane and chitosan-coated cellulose/soy protein composite membrane were characterized by FT-IR, XRD, SEM, water contact angle testing, and tensile testing. Chitosan-coated cellulose/SPI membranes had smoother surface microstructure and enhanced mechanical properties as compared with the corresponding cellulose/SPI membranes. The cytocompatibility and hemocompatibility of cellulose/SPI membranes and coated cellulose/SPI membranes were evaluated by cell culture, MTT assay, in vitro platelet adhesion testing, plasma recalcification time measurement, and hemolysis assay. The higher cell adherence and improved cytocompatibility of chitosan-coated cellulose/SPI membranes were mainly ascribed to the coated chitosan and the altered surface microstructure of cellulose/SPI membranes. Chitosan-coated cellulose/SPI membranes also showed lower platelet adhesion, longer PRT, and a lower hemolysis rate, all resulting from the good hemocompatibility of chitosan and the smoother membrane surface after chitosan coating. Undoubtedly, surface coating with chitosan improved the microstructure, mechanical properties, cytocompatibility, and hemocompatibility, thus widening the possible range of applications of cellulose/soy protein-based biomaterials.
In conclusion, several series of chitosan/soy protein membranes, heparinized chitosan/SPI membranes and chitosan/soy protein composite sponges were successfully prepared in this work. The structure and properties of the membranes and sponges were characterized by methods of polymer chemistry and physics. The cytocompatibility and tissue compatibility of the biocomposites were evaluated by in vitro cell culture and in vivo animal experiments. And the hemocompatibility was evaluated by anticoagulation experiments. Thereby it obtained the chitosan/soy protein composite biomaterials that had good cytocompatibility, tissue compatibility and good hemocompatibility, and provided the theory basis and the experimental data for potential applications.
肝素作为临床上最常用的抗凝剂,其主要给药途径为静脉注射,存在全身用药、用量大、易引起出血、血小板减少、过敏等副作用,而肝素化生物材料是减少这些副作用最有效的途径,肝素化材料也是最主要的抗凝血材料。本论文拟以醋酸为主要溶剂体系,以壳聚糖和大豆蛋白质这两种具有良好生物相容性和生物降解性的天然高分子为主要原料,制备不同组成和结构的壳聚糖/大豆蛋白质复合材料；利用肝素分子与蛋白质、壳聚糖分子间的物理和化学作用,将肝素结合到材料上,制备肝素化生物材料。通过不同的肝素化工艺来控制肝素在材料上的分布和结合程度。通过体外和体内实验,系统评价肝素化生物材料的血液和组织相容性及其抗凝血功能,揭示影响其性能和功能的规律,以期获得新型肝素化生物材料。本工作的主要内容包括以下几个方面：
(1)壳聚糖/大豆蛋白质复合膜的制备及其生物学性能评价：以壳聚糖和大豆蛋白质为原料,以醋酸水溶液为溶剂,通过共混和流延法制备了一系列壳聚糖/大豆蛋白质复合膜。通过扫描电镜观察、红外光谱分析、x-射线衍射分析、水接触角测试、力学性能测试、体外细胞培养及动物体内埋植实验等方法研究了不同组成的壳聚糖/大豆蛋白质复合膜的结构与性能。结果表明,随着复合膜中大豆蛋白质含量的增加,复合膜的结晶度降低,亲水性增加。在大豆蛋白质含量为10%时力学性能最高。大豆蛋白质的存在,具有促进细胞增殖,提高细胞相容性、组织相容性和生物降解性的作用。因此,可以通过调节大豆蛋白质的含量来调控复合材料的微观结构、力学性能和生物学性能。
(2)表面肝素化壳聚糖/大豆蛋白质复合膜的制备及抗凝血功能研究：以EDC为交联剂,将肝素接枝到壳聚糖/大豆蛋白质复合膜表面,获得表面肝素化壳聚糖/大豆蛋白质复合膜。通过甲苯胺蓝法、红外光谱分析、静态水接触角测试、力学性能测试等方法评价了表面肝素化壳聚糖/大豆蛋白质复合膜的结构和物理化学性能；通过体外细胞培养和抗凝血试验评价了表面肝素化复合材料的细胞相容性和血液相容性。结果表明,经表面肝素化的壳聚糖/大豆蛋白质复合膜的亲水性能明显提高,但力学性能有所降低,表面肝素密度在0.59～1.12μg/cm2之间；体外细胞培养实验结果显示,肝素化壳聚糖/大豆蛋白质复合膜能促进细胞粘附和生长,具有良好的细胞相容性；抗凝血试验结果显示,表面肝素化显著地减少了血小板的粘附,显著延长了复钙时间(表面肝素化组338 s-352s,未肝素化组112s-201 s1,抑制了血栓的形成,而且几乎没有溶血发生,表现出较好的血液相容性。
(3)共混法制备肝素化壳聚糖/大豆蛋白质复合膜及其抗凝血性能：采用共混法制备了一系列交联型(EDC为交联剂)和未交联型肝素化壳聚糖/大豆蛋白质复合膜。通过甲苯胺蓝法、红外光谱分析、静态水接触角测试、力学性能测试等方法评价了肝素化壳聚糖/大豆蛋白质复合膜的结构和物理化学性能；通过体外细胞培养和抗凝血试验评价了肝素化复合材料的细胞相容性和血液相容性。结果表明,交联型肝素化复合膜比未交联型以及表面肝素化复合膜的肝素结合量大(交联型组1.24～2.47μg/cm2；未交联型组0.67～1.29μg/cm2；表面肝素化组0.59～1.12μg/cm2),具有更好的力学性能,其亲水性能也较好；体外细胞培养实验结果显示,交联型肝素化壳聚糖/大豆蛋白质复合膜能促进细胞生长和增殖,具有良好的细胞相容性；抗凝血试验结果显示,交联型肝素化有效地减少了血小板的粘附,显著延长了复钙时间((交联型组903s-1179 s；未交联型组292s-306 s；表面肝素化组338 s-352s,未肝素化组112s-201 s),抑制了血栓的形成,而且几乎没有溶血发生,表现出良好的血液相容性。
(4)壳聚糖/大豆蛋白质复合海绵的制备及其生物学性能评价：采用冷冻干燥法制备了一系列壳聚糖/大豆蛋白质复合海绵。通过红外光谱分析、X-衍射分析及扫描电镜观察等方法研究大豆蛋白质含量对复合海绵结构与性能的影响；通过体外细胞培养实验和体内植入实验综合评价了壳聚糖/大豆蛋白质复合海绵的生物相容性和生物降解性。结果表明,这种复合海绵材料具有三维多孔结构。体外细胞培养实验显示,复合海绵材料中所含的大豆蛋白质能为细胞生长提供营养成分,促进细胞在复合海绵表面及内部粘附和生长,提高细胞的增殖活性。动物体内埋植实验结果表明,壳聚糖/大豆蛋白质复合海绵材料具有良好的组织相容性和降解性,大豆蛋白质促进其降解,多孔结构有利于组织进入也促进其降解。因此复合海绵的降解速度快于相对应的复合膜。由此,壳聚糖/大豆蛋白质复合海绵具有良好的生物相容性和降解性,具有作为组织工程支架材料的潜力。
(5)壳聚糖涂层纤维素/大豆蛋白质复合膜的制备及其细胞相容性和血液相容性研究：以氢氧化钠/尿素溶液为共溶剂,制备一系列纤维素/大豆蛋白质复合膜,然后将较低分子量壳聚糖(50000 Da)涂层在纤维素/大豆蛋白质复合膜表面。经红外光谱分析、X-射线衍射分析、扫描电镜观察、水接触角测试以及力学性能检测等评价壳聚糖涂层对于复合材料的结构和性能的影响；通过体外细胞培养和抗凝血试验评价了壳聚糖涂层复合材料的细胞相容性和血液相容性。结果表明,壳聚糖涂层粘附在多孔的原始纤维素/大豆蛋白质复合膜表面,并且形成了一层光滑平整的表面。力学性能测试表明,壳聚糖涂层增强了复合膜的力学性能,尤其是湿态条件下的力学性能。细胞培养实验和MTT测试结果显示,壳聚糖涂层改变了纤维素/大豆蛋白质复合膜的组分和微观结构,并且减缓了大豆蛋白质在细胞培养介质中的释放速度,能够促进细胞在复合膜表面粘附,提高了细胞增殖活性。血液相容性评价结果表明,壳聚糖涂层有效地减少了血小板的粘附,延长了复钙时间,降低了溶血率。因此,壳聚糖表面涂层是提高和改善纤维素/大豆蛋白质复合膜力学性能、细胞相容性以及血液相容性的一种简便而行之有效的方法。
综上所述,本工作制备了不同系列的壳聚糖/大豆蛋白质复合膜、肝素化壳聚糖/大豆蛋白质复合膜以及壳聚糖/大豆蛋白质复合海绵,通过高分子化学与物理方法表征了各类复合膜与复合海绵的结构与理化性能,通过体外细胞培养和体内植入实验综合评价了复合膜和复合海绵的细胞相容性与组织相容性,通过抗凝血实验评价了其血液相容性,从而获得了具有良好细胞相容性、组织相容性和抗凝血功能的壳聚糖/大豆蛋白质复合材料,为其应用提供了理论依据和实验数据。
Anticoagulant material, an important part of biological materials, which has been widely used as medical device and tissue engeering materials contacted with blood, such as artificial heart valve, hemodialysis system, extracorporeal circulation system, blood vessels embolic agents, heart pacemakers, artificial vascular, stents, interventional catheter, surgical line. The materials which directly contact with blood should have not only histocompatibility without inflammation, but also have good blood compatibility such as antithrombotic, without clotting phenomenon. In addition, it is required that the materials'mechanical properties such as elasticity and ductility are similar with human tissue and favorable fatiguedurability. Therefore, it is importantly to develop biomedical anticoagulant materials which have strong antithrombotic ability, good biocompatibility and mechanical properties without injecting anticoagulants as a substitutes.
Heparin is the most commonly clinlic anticoagulation drug. The mostly delivery method is intravenous injection. However, it caused some side-effects such as dosage, bleeding, thrombocytopenia, allergies. Heparinization is one of the most effective ways that reduce the side effects which direct injection of heparin caused. And heparinized materials are the uppermost anticogulant materials.
In this work, acetic acid was used as the co-solvent and two kinds of natural polymers, chitosan and soy protein, were used as main raw materials to prepare chitosan/soy protein composites with different composition and structure. The heparinized biomaterials were prepared with the physical or chemical interaction between heparin molecules and protein molecules, as well as chitosan molecules. The distribution and binding degree of heparin ware controlled by different heparinization technologies. The biological characteristics of the chitosan/soy protein composites including blood compability and histocompatibility were systematically evaluated by in vitro testing and in vivo animal experiments. Meanwhile, the factors affected on the properties and function of the new heparinized biomaterials were revealed. The main contents are as following:
(1) Preparation and characterization of chitosan/soy protein composite membrane materials:A series of chitosan/soy protein composite membrane was prepared by blending and casting using chitosan and soy protein isolate (SPI) as the raw materials and acetic acid aqueous solution as co-solvent. The effects of SPI content on the structure and properties of the final chitosan/soy protein composite membranes were investigated by scanning electron microscope (SEM), Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), water contact angle, tensile testing, in vitro cell culture and in vivo implantation experiments. The results revealed that the crystallinity decreased and the hydrophilicity of the composite membranes increased with the increase of SPI content. It was found that the mechanical properties of chitosan/soy protein composite membranes were excellent when SPI content was 10%. SPI had obvious promoted cell proliferation and improved cytocompatibility, tissue compatibility and biodegradability of the membranes. Therefore, it could regulate the microstructure, mechanical properties and biological properties of the materials by adjusting SPI content.
(2) Preparation, characterization and hemocompability evaluation of surface-heparinized chitosan/soy protein composite membranes:Using EDC as cross-linker, heparin was grafted on to the surface of chitosan/soy protein composite membranes for hepariniztion. The structure and properties of the surface-heparinized chitosan/soy protein composite membranes were investigated by assay with toluidine blue, attenuated total reflection-fourier transforms infrared spectrometry, water contact angle test and tensile testing; The cytocompability and hemocompability of surface-heparinzed chitosan/soy protein composite membranes in vitro cell culture and anticoagulation experiments. The results revealed that the hydrophilicity of chitosan/soy protein composite membranes were remarkably improved by suface-grafting of heparin, but the mechanical properties decreased and the content of immobiled-heparin was 0.59～1.12μg/cm2. Moreover, the heparinized membranes could improve of growth of L929 cells and showed good cytocompability. Surface-heparinization could effectively reduce platelet adhesion, extend the plasma recalcification time (surface-heparinization groups 338 s～352 s, non-heparinization groups 112 s～201 s), curb thrombosis and reduce the hemolysis rate. It indicated that the surface-heparinized membranes have good blood compatibility.
(3) Preparation, characterization and hemocompability evaluation of heparinized chitosan/soy protein composite membranes:A series of heparinized chitosan/soy protein composite membranes were prepared by blending, with or without cross-linking. The structure and properties of the heparinized chitosan/soy protein composite membranes were investigated by assay with toluidine blue, Attenuated total reflection-Fourier transforms infrared spectrometry, water contact angle test and tensile testing; The cytocompability and hemocompability of the heparinized chitosan/soy protein composite membranes were evaluated by in vitro cell culture and anticoagulation experiments. The results revealed that the amount of immobilized-heparin of the cross-linking heparinized chitosan/soy protein composite membranes was higher than that on the non-crosslinking heparinized and surface-heparinized chitosan/soy protein composite membranes (crosslinking heparinized groups 1.24～2.47μg/cm, non-crosslinking heparinized groups 0.67-1.29μg/cm2, surface-heparinization groups 0.59～1.12μg/cm2). The cross-linking heparinized membranes were more hydrophilic than the non-crosslinking heparinized membranes, and showed the mechanical properties than he non-crosslinking heparinized and surface-heparinized membranes. Moreover, the cross-linking heparinized membranes could improve the proliferation of L929 cells, and showed good cytocompability. Cross-linking heparinization can effectively reduce platelet adhesion, extended the plasma recalcification time (crosslinking heparinized groups 903 s～1179 s, non-crosslinking heparinized groups 292 s～306 s, surface-heparinization groups 338 s～352 s, non-heparinization groups 112 s～201 s), curb thrombosis and reduce the hemolysis rate. The cross-linking heparinized membranes showed better blood compatibility than the non-crosslinking heparinized membranes and surface-heparinized membranes.
(4) The chitosan/soy protein sponges were fabricated in order to enhance the biodegradability of chitosan-based composites. A series of chitosan/soy protein isolate sponges were prepared by freeze-drying process. The effects of soy protein content on the structure and properties of the sponges were investigated by FT-IR, XRD and SEM. The biocompatibility and biodegradability of chitosan/soy protein sponges were evaluated by in vitro cell culture and in vivo implantation experiments. The results showed that the chitosan/soy protein sponges exhibited uniform three-dimensional porous structure, and the pore structure of the chitosan/SPI sponges can keep well with an increase in soy protein content. The in vitro cell culture process showed that the incorporation of soy protein isolate in the composite sponges could provide nutrients for cell growth, which was beneficial to the cell's growth and spread on the sponges, as well as to the enhancement of cell viability during cell culture. The sponges implanted into rats showed good biocompatibility and biodegradability. The biodegradation rate of the chitosan/soy protein sponges was higher than the corresponding membranes, which is due to the incorporation of SPI, the three-dimensional porous structure. Therefore, chitosan/soy protein sponges may be used as cell scaffolds with good biodegradability and biodegradability.
(5) Preparation and characterization of chitosan-coated cellulose/soy protein composite membrane with improved physical properties and hemocompability:A series of cellulose/soy protein membranes was prepared using NaOH/urea solution as co-solvent, then chitosan (50000Da) was coated on the surface of cellulose/soy protein membranes. The original cellulose/soy protein composite membrane and chitosan-coated cellulose/soy protein composite membrane were characterized by FT-IR, XRD, SEM, water contact angle testing, and tensile testing. Chitosan-coated cellulose/SPI membranes had smoother surface microstructure and enhanced mechanical properties as compared with the corresponding cellulose/SPI membranes. The cytocompatibility and hemocompatibility of cellulose/SPI membranes and coated cellulose/SPI membranes were evaluated by cell culture, MTT assay, in vitro platelet adhesion testing, plasma recalcification time measurement, and hemolysis assay. The higher cell adherence and improved cytocompatibility of chitosan-coated cellulose/SPI membranes were mainly ascribed to the coated chitosan and the altered surface microstructure of cellulose/SPI membranes. Chitosan-coated cellulose/SPI membranes also showed lower platelet adhesion, longer PRT, and a lower hemolysis rate, all resulting from the good hemocompatibility of chitosan and the smoother membrane surface after chitosan coating. Undoubtedly, surface coating with chitosan improved the microstructure, mechanical properties, cytocompatibility, and hemocompatibility, thus widening the possible range of applications of cellulose/soy protein-based biomaterials.
In conclusion, several series of chitosan/soy protein membranes, heparinized chitosan/SPI membranes and chitosan/soy protein composite sponges were successfully prepared in this work. The structure and properties of the membranes and sponges were characterized by methods of polymer chemistry and physics. The cytocompatibility and tissue compatibility of the biocomposites were evaluated by in vitro cell culture and in vivo animal experiments. And the hemocompatibility was evaluated by anticoagulation experiments. Thereby it obtained the chitosan/soy protein composite biomaterials that had good cytocompatibility, tissue compatibility and good hemocompatibility, and provided the theory basis and the experimental data for potential applications.
引文
[1]柏乃庆,血液保存.上海人民出版社.1973,7,1-2.
[2]高宁国,程秀兰,杨敬,张树政.肝素结构与功能的研究进展.生物工程进展,1999,19,4-13.
[3]Damus P.S., Hicks M., Rosenberg R.D. Anticoagulant action of heparin. Nature, 1973,246,355-357.
[4]Hassan Y., Awaisu A., Aziz N.A., Aziz N.H., Ismail O. Heparin-induced thrombocytopenia and recent advances in its therapy. J. Clin. Pharm. Ther.,2007, 32,535-544.
[5]陈中伟,张键.断肢再植的现状与展望.中国处方药,2004,22,8-11.
[6]宋开芳,陈艺新,陈克洲,薛向东,贾湘谦,肖杰,秦杰,李青松.指腹皮下肝素浸润预防断指再植术后血管危象.中华显微外科杂志,2002,25,224-225.
[7]Jordan S.W., Chaikof E.L. Novel thromboresistant materials. J. Vasc. Surg.2007, 45 Suppl A:A,104-115.
[8]Bajpai A.K., Bhanu S. Dynamics of controlled release of heparin from swellable crosslinked starch microspheres. J. Mater. Sci. Mater. Med.,2007,18, 1613-1621.
[9]Lin W.C., Liu T.Y., Yang M.C. Hemocompatibility of polyacrylonitrile dialysis membrane immobilized with chitosan and heparin conjugate. Biomaterials,2004, 25,1947-1957.
[10]Luong-Van E., Gr(?)ndahl L., Chua K.N., Leong K.W., Nurcombe V., Cool S.M. Controlled release of heparin from poly (epsilon-caprolactone) electrospun fibers. Biomaterials,2006,27,2042-2050.
[11]Moon H.T., Lee Y, Han J.K., Byun Y A novel formulation for controlled release of heparin-DOCA conjugate dispersed as nanoparticles in polyurethane. Biomaterials,2001,22,281-289.
[12]Roveri N., Morpurgo M., Palazzo B., Parma B., Vivi L. Silica xerogels as a delivery system for the controlled release of different molecular weight heparins. Anal. Bioanal. Chem.,2005,381,601-606.
[13]徐鹏,李翔,杜强国,杨玉良.聚氯乙烯表面肝素化的研究.复旦学报(自然科学版),2001,40,372-375.
[14]侯长军,张文彬,霍丹群,陈柄灿,任艳容,郑书家.肝素化结合方式及本体材料的研究进展.化工进展,2003,22,703-707.
[15]Kumar M.N.V.R. A review of chitin and chitosan applications. React. Funct. Polym.,2000,46,1-27.
[16]Kweon D.K., Lim S.T. Preparation and characteristics of a water-soluble chitosan-heparin complex. J. Appl. Polym. Sci.,2003,87,1784-1789.
[17]袁伟永,计剑,付金红,沈家骢.层层静电自组装构建壳聚糖/肝素抗菌多层膜的研究.高等学校化学学报,2005,26,1963-1965.
[18]Wang X.H., Li D., Wang W.J., Feng Q.L., Cui F.Z., Xu Y.X., Song X.H. Covalent immobilization of chitosan and heparin on PLGA surface. Int. J. Biolog. Macromol.,2003,33,95-100.
[19]Jacobucci H.B., Sgarbieri V.C, Dias N.F.G.P., Borges P., Tanikawa C. Impact of different dietary protein on rat growth, blood serum lipids and protein and liver cholesterol. Nutr. Res.,2001,21,905-915.
[20]Vaz C.M., Fossen M., Van T.R.F., De Graaf L.A., Reis R.L., Cunha A.M. Casein and soybean protein-based thermoplastics and composites as alternative biodegradable polymers for biomedical applications. J. Biomed. Mater. Res. Part A,2003,65A,60-70.
[21]Chen Y, Zhang L., Gu J., Liu J. Physical properties of microporous membranes prepared by hydrolyzing cellulose/soy protein blends. J. Membr. Sci.,2004,241, 393-402.
[22]Zhou Z., Zheng H. Wei M., Huang J., Chen Y. Structure and mechanical properties of cellulose derivatives/soy protein isolate blends. J. Appl. Polym. Sci.,2008,107,3267-3274.
[23]Luo L.H., Wang X.M., Zhang Y.F., Liu Y.M., Wang Y., Chang P.R., Chen Y Preparation, characterization and biocompatibility evaluation of cellulose/soy protein isolate films coagulated from acetic acid solution. J. Biomater. Sci. Polym. Ed.,2008,19,479-496.
[24]Silva S.S., Santos M.I., Coutinho C.P., Mano J.F., Reis R.L. Physical properties and biocompatibility of chitosan/soy blended membranes. J. Mater. Sci. Mater. Med.,2005,16,575-579.
[25]Jia D.Y, Fang Y, Yao K. Water vapor barrier and mechanical properties of konjac glucomannan-chitosan-soy protein isolate edible films. Food Bioprod. Process.,2009,87,7-10.
[26]Silva S.S., Goodfellow B.J., Benesch J., Rocha J., Mano J.F., Reis R.L. Morphology and miscibility of chitosan/soy protein blended membranes. Carbohyd. Polym.,2007,70,25-31.
[27]Cervera M.F., Heinamaki J., Rasanen M., Maunu S.L., Karjalainen M., Acosta O.M.N., Colarte A.I., Yliruusi J. Solid-state characterization of chitosans derived from lobster chitin. Carbohyd. Polym.,2004,58,401-408.
[28]Hattori M., Numamoto K., Kobayashi K., Takahashi K. Functional changes in beta-lactoglobulin by conjugation with cationic saccharides. J. Agric. Food Chem.,2000,48,2050-2056.
[29]Suh J.K.F., Matthew H.W.T. Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering:a review. Biomaterials,2000,21, 2589-2598.
[30]Cho S.Y., Rhee C. Sorption characteristics of soy protein films and their relation to mechanical properties. Lebensm.Wiss. Technol.,2002,35,151-157.
[31]Tang R.P., Du Y.M., Zheng H., Fan L.H. Preparation and characterization of soy protein isolate-carboxymethylated konjac glucomannan blend films. J. Appl. Polym. Sci.,2003,88,1095-1099.
[32]ISO 10993-5:2009. Biological evaluation of medical devices Part 5:Tests for in vitro cytotoxicity.
[33]Serrano M.C., Pagani R., Vallet-Regi M., Pena J., Ramila A., Izquierdo I., Portoles M.T. In vitro biocompatibility assessment of poly (ε-caprolactone) films using L929 mouse fibroblasts. Biomaterials,2004,25,5603-5611.
[34]Velayudhan S., Anilkumar T.V., Mohanan P.V., Fernandez A.C., Varma H.K., Ramesh P. Biological evaluation of pliable hydroxyapatite-ethylene vinyl acetate co-polymer composites intended for cranioplasty. Acta. Biomater.,2005,1, 201-209.
[35]ISO 10993-6:2009. Biological evaluation of medical devices part 6:tests for local effects after implantation.
[36]Almeida E.V.R., Frollini E., Castellan A., Coma V. Chitosan, sisal cellulose, and biocomposite chitosan/sisal cellulose films prepared from thiourea/NaOH aqueous solution. Carbohyd. Polym.,2010,80,655-664.
[37]吕彩霞,姚子华.纳米羟基磷灰石/壳聚糖-硫酸软骨素复合材料的制备及其性能研究.复合材料学报,2007,24,110-115.
[38]杨前荣,陈新,邵正中.天然聚电解质壳聚糖/羧甲基壳聚糖配合物膜的研制.化学学报,2005,63,259-262.
[39]Koning C., van Duin M., Pagnoulle C., Jerome R. Strategies for compatibilization of polymer blends. Prog. Polym. Sci.,1998,23,707-757.
[40]Murakami R., Takashima R. Mechanical properties of the capsules of chitosan-soy globulin polyelectrolyte complex. Food Hydrocolloid.2003,17, 885-888.
[41]Franek F., Hohenwarter O., Katinger H. Plant protein hydrolysates:preparation of defined peptide fractions promoting growth and production in animal cells cultures. Biotechnol. Prog.,2000,16,688-692.
[42]Lee Y.K., Kim S.Y., Kim K.H., Chun B.H., Lee K.H., Oh D.J., Chung, N. Use of soybean protein hydrolysates for promoting proliferation of human keratinocytes in serum-free medium. Biotechnol. Lett.,2008,30,1931-1936.
[1]Ueno H., Mori T., Fujinaga T. Topical formulations and wound healing applications of chitosan. Adv. Drug Deliver. Rev.,2001,52,105-115
[2]Usami Y., Minami S., Okamoto Y., Matsuhashi A., Shigemasa Y. Influence of chain length of N-acetyl-D-glucosamine and D-glucosamine residues on direct and complement-mediated chemotactic activities for canine polymorphonuclear cells. Carbohyd. Polym.,1997,32,115-122.
[3]Suzuki Y., Miyatake K., Okamoto Y, Muraki E., Minami S. Influence of the chain length of chitosan on complement activation. Carbohyd. Polym.,2003,54, 465-469.
[4]Suzuki Y, Okamoto Y, Morimoto M., Sashiwa H., Saimoto H., Tanioka S.-i., Shigemasa Y, Minami S. Influence of physico-chemical properties of chitin and chitosan on complement activation. Carbohyd. Polym.,2000,42,307-310.
[5]Silva S.S., Santos M.I., Coutinho O.P., Mano J.F., Reis R.L. Physical properties and biocompatibility of chitosan/soy blended membranes. J. Mater. Sci. Mater. Med.,2005,16,575-579.
[6]Silva S.S., Goodfellow B.J., Benesch J., Rocha J., Mano J.F., Reis R.L Morphology and miscibility of chitosan/soy protein blended membranes. Carbohyd. Polym.,2007,70,25-31.
[7]Paquet O., Krouit M., Bras J., Thielemans W., Belgacem M.H. Surface modification of cellulose by PCL grafts. Acta Mater.,2010,58,792-801.
[8]Davarpanah S., Mahmoodi N.M., Arami M., Bahrami H., Mazaheri F. Environmentally friendly surface modification of silk fiber:Chitosan grafting and dyeing. Appl. Surf. Sci.,2009,255,4171-4176.
[9]Li J., Zhu B.Q., Shao YY, Liu X.R., Yang X.L., Yu Q. Construction of anticoagulant poly (lactic acid) films via surface covalent graft of heparin-carrying microcapsules. Colloids Surf., B,2009,70,15-19.
[10]Baumann H., Kokott A. Surface modification of the polymers present in a polysulfone hollow fiber hemodialyser by covalent binding of heparin or endothelial cell surface heparan sulfate:flow characteristics and platelet adhesion. J. Biomed. Sci., Polym. Ed.,2000,11,245-272.
[11]Olsson P., Sanchez J., Mollnes T.E., Riesenfeld J. On the blood compatibility of end-point immobilized heparin. J. Biomed. Sci., Polym. Ed.,2000,11, 1261-1273.
[12]Goosen M.F.A., Sefton M.W., Hatton M.W.C. Inactivation of thrombin by antithrombin Ⅲ on a heparinized biomaterial. Thromb. Res.,1980,20,534-554.
[13]Byun Y., Jacobs H.A., Kim S.W. Binding kinetics of thrombin and antithrombin Ⅲ with immobilized heparin using a spacer. Asaio J.,1992,38, M649-653.
[14]项昭保,霍丹群,候长军.肝素化聚醚砜抗凝血材料的研究.化工新型材料,2005,33,57-59.
[15]Kim Y.J., Kang I.K., Huh M.W., Yoon S.C. Surface characterization and in vitro blood compatibility of poly (ethylene terephthalate) immobilized with insulin and/or heparin using plasma glow discharge. Biomaterials,2000,21,121-130.
[16]Smith P.K., Mallia A.K., Hermanson G.T. Calorimetric method for the assay of heparin content in immobilized heparin preparations. Anal. Biochem.,1980, 109,466-473.
[17]Yang M.C., Lin W.C. Surface modification and blood compatibility of polyacrylonitrile membrane with immobilized chitosan-heparin conjugate. J. Polym. Res.,2002,9,201-206.
[18]ISO 10993-5:2009. Biological evaluation of medical devices Part 5:Tests for in vitro cytotoxicity.
[19]Serrano M.C., Pagani R., Vallet-Regi M., Pena J., Ramila A., Izquierdo I., Portoles M.T. In vitro biocompatibility assessment of poly (e-caprolactone) films using L929 mouse fibroblasts. Biomaterials,2004,25,5603-5611.
[20]Suzuki S., Gr(?)ndahl L., Leavesley D., Wentrup-Byrne E. In vitro bioactivity of MOEP grafted ePTFE membranes for craniofacial applications. Biomaterials, 2005,26,5303-5312.
[21]Shen F., Zhang E.L., Wei Z.J. In vitro blood compatibility of poly (hydroxybutyrate-co-hydroxyhexanoate) and the influence of surface modification by alkali treatment. Mater. Sci. Eng. C.,2010,30,369-375.
[22]Zhao J., Shi Q.A., Yin L.G., Luan S.F., Shi H.C., Song L.J., Yin J.H., Stagnaro P. Polypropylene modified with 2-hydroxyethyl acrylate-g-2-methacryloyloxyethyl phosphorycholine and its hemocompatibility Appl. Surf. Sci.,2010,256, 7071-7076.
[23]Xu J.P., Wang X.L., Fan D.Z., Ji J., Shen J.C. Construction of phospholipid anti-biofouling multilayer on biomedical PET surfaces. Appl. Surf. Sci.,2008, 255,538-540.
[24]He Q., Ao Q., Gong K., Zhang L.H., Hu M., Gong Y.D., Zhang X.F. Preparation and characterization of chitosan-heparin composite matrices for blood contacting tissue engineering. Biomed. Mater.,2010,5,055001 (16pp).
[25]Ho Y.C., Wu S.J., Mi F.L., Chiu Y.L., Yu S.H., Panda N., Sung H.W. Thiol-modified chitosan sulfate nanoparticles for protection and release of basic fibroblast growth factor. Bioconjug. Chem.,2010,21,28-38.
[26]Ho Y.C., Mi F.L., Sung H.W., Kuo P.L. Heparin-functionalized chitosan-alginate polyelectrolyte complex scaffolds for the stabilization and sustained release of basic fibroblast growth factor. Int. J. Pharm.,2009,376,69-75.
[27]Tang D.W., Yu S.H., Ho Y.C., Mi F.L., Kuo P.L., Sung H.W. Heparinized chitosan/poly (γ-glutamic acid) nanoparticles for multi-functional delivery of fibroblast growth factor and heparin. Biomaterials,2010,31 9320-9332.
[28]Yu S.H., Wu Y.B., Mi F.L., Shyu S.S. Polysaccharide-based artificial extracellular matrix:preparation and characterization of three-dimensional, macroporous chitosan, and heparin composite scaffold. J. Appl. Polym. Sci., 2008,109,3639-3644.
[29]Ma K.W., Ma L., Cai S.X., Wang X., Liu B., Xu Z.L., Dai X.Z., Yang J.Y., Jing A.H., Lei W.J. Preparation of heparin-immobilized PVA and its adsorption for low-density lipoprotein from hyperlipemia plasma. J. Mater. Sci.:Mater Med., 2008,19,3255-3261.
[30]Shu Y, Ou G.M., Wang L., Zou J.C., Li Q.L. Surface modification of titanium with heparin-chitosan multilayers via layer-by-layer self-assembly technique. J. Nanomate.,2011 doi:10.1155/2011/423686.
[31]Michiardia A., Aparicioa C., Ratnerb B.D., Planella J.A., Gil J. The influence of surface energy on competitive protein adsorption on oxidized NiTi surfaces. Biomaterials,2007,28,586-594.
[32]Qu X.H., Wu Q., Chen G.Q. In vitro study on hemocompatibility and cytocompatibility of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate). J. Biomater. Sci.,Polym. Ed.,2006,17,1107-1121.
[33]Wang A.F., Cao T., Tang H.Y., Liang X.M., Salley S.O., Ng K.Y. In vitro haemocompatibility and stability of two types of heparin-immobilized silicon surfaces. Colloids Surf. B,2005,43,245-255.
[34]Murakami R., Takashima R. Mechanical properties of the capsules of chitosan-soy globulin polyelectrolyte complex. Food Hydrocolloid.2003,17, 885-888.
[35]Lin C.H., Jao W.C., Yeh Y.H., Lin W.C., Yang M.C. Hemocompatibility and cytocompatibility of styrenesulfonate-grafted PDMS-polyurethane-HEMA hydrogel. Colloids Surf. B,2009,70,132-141.
[36]Yang J., Liu F., Tu S., Chen Y.W., Luo X.L., Lu Z.Q., Wei J., Li S.M. Haemo-and cytocompatibility of bioresorbable homo- and copolymers prepared from 1,3-trimethylene carbonate, lactides, and ε-caprolactone. J. Biomed. Mater. Res. A,2010,94A,396-407.
[37]Lee Y.K., Kim S.Y., Kim K.H., Chun B.H., Lee K.H., Oh D.J., Chung N. Use of soybean protein hydrolysates for promoting proliferation of human keratinocytes in serum-free medium. Biotechnol. Lett.2008,30,1931-1936.
[38]Cai K.Y, Yao K.D., Cui Y.L., Lin S.B., Yang Z.M., Li X.Q., Xie H.Q., Qing T.W., Luo J. Surface modification of poly (D, L-lactic acid) with chitosan and its effects on the culture of osteoblasts in vitro. J. Biomed. Mater. Res.,2002,60, 398-404.
[39]Lee Y.K., Kim S.Y, Kim K.H., Chun B.H., Lee K.H., Oh D.J., Chung N. Use of soybean protein hydrolysates for promoting proliferation of human keratinocytes in serum-free medium. Biotechnol. Lett.,2008,30,1931-1936.
[40]Luo L.H., Wang X.M., Zhang Y.F., Liu Y.M., Wang Y, Chang P.R., Chen Y. Physical properties and biocompatibility of cellulose/soy protein isolate membranes coagulated from acetic aqueous solution. J. Biomater. Sci., polym. Ed.,2008,19,479-496.
[41]Yang Z.L., Wang J., Luo R.F., Maitz M.F., Jing F.J., Sun H., Huang N. The covalent immobilization of heparin to pulsed-plasma polymeric allylamine films on 316L stainless steel and the resulting effects on hemocompatibility. Biomaterials,2010,31,2072-2083.
[42]Chou T.C., Fu E., Wu C.J., Yeh J.H. Chitosan enhances platelet adhesion and aggregation. Biochem. Biophys. Res. Commun.,2003,302,480-483.
[43]Lin W.C., Liu T.Y., Yang M.C. Hemocompatibility of polyacrylonitrile dialysis membrane immobilized with chitosan and heparin conjugate. Biomaterials,2004, 25,1947-1957.
[44]Xu F.J., Li Y.L., Kang E.T., Neoh K.G. Heparin-coupled poly (poly (ethylene glycol) monomethacrylate)-Si(111) hybrids and their blood compatible surfaces. Biomacromolecules,2005,6,1759-1768.
[45]Zhang W.F., Zhou H.Y., Chen X.G., Tang S.H., Zhang J.J. Biocompatibility study of the ophylline/chitosan/β-cyclodextrin microspheres as pulmonary delivery carriers. J. Mater. Sci.:Mater. Med.,2009,20,1321-1330.
[46]程青,王国斌.生物材料血液相容性评价研究进展.上海生物医学工程,2001,22，31-34.
[47]Amiji M.M. Permeability and blood compatibility properties of chitosan-poly (ethylene oxide) blend membranes for haemodialysis. Biomaterials,1995,16, 593-399.
[48]Jumaa M., Furkert F.H., Muller B.W. A new lipid emulsion formulation with high antimicrobial efficacy using chitosan. Eur. J. Pharm. Biopharm.,2002,53, 115-123.
[1]侯长军,张文彬,霍丹群,陈柄灿,任艳容,郑书家肝素化结合方式及本体材料的研究进展.化工进展,2003,22,703-708.
[2]李娟,吴英锋,杨新林.肝素功能化生物材料的研究进展.有机化学,2010,30，359-367.
[3]Kim Y.J., Kang I.K., Huh M.W., Yoon S.C. Surface characterization and in vitro blood compatibility of poly (ethylene terephthalate) immobilized with insulin and/or heparin using plasma glow discharge. Biomaterials,2000,21,121-130.
[4]Smith P.K., Mallia A.K., Hermanson G.T. Calorimetric method for the assay of heparin content in immobilized heparin preparations. Anal. Biochem.,1980, 109,466-473.
[5]Yang M.C., Lin W.C. Surface modification and blood compatibility of polyacrylonitrile membrane with immobilized chitosan-heparin conjugate. J. Polym. Res.,2002,9,201-206.
[6]Zhu A.P., Zhang M., Shen J. Blood compatibility of chitosan/heparin complex surface modified ePTFE vascular graft. Appl. Surf. Sci.,2005,241,485-492.
[7]ISO 10993-5:2009. Biological evaluation of medical devices Part 5:Tests for in vitro cytotoxicity.
[8]Silva S.S., Santos M.I., Coutinho O.P., Mano J.F., Reis R.L. Physical properties and biocompatibility of chitosan/soy blended membranes. J. Mater. Sci.:Mater. Med.,2005,16,575-579.
[9]Serrano M.C., Pagani R., Vallet-Regi M., Peua J., Ramila A., Izquierdo I., Portoles M.T. In vitro biocompatibility assessment of poly (ε-caprolactone) films using L929 mouse fibroblasts. Biomaterials,2004,25,5603-5611.
[10]Shen F., Zhang E.L., Wei Z.J. In vitro blood compatibility of poly (hydroxybutyrate-co-hydroxyhexanoate) and the influence of surface modification by alkali treatment Mater. Sci. Eng. C.,2010,30,369-375.
[11]Zhao J., Shi Q.A., Yin L.G., Luan S.F., Shi H.C., Song L.J., Yin J.H., Stagnaro P. Polypropylene modified with 2-hydroxyethyl acrylate-g-2-methacryloyloxyethyl phosphorycholine and its hemocompatibility. Appl. Surf. Sci.,2010,256, 7071-7076.
[12]Xu J.P., Wang X.L., Fan D.Z., Ji J., Shen J.C. Construction of phospholipid anti-biofouling multilayer on biomedical PET surfaces. Appl. Surf. Sci.,2008, 255,538-540.
[13]He Q., Ao Q., Gong K., Zhang L.H., Hu M., Gong Y.D., Zhang X.F. Preparation and characterization of chitosan-heparin composite matrices for blood contacting tissue engineering. Biomed. Mater.,2010,5,055001 (16pp).
[14]Shu Y, Ou G.M., Wang L., Zou J.C., Li Q.L. Surface modification of titanium with heparin-chitosan multilayers via mayer-by-mayer self-assembly technique. J. Nanomater.,2011, doi:10.1155/2011/423686.
[15]Kweon D.K., Song S.B., Park Y.Y. Preparation of water-soluble chitosan/heparin complex and its application as wound healing accelerator. Biomaterials,2003, 24,1595-1601.
[16]Yu S.H., Wu Y.B., Mi F.L., Shyu S.S. Polysaccharide-based artificial extracellular matrix:preparation and characterization of three-dimensional, macroporous chitosan, and heparin composite scaffold. J. Appl. Polym. Sci., 2008,109,3639-3644.
[17]Lee Y.K., Kim S.Y., Kim K.H., Chun B.H., Lee K.H, Oh D.J., Chung N. Use of soybean protein hydrolysates for promoting proliferation of human keratinocytes in serum-free medium. Biotechnol. Lett.,2008,30,1931-1936.
[18]Luo L.H., Wang X.M., Zhang Y.F., Liu Y.M., Wang Y, Chang P.R., Chen Y. Physical properties and biocompatibility of cellulose/soy protein isolate membranes coagulated from acetic aqueous solution. J. Biomater. Sci., Polym. Ed.,2008,19,479-496.
[19]Qu X.H., Wu Q., Chen G.Q. In vitro study on hemocompatibility and cytocompatibility of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate). J. Biomater. Sci. Polym. Ed.,2006,17,1107-1121.
[1]Kim B.S., Mooney D.J. Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol.,1998,6,224-230.
[2]Kim S.E., Park J.H, Cho Y.W., Chung H., Jeong S.Y., Lee E.B., Kwon I.C. Porous chitosan scaffold containing microspheres loaded with transforming growth factor-β1:Implications for cartilage tissue engineering. J. Control. Release,2003,91,365-374.
[3]刑桂荣,王敬湘.壳聚糖在医药领域的研究进展.中国药业,2003,12,74-75.
[4]Vaz C.M., van Doeveren P.F.N.M., Reis R.L., Cunha A.M. Soy matrix drug delivery systems obtained by melt-processing techniques. Biomacromolecules, 2003,4,1520-1529.
[5]Schoof H., Apel J., Heschel I., Rau G. Control of pore structure and size in freeze-dried collagen sponges. J. Biomed. Mater. Res.,2001,58,352-357.
[6]Ryan C.K., Sax H.C. Evaluation of a carboxymethylcellulose sponge for prevention of postoperative adhesions. Am. J. Surg.,1995,169,154-160.
[7]ISO 10993-5:2009. Biological evaluation of medical devices Part 5:Tests for in vitro cytotoxicity.
[8]ISO 10993-12:2009. Biological evaluation of medical devices part 12:sample preparation and reference materials.
[9]Silva S.S., Santos M.I., Coutinho O.P., Mano J.F., Reis R.L. Physical properties and biocompatibility of chitosan/soy blended membranes. J. Mater. Sci.:Mater. Med.2005,16,575-579.
[10]Serrano M.C., Pagani R., Vallet-Regi M., Pena J., Ramila A., Izquierdo I., Portoles M.T. In vitro biocompatibility assessment of poly (ε-caprolactone) films using L929 mouse fibroblasts. Biomaterials,2004,25,5603-5611.
[11]Velayudhan S., Anilkumar T.V., Mohanan P.V., Fernandez A.C., Varma H.K., Ramesh P. Biological evaluation of pliable hydroxyapatite-ethylene vinyl acetate co-polymer composites intended for cranioplasty. Acta. Biomater.,2005,1, 201-209.
[12]ISO 10993-6:2009. Biological evaluation of medical devices part 6:tests for local effects after implantation.
[13]Almeida E.V.R., Frollini E., Castellan A., Coma V. Chitosan, sisal cellulose, and biocomposite chitosan/sisal cellulose films prepared from thiourea/NaOH aqueous solution. Carbohyd. Polym.,2010,80,655-664.
[14]Franek F., Hohenwarter O., Katinger H. Plant protein hydrolysates:preparation of defined peptide fractions promoting growth and production in animal cells cultures. Biotechnol. Prog.,2000; 16,688-692.
[15]Lee Y.K., Kim S.Y., Kim K.H., Chun B.H., Lee K.H., Oh D.J., Chung, N. Use of soybean protein hydrolysates for promoting proliferation of human keratinocytes in serum-free medium. Biotechnol. Lett.,2008,30,1931-1936.
[1]Schurz J.'Trends in polymer science-A bright future for cellulose. Prog. Polym. Sci.,1999,24,481-483.
[2]Entcheva E., Bien H., Yin L., Chung C.Y., Farrell M., Kostov Y. Functional cardiac cell constructs on cellulose-based scaffolding. Biomaterials,2004,25, 5753-5762.
[3]Luo X.G., Zhang L. New solvents and functional materials prepared from cellulose solutions in alkali/urea aqueous system. Food Res. Int.,2010 in press. (doi:10.1016/j.foodres.2010.05.016.)
[4]Cai J., Zhang L., Zhou J., Qi H., Chen H., Kondo T., Chen X., Chu B. Multifilament fibers based on dissolution of cellulose in NaOH/urea aqueous solution:structure and properties. Adv. Mater.,2007,19,821-825.
[5]Abe Y., Mochizuki A. Hemodialysis membrane prepared from cellulose/n-methylmorpholine-n-oxide solution. Ⅲ. The relationship between the drying condition of the membrane and its permeation behavior J. Appl. Polym. Sci.,2003,89,1671-1681.
[6]Bryjak J., Aniulyte J., Liesiene J. Evaluation of man-tailored cellulose-based carriers in glucoamylase immobilization. Carbohyd. Res.,2007,342,1105-1109.
[7]Sharma J.B., Gupta N., Mital S. Creation of neovagina using oxidized cellulose (surgicel) as a surgical treatment of vaginal agenesis. Arch. Gynecol. Obstet. 2007,275,231-235.
[8]Muller F.A., Muller L., Hofmann I., Greil P., Wenzel M.M., Staudenmaier R. Cellulose-based scaffold materials for cartilage tissue engineering. Biomaterials, 2006,27,3955-3963.
[9]Zhang J., Yuan J., Yuan Y.L., Shen J., Lin S.C. Chemical modification of cellulose membranes with sulfo mmonium zwitterionic vinyl monomer to improve hemocompatibility. Colloids Surf., B,2003,30,249-257.
[10]Eller L.K., Reimer, R.A. A high calcium, skim milk powder diet results in a lower fat mass in male, energy-restricted, obese rats more than a low calcium, casein, or soy protein diet. J. Nutr.2010,140,1234-1241.
[11]Qi G.Y, Sun X.S. Peel adhesion properties of modified soy protein adhesive on a glass panel. Ind. Crop. Prod.,2010,32,208-212.
[12]Kumar R., Liu D., Zhang L. Advances in proteinous biomaterials J. Biobased Mater. Bio.,2008,2,1-24.
[13]Giavaresi G, Fini M., Salvage J., Aldini N.N., Giardino R., Ambrosio L., Nicolais L., Santin M. Bone regeneration potential of a soybean-based filler: Experimental study in a rabbit cancellous bone defects. J. Mater. Sci. Mater. Med.,2010,21,615-626.
[14]Vaz C.M., van Doeveren P.F., Reis R.L., Cunha A.M. Soy matrix drug delivery systems obtained by melt-processing techniques. Biomacromolecules,2003,4, 1520-1529.
[15]Lee Y.K., Kim S.Y., Kim K.H., Chun B.H., Lee K.H., Oh D.J., Chung N. Use of soybean protein hydrolysates for promoting proliferation of human keratinocytes in serum-free medium. Biotechnol. Lett.,2008,30,1931-1936.
[16]Merolli A., Nicolais L., Ambrosio L., Santin M. A degradable soybean-based biomaterial used effectively as a bone filler in vivo in a rabbit. Biomed. Mater., 2010,5,015008.
[17]Franek F., Hohenwarter O., Katinger H. Plant protein hydrolysates:Preparation of defined peptide fractions promoting growth and production in animal cells cultures. Biotechnol. Prog.,2000,16,688-692.
[18]Chen Y., Zhang L. Blend membranes prepared from cellulose and soy protein isolate in NaOH/thiourea aqueous solution. J. Appl. Polym. Sci.,2004,94, 748-757.
[19]Chen Y., Zhang L., Gu J., Liu J. Physical properties of microporous membranes prepared by hydrolyzing cellulose/soy protein blends. J. Membr. Sci.,2004,241, 393-402.
[20]Luo L.H., Wang X.M., Zhang Y.F., Liu Y.M., Chang P.R., Wang Y, Chen Y. Physical properties and biocompatibility of cellulose/soy protein isolate membranes coagulated from acetic aqueous solution. J. Biomater. Sci. Polym. Ed.,2008,19,479-496
[21]Luo L.H., Zhang Y.F., Wang X.M., Wan Y, Chang P.R., Anderson D.P., Chen Y. Preparation, characterization, and in vitro and in vivo evaluation of cellulose/soy protein isolate composite sponges. J. Biomater. Appl.,2010,24,503-526.
[22]Kumar M.N.V.R. A review of chitin and chitosan applications. React. Funct. Polym.,2000,46,1-27.
[23]Cui Y.L., Qi A.D., Liu W.G., Wang X.H., Wang H., Ma D.M., Yao K.D. Biomimetic surface modification of poly (1-lactic acid) with chitosan and its effects on articular chondrocytes in vitro. Biomaterials,2003,24,3859-3868.
[24]Xiao Y.M., Li D.X., Chen X.N., Lu J., Fan H.S., Zhang X.D. Preparation and cytocompatibility of chitosan-modified polylactide. J. Appl. Polym. Sci.,2008, 110,408-412.
[25]Rong H.C., Horng Dar H. Effect of molecular weight of chitosan with the same degree of deacetylation on the thermal, mechanical, and permeability properties of the prepared membrane. Carbohyd. Polym.,1996,29,353-358.
[26]Suzuki Y, Miyatake K., Okamoto Y, Muraki E., Minami S. Influence of the chain length of chitosan on complement activation. Carbohyd. Polym.,2003,54, 465-469.
[27]Suzuki Y., Okamoto Y., Morimoto M., Sashiwa H., Saimoto H., Tanioka S.-i., Shigemasa Y, Minami S. Influence of physico-chemical properties of chitin and chitosan on complement activation. Carbohyd. Polym.,2000,42,307-310.
[28]张守松,邹翰.甲壳糖血液相容性研究.高分子材料,1997,4,21-23.
[29]ISO 10993-5:2009. Biological evaluation of medical devices Part 5:Tests for in vitro cytotoxicity.
[30]Silva S.S., Santos M.I., Coutinho O.P., Mano J.F., Reis R.L. Physical properties and biocompatibility of chitosan/soy blended membranes. J. Mater. Sci.:Mater. Med.,2005,16,575-579.
[31]Serrano M.C., Pagani R., Vallet-Regi M., Pena J., Ramila A., Izquierdo I., Portoles M.T. In vitro biocompatibility assessment of poly (s-caprolactone) films using L929 mouse fibroblasts. Biomaterials,2004,25,5603-5611.
[32]Suzuki S., Gr(?)ndahl L., Leavesley D., Wentrup-Byrne E. In vitro bioactivity of MOEP grafted ePTFE membranes for craniofacial applications. Biomaterials, 2005,26,5303-5312.
[33]Shen F., Zhang E.L., Wei Z.J. In vitro blood compatibility of poly (hydroxybutyrate-co-hydroxyhexanoate) and the influence of surface modification by alkali treatment. Mater. Sci. Eng. C.,2010,30,369-375.
[34]Zhao J., Shi Q.A., Yin L.G., Luan S.F., Shi H.C., Song L.J., Yin J.H., Stagnaro P. Polypropylene modified with 2-hydroxyethyl acrylate-g-2-methacryloyloxyethyl phosphorycholine and its hemocompatibility. Appl. Surf. Sci.,2010,256, 7071-7076.
[35]Almeida E.V.R., Frollini E., Castellan A., Coma V. Chitosan, sisal cellulose, and biocomposite chitosan/sisal cellulose films prepared from thiourea/NaOH aqueous solution. Carbohyd. Polym.,2010,80,655-664.
[36]Pawlak A., Mucha M. Thermogravimetric and FTIR studies of chitosan blends. Thermochimica Acta.,2003,396,153-156.
[37]Qu X.H., Wu Q., Chen G.Q. In vitro study on hemocompatibility and cytocompatibility of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate. J. Biomater. Sci., Polym. Ed.,2006,17,1107-1121.
[38]Da Roz A.L., Leite F.L., Pereiro L.V., Nascente P.A.P., Zucolotto V., Oliveira Jr.O.N., Carvalho A.J.F. Adsorption of chitosan on spin-coated cellulose films. Carbohyd. Polym.,2010,80,65-70.
[39]Murakami R., Takashima R. Mechanical properties of the capsules of chitosan-soy globulin polyelectrolyte complex. Food Hydrocolloid.,2003,17, 885-888.
[40]Cai K.Y., Yao K.D., Cui Y.L., Lin S.B., Yang Z.M., Li X.Q., Xie H.Q., Qing T.W., Luo J. Surface modification of poly (D, L-lactic acid) with chitosan and its effects on the culture of osteoblasts in vitro. J. Biomed. Mater. Res.,2002,60, 398-404.
[41]Guo Z., Meng S., Zhong W., Du Q.G., Chou L.S.L. Self-assembly of silanated poly (ethylene glycol) on silicon and glass surfaces for improved haemocompatibility. Appl. Surf. Sci.,2009,255,6771-6780.
[42]Roy R.K., Choi H.W., Yi J.W., Moon M.W., Lee K.R., Han D.K., Shin J.H., Kamijo A., Hasebe T. Hemocompatibility of surface-modified, silicon-incorporated, diamond-like carbon films. Acta Biomater.,2009,5, 249-256.
[43]Kang I.K., Kwon O.H., Lee Y.M., Sung Y.K. Preparation and surface characterization of functional group-grafted and heparin-immobilized polyurethanes by plasma glow discharge. Biomaterials,1996,17,841-847.
[44]Lin C.H., Jao W.C., Yeh Y.H., Lin W.C., Yang M.C. Hemocompatibility and cytocompatibility of styrenesulfonate-grafted PDMS-polyurethane-HEMA hydrogel. Colloids Surf, B,2009,70,132-141.
[45]Liu L., Guo S.R., Chang J., Ning C.Q., Dong C.M., Yan D.Y. Surface modification of polycaprolactone membrane via layer-by-layer deposition for promoting blood compatibility. J. Biomed. Mater. Res., Part B,2008,87, 244-250.
[46]Zhang W.F., Zhou H.Y., Chen X.G., Tang S.H., Zhang J.J. Biocompatibility study of theophylline/chitosan/b-cyclodextrin microspheres as pulmonary delivery carriers. J. Mater. Sci.:Mater. Med.,2009,20,1321-1330.
[47]程青,王国斌.生物材料血液相容性评价研究进展.上海生物医学工程,2001,22，31-34.
[48]Wang L.C., Chen X.G., Zhong D.Y., Xu Q.C. Study on poly (vinyl alcohol)/carboxymethyl-chitosan blend film as local drug delivery system. J. Mater. Sci.:Mater. Med.,2007,18,1125-1133.
[1]Boretos J.W., Eden M. Contemporary Biomaterials,1984.
[2]顾汉卿,徐国凤.生物医学材料学.天津：天津科技翻译出版公司,1993,8,175-179.
[3]杨晓芳,奚廷斐.生物相容性评价的发展趋势.国外医学生物医学工程分册,1999,22,237-242.
[4]李爱民,孙康宁,尹衍升,卢志华,王振光,毕见强.生物材料的发展、应用、评价和展望.山东大学学报,2002,32,287-293.
[5]何淑漫,周健.抗凝血生物材料.化学进展,2010,22,760-772.
[6]项昭保,霍丹群,候长军,蔡绍哲.肝素化抗凝血生物材料的研究.现代医学仪器与应用,2002,14,25-29.
[7]Gott V.L., Whiffen J.D., Dutton R.C. Heparin bonding on colloidal graphite surfaces. Science,1963,142,1297-1298.
[8]Aldenhoff Y.B.J., Knetsch M.L.W., Hanssen J.H.L., Lindhout T., Wielders S.J.H., Kool L.H. Coils and tubes releasing heparin. Studies on a new vascular graft prototype. Biomaterials,2004,25,3125-3133.
[9]侯长军,张文彬,霍丹群,陈柄灿,任艳容,郑书家.肝素化结合方式及本体材料的研究进展.化工进展,2003,22,703-707.
[10]McLean J. The discovery of heparin. Circulation,1959,19,75-78.
[11]Murugesan S., Xie J.. Linhardt R.J. Immobilization of heparin:approaches and applications. Curr. Top. Med. Chem.,2008,8,80-100.
[12]Schramm R., Nickels R.M., Harder Y., Langer F., Menger M.D., Schafers H.J. Heparin-protamine does not aggravate local lps-provoked leukocytic inflammation in vivo. Thorac Cardio. Surg.,2006,16,506-511.
[13]Elmaleh D.R., Brown N.V., Geiben-Lynn R. Anti-viral ctivity of Human antithrombin Ⅲ. Int. J. Mol. Med.,2005,16,191-200.
[14]Icli F., Akbulut H., Utkan G., Yalcin B., Dincol D., Isikdogan A., Demirkazik A. Onur H., Cay F., Buyukcelik A. Low molecular weight heparin (LMWH) increases the efficacy of cisplatinum plus gemcitabine combination in advanced pancreatic cancer. J. Surg. Oncol.,2007,95,507-512.
[15]戴敏.肝素的临床新应用.中国药物与临床,2004,4,785-786.
[16]Damus P.S., Hicks M., Rosenberg R.D. Anticoagulant action of heparin. Nature, 1973,246,355-357.
[17]Vlodavsky I., Ilan N., Nadir Y., Brenner B., Katz B.Z., Naggi A., Torri G., Casu B., Sasisekharan R. Heparanase, heparin and the coagulation system in cancer progression. Thromb. Res.,2007,120,112-120.
[18]施洪臣,李宝山,章雪松,郭健.肝素在临床上的应用.临床军医杂志,2003,31，100-101.
[19]Hassan Y., Awaisu A., Aziz N.A., Aziz N.H., Ismail O. Heparin-induced thrombocytopenia and recent advances in its therapy. J. Clin. Pharm. Ther.,2007, 32,535-544.
[20]Basmadjian D., Sefton M.V. Relationship between release rate and surface concentration for heparinized materials. J. Biomed.Mater. Res.,1983,17, 509-518.
[21]Mori Y. The effect of released heparin from the heparinized hydrophilic polymer on the process of thrombus formation. Trans. Am. Soc.,1998,10,736-744.
[22]Yang Z.L., Wang J., Luo R.F., Maitz M.F., Jing F.J., Sun H., Huang N. The covalent immobilization of heparin to pulsed-plasma polymeric allylamine films on 316L stainless steel and the resulting effects on hemocompatibility. Biomaterials,2010,31,2072-2083.
[23]Li J., Zhu B.Q., Shao Y.Y., Liu X.R., Yang X.L., Yu Q. Construction of anticoagulant poly (lactic acid) films via surface covalent graft of heparin-carrying microcapsules. Colloids Surf. B,2009,70,15-19.
[24]Zhu A.P., Zhang M., Wu J., Shen J. Covalent immobilization of chitosan/heparin complex with a photosensitive hetero-bifunctional crosslinking reagent on PLA surface. Biomaterials,2002,23,4657-4665.
[25]Wang X.H., Li D.P., Wang W.J., Feng Q.L., Cui F.Z., Xu Y.X., Song X.H. Covalent immobilization of chitosan and heparin on PLGA surface. Int. J. Biol. Macromol.,2003,33,95-100.
[26]Kim I.C, Tak T.M, Choi J.G. Sulfonated polyether-sulfone by heterogeneous method and its membraneperformances. J. Appl. Polym. Sci.,1999,74, 2046-2055.
[27]Moon H.T., Lee Y.K., Han J.K., Byu Y. A novel formulation for controlled release of heparin-DOCA conjugate dispersed as nanoparticles in polyurethane film. Biomaterials,2001,22,281-289.
[28]Wang H.J., Lin Z.X., Liu X.M., Sheng S.Y., Wang J.Y Heparin-loaded zein microsphere film and hemocompatibility. J. Control. Release,2005,105, 120-131.
[29]Wilson R.S., Lelah M.D., Cooper S.L. Blood-material interactions:Assessment of in vitro and in vivo test methods. In:Williams D.F., editor. Techniques in biocompatibility testing. Bocaraton, FL:CRC Press,1988,151-181.
[30]奚廷斐.生物材料血液相容性评价方法的研究.生物医学工程学杂志,1987,4，42-48.
[31]Jordan S.W., Chaikof E.L. Novel thromboresistant materials. J. Vasc. Surg. 2007,45 Suppl A:A,104-115.
[32]Bajpai A.K., Bhanu S. Dynamics of controlled release of heparin from swellable crosslinked starch microspheres. J. Mater. Sci. Mater. Med.,2007,18, 1613-1621.
[33]Lin W.C., Liu T.Y., Yang M.C. Hemocompatibility of polyacrylonitrile dialysis membrane immobilized with chitosan and heparin conjugate. Biomaterials,2004, 25,1947-1957.
[34]Luong-Van E., Gr(?)ndahl L., Chua K.N., Leong K.W., Nurcombe V., Cool S.M. Controlled release of heparin from poly (epsilon-caprolactone) electrospun fibers. Biomaterials,2006,27,2042-2050.
[35]Roveri N., Morpurgo M., Palazzo B., Parma B., Vivi L. Silica xerogels as a delivery system for the controlled release of different molecular weight heparins. Anal. Bioanal. Chem.,2005,381,601-606.
[36]徐鹏,李翔,杜强国,杨玉良.聚氯乙烯表面肝素化的研究.复旦大学学报(自然科学版),2001,40,372-375.
[37]Kumar M.N.V.R. A review of chitin and chitosan applications. React. Funct. Polym.,2000,46,1-27.
[38]Hayes R., Davies D.H., Munvel V.G. Proceedings and the first international conference on chitin-chitosan, Boston,1977, edited by Muarelli R.A.A.,1979, 103.
[39]Liu Z.H., Jiao Y.P., Zhang Z.Y., Zhou C.G. Surface modification of poly (1-lactic acid) by entrapment of chitosan and its derivatives to promote osteoblasts-like compatibility. J. Biomed. Mater. Res.,2007,83A,1110-1116.
[40]王启钊,陈西广,刘成圣,孟祥红,刘晨光,于乐军,刘楠.壳聚糖的血液相容性.中国生物工程杂志,2005,194-198.
[41]Chou T.C., Fu E., Wu C.J., Yeh J.H. Chitosan enhances platelet adhesion and aggregation. Biochem. Biophys. Res. Commun.,2003,302,480-483.
[42]Okamoto Y., Yano R., Miyatake K., Tomohiro I., Shigemasa Y, Minami S. Effects of chitin and chitosan on blood coagulation. Carbohyd. Polym.,2003,53, 337-342.
[43]Ueno H., Mori T., Fujinaga T. Topical formulations and wound healing applications of chitosan. Adv. Drug Delivery Rev.,2001,52,105-115.
[44]Usami Y, Minami S., Okamoto Y, Matsuhashi A., Shigemasa Y. Influence of chain length of N-acetyl-D-glucosamine and D-glucosamine residues on direct and complement-mediated chemotactic activities for canine polymorphonuclear cells. Carbohyd. Polym.,1997,32,115-122.
[45]Amiji M.M. Permeability and blood compatibility properties of chitosan-poly (ethylene oxide) blend membranes for haemodialysis. Biomaterials,1995,16, 593-399.
[46]Jumaa M., Furkert F.H., Muller B.W. A new lipid emulsion formulation with high antimicrobial efficacy using chitosan. Eur. J. Pharm. Biopharm.,2002,53, 115-123.
[47]Notara M., Scotchford C.A., Grant D.M., Weston N., Roberts G.A.F. Cytocompatibility and hemocompatibility of a novel chitosan-alginate gel system. J. Biomed. Mater. Res. A,2009,89A,854-864.
[48]Carreno-Gomez B., Duncan R. Evaluation of the biological properties of soluble chitosan and chitosan microspheres. Int. J. Pharm.,1997,148,231-240.
[49]Amiji M.M. Synthesis of anionic poly (ethylene glycol) derivative for chitosan surface modification in blood-contacting applications. Carbohyd. Polym.,1997, 32,193-199.
[50]Suzuki Y., Miyatake K., Okamoto Y, Muraki E., Minami S. Influence of the chain length of chitosan on complement activation. Carbohyd. Polym.,2003,54, 465-469.
[51]Suzuki Y., Okamoto Y., Morimoto M., Sashiwa H., Saimoto H., Tanioka S.-i., Shigemasa Y, Minami S. Influence of physico-chemical properties of chitin and chitosan on complement activation. Carbohyd. Polym.,2000,42,307-310.
[52]Chandy T., Sharma C.P. Chitosan-as a biomaterial. Biomater. Art. Cells Artif. Organs.,1990,18,1-24.
[53]Madhumathi K., Sudheesh Kumar P.T., Abilash S., Sreeja V., Tamura H., Manzoor K., Nair S.V., Jayakumar R. Development of novel chitin/nanosilver composite scaffolds for wound dressing applications. J. Mater. Sci.:Mater. Med., 2010,21,807-813.
[54]李静,伍津津,鲁元刚,朱堂友,李文维,贺萍,杨宏珍.复合壳多糖人工皮肤移植真皮再构建的初步研究.中国临床康复,2003,7,572-573.
[55]Koide M., Konishi J., Ikegami K., Osaki k. Multilayer wound covering materials comprising a supporting layer and moisture permeation cont rolling layer and method for their manufacture. [P]. US 5,359,305,1995-3-7.
[56]Yannas I.V., Burke H.F., Orgill D.P., Skrabut E.M. Wound tissue can utilise a polymeric template to synthesise a functional extension of skin. Science,1982, 215,174-176.
[57]Ignatova M., Starboya K., Markova N., Manolova N., Rashkov I. Electrospun nano-fibre mats with antibacterial properties from quarternised chitosan and poly (vinyl alcohol). Carbohyd. Res.,2006,341,2098-2107.
[58]Le Y, Anand S.C., Horrocks A.R. Development of anti-bacterial polysaccharide fibres and their performance, in:European Conference on Advances in Wound Management, Amsterdam, Netherlands, October,1996.
[59]邓先模,李孝红.生物医用高分子在癌症药物治疗中的应用.高分子通报,1999,3,94-98.
[60]Aksungur P., Sungur A., Unal S., Iskit A.B., Squier C.A., Senel S. Chitosan delivery systems for the treatment of oral mucositis:in vitro and in vivo studies. J. Control. Release,2004,98,269-279.
[61]Ta H.T., Han H., Larson I., Dass C.R., Dunstan D.E. Chitosan-dibasic orthophosphate hydrogel:A potential drug delivery system. Int. J. Pharm.,2009, 371,134-141.
[62]Ishihara M., Obara K., Ishizuka T., Fujita M., Sato M., Masuoka K., Saito Y., Yura H., Matsui T., Hattori H., Kikuchi M., Kurita A. Controlled release of fibroblast growth factors and heparin from photocrosslinked chitosan hydrogels and subsequent effect on in vivo vascularization. J. Biomed. Mater. Res.,2003, 64A,551-559.
[63]Peng X.H., Zhang L.N., Kennedy J.F. Release behavior of microspheres from cross-linked N-methylated chitosan encapsulated ofloxacin. Carbohyd. Polym., 2006,65,288-295.
[64]季娟娟,丁仲鹃,杨雪莲.壳聚糖缓释膜的制备及性能研究.华西口腔医学杂志,2009,27,248-252.
[65]Kanke M., Katayama H., Tsuzuki S., Kuramoto H. Application of chitin and chitosan to pharmaceutical preparation. I. Film Preparation and in vitro evaluation. Chem. Pharm. Bull,1989,37,523.
[66]Shu X.Z, Zhu K.J., Weihong S. Novel pH-sensitive citrate cross-linked chitosan film for drug controlled release. Int. J. Pharm.,2001,21,19-28.
[67]何强芳,李国明,巫海珍,卢志敏,李良.5-氟尿嘧啶壳聚糖微球的制备及其释药性能.应用化学,2004,21,192-196.
[68]Agnihotris S.A., Aminabhavit T.M. Novel interpenetrating network chitosan-poly (ethylene oxidegacrylamide) hydrogel microspheres for the controlled release of capecitabine. Int. J. Pharm.,2006,324,103-115.
[69]Dev A., Binulal N.S., Anitha A., Nair S.V., Furuike T., Tamura H., Jayakumar R. Preparation of novel poly (lactic acid)/chitosan nanoparticles for anti HIV drug delivery applications. Carbohyd. Polym.,2010,80,833-838.
[70]张爱迪,丁德润.壳聚糖基生物医药材料的应用进展.上海工程技术大学学报,2009,23,63-67.
[71]Borchard G. Chitosans for gene delivery. Adv. Drug Deliver. Rev.,2001,52, 145-150.
[72]Csaba N., Koping-Hoggard M., Alonso M.J. Ionically crosslinked chitosan/tripolyphosphate nanoparticles for oligonucleotide and plasmid DNA delivery. Int. J. Pharm.,2009,382,205-214.
[73]Opanasopit P., Petchsangsai M., Rojanarata T., Ngawhirunpat T., Sajomsang W., Ruktanonchai U. Methylated N-(4-N, N-dimethylaminobenzyl) chitosan as effective gene carriers:Effect of degree of substitution. Carbohyd. Polym.,2009, 75,143-149.
[74]Mumper R.J., Wang J., Claspell J.M, Rolland A.P. Novel polymeric condensing carriers for gene delivery. Pro. Int. Symp. Control. Rel. Bioact. Mater.,1995,22, 178-179.
[75]Mao H.Q., Roy K., Walsh S.M., August J.T., Leong K.W. DNA-chitosan nanospheres for gene delivery. Pro. Int. Symp. Control. Rel. Bioact. Mater., 1996,23,401-402.
[76]宗莉,陈伶俐,张淑芸,杨晓容,朱家壁.壳聚糖纳米粒作为基因载体的研究：制备,特征和对DNA的保护.中国药科大学学报,2005,36,526-530.
[77]Jiang H.L., Lim H.T., Kim Y.K., Arote R., Shin J.Y., Kwon J.T., Kim J.E., Kim J.H., Kim D., Chae C., Nah J.W., Choi Y.J., Cho C.S., Cho M.H. Chitosan-graft-spermine as a gene carrier in vitro and in vivo. Eur. J. Pharm. Biopharm.,2011,77,36-42.
[78]Yu H.J., Deng C., Tian H.Y., Lu T.C., Chen X.S., Jing X.B. Chemo-physical and biological evaluation of poly (1-lysine)-grafted chitosan copolymers used for highly efficient gene delivery. Macromol. Biosci.,2011,11,352-361.
[79]Venkatesan J., Kim S.K. Chitosan composites for bone tissue engineering. Mar. Drugs,2010,8,2252-2266.
[80]Wang M. Developing bioactive composite materials for tissue replacement. Biomaterials,2003,24,2133-2151.
[81]Choi S.W., Xie J.W., Xia Y.N. Chitosan-based inverse opals:three-dimensional scaffolds with uniform pore structures for cell culture. Adv. Mater.,2009,21, 2997-3001.
[82]Jiang L.Y., Li Y.B., Xiong C.D. Preparation and biological properties of a novel composite scaffold of nano-hydroxyapatite/chitosan/carboxymethyl cellulose for bone tissue engineering. J. Biomed. Sci.,2009,16,65-74.
[83]刘阳,朱立新,杨宏,田京,许勇,于博,李志浩,冯庆玲,黄智.可注射性纳米羟基磷灰石/壳聚糖复合骨髓间充质干细胞促进骨缺损的修复.中国组织工程研究与临床康复,2010,14,6278-6282.
[84]Zhu A.P., Zhang M., Shen J. Blood compatibility of chitosan/heparin complex surface modified ePTFE vascular graft. Appl. Surf. Sci.,2005,241,485-492.
[85]Vaz C.M., Fossen M., Van T.R.F., De Graaf L.A., Reis R.L., Cunha A.M. Casein and soybean protein-based thermoplastics and composites as alternative biodegradable polymers for biomedical applications. J. Biomed. Mater. Res. Part A,2003,65A,60-70.
[86]Mizuno A., Mitsuiki M. Motoki M. Effect of transglutaminase treatment on the glass transition soy protein. J. Agric. Food Chem.,2000,48,3286-3291.
[87]Ortiz S.E.M, Cristina A.M. Analysis of products, mechanisms of reaction, and some functional properties of soy protein hydrolysates. J. Am. Oil Chem. Soc., 2000,77,1293-1301.
[88]Kinsella J.M. Functional properties of soy proteins. J. Am. Oil Chem. Soc.,1979, 56,242.
[89]周瑞宝,周兵.大豆7 S和11 S球蛋白的结构和功能性质.中国粮油学报,1998,13,39-42.
[90]Lee K.H., Ryu H.S., Rhee K.C. Protein solubility characteristics of commercial soy protein products. J. Am. Oil Chem. Soc.,2003,80,85-90.
[91]Chen Y., Zhang L. Gu J., Liu J. Physical properties of microporous membranes prepared by hydrolyzing cellulose/soy protein blends. J. Membr. Sci.,2004,241, 393-402.
[92]Zhou Z., Zheng H., Wei M., Huang J., Chen Y. Structure and mechanical properties of cellulose derivatives/soy protein isolate blends. J. Appl. Polym. Sci.,2008,107,3267-3274.
[93]Vaz C.M., van Doeveren P.F.N.M., Reis R.L., Cunha A.M. Soy matrix drug delivery systems obtained by melt-processing techniques. Biomacromolecules, 2003,4,1520-1529.
[94]Xu W., Yang Y. Drug sorption onto and release from soy protein fibers. J. Mater. Sci. Mater. Med.,2009,20,2477-2486.
[95]Caillard R., Mateescu M.A., Subirade M. Maillard-type cross-linked soy protein hydrogels as devices for the release of ionic compounds:an in vitro study. Food Res. Int.,2010,43,2349-2355.
[96]Maltais A., Remondetto G.E., Subirade M. Soy protein cold-set hydrogels as controlled delivery devices for nutraceutical compounds. Food Hydrocolloid., 2009,23,1647-1653.
[97]Curt S., Subirade M., Rouabhia M. Production and in vitro evaluation of soy protein-based biofilms as a support for human keratinocyte and fibroblast culture. Tissue Eng. Part A,2009,15,1223-1232.
[98]Silva S.S., Oliveira J.M., Mano J.F., Reis R.L. Physicochemical characterization of novel chitosan-soy protein/TEOS porous hybrids for tissue engineering applications. Adv. Mater. Forum III,2006,1000-1004.
[99]刘世清,李皓桓,彭昊,徐怡.新型纤维素导管桥接周围神经缺损的研究.中华实验外科杂志,2005,22,593-595.
[100]Su Y., Simmen F.A., Xiao R., Simmen R.C.M. Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in die tary protection from mammary tumors. Physiol. Genomics,2007,30,8-16.
[101]Eason R.R., Till S.R., Velarde M.C., Geng Y., Gu L., Jr L.C., Badger T.M., Simmen F.A., Simmen R.C.M. Uterine phenotype of young adult rats exposed to dietary soy or genistein during development. J. Nutr. Biochem.,2005,16, 625-632.
[102]Demonty I., Lamarche B., Deshaies Y, Jacques H. Role of soy isoflavones in the hypotriglyceridemic effect of soy protein in the rat. J. Nutr. Biochem., 2002,13,671-677.
[103]Shukla A., Brandsch C., Bettzieche A., Hirche F., Stangl G.I., Eder K. Isoflavone-poor soy protein alters the lipid metabolism of rats by SREBP-mediated down-regulation of hepatic genes. J. Nutr. Biochem.,2007,18, 313-321.
[104]Yonezawa K., Nakagama H., Tajima R., Ushigome M., Ogra Y., Suzuki K.T., Yoshikawa K., Nagao M. Efects of soy protein isolate on LEC rats, a model of wilson disease:mechanisms underlying enhancement of liver cell damage. Biochem. Biophys. Res. Commun.,2003,302,271-274.
[105]Tsai P.J., Huang P.C. Effects of isoflavones containing soy protein isolate compared with fish protein on serum lipids and susceptibility of low density lipoprotein and liver lipids to in vitro oxidation in hamsters. J. Nutr. Biochem., 1999,10,631-637.
[106]Escobedo R.M., Robles-Ramirez M.C., Gallegos E. R., Aleman R.R. Effect of protein hydrolysates from germinated soybean on cancerous cells of the human cervix:an in vitro study. Plant Foods Hum. Nutr.,2009,64,271-278.
[107]Nagasawa A., Fukui K., Kojima M., Kishida K., Maeda N., Nagaretani H., Hibuse T., Nishizawa H., Kihara S., Waki M., Takamatsu K., Funahashi T., Matsuzawa Y. Divergent efects of soy protein diet on the expression of adipocytokines. Biochem. Biophys. Res. Commun.,2003,311,909-914.
[108]Power K.A., Chen J.M., Saarinen N.M., Thompson L.U. Changes in biomarkers of estrogen receptor and growth factor signaling pathways in MCF-7 tumors after short- and long-term treatment with soy and flaxseed. J. Steroid Biochem. Mol. Biol.,2008,112,13-19.
[109]Mukhopadhyay S., Ballard B.R., Mukherjee S., Kabir S.M., Das S.K. Beneficial effects of soy protein in the initiation and progression against dimethylbenz [a] anthracene-induced breast tumors in female rats. Mol. Cell. Biochem.,2006,290,169-176.
[110]Radcliffe J.D., Narins D.M.C. A comparison of the effectiveness of soy protein isolate and fish oil for reducing the severity of retinoid-induced hypertriglyceridemia. J. Nutr. Biochem.,2004,15,163-168.
[111]Huntley A.L., Ernst E. Soy for the tyeatment of perimenopausal symptoms-a systematic review. Maturitas,2004,47,1-9.
[112]Jia D.Y., Fang Y., Yao K. Water vapor barrier and mechanical properties of konjac glucomannan-chitosan-soy protein isolate edible films. Food Bioprod. Process.,2009,87,7-10.
[113]Silva S.S., Goodfellow B.J., Benesch J., Rocha J., Mano J.F., Reis R.L. Morphology and miscibility of chitosan/soy protein blended membranes. Carbohyd. Polym.,2007,70,25-31.
[114]Silva S.S., Santos M.I., Coutinho O.P., Mano J.F., Reis R.L. Physical properties and biocompatibility of chitosan/soy blended membranes. J. Mater. Sci.:Mater Med.,2005,16,575-579.
[2]高宁国,程秀兰,杨敬,张树政.肝素结构与功能的研究进展.生物工程进展,1999,19,4-13.
[3]Damus P.S., Hicks M., Rosenberg R.D. Anticoagulant action of heparin. Nature, 1973,246,355-357.
[4]Hassan Y., Awaisu A., Aziz N.A., Aziz N.H., Ismail O. Heparin-induced thrombocytopenia and recent advances in its therapy. J. Clin. Pharm. Ther.,2007, 32,535-544.
[5]陈中伟,张键.断肢再植的现状与展望.中国处方药,2004,22,8-11.
[6]宋开芳,陈艺新,陈克洲,薛向东,贾湘谦,肖杰,秦杰,李青松.指腹皮下肝素浸润预防断指再植术后血管危象.中华显微外科杂志,2002,25,224-225.
[7]Jordan S.W., Chaikof E.L. Novel thromboresistant materials. J. Vasc. Surg.2007, 45 Suppl A:A,104-115.
[8]Bajpai A.K., Bhanu S. Dynamics of controlled release of heparin from swellable crosslinked starch microspheres. J. Mater. Sci. Mater. Med.,2007,18, 1613-1621.
[9]Lin W.C., Liu T.Y., Yang M.C. Hemocompatibility of polyacrylonitrile dialysis membrane immobilized with chitosan and heparin conjugate. Biomaterials,2004, 25,1947-1957.
[10]Luong-Van E., Gr(?)ndahl L., Chua K.N., Leong K.W., Nurcombe V., Cool S.M. Controlled release of heparin from poly (epsilon-caprolactone) electrospun fibers. Biomaterials,2006,27,2042-2050.
[11]Moon H.T., Lee Y, Han J.K., Byun Y A novel formulation for controlled release of heparin-DOCA conjugate dispersed as nanoparticles in polyurethane. Biomaterials,2001,22,281-289.
[12]Roveri N., Morpurgo M., Palazzo B., Parma B., Vivi L. Silica xerogels as a delivery system for the controlled release of different molecular weight heparins. Anal. Bioanal. Chem.,2005,381,601-606.
[13]徐鹏,李翔,杜强国,杨玉良.聚氯乙烯表面肝素化的研究.复旦学报(自然科学版),2001,40,372-375.
[14]侯长军,张文彬,霍丹群,陈柄灿,任艳容,郑书家.肝素化结合方式及本体材料的研究进展.化工进展,2003,22,703-707.
[15]Kumar M.N.V.R. A review of chitin and chitosan applications. React. Funct. Polym.,2000,46,1-27.
[16]Kweon D.K., Lim S.T. Preparation and characteristics of a water-soluble chitosan-heparin complex. J. Appl. Polym. Sci.,2003,87,1784-1789.
[17]袁伟永,计剑,付金红,沈家骢.层层静电自组装构建壳聚糖/肝素抗菌多层膜的研究.高等学校化学学报,2005,26,1963-1965.
[18]Wang X.H., Li D., Wang W.J., Feng Q.L., Cui F.Z., Xu Y.X., Song X.H. Covalent immobilization of chitosan and heparin on PLGA surface. Int. J. Biolog. Macromol.,2003,33,95-100.
[19]Jacobucci H.B., Sgarbieri V.C, Dias N.F.G.P., Borges P., Tanikawa C. Impact of different dietary protein on rat growth, blood serum lipids and protein and liver cholesterol. Nutr. Res.,2001,21,905-915.
[20]Vaz C.M., Fossen M., Van T.R.F., De Graaf L.A., Reis R.L., Cunha A.M. Casein and soybean protein-based thermoplastics and composites as alternative biodegradable polymers for biomedical applications. J. Biomed. Mater. Res. Part A,2003,65A,60-70.
[21]Chen Y, Zhang L., Gu J., Liu J. Physical properties of microporous membranes prepared by hydrolyzing cellulose/soy protein blends. J. Membr. Sci.,2004,241, 393-402.
[22]Zhou Z., Zheng H. Wei M., Huang J., Chen Y. Structure and mechanical properties of cellulose derivatives/soy protein isolate blends. J. Appl. Polym. Sci.,2008,107,3267-3274.
[23]Luo L.H., Wang X.M., Zhang Y.F., Liu Y.M., Wang Y., Chang P.R., Chen Y Preparation, characterization and biocompatibility evaluation of cellulose/soy protein isolate films coagulated from acetic acid solution. J. Biomater. Sci. Polym. Ed.,2008,19,479-496.
[24]Silva S.S., Santos M.I., Coutinho C.P., Mano J.F., Reis R.L. Physical properties and biocompatibility of chitosan/soy blended membranes. J. Mater. Sci. Mater. Med.,2005,16,575-579.
[25]Jia D.Y, Fang Y, Yao K. Water vapor barrier and mechanical properties of konjac glucomannan-chitosan-soy protein isolate edible films. Food Bioprod. Process.,2009,87,7-10.
[26]Silva S.S., Goodfellow B.J., Benesch J., Rocha J., Mano J.F., Reis R.L. Morphology and miscibility of chitosan/soy protein blended membranes. Carbohyd. Polym.,2007,70,25-31.
[27]Cervera M.F., Heinamaki J., Rasanen M., Maunu S.L., Karjalainen M., Acosta O.M.N., Colarte A.I., Yliruusi J. Solid-state characterization of chitosans derived from lobster chitin. Carbohyd. Polym.,2004,58,401-408.
[28]Hattori M., Numamoto K., Kobayashi K., Takahashi K. Functional changes in beta-lactoglobulin by conjugation with cationic saccharides. J. Agric. Food Chem.,2000,48,2050-2056.
[29]Suh J.K.F., Matthew H.W.T. Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering:a review. Biomaterials,2000,21, 2589-2598.
[30]Cho S.Y., Rhee C. Sorption characteristics of soy protein films and their relation to mechanical properties. Lebensm.Wiss. Technol.,2002,35,151-157.
[31]Tang R.P., Du Y.M., Zheng H., Fan L.H. Preparation and characterization of soy protein isolate-carboxymethylated konjac glucomannan blend films. J. Appl. Polym. Sci.,2003,88,1095-1099.
[32]ISO 10993-5:2009. Biological evaluation of medical devices Part 5:Tests for in vitro cytotoxicity.
[33]Serrano M.C., Pagani R., Vallet-Regi M., Pena J., Ramila A., Izquierdo I., Portoles M.T. In vitro biocompatibility assessment of poly (ε-caprolactone) films using L929 mouse fibroblasts. Biomaterials,2004,25,5603-5611.
[34]Velayudhan S., Anilkumar T.V., Mohanan P.V., Fernandez A.C., Varma H.K., Ramesh P. Biological evaluation of pliable hydroxyapatite-ethylene vinyl acetate co-polymer composites intended for cranioplasty. Acta. Biomater.,2005,1, 201-209.
[35]ISO 10993-6:2009. Biological evaluation of medical devices part 6:tests for local effects after implantation.
[36]Almeida E.V.R., Frollini E., Castellan A., Coma V. Chitosan, sisal cellulose, and biocomposite chitosan/sisal cellulose films prepared from thiourea/NaOH aqueous solution. Carbohyd. Polym.,2010,80,655-664.
[37]吕彩霞,姚子华.纳米羟基磷灰石/壳聚糖-硫酸软骨素复合材料的制备及其性能研究.复合材料学报,2007,24,110-115.
[38]杨前荣,陈新,邵正中.天然聚电解质壳聚糖/羧甲基壳聚糖配合物膜的研制.化学学报,2005,63,259-262.
[39]Koning C., van Duin M., Pagnoulle C., Jerome R. Strategies for compatibilization of polymer blends. Prog. Polym. Sci.,1998,23,707-757.
[40]Murakami R., Takashima R. Mechanical properties of the capsules of chitosan-soy globulin polyelectrolyte complex. Food Hydrocolloid.2003,17, 885-888.
[41]Franek F., Hohenwarter O., Katinger H. Plant protein hydrolysates:preparation of defined peptide fractions promoting growth and production in animal cells cultures. Biotechnol. Prog.,2000,16,688-692.
[42]Lee Y.K., Kim S.Y., Kim K.H., Chun B.H., Lee K.H., Oh D.J., Chung, N. Use of soybean protein hydrolysates for promoting proliferation of human keratinocytes in serum-free medium. Biotechnol. Lett.,2008,30,1931-1936.
[1]Ueno H., Mori T., Fujinaga T. Topical formulations and wound healing applications of chitosan. Adv. Drug Deliver. Rev.,2001,52,105-115
[2]Usami Y., Minami S., Okamoto Y., Matsuhashi A., Shigemasa Y. Influence of chain length of N-acetyl-D-glucosamine and D-glucosamine residues on direct and complement-mediated chemotactic activities for canine polymorphonuclear cells. Carbohyd. Polym.,1997,32,115-122.
[3]Suzuki Y., Miyatake K., Okamoto Y, Muraki E., Minami S. Influence of the chain length of chitosan on complement activation. Carbohyd. Polym.,2003,54, 465-469.
[4]Suzuki Y, Okamoto Y, Morimoto M., Sashiwa H., Saimoto H., Tanioka S.-i., Shigemasa Y, Minami S. Influence of physico-chemical properties of chitin and chitosan on complement activation. Carbohyd. Polym.,2000,42,307-310.
[5]Silva S.S., Santos M.I., Coutinho O.P., Mano J.F., Reis R.L. Physical properties and biocompatibility of chitosan/soy blended membranes. J. Mater. Sci. Mater. Med.,2005,16,575-579.
[6]Silva S.S., Goodfellow B.J., Benesch J., Rocha J., Mano J.F., Reis R.L Morphology and miscibility of chitosan/soy protein blended membranes. Carbohyd. Polym.,2007,70,25-31.
[7]Paquet O., Krouit M., Bras J., Thielemans W., Belgacem M.H. Surface modification of cellulose by PCL grafts. Acta Mater.,2010,58,792-801.
[8]Davarpanah S., Mahmoodi N.M., Arami M., Bahrami H., Mazaheri F. Environmentally friendly surface modification of silk fiber:Chitosan grafting and dyeing. Appl. Surf. Sci.,2009,255,4171-4176.
[9]Li J., Zhu B.Q., Shao YY, Liu X.R., Yang X.L., Yu Q. Construction of anticoagulant poly (lactic acid) films via surface covalent graft of heparin-carrying microcapsules. Colloids Surf., B,2009,70,15-19.
[10]Baumann H., Kokott A. Surface modification of the polymers present in a polysulfone hollow fiber hemodialyser by covalent binding of heparin or endothelial cell surface heparan sulfate:flow characteristics and platelet adhesion. J. Biomed. Sci., Polym. Ed.,2000,11,245-272.
[11]Olsson P., Sanchez J., Mollnes T.E., Riesenfeld J. On the blood compatibility of end-point immobilized heparin. J. Biomed. Sci., Polym. Ed.,2000,11, 1261-1273.
[12]Goosen M.F.A., Sefton M.W., Hatton M.W.C. Inactivation of thrombin by antithrombin Ⅲ on a heparinized biomaterial. Thromb. Res.,1980,20,534-554.
[13]Byun Y., Jacobs H.A., Kim S.W. Binding kinetics of thrombin and antithrombin Ⅲ with immobilized heparin using a spacer. Asaio J.,1992,38, M649-653.
[14]项昭保,霍丹群,候长军.肝素化聚醚砜抗凝血材料的研究.化工新型材料,2005,33,57-59.
[15]Kim Y.J., Kang I.K., Huh M.W., Yoon S.C. Surface characterization and in vitro blood compatibility of poly (ethylene terephthalate) immobilized with insulin and/or heparin using plasma glow discharge. Biomaterials,2000,21,121-130.
[16]Smith P.K., Mallia A.K., Hermanson G.T. Calorimetric method for the assay of heparin content in immobilized heparin preparations. Anal. Biochem.,1980, 109,466-473.
[17]Yang M.C., Lin W.C. Surface modification and blood compatibility of polyacrylonitrile membrane with immobilized chitosan-heparin conjugate. J. Polym. Res.,2002,9,201-206.
[18]ISO 10993-5:2009. Biological evaluation of medical devices Part 5:Tests for in vitro cytotoxicity.
[19]Serrano M.C., Pagani R., Vallet-Regi M., Pena J., Ramila A., Izquierdo I., Portoles M.T. In vitro biocompatibility assessment of poly (e-caprolactone) films using L929 mouse fibroblasts. Biomaterials,2004,25,5603-5611.
[20]Suzuki S., Gr(?)ndahl L., Leavesley D., Wentrup-Byrne E. In vitro bioactivity of MOEP grafted ePTFE membranes for craniofacial applications. Biomaterials, 2005,26,5303-5312.
[21]Shen F., Zhang E.L., Wei Z.J. In vitro blood compatibility of poly (hydroxybutyrate-co-hydroxyhexanoate) and the influence of surface modification by alkali treatment. Mater. Sci. Eng. C.,2010,30,369-375.
[22]Zhao J., Shi Q.A., Yin L.G., Luan S.F., Shi H.C., Song L.J., Yin J.H., Stagnaro P. Polypropylene modified with 2-hydroxyethyl acrylate-g-2-methacryloyloxyethyl phosphorycholine and its hemocompatibility Appl. Surf. Sci.,2010,256, 7071-7076.
[23]Xu J.P., Wang X.L., Fan D.Z., Ji J., Shen J.C. Construction of phospholipid anti-biofouling multilayer on biomedical PET surfaces. Appl. Surf. Sci.,2008, 255,538-540.
[24]He Q., Ao Q., Gong K., Zhang L.H., Hu M., Gong Y.D., Zhang X.F. Preparation and characterization of chitosan-heparin composite matrices for blood contacting tissue engineering. Biomed. Mater.,2010,5,055001 (16pp).
[25]Ho Y.C., Wu S.J., Mi F.L., Chiu Y.L., Yu S.H., Panda N., Sung H.W. Thiol-modified chitosan sulfate nanoparticles for protection and release of basic fibroblast growth factor. Bioconjug. Chem.,2010,21,28-38.
[26]Ho Y.C., Mi F.L., Sung H.W., Kuo P.L. Heparin-functionalized chitosan-alginate polyelectrolyte complex scaffolds for the stabilization and sustained release of basic fibroblast growth factor. Int. J. Pharm.,2009,376,69-75.
[27]Tang D.W., Yu S.H., Ho Y.C., Mi F.L., Kuo P.L., Sung H.W. Heparinized chitosan/poly (γ-glutamic acid) nanoparticles for multi-functional delivery of fibroblast growth factor and heparin. Biomaterials,2010,31 9320-9332.
[28]Yu S.H., Wu Y.B., Mi F.L., Shyu S.S. Polysaccharide-based artificial extracellular matrix:preparation and characterization of three-dimensional, macroporous chitosan, and heparin composite scaffold. J. Appl. Polym. Sci., 2008,109,3639-3644.
[29]Ma K.W., Ma L., Cai S.X., Wang X., Liu B., Xu Z.L., Dai X.Z., Yang J.Y., Jing A.H., Lei W.J. Preparation of heparin-immobilized PVA and its adsorption for low-density lipoprotein from hyperlipemia plasma. J. Mater. Sci.:Mater Med., 2008,19,3255-3261.
[30]Shu Y, Ou G.M., Wang L., Zou J.C., Li Q.L. Surface modification of titanium with heparin-chitosan multilayers via layer-by-layer self-assembly technique. J. Nanomate.,2011 doi:10.1155/2011/423686.
[31]Michiardia A., Aparicioa C., Ratnerb B.D., Planella J.A., Gil J. The influence of surface energy on competitive protein adsorption on oxidized NiTi surfaces. Biomaterials,2007,28,586-594.
[32]Qu X.H., Wu Q., Chen G.Q. In vitro study on hemocompatibility and cytocompatibility of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate). J. Biomater. Sci.,Polym. Ed.,2006,17,1107-1121.
[33]Wang A.F., Cao T., Tang H.Y., Liang X.M., Salley S.O., Ng K.Y. In vitro haemocompatibility and stability of two types of heparin-immobilized silicon surfaces. Colloids Surf. B,2005,43,245-255.
[34]Murakami R., Takashima R. Mechanical properties of the capsules of chitosan-soy globulin polyelectrolyte complex. Food Hydrocolloid.2003,17, 885-888.
[35]Lin C.H., Jao W.C., Yeh Y.H., Lin W.C., Yang M.C. Hemocompatibility and cytocompatibility of styrenesulfonate-grafted PDMS-polyurethane-HEMA hydrogel. Colloids Surf. B,2009,70,132-141.
[36]Yang J., Liu F., Tu S., Chen Y.W., Luo X.L., Lu Z.Q., Wei J., Li S.M. Haemo-and cytocompatibility of bioresorbable homo- and copolymers prepared from 1,3-trimethylene carbonate, lactides, and ε-caprolactone. J. Biomed. Mater. Res. A,2010,94A,396-407.
[37]Lee Y.K., Kim S.Y., Kim K.H., Chun B.H., Lee K.H., Oh D.J., Chung N. Use of soybean protein hydrolysates for promoting proliferation of human keratinocytes in serum-free medium. Biotechnol. Lett.2008,30,1931-1936.
[38]Cai K.Y, Yao K.D., Cui Y.L., Lin S.B., Yang Z.M., Li X.Q., Xie H.Q., Qing T.W., Luo J. Surface modification of poly (D, L-lactic acid) with chitosan and its effects on the culture of osteoblasts in vitro. J. Biomed. Mater. Res.,2002,60, 398-404.
[39]Lee Y.K., Kim S.Y, Kim K.H., Chun B.H., Lee K.H., Oh D.J., Chung N. Use of soybean protein hydrolysates for promoting proliferation of human keratinocytes in serum-free medium. Biotechnol. Lett.,2008,30,1931-1936.
[40]Luo L.H., Wang X.M., Zhang Y.F., Liu Y.M., Wang Y, Chang P.R., Chen Y. Physical properties and biocompatibility of cellulose/soy protein isolate membranes coagulated from acetic aqueous solution. J. Biomater. Sci., polym. Ed.,2008,19,479-496.
[41]Yang Z.L., Wang J., Luo R.F., Maitz M.F., Jing F.J., Sun H., Huang N. The covalent immobilization of heparin to pulsed-plasma polymeric allylamine films on 316L stainless steel and the resulting effects on hemocompatibility. Biomaterials,2010,31,2072-2083.
[42]Chou T.C., Fu E., Wu C.J., Yeh J.H. Chitosan enhances platelet adhesion and aggregation. Biochem. Biophys. Res. Commun.,2003,302,480-483.
[43]Lin W.C., Liu T.Y., Yang M.C. Hemocompatibility of polyacrylonitrile dialysis membrane immobilized with chitosan and heparin conjugate. Biomaterials,2004, 25,1947-1957.
[44]Xu F.J., Li Y.L., Kang E.T., Neoh K.G. Heparin-coupled poly (poly (ethylene glycol) monomethacrylate)-Si(111) hybrids and their blood compatible surfaces. Biomacromolecules,2005,6,1759-1768.
[45]Zhang W.F., Zhou H.Y., Chen X.G., Tang S.H., Zhang J.J. Biocompatibility study of the ophylline/chitosan/β-cyclodextrin microspheres as pulmonary delivery carriers. J. Mater. Sci.:Mater. Med.,2009,20,1321-1330.
[46]程青,王国斌.生物材料血液相容性评价研究进展.上海生物医学工程,2001,22，31-34.
[47]Amiji M.M. Permeability and blood compatibility properties of chitosan-poly (ethylene oxide) blend membranes for haemodialysis. Biomaterials,1995,16, 593-399.
[48]Jumaa M., Furkert F.H., Muller B.W. A new lipid emulsion formulation with high antimicrobial efficacy using chitosan. Eur. J. Pharm. Biopharm.,2002,53, 115-123.
[1]侯长军,张文彬,霍丹群,陈柄灿,任艳容,郑书家肝素化结合方式及本体材料的研究进展.化工进展,2003,22,703-708.
[2]李娟,吴英锋,杨新林.肝素功能化生物材料的研究进展.有机化学,2010,30，359-367.
[3]Kim Y.J., Kang I.K., Huh M.W., Yoon S.C. Surface characterization and in vitro blood compatibility of poly (ethylene terephthalate) immobilized with insulin and/or heparin using plasma glow discharge. Biomaterials,2000,21,121-130.
[4]Smith P.K., Mallia A.K., Hermanson G.T. Calorimetric method for the assay of heparin content in immobilized heparin preparations. Anal. Biochem.,1980, 109,466-473.
[5]Yang M.C., Lin W.C. Surface modification and blood compatibility of polyacrylonitrile membrane with immobilized chitosan-heparin conjugate. J. Polym. Res.,2002,9,201-206.
[6]Zhu A.P., Zhang M., Shen J. Blood compatibility of chitosan/heparin complex surface modified ePTFE vascular graft. Appl. Surf. Sci.,2005,241,485-492.
[7]ISO 10993-5:2009. Biological evaluation of medical devices Part 5:Tests for in vitro cytotoxicity.
[8]Silva S.S., Santos M.I., Coutinho O.P., Mano J.F., Reis R.L. Physical properties and biocompatibility of chitosan/soy blended membranes. J. Mater. Sci.:Mater. Med.,2005,16,575-579.
[9]Serrano M.C., Pagani R., Vallet-Regi M., Peua J., Ramila A., Izquierdo I., Portoles M.T. In vitro biocompatibility assessment of poly (ε-caprolactone) films using L929 mouse fibroblasts. Biomaterials,2004,25,5603-5611.
[10]Shen F., Zhang E.L., Wei Z.J. In vitro blood compatibility of poly (hydroxybutyrate-co-hydroxyhexanoate) and the influence of surface modification by alkali treatment Mater. Sci. Eng. C.,2010,30,369-375.
[11]Zhao J., Shi Q.A., Yin L.G., Luan S.F., Shi H.C., Song L.J., Yin J.H., Stagnaro P. Polypropylene modified with 2-hydroxyethyl acrylate-g-2-methacryloyloxyethyl phosphorycholine and its hemocompatibility. Appl. Surf. Sci.,2010,256, 7071-7076.
[12]Xu J.P., Wang X.L., Fan D.Z., Ji J., Shen J.C. Construction of phospholipid anti-biofouling multilayer on biomedical PET surfaces. Appl. Surf. Sci.,2008, 255,538-540.
[13]He Q., Ao Q., Gong K., Zhang L.H., Hu M., Gong Y.D., Zhang X.F. Preparation and characterization of chitosan-heparin composite matrices for blood contacting tissue engineering. Biomed. Mater.,2010,5,055001 (16pp).
[14]Shu Y, Ou G.M., Wang L., Zou J.C., Li Q.L. Surface modification of titanium with heparin-chitosan multilayers via mayer-by-mayer self-assembly technique. J. Nanomater.,2011, doi:10.1155/2011/423686.
[15]Kweon D.K., Song S.B., Park Y.Y. Preparation of water-soluble chitosan/heparin complex and its application as wound healing accelerator. Biomaterials,2003, 24,1595-1601.
[16]Yu S.H., Wu Y.B., Mi F.L., Shyu S.S. Polysaccharide-based artificial extracellular matrix:preparation and characterization of three-dimensional, macroporous chitosan, and heparin composite scaffold. J. Appl. Polym. Sci., 2008,109,3639-3644.
[17]Lee Y.K., Kim S.Y., Kim K.H., Chun B.H., Lee K.H, Oh D.J., Chung N. Use of soybean protein hydrolysates for promoting proliferation of human keratinocytes in serum-free medium. Biotechnol. Lett.,2008,30,1931-1936.
[18]Luo L.H., Wang X.M., Zhang Y.F., Liu Y.M., Wang Y, Chang P.R., Chen Y. Physical properties and biocompatibility of cellulose/soy protein isolate membranes coagulated from acetic aqueous solution. J. Biomater. Sci., Polym. Ed.,2008,19,479-496.
[19]Qu X.H., Wu Q., Chen G.Q. In vitro study on hemocompatibility and cytocompatibility of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate). J. Biomater. Sci. Polym. Ed.,2006,17,1107-1121.
[1]Kim B.S., Mooney D.J. Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol.,1998,6,224-230.
[2]Kim S.E., Park J.H, Cho Y.W., Chung H., Jeong S.Y., Lee E.B., Kwon I.C. Porous chitosan scaffold containing microspheres loaded with transforming growth factor-β1:Implications for cartilage tissue engineering. J. Control. Release,2003,91,365-374.
[3]刑桂荣,王敬湘.壳聚糖在医药领域的研究进展.中国药业,2003,12,74-75.
[4]Vaz C.M., van Doeveren P.F.N.M., Reis R.L., Cunha A.M. Soy matrix drug delivery systems obtained by melt-processing techniques. Biomacromolecules, 2003,4,1520-1529.
[5]Schoof H., Apel J., Heschel I., Rau G. Control of pore structure and size in freeze-dried collagen sponges. J. Biomed. Mater. Res.,2001,58,352-357.
[6]Ryan C.K., Sax H.C. Evaluation of a carboxymethylcellulose sponge for prevention of postoperative adhesions. Am. J. Surg.,1995,169,154-160.
[7]ISO 10993-5:2009. Biological evaluation of medical devices Part 5:Tests for in vitro cytotoxicity.
[8]ISO 10993-12:2009. Biological evaluation of medical devices part 12:sample preparation and reference materials.
[9]Silva S.S., Santos M.I., Coutinho O.P., Mano J.F., Reis R.L. Physical properties and biocompatibility of chitosan/soy blended membranes. J. Mater. Sci.:Mater. Med.2005,16,575-579.
[10]Serrano M.C., Pagani R., Vallet-Regi M., Pena J., Ramila A., Izquierdo I., Portoles M.T. In vitro biocompatibility assessment of poly (ε-caprolactone) films using L929 mouse fibroblasts. Biomaterials,2004,25,5603-5611.
[11]Velayudhan S., Anilkumar T.V., Mohanan P.V., Fernandez A.C., Varma H.K., Ramesh P. Biological evaluation of pliable hydroxyapatite-ethylene vinyl acetate co-polymer composites intended for cranioplasty. Acta. Biomater.,2005,1, 201-209.
[12]ISO 10993-6:2009. Biological evaluation of medical devices part 6:tests for local effects after implantation.
[13]Almeida E.V.R., Frollini E., Castellan A., Coma V. Chitosan, sisal cellulose, and biocomposite chitosan/sisal cellulose films prepared from thiourea/NaOH aqueous solution. Carbohyd. Polym.,2010,80,655-664.
[14]Franek F., Hohenwarter O., Katinger H. Plant protein hydrolysates:preparation of defined peptide fractions promoting growth and production in animal cells cultures. Biotechnol. Prog.,2000; 16,688-692.
[15]Lee Y.K., Kim S.Y., Kim K.H., Chun B.H., Lee K.H., Oh D.J., Chung, N. Use of soybean protein hydrolysates for promoting proliferation of human keratinocytes in serum-free medium. Biotechnol. Lett.,2008,30,1931-1936.
[1]Schurz J.'Trends in polymer science-A bright future for cellulose. Prog. Polym. Sci.,1999,24,481-483.
[2]Entcheva E., Bien H., Yin L., Chung C.Y., Farrell M., Kostov Y. Functional cardiac cell constructs on cellulose-based scaffolding. Biomaterials,2004,25, 5753-5762.
[3]Luo X.G., Zhang L. New solvents and functional materials prepared from cellulose solutions in alkali/urea aqueous system. Food Res. Int.,2010 in press. (doi:10.1016/j.foodres.2010.05.016.)
[4]Cai J., Zhang L., Zhou J., Qi H., Chen H., Kondo T., Chen X., Chu B. Multifilament fibers based on dissolution of cellulose in NaOH/urea aqueous solution:structure and properties. Adv. Mater.,2007,19,821-825.
[5]Abe Y., Mochizuki A. Hemodialysis membrane prepared from cellulose/n-methylmorpholine-n-oxide solution. Ⅲ. The relationship between the drying condition of the membrane and its permeation behavior J. Appl. Polym. Sci.,2003,89,1671-1681.
[6]Bryjak J., Aniulyte J., Liesiene J. Evaluation of man-tailored cellulose-based carriers in glucoamylase immobilization. Carbohyd. Res.,2007,342,1105-1109.
[7]Sharma J.B., Gupta N., Mital S. Creation of neovagina using oxidized cellulose (surgicel) as a surgical treatment of vaginal agenesis. Arch. Gynecol. Obstet. 2007,275,231-235.
[8]Muller F.A., Muller L., Hofmann I., Greil P., Wenzel M.M., Staudenmaier R. Cellulose-based scaffold materials for cartilage tissue engineering. Biomaterials, 2006,27,3955-3963.
[9]Zhang J., Yuan J., Yuan Y.L., Shen J., Lin S.C. Chemical modification of cellulose membranes with sulfo mmonium zwitterionic vinyl monomer to improve hemocompatibility. Colloids Surf., B,2003,30,249-257.
[10]Eller L.K., Reimer, R.A. A high calcium, skim milk powder diet results in a lower fat mass in male, energy-restricted, obese rats more than a low calcium, casein, or soy protein diet. J. Nutr.2010,140,1234-1241.
[11]Qi G.Y, Sun X.S. Peel adhesion properties of modified soy protein adhesive on a glass panel. Ind. Crop. Prod.,2010,32,208-212.
[12]Kumar R., Liu D., Zhang L. Advances in proteinous biomaterials J. Biobased Mater. Bio.,2008,2,1-24.
[13]Giavaresi G, Fini M., Salvage J., Aldini N.N., Giardino R., Ambrosio L., Nicolais L., Santin M. Bone regeneration potential of a soybean-based filler: Experimental study in a rabbit cancellous bone defects. J. Mater. Sci. Mater. Med.,2010,21,615-626.
[14]Vaz C.M., van Doeveren P.F., Reis R.L., Cunha A.M. Soy matrix drug delivery systems obtained by melt-processing techniques. Biomacromolecules,2003,4, 1520-1529.
[15]Lee Y.K., Kim S.Y., Kim K.H., Chun B.H., Lee K.H., Oh D.J., Chung N. Use of soybean protein hydrolysates for promoting proliferation of human keratinocytes in serum-free medium. Biotechnol. Lett.,2008,30,1931-1936.
[16]Merolli A., Nicolais L., Ambrosio L., Santin M. A degradable soybean-based biomaterial used effectively as a bone filler in vivo in a rabbit. Biomed. Mater., 2010,5,015008.
[17]Franek F., Hohenwarter O., Katinger H. Plant protein hydrolysates:Preparation of defined peptide fractions promoting growth and production in animal cells cultures. Biotechnol. Prog.,2000,16,688-692.
[18]Chen Y., Zhang L. Blend membranes prepared from cellulose and soy protein isolate in NaOH/thiourea aqueous solution. J. Appl. Polym. Sci.,2004,94, 748-757.
[19]Chen Y., Zhang L., Gu J., Liu J. Physical properties of microporous membranes prepared by hydrolyzing cellulose/soy protein blends. J. Membr. Sci.,2004,241, 393-402.
[20]Luo L.H., Wang X.M., Zhang Y.F., Liu Y.M., Chang P.R., Wang Y, Chen Y. Physical properties and biocompatibility of cellulose/soy protein isolate membranes coagulated from acetic aqueous solution. J. Biomater. Sci. Polym. Ed.,2008,19,479-496
[21]Luo L.H., Zhang Y.F., Wang X.M., Wan Y, Chang P.R., Anderson D.P., Chen Y. Preparation, characterization, and in vitro and in vivo evaluation of cellulose/soy protein isolate composite sponges. J. Biomater. Appl.,2010,24,503-526.
[22]Kumar M.N.V.R. A review of chitin and chitosan applications. React. Funct. Polym.,2000,46,1-27.
[23]Cui Y.L., Qi A.D., Liu W.G., Wang X.H., Wang H., Ma D.M., Yao K.D. Biomimetic surface modification of poly (1-lactic acid) with chitosan and its effects on articular chondrocytes in vitro. Biomaterials,2003,24,3859-3868.
[24]Xiao Y.M., Li D.X., Chen X.N., Lu J., Fan H.S., Zhang X.D. Preparation and cytocompatibility of chitosan-modified polylactide. J. Appl. Polym. Sci.,2008, 110,408-412.
[25]Rong H.C., Horng Dar H. Effect of molecular weight of chitosan with the same degree of deacetylation on the thermal, mechanical, and permeability properties of the prepared membrane. Carbohyd. Polym.,1996,29,353-358.
[26]Suzuki Y, Miyatake K., Okamoto Y, Muraki E., Minami S. Influence of the chain length of chitosan on complement activation. Carbohyd. Polym.,2003,54, 465-469.
[27]Suzuki Y., Okamoto Y., Morimoto M., Sashiwa H., Saimoto H., Tanioka S.-i., Shigemasa Y, Minami S. Influence of physico-chemical properties of chitin and chitosan on complement activation. Carbohyd. Polym.,2000,42,307-310.
[28]张守松,邹翰.甲壳糖血液相容性研究.高分子材料,1997,4,21-23.
[29]ISO 10993-5:2009. Biological evaluation of medical devices Part 5:Tests for in vitro cytotoxicity.
[30]Silva S.S., Santos M.I., Coutinho O.P., Mano J.F., Reis R.L. Physical properties and biocompatibility of chitosan/soy blended membranes. J. Mater. Sci.:Mater. Med.,2005,16,575-579.
[31]Serrano M.C., Pagani R., Vallet-Regi M., Pena J., Ramila A., Izquierdo I., Portoles M.T. In vitro biocompatibility assessment of poly (s-caprolactone) films using L929 mouse fibroblasts. Biomaterials,2004,25,5603-5611.
[32]Suzuki S., Gr(?)ndahl L., Leavesley D., Wentrup-Byrne E. In vitro bioactivity of MOEP grafted ePTFE membranes for craniofacial applications. Biomaterials, 2005,26,5303-5312.
[33]Shen F., Zhang E.L., Wei Z.J. In vitro blood compatibility of poly (hydroxybutyrate-co-hydroxyhexanoate) and the influence of surface modification by alkali treatment. Mater. Sci. Eng. C.,2010,30,369-375.
[34]Zhao J., Shi Q.A., Yin L.G., Luan S.F., Shi H.C., Song L.J., Yin J.H., Stagnaro P. Polypropylene modified with 2-hydroxyethyl acrylate-g-2-methacryloyloxyethyl phosphorycholine and its hemocompatibility. Appl. Surf. Sci.,2010,256, 7071-7076.
[35]Almeida E.V.R., Frollini E., Castellan A., Coma V. Chitosan, sisal cellulose, and biocomposite chitosan/sisal cellulose films prepared from thiourea/NaOH aqueous solution. Carbohyd. Polym.,2010,80,655-664.
[36]Pawlak A., Mucha M. Thermogravimetric and FTIR studies of chitosan blends. Thermochimica Acta.,2003,396,153-156.
[37]Qu X.H., Wu Q., Chen G.Q. In vitro study on hemocompatibility and cytocompatibility of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate. J. Biomater. Sci., Polym. Ed.,2006,17,1107-1121.
[38]Da Roz A.L., Leite F.L., Pereiro L.V., Nascente P.A.P., Zucolotto V., Oliveira Jr.O.N., Carvalho A.J.F. Adsorption of chitosan on spin-coated cellulose films. Carbohyd. Polym.,2010,80,65-70.
[39]Murakami R., Takashima R. Mechanical properties of the capsules of chitosan-soy globulin polyelectrolyte complex. Food Hydrocolloid.,2003,17, 885-888.
[40]Cai K.Y., Yao K.D., Cui Y.L., Lin S.B., Yang Z.M., Li X.Q., Xie H.Q., Qing T.W., Luo J. Surface modification of poly (D, L-lactic acid) with chitosan and its effects on the culture of osteoblasts in vitro. J. Biomed. Mater. Res.,2002,60, 398-404.
[41]Guo Z., Meng S., Zhong W., Du Q.G., Chou L.S.L. Self-assembly of silanated poly (ethylene glycol) on silicon and glass surfaces for improved haemocompatibility. Appl. Surf. Sci.,2009,255,6771-6780.
[42]Roy R.K., Choi H.W., Yi J.W., Moon M.W., Lee K.R., Han D.K., Shin J.H., Kamijo A., Hasebe T. Hemocompatibility of surface-modified, silicon-incorporated, diamond-like carbon films. Acta Biomater.,2009,5, 249-256.
[43]Kang I.K., Kwon O.H., Lee Y.M., Sung Y.K. Preparation and surface characterization of functional group-grafted and heparin-immobilized polyurethanes by plasma glow discharge. Biomaterials,1996,17,841-847.
[44]Lin C.H., Jao W.C., Yeh Y.H., Lin W.C., Yang M.C. Hemocompatibility and cytocompatibility of styrenesulfonate-grafted PDMS-polyurethane-HEMA hydrogel. Colloids Surf, B,2009,70,132-141.
[45]Liu L., Guo S.R., Chang J., Ning C.Q., Dong C.M., Yan D.Y. Surface modification of polycaprolactone membrane via layer-by-layer deposition for promoting blood compatibility. J. Biomed. Mater. Res., Part B,2008,87, 244-250.
[46]Zhang W.F., Zhou H.Y., Chen X.G., Tang S.H., Zhang J.J. Biocompatibility study of theophylline/chitosan/b-cyclodextrin microspheres as pulmonary delivery carriers. J. Mater. Sci.:Mater. Med.,2009,20,1321-1330.
[47]程青,王国斌.生物材料血液相容性评价研究进展.上海生物医学工程,2001,22，31-34.
[48]Wang L.C., Chen X.G., Zhong D.Y., Xu Q.C. Study on poly (vinyl alcohol)/carboxymethyl-chitosan blend film as local drug delivery system. J. Mater. Sci.:Mater. Med.,2007,18,1125-1133.
[1]Boretos J.W., Eden M. Contemporary Biomaterials,1984.
[2]顾汉卿,徐国凤.生物医学材料学.天津：天津科技翻译出版公司,1993,8,175-179.
[3]杨晓芳,奚廷斐.生物相容性评价的发展趋势.国外医学生物医学工程分册,1999,22,237-242.
[4]李爱民,孙康宁,尹衍升,卢志华,王振光,毕见强.生物材料的发展、应用、评价和展望.山东大学学报,2002,32,287-293.
[5]何淑漫,周健.抗凝血生物材料.化学进展,2010,22,760-772.
[6]项昭保,霍丹群,候长军,蔡绍哲.肝素化抗凝血生物材料的研究.现代医学仪器与应用,2002,14,25-29.
[7]Gott V.L., Whiffen J.D., Dutton R.C. Heparin bonding on colloidal graphite surfaces. Science,1963,142,1297-1298.
[8]Aldenhoff Y.B.J., Knetsch M.L.W., Hanssen J.H.L., Lindhout T., Wielders S.J.H., Kool L.H. Coils and tubes releasing heparin. Studies on a new vascular graft prototype. Biomaterials,2004,25,3125-3133.
[9]侯长军,张文彬,霍丹群,陈柄灿,任艳容,郑书家.肝素化结合方式及本体材料的研究进展.化工进展,2003,22,703-707.
[10]McLean J. The discovery of heparin. Circulation,1959,19,75-78.
[11]Murugesan S., Xie J.. Linhardt R.J. Immobilization of heparin:approaches and applications. Curr. Top. Med. Chem.,2008,8,80-100.
[12]Schramm R., Nickels R.M., Harder Y., Langer F., Menger M.D., Schafers H.J. Heparin-protamine does not aggravate local lps-provoked leukocytic inflammation in vivo. Thorac Cardio. Surg.,2006,16,506-511.
[13]Elmaleh D.R., Brown N.V., Geiben-Lynn R. Anti-viral ctivity of Human antithrombin Ⅲ. Int. J. Mol. Med.,2005,16,191-200.
[14]Icli F., Akbulut H., Utkan G., Yalcin B., Dincol D., Isikdogan A., Demirkazik A. Onur H., Cay F., Buyukcelik A. Low molecular weight heparin (LMWH) increases the efficacy of cisplatinum plus gemcitabine combination in advanced pancreatic cancer. J. Surg. Oncol.,2007,95,507-512.
[15]戴敏.肝素的临床新应用.中国药物与临床,2004,4,785-786.
[16]Damus P.S., Hicks M., Rosenberg R.D. Anticoagulant action of heparin. Nature, 1973,246,355-357.
[17]Vlodavsky I., Ilan N., Nadir Y., Brenner B., Katz B.Z., Naggi A., Torri G., Casu B., Sasisekharan R. Heparanase, heparin and the coagulation system in cancer progression. Thromb. Res.,2007,120,112-120.
[18]施洪臣,李宝山,章雪松,郭健.肝素在临床上的应用.临床军医杂志,2003,31，100-101.
[19]Hassan Y., Awaisu A., Aziz N.A., Aziz N.H., Ismail O. Heparin-induced thrombocytopenia and recent advances in its therapy. J. Clin. Pharm. Ther.,2007, 32,535-544.
[20]Basmadjian D., Sefton M.V. Relationship between release rate and surface concentration for heparinized materials. J. Biomed.Mater. Res.,1983,17, 509-518.
[21]Mori Y. The effect of released heparin from the heparinized hydrophilic polymer on the process of thrombus formation. Trans. Am. Soc.,1998,10,736-744.
[22]Yang Z.L., Wang J., Luo R.F., Maitz M.F., Jing F.J., Sun H., Huang N. The covalent immobilization of heparin to pulsed-plasma polymeric allylamine films on 316L stainless steel and the resulting effects on hemocompatibility. Biomaterials,2010,31,2072-2083.
[23]Li J., Zhu B.Q., Shao Y.Y., Liu X.R., Yang X.L., Yu Q. Construction of anticoagulant poly (lactic acid) films via surface covalent graft of heparin-carrying microcapsules. Colloids Surf. B,2009,70,15-19.
[24]Zhu A.P., Zhang M., Wu J., Shen J. Covalent immobilization of chitosan/heparin complex with a photosensitive hetero-bifunctional crosslinking reagent on PLA surface. Biomaterials,2002,23,4657-4665.
[25]Wang X.H., Li D.P., Wang W.J., Feng Q.L., Cui F.Z., Xu Y.X., Song X.H. Covalent immobilization of chitosan and heparin on PLGA surface. Int. J. Biol. Macromol.,2003,33,95-100.
[26]Kim I.C, Tak T.M, Choi J.G. Sulfonated polyether-sulfone by heterogeneous method and its membraneperformances. J. Appl. Polym. Sci.,1999,74, 2046-2055.
[27]Moon H.T., Lee Y.K., Han J.K., Byu Y. A novel formulation for controlled release of heparin-DOCA conjugate dispersed as nanoparticles in polyurethane film. Biomaterials,2001,22,281-289.
[28]Wang H.J., Lin Z.X., Liu X.M., Sheng S.Y., Wang J.Y Heparin-loaded zein microsphere film and hemocompatibility. J. Control. Release,2005,105, 120-131.
[29]Wilson R.S., Lelah M.D., Cooper S.L. Blood-material interactions:Assessment of in vitro and in vivo test methods. In:Williams D.F., editor. Techniques in biocompatibility testing. Bocaraton, FL:CRC Press,1988,151-181.
[30]奚廷斐.生物材料血液相容性评价方法的研究.生物医学工程学杂志,1987,4，42-48.
[31]Jordan S.W., Chaikof E.L. Novel thromboresistant materials. J. Vasc. Surg. 2007,45 Suppl A:A,104-115.
[32]Bajpai A.K., Bhanu S. Dynamics of controlled release of heparin from swellable crosslinked starch microspheres. J. Mater. Sci. Mater. Med.,2007,18, 1613-1621.
[33]Lin W.C., Liu T.Y., Yang M.C. Hemocompatibility of polyacrylonitrile dialysis membrane immobilized with chitosan and heparin conjugate. Biomaterials,2004, 25,1947-1957.
[34]Luong-Van E., Gr(?)ndahl L., Chua K.N., Leong K.W., Nurcombe V., Cool S.M. Controlled release of heparin from poly (epsilon-caprolactone) electrospun fibers. Biomaterials,2006,27,2042-2050.
[35]Roveri N., Morpurgo M., Palazzo B., Parma B., Vivi L. Silica xerogels as a delivery system for the controlled release of different molecular weight heparins. Anal. Bioanal. Chem.,2005,381,601-606.
[36]徐鹏,李翔,杜强国,杨玉良.聚氯乙烯表面肝素化的研究.复旦大学学报(自然科学版),2001,40,372-375.
[37]Kumar M.N.V.R. A review of chitin and chitosan applications. React. Funct. Polym.,2000,46,1-27.
[38]Hayes R., Davies D.H., Munvel V.G. Proceedings and the first international conference on chitin-chitosan, Boston,1977, edited by Muarelli R.A.A.,1979, 103.
[39]Liu Z.H., Jiao Y.P., Zhang Z.Y., Zhou C.G. Surface modification of poly (1-lactic acid) by entrapment of chitosan and its derivatives to promote osteoblasts-like compatibility. J. Biomed. Mater. Res.,2007,83A,1110-1116.
[40]王启钊,陈西广,刘成圣,孟祥红,刘晨光,于乐军,刘楠.壳聚糖的血液相容性.中国生物工程杂志,2005,194-198.
[41]Chou T.C., Fu E., Wu C.J., Yeh J.H. Chitosan enhances platelet adhesion and aggregation. Biochem. Biophys. Res. Commun.,2003,302,480-483.
[42]Okamoto Y., Yano R., Miyatake K., Tomohiro I., Shigemasa Y, Minami S. Effects of chitin and chitosan on blood coagulation. Carbohyd. Polym.,2003,53, 337-342.
[43]Ueno H., Mori T., Fujinaga T. Topical formulations and wound healing applications of chitosan. Adv. Drug Delivery Rev.,2001,52,105-115.
[44]Usami Y, Minami S., Okamoto Y, Matsuhashi A., Shigemasa Y. Influence of chain length of N-acetyl-D-glucosamine and D-glucosamine residues on direct and complement-mediated chemotactic activities for canine polymorphonuclear cells. Carbohyd. Polym.,1997,32,115-122.
[45]Amiji M.M. Permeability and blood compatibility properties of chitosan-poly (ethylene oxide) blend membranes for haemodialysis. Biomaterials,1995,16, 593-399.
[46]Jumaa M., Furkert F.H., Muller B.W. A new lipid emulsion formulation with high antimicrobial efficacy using chitosan. Eur. J. Pharm. Biopharm.,2002,53, 115-123.
[47]Notara M., Scotchford C.A., Grant D.M., Weston N., Roberts G.A.F. Cytocompatibility and hemocompatibility of a novel chitosan-alginate gel system. J. Biomed. Mater. Res. A,2009,89A,854-864.
[48]Carreno-Gomez B., Duncan R. Evaluation of the biological properties of soluble chitosan and chitosan microspheres. Int. J. Pharm.,1997,148,231-240.
[49]Amiji M.M. Synthesis of anionic poly (ethylene glycol) derivative for chitosan surface modification in blood-contacting applications. Carbohyd. Polym.,1997, 32,193-199.
[50]Suzuki Y., Miyatake K., Okamoto Y, Muraki E., Minami S. Influence of the chain length of chitosan on complement activation. Carbohyd. Polym.,2003,54, 465-469.
[51]Suzuki Y., Okamoto Y., Morimoto M., Sashiwa H., Saimoto H., Tanioka S.-i., Shigemasa Y, Minami S. Influence of physico-chemical properties of chitin and chitosan on complement activation. Carbohyd. Polym.,2000,42,307-310.
[52]Chandy T., Sharma C.P. Chitosan-as a biomaterial. Biomater. Art. Cells Artif. Organs.,1990,18,1-24.
[53]Madhumathi K., Sudheesh Kumar P.T., Abilash S., Sreeja V., Tamura H., Manzoor K., Nair S.V., Jayakumar R. Development of novel chitin/nanosilver composite scaffolds for wound dressing applications. J. Mater. Sci.:Mater. Med., 2010,21,807-813.
[54]李静,伍津津,鲁元刚,朱堂友,李文维,贺萍,杨宏珍.复合壳多糖人工皮肤移植真皮再构建的初步研究.中国临床康复,2003,7,572-573.
[55]Koide M., Konishi J., Ikegami K., Osaki k. Multilayer wound covering materials comprising a supporting layer and moisture permeation cont rolling layer and method for their manufacture. [P]. US 5,359,305,1995-3-7.
[56]Yannas I.V., Burke H.F., Orgill D.P., Skrabut E.M. Wound tissue can utilise a polymeric template to synthesise a functional extension of skin. Science,1982, 215,174-176.
[57]Ignatova M., Starboya K., Markova N., Manolova N., Rashkov I. Electrospun nano-fibre mats with antibacterial properties from quarternised chitosan and poly (vinyl alcohol). Carbohyd. Res.,2006,341,2098-2107.
[58]Le Y, Anand S.C., Horrocks A.R. Development of anti-bacterial polysaccharide fibres and their performance, in:European Conference on Advances in Wound Management, Amsterdam, Netherlands, October,1996.
[59]邓先模,李孝红.生物医用高分子在癌症药物治疗中的应用.高分子通报,1999,3,94-98.
[60]Aksungur P., Sungur A., Unal S., Iskit A.B., Squier C.A., Senel S. Chitosan delivery systems for the treatment of oral mucositis:in vitro and in vivo studies. J. Control. Release,2004,98,269-279.
[61]Ta H.T., Han H., Larson I., Dass C.R., Dunstan D.E. Chitosan-dibasic orthophosphate hydrogel:A potential drug delivery system. Int. J. Pharm.,2009, 371,134-141.
[62]Ishihara M., Obara K., Ishizuka T., Fujita M., Sato M., Masuoka K., Saito Y., Yura H., Matsui T., Hattori H., Kikuchi M., Kurita A. Controlled release of fibroblast growth factors and heparin from photocrosslinked chitosan hydrogels and subsequent effect on in vivo vascularization. J. Biomed. Mater. Res.,2003, 64A,551-559.
[63]Peng X.H., Zhang L.N., Kennedy J.F. Release behavior of microspheres from cross-linked N-methylated chitosan encapsulated ofloxacin. Carbohyd. Polym., 2006,65,288-295.
[64]季娟娟,丁仲鹃,杨雪莲.壳聚糖缓释膜的制备及性能研究.华西口腔医学杂志,2009,27,248-252.
[65]Kanke M., Katayama H., Tsuzuki S., Kuramoto H. Application of chitin and chitosan to pharmaceutical preparation. I. Film Preparation and in vitro evaluation. Chem. Pharm. Bull,1989,37,523.
[66]Shu X.Z, Zhu K.J., Weihong S. Novel pH-sensitive citrate cross-linked chitosan film for drug controlled release. Int. J. Pharm.,2001,21,19-28.
[67]何强芳,李国明,巫海珍,卢志敏,李良.5-氟尿嘧啶壳聚糖微球的制备及其释药性能.应用化学,2004,21,192-196.
[68]Agnihotris S.A., Aminabhavit T.M. Novel interpenetrating network chitosan-poly (ethylene oxidegacrylamide) hydrogel microspheres for the controlled release of capecitabine. Int. J. Pharm.,2006,324,103-115.
[69]Dev A., Binulal N.S., Anitha A., Nair S.V., Furuike T., Tamura H., Jayakumar R. Preparation of novel poly (lactic acid)/chitosan nanoparticles for anti HIV drug delivery applications. Carbohyd. Polym.,2010,80,833-838.
[70]张爱迪,丁德润.壳聚糖基生物医药材料的应用进展.上海工程技术大学学报,2009,23,63-67.
[71]Borchard G. Chitosans for gene delivery. Adv. Drug Deliver. Rev.,2001,52, 145-150.
[72]Csaba N., Koping-Hoggard M., Alonso M.J. Ionically crosslinked chitosan/tripolyphosphate nanoparticles for oligonucleotide and plasmid DNA delivery. Int. J. Pharm.,2009,382,205-214.
[73]Opanasopit P., Petchsangsai M., Rojanarata T., Ngawhirunpat T., Sajomsang W., Ruktanonchai U. Methylated N-(4-N, N-dimethylaminobenzyl) chitosan as effective gene carriers:Effect of degree of substitution. Carbohyd. Polym.,2009, 75,143-149.
[74]Mumper R.J., Wang J., Claspell J.M, Rolland A.P. Novel polymeric condensing carriers for gene delivery. Pro. Int. Symp. Control. Rel. Bioact. Mater.,1995,22, 178-179.
[75]Mao H.Q., Roy K., Walsh S.M., August J.T., Leong K.W. DNA-chitosan nanospheres for gene delivery. Pro. Int. Symp. Control. Rel. Bioact. Mater., 1996,23,401-402.
[76]宗莉,陈伶俐,张淑芸,杨晓容,朱家壁.壳聚糖纳米粒作为基因载体的研究：制备,特征和对DNA的保护.中国药科大学学报,2005,36,526-530.
[77]Jiang H.L., Lim H.T., Kim Y.K., Arote R., Shin J.Y., Kwon J.T., Kim J.E., Kim J.H., Kim D., Chae C., Nah J.W., Choi Y.J., Cho C.S., Cho M.H. Chitosan-graft-spermine as a gene carrier in vitro and in vivo. Eur. J. Pharm. Biopharm.,2011,77,36-42.
[78]Yu H.J., Deng C., Tian H.Y., Lu T.C., Chen X.S., Jing X.B. Chemo-physical and biological evaluation of poly (1-lysine)-grafted chitosan copolymers used for highly efficient gene delivery. Macromol. Biosci.,2011,11,352-361.
[79]Venkatesan J., Kim S.K. Chitosan composites for bone tissue engineering. Mar. Drugs,2010,8,2252-2266.
[80]Wang M. Developing bioactive composite materials for tissue replacement. Biomaterials,2003,24,2133-2151.
[81]Choi S.W., Xie J.W., Xia Y.N. Chitosan-based inverse opals:three-dimensional scaffolds with uniform pore structures for cell culture. Adv. Mater.,2009,21, 2997-3001.
[82]Jiang L.Y., Li Y.B., Xiong C.D. Preparation and biological properties of a novel composite scaffold of nano-hydroxyapatite/chitosan/carboxymethyl cellulose for bone tissue engineering. J. Biomed. Sci.,2009,16,65-74.
[83]刘阳,朱立新,杨宏,田京,许勇,于博,李志浩,冯庆玲,黄智.可注射性纳米羟基磷灰石/壳聚糖复合骨髓间充质干细胞促进骨缺损的修复.中国组织工程研究与临床康复,2010,14,6278-6282.
[84]Zhu A.P., Zhang M., Shen J. Blood compatibility of chitosan/heparin complex surface modified ePTFE vascular graft. Appl. Surf. Sci.,2005,241,485-492.
[85]Vaz C.M., Fossen M., Van T.R.F., De Graaf L.A., Reis R.L., Cunha A.M. Casein and soybean protein-based thermoplastics and composites as alternative biodegradable polymers for biomedical applications. J. Biomed. Mater. Res. Part A,2003,65A,60-70.
[86]Mizuno A., Mitsuiki M. Motoki M. Effect of transglutaminase treatment on the glass transition soy protein. J. Agric. Food Chem.,2000,48,3286-3291.
[87]Ortiz S.E.M, Cristina A.M. Analysis of products, mechanisms of reaction, and some functional properties of soy protein hydrolysates. J. Am. Oil Chem. Soc., 2000,77,1293-1301.
[88]Kinsella J.M. Functional properties of soy proteins. J. Am. Oil Chem. Soc.,1979, 56,242.
[89]周瑞宝,周兵.大豆7 S和11 S球蛋白的结构和功能性质.中国粮油学报,1998,13,39-42.
[90]Lee K.H., Ryu H.S., Rhee K.C. Protein solubility characteristics of commercial soy protein products. J. Am. Oil Chem. Soc.,2003,80,85-90.
[91]Chen Y., Zhang L. Gu J., Liu J. Physical properties of microporous membranes prepared by hydrolyzing cellulose/soy protein blends. J. Membr. Sci.,2004,241, 393-402.
[92]Zhou Z., Zheng H., Wei M., Huang J., Chen Y. Structure and mechanical properties of cellulose derivatives/soy protein isolate blends. J. Appl. Polym. Sci.,2008,107,3267-3274.
[93]Vaz C.M., van Doeveren P.F.N.M., Reis R.L., Cunha A.M. Soy matrix drug delivery systems obtained by melt-processing techniques. Biomacromolecules, 2003,4,1520-1529.
[94]Xu W., Yang Y. Drug sorption onto and release from soy protein fibers. J. Mater. Sci. Mater. Med.,2009,20,2477-2486.
[95]Caillard R., Mateescu M.A., Subirade M. Maillard-type cross-linked soy protein hydrogels as devices for the release of ionic compounds:an in vitro study. Food Res. Int.,2010,43,2349-2355.
[96]Maltais A., Remondetto G.E., Subirade M. Soy protein cold-set hydrogels as controlled delivery devices for nutraceutical compounds. Food Hydrocolloid., 2009,23,1647-1653.
[97]Curt S., Subirade M., Rouabhia M. Production and in vitro evaluation of soy protein-based biofilms as a support for human keratinocyte and fibroblast culture. Tissue Eng. Part A,2009,15,1223-1232.
[98]Silva S.S., Oliveira J.M., Mano J.F., Reis R.L. Physicochemical characterization of novel chitosan-soy protein/TEOS porous hybrids for tissue engineering applications. Adv. Mater. Forum III,2006,1000-1004.
[99]刘世清,李皓桓,彭昊,徐怡.新型纤维素导管桥接周围神经缺损的研究.中华实验外科杂志,2005,22,593-595.
[100]Su Y., Simmen F.A., Xiao R., Simmen R.C.M. Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in die tary protection from mammary tumors. Physiol. Genomics,2007,30,8-16.
[101]Eason R.R., Till S.R., Velarde M.C., Geng Y., Gu L., Jr L.C., Badger T.M., Simmen F.A., Simmen R.C.M. Uterine phenotype of young adult rats exposed to dietary soy or genistein during development. J. Nutr. Biochem.,2005,16, 625-632.
[102]Demonty I., Lamarche B., Deshaies Y, Jacques H. Role of soy isoflavones in the hypotriglyceridemic effect of soy protein in the rat. J. Nutr. Biochem., 2002,13,671-677.
[103]Shukla A., Brandsch C., Bettzieche A., Hirche F., Stangl G.I., Eder K. Isoflavone-poor soy protein alters the lipid metabolism of rats by SREBP-mediated down-regulation of hepatic genes. J. Nutr. Biochem.,2007,18, 313-321.
[104]Yonezawa K., Nakagama H., Tajima R., Ushigome M., Ogra Y., Suzuki K.T., Yoshikawa K., Nagao M. Efects of soy protein isolate on LEC rats, a model of wilson disease:mechanisms underlying enhancement of liver cell damage. Biochem. Biophys. Res. Commun.,2003,302,271-274.
[105]Tsai P.J., Huang P.C. Effects of isoflavones containing soy protein isolate compared with fish protein on serum lipids and susceptibility of low density lipoprotein and liver lipids to in vitro oxidation in hamsters. J. Nutr. Biochem., 1999,10,631-637.
[106]Escobedo R.M., Robles-Ramirez M.C., Gallegos E. R., Aleman R.R. Effect of protein hydrolysates from germinated soybean on cancerous cells of the human cervix:an in vitro study. Plant Foods Hum. Nutr.,2009,64,271-278.
[107]Nagasawa A., Fukui K., Kojima M., Kishida K., Maeda N., Nagaretani H., Hibuse T., Nishizawa H., Kihara S., Waki M., Takamatsu K., Funahashi T., Matsuzawa Y. Divergent efects of soy protein diet on the expression of adipocytokines. Biochem. Biophys. Res. Commun.,2003,311,909-914.
[108]Power K.A., Chen J.M., Saarinen N.M., Thompson L.U. Changes in biomarkers of estrogen receptor and growth factor signaling pathways in MCF-7 tumors after short- and long-term treatment with soy and flaxseed. J. Steroid Biochem. Mol. Biol.,2008,112,13-19.
[109]Mukhopadhyay S., Ballard B.R., Mukherjee S., Kabir S.M., Das S.K. Beneficial effects of soy protein in the initiation and progression against dimethylbenz [a] anthracene-induced breast tumors in female rats. Mol. Cell. Biochem.,2006,290,169-176.
[110]Radcliffe J.D., Narins D.M.C. A comparison of the effectiveness of soy protein isolate and fish oil for reducing the severity of retinoid-induced hypertriglyceridemia. J. Nutr. Biochem.,2004,15,163-168.
[111]Huntley A.L., Ernst E. Soy for the tyeatment of perimenopausal symptoms-a systematic review. Maturitas,2004,47,1-9.
[112]Jia D.Y., Fang Y., Yao K. Water vapor barrier and mechanical properties of konjac glucomannan-chitosan-soy protein isolate edible films. Food Bioprod. Process.,2009,87,7-10.
[113]Silva S.S., Goodfellow B.J., Benesch J., Rocha J., Mano J.F., Reis R.L. Morphology and miscibility of chitosan/soy protein blended membranes. Carbohyd. Polym.,2007,70,25-31.
[114]Silva S.S., Santos M.I., Coutinho O.P., Mano J.F., Reis R.L. Physical properties and biocompatibility of chitosan/soy blended membranes. J. Mater. Sci.:Mater Med.,2005,16,575-579.