【作者】 李建新；

【导师】 王进；

【作者基本信息】 西南交通大学 ， 材料物理与化学， 2006， 硕士

【摘要】 近几十年来，合成高分子材料被广泛应用于包括心血管人工器官在内的植入材料。然而当高分子材料与血液接触时，在界面处会发生一系列复杂的相互作用，导致凝血反应和血栓的形成。同时以生物医用材料为中心的感染（Biomaterial Centered Infection，BCI）的发生，对植入者的生命带来致命的威胁。细菌粘附是引起这类感染的起始原因，如何抑制细菌在植入材料表面的粘附和生长是至关重要的。因此对高分子材料进行表面改性以提高材料的抗凝血性能和抗菌性能成为研究的热点。本文以涤纶（聚对苯二甲酸乙二醇酯，PET）和聚氯乙烯（PVC）两种常用的与血液接触高分子材料为研究对象，分别采用等离子体法和臭氧法预处理材料表面，再经过紫外光辐照辅助丙烯酸聚合，实现聚丙烯酸分子在PET表面的共价接枝；再进一步通过羧基和氨基的缩合作用，固定壳聚糖分子；再以壳聚糖分子为“桥梁”，共价固定肝素分子。X光电子能谱（XPS）测量结果表明这两种预处理方法均能有效引发丙烯酸在PET和PVC表面的接枝聚合，并共价固定壳聚糖和肝素。等离子体法预处理和臭氧预处理的PET表面共价固定的肝素量可以达到7.2μg／cm²和4.5μg／cm²。接触角测量结果表明改性后PET表面的亲水性较改性前均有显著提高。血小板粘附实验表明，PET和PVC表面共价固定肝素后其血小板粘附量显著减少，而且基本不变形。等离子体预处理表面共价固定肝素的PET和PVC，其部分凝血活酶时间（APTT）分别为60.5s和100s，比原血浆APTT分别增加23.1s和57.4s。臭氧预处理表面固定肝素分子的PET，其部分凝血活酶时间比原血浆延长15.8s；上述结果说明改性后材料对内源性凝血系统有一定的抑制作用。本文采用银视线离子注入、银等离子体浸没离子注入与沉积两种表面改性技术对涤纶材料进行表面改性。X射线衍射（XRD）和XPS的结果表明通过视线离子注入，银离子已经成功地注入到PET表面，而通过银等离子体浸没离子注入与沉积在PET表面制备了一层银沉积层。运用原子吸收光谱（AAS）来研究银改性后样品在水中银离子释放结果表明：相比于银等离子体浸没离子注入，视线离子注入的PET样品在相同时间点具有更高浓度的银离子释放。经银改性后的PET表面均能够明显抑制表皮葡萄球菌的粘附，当培养时间为24h时，SE对未经改性PET表面的粘附浓度是2.23×10⁷CFU／ml，而对视线离子注入改性后的PET、等离子体浸没离子注入与沉积改性的PET表面的粘附浓度分别是5.3×10⁶CFU／ml和1.12×10⁷CFU／ml。通过比较可以看出经两种工艺改性后的样品其表面对细菌的粘附具有抑制作用，且视线离子注入改性的样品其抑菌效果更好。这可能是视线离子注入改性后的样品表面银离子的释放浓度更大的原因。银改性后PET表面亲水性提高。通过计算表皮葡萄球菌对改性前后PET表面的粘附自由能△F_adh，细菌对未改性涤纶表面的粘附自由能为负，这表明细菌对涤纶表面的粘附是一个自发过程。而细菌对银改性PET表面的粘附自由均为正，说明SE对银改性后涤纶表面的粘附是一个热力学非自发过程。乳酸脱氢酶（LDH）评价证明经银视线离子注入和银等离子体浸没离子注入与沉积改性的PET表面对内皮细胞没有呈现出急性毒性；Alamar Blue评价表明银改性后PET较未改性的PET表面对内皮细胞的生长呈现出一定的抑制作用，其中银等离子体浸没离子注入与沉积改性的PET表面对内皮细胞粘附、增殖的抑制力更强。更多还原

【Abstract】 In recent years, synthetic polymers are widely used in biomedical materials for artificial organs including cardiovascular artificial organs. However, when the blood-contacting polymers contact with blood, complicated interaction will happen on the interface so as to form coagulating reaction and thrombus. The patient’s life is threatened by Biomaterial Centered Infection （BCI） and the bacteria adhesion is the first step of this infection, so inhibition of the bacteria adhesion and growth onto the surface of biomaterials is very important. Therefore, blood-contacting polymers need to be modified to improve their antithrombogenic and antibacterial properties, which have been focused in research.Polyethylene terephthalate （PET） and polyvinyl chloride （PVC） are chosen as the materials in our reseach. These materials are pre-treated by oxygen radio frequency plasma method or ozone method. Then polyacrylic acid molecules are grafted by ultraviolet （UV） irradiation. Furthermore, the chitosan molecules are immobilized through chitosans’ amino groups reacting with carboxyl group of polyacrylic acid. Finally, the immobilized chitosan can act as the bridge and react with the heparin molecules.According to the result of X-ray photoelectron spectroscopy （XPS）, polyacrylic acid, chitosan and heparin have been effectively grafted and immobilized by two modified methods on the PET and PVC surfaces. The concentration of the immobilized heparin is 7.2μg/cm² and 4.5μg/cm² respectively on the PET surface pre-treated by oxygen plasma and ozone. The results of static contact angle indicate the hydrophilicity of the modified PET surface is more remarkably improved than that of the unmodified PET surface. The results of platelet adhesion show that the numbers of adhered platelet decrease and platelets don’t aggregate and distort on the PET and PVC surfaces immoilized with heparin. The results of coagulant factor tests reveal that the activated partially thromboplastion time （APTT） of PET and PVC immobilized with heparin by oxygen plasma pre-treated method is 23.1s and 57.4s which is longer than that of the virgin plasma. The APTT of PET and PVC immobilized with the heparin by plasma pre-treated method is 60.5s and 100s respectively. While APTT of PET immobilized the heparin by ozone pre-treated method is 15.8s which is longer than that of virgin plasma. The change of APTT indicates that the modified PET and PVC films can suppress intrinsic coagulant system.Silver beam ion implantation （BII） and silver plasma immersion ion implantation-deposition （PIII-D） techniques have been used to treat PET in order to improve its antibacterial activity. The results of the X-Ray diffraction （ XRD ） and XPS analysis indicate that silver has been successfully implanted into the surface of PET modified by silver BII, and silver coating is deposited on the surface of PET modified by silver PIII-D. The atomic absorption spectrometry （AAS） analyzes the silver ions releasing under the water medium. The result indicates that the releasing concentration of silver ions of the PET modified by the silver BII is higher than that of the PET modified by silver PIII-D. The capacities of Staphylococcus epidermidis （SE） adhered on PET are suppressed by silver BII and PIII-D. The adhered concentration of SE surface is 2.23×10⁷CFU/ml on the control PET surface but that is 5.3×10⁶CFU/ml and 1.12×10⁷ CFU/ml on the PET surfaces modified by silver BII and PIII-D respectively with incubation time of 24h. The concentration of antibacterial silver ion is higher which may make less SE adhere to the PET surfacemodified by silver BUThe results of static contact angle show the hydrophilic property of the modified PET is improved. The free energy of adhesion (△F_Adh) predicts whethermicrobial adhesion is energetically favorable (△F_Adh<0) or not (△F_Adh>0). Thecalculated results show that bacterial adhesion is energetically unfavorable on the modified PET surface. The results of lactate dehydrogenase （LDH） show that the PET surface modified by silver BII and PIII-D do not have acute toxicity on the endothelium cell （EC）. Alamar Blue evaluation indicates that the modified PET surface can inhibit the growth and proliferation of EC, and especially the higher inhition on the adhesion and proliferation of EC on the PET surface modified by silver PIII-D can be observed.更多还原