磷铵—聚氨酯纳米微球表面修饰聚氨酯血液相容性材料及其性能研究

发布时间：2018-05-19 08:13

本文选题：磷铵-聚氨酯纳米微球 + 表面改性　；参考：《南京师范大学》2012年硕士论文

【摘要】：作为植入或介入人体内的血液接触医用高分子材料,其必须具有良好的血液相容性、组织相容性和力学性能。其中,目前该类生物材料最为突出的问题是其进入人体会引起血栓形成等,这严重制约新型血液相容性生物材料开发的瓶颈。因而,具有良好血液相容性的生物高分子材料的研制已成为生物医学工程的前沿课题和关键所在。聚氨酯(PU)是一种含有氨基甲酸基团的高聚物,被广泛应用于工业生产以及日常生活中。聚氨酯具有相对较好的生物相容性、机械性能和一定的血液相容性,因而被作为重要的血液接触材料,应用于血管移植物、人工导管、人工心脏等方面。但是,同其他生物医用聚合物材料一样,聚氨酯在体内使用后也存在明显的诱导血栓形成等血液相容性的问题。因此,该类材料在应用于血液接触材料时,必须对其进行抗凝血改性,提高其血液相容性。如何提高聚氨酯基人工合成心、血管替代材料的血液相容性是生物医用材料领域中一个非常重要但尚未圆满解决的关键问题。为了改善作为心、血管替代材料的聚氨酯材料的血液相容性,研究人员一直采用表面改性等方法对其进行改性。南京大学沈健课题组率先使用磷铵、羧胺、磺胺等两性离子对PU等聚合物材料进行表面改性,并取得了极其明显的抗凝血效果。本论文在本课题组研究的基础上,用共沉淀法将磷铵两性离子表面修饰聚氨酯纳米微球(PUI-NPs)对医用聚氨酯进行表面改性,并对其表面结构进行有效的表征,并对其血液相容性、细胞相容性及机械性能进行研究。通过扫描电子显微镜(SEM)观察可知,和未改性PU相比,改性的PU材料表面均匀分布了大量微小突起,且在PU表面分布较为均匀,说明共沉淀法已成功的将PUI-NPs纳米微球引入PU膜的表面。XPS测试,在PU/PU-NPs的表面可以观测到在133.6eV处有P2p峰。这进一步说明,PUI-NPs纳米微球已经成功接枝到PU的表面。ATR-FTIR的测试发现,改性的PU在3460cm-1处的吸收峰,这个吸收峰可认为是由PUI-NPs表面残留的N-H基团引起的,该结果也进一步证明了PUI-NPs已经被成功引入空白PU膜的表面。同时,静态接触角试验表明,改性过程能略微提高了PU表面的亲水性,说明PUI-NPs的表面改性改善了PU的亲水性。我们主要对材料的血液相容性进行了深入研究。溶血实验结果表明,经PUI-NPs纳米微球改性过PU的溶血率小于5%,试验结果符合国际标准。复钙化凝血时间实验表明,相较于未改性的PU,材料的复钙时间有明显的延长,说明聚氨酯纳米复合材料血液相容性得到提高。血小板粘附实验结果证明,经磷铵两性离子表面修饰聚氨酯纳米微球改性过的聚氨酯材料的抗血小板粘附能力有了较大的提高。同时,动态凝血试验结果表明,改性材料抗凝血性能稍微比原材料提高一些。细胞毒性实验结果表明,相比较于未改性PU的毒性,改性过的PU在与活细胞作用24h和72h后,显示出更低的细胞毒性,完全符合生物材料的医用标准。同时,内皮细胞生长实验表明,内皮细胞能更好的在改性过的PU表面粘附生长,且不发生组织增生等问题。之后,我们还对复合材料机械性能进行了研究。力学性能拉伸实验和SEM观测断裂面结果证明,经共沉淀法改性后的聚氨酯,在提高PU膜抗凝血性能的同时,并不会对PU膜的机械性能产生不利影响,其机械仍可得以保持。同时,流变测试结果表明,PUI-NPs纳米微球与PU之间可以同时形成共价键和氢键相互作用,且可以进一步形成一定的交联,且交联结构在各个温度下均能稳定存在。因此证明共沉淀法制备的PU/PUI-NPs复合材料PUI-NPs纳米微球与PU之间的界面作用较强,且在不同温度下均可稳定存在。在上述工作的基础上,我们制备出了一种新型的具有优良抗凝血性功能和良好力学性能的聚氨酯／纳米复合材料,期望能在生物医学工程方面得到广泛的应用。
[Abstract]:As a medical polymer implanted or intervened in the human body, it must have good blood compatibility, histocompatibility and mechanical properties. Among them, the most prominent problem of this kind of biomaterial is that its entry into the human body will cause thrombosis and so on, which seriously restricts the development of new blood compatible biomaterials. Therefore, the development of biopolymer with good blood compatibility has become a frontier topic and key point in biomedical engineering.
Polyurethane (PU) is a kind of polymer containing carbamate group, which is widely used in industrial production and daily life. Polyurethane has relatively good biocompatibility, mechanical properties and certain blood compatibility. Therefore, it is used as an important blood contact material and should be used in vascular graft, artificial catheter, artificial heart and so on. However, as with other biomedical polymer materials, after the use of polyurethane in the body, there is a significant problem of inducing blood compatibility, such as thrombus formation. Therefore, this kind of material must be used in blood contact material, it must be modified to improve its blood compatibility.
How to improve the blood compatibility of the polyurethane based synthetic heart and the blood vessel substitute material is a very important problem in the biomedical materials field. In order to improve the blood compatibility of the polyurethane material as the heart and the replacement material of the blood vessel, the researchers have been using the surface modification methods to modify it. The Shen Jian team of Nanjing University took the lead in the surface modification of PU and other polymer materials such as ammonium phosphate, carboxyamine, sulfonamides and other amphoteric ions, and achieved very obvious anticoagulant effect.
On the basis of this research group, the surface modified polyurethane nano microspheres (PUI-NPs) were modified by coprecipitation method, and the surface structure of the polyurethane was characterized effectively, and the blood compatibility, cell compatibility and mechanical properties were studied.
Through the scanning electron microscope (SEM) observation, it is found that the surface of the modified PU material is evenly distributed in a large number of small protrusions compared with the unmodified PU, and the distribution of the PU surface is more uniform. It shows that the co precipitation method has successfully introduced the PUI-NPs nanospheres into the.XPS test of the PU film, and the P2p peak can be observed at 133.6eV at the surface of PU/PU-NPs. This further illustrates that the PUI-NPs nanospheres have been successfully grafted on the surface of the surface of the PU and found that the absorption peak of the modified PU at 3460cm-1 is considered to be caused by the N-H group remaining on the PUI-NPs surface, which further proves that PUI-NPs has been successfully introduced to the surface of the blank PU membrane. At the same time, the static connection is still connected. The results showed that the hydrophilicity of PU surface was slightly increased by the modification process, indicating that the surface modification of PUI-NPs improved the hydrophilicity of PU.
The blood compatibility of the material was studied in depth. The results of hemolysis test showed that the hemolysis rate of PUI-NPs nanospheres modified by PU was less than 5%, and the experimental results accorded with the international standard. The blood compatibility of the material was improved. The platelet adhesion test results showed that the anti platelet adhesion ability of the polyurethane modified by the amphoteric surface modified polyurethane nanospheres was greatly improved. Meanwhile, the dynamic coagulation test showed that the anticoagulant properties of the modified materials were slightly higher than those of the raw materials.
The cytotoxicity test showed that compared with the toxicity of unmodified PU, the modified PU showed lower cytotoxicity and fully conformed to the medical standards of biomaterials after the action of 24h and 72h with living cells. Meanwhile, endothelial cell growth experiments showed that endothelial cells could be better adhered to the modified PU surface and did not occur in tissue. Hyperplasia and other problems.
After that, the mechanical properties of the composites were also studied. The tensile test of mechanical properties and the results of the SEM observation fracture surface showed that the polyurethane modified by coprecipitation could not have a negative effect on the mechanical properties of the PU film while improving the anticoagulant properties of the PU film, and the mechanical properties of the polyurethane could still be maintained. It is shown that the interaction between covalent and hydrogen bonds between PUI-NPs nanospheres and PU can be formed at the same time, and a certain cross-linking can be formed, and the cross-linking structure can be stable at various temperatures. Therefore, it is proved that the interface between PUI-NPs nanospheres of PU/PUI-NPs composite prepared by co precipitation method is stronger and is different from that of PU. It can be stable at temperature.
On the basis of the above work, a new type of polyurethane / nano composite with excellent anticoagulant function and good mechanical properties is prepared. It is expected to be widely used in biomedical engineering.
【学位授予单位】：南京师范大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R318.08

【参考文献】