医用聚乙烯导管多功能表面涂层材料的研究

Poly (ethylene) (PE) based plastics are often used in the preparation of central venous catheters(CVCs) which has become indispensable in the treatment of patients undergoing chemotherapy or hemodialysis. PE, while having excellent mechanical properties, is quite hydrophobic, binds microbes, and has poor blood compatibility, resulting in bloodstream infection and rapid clot formation..In this proposal, a new trifunctional coating concept that can be applied to make CVC surfaces antimicrobial, antithrombogenic and hydrophilic at the same time will be presented. Silver ion will be firstly absorbed onto the catheter surface which is treated with sulphydryl functionality. Ethylenediamine hyaluronan and 2,6-diaminopyridinyl heparin will be then synthesised and as reducing and stabilization agents, reduce in situ silver ions into silver nanoparticles (AgNPs). The complexe coating of CVCs combine the well-known broad-spectrum antimicrobial features of silver with the anticoagulant activity of heparin and hydrophilic property of hyaluronan. The whole process is simple and environmentally benign..The studies will investigate the effect of the morphology, structure, content of the AgNPs on the antimicrobial activity, the content and proportion of the derivatized hyaluronan and derivatized heparin on the anticoagulant, hydrophilic activity. Hydrophilic, highly hydrated surfaces obtained by heparin and Hyaluronic acid coatings consist in effective low adhesion surfaces. The multiple mechanisms of Bacterial adhesion, Protein adsorption, and blood platelets adhesion on biomaterial surfaces through physico-chemical surface interactions will be.revealed.In addition, the synergistic effect between silver, heparin and hyaluronan on the antimicrobial activity will also be examined to better.understand the mechanism. .This work will open a new route to safer blood-contacting medical devices and make rational design of such coatings become possible. The mechanistic details can be helpful to explore potential new combinations of biopolymer-nanoparticle.combinations with multiple function.

医用聚乙烯导管已成为病人化疗或血液透析不可或缺的器械，但是聚乙烯疏水、易结合微生物和血液相容性差，作为中心静脉导管，会产生严重的血液感染和血栓栓塞。本项目提出一个三功能化的涂层思路，在导管表面化学键合吸附上银离子，将具有抗凝血功能的肝素衍生物和亲水功能的透明质酸衍生物，既作为还原剂又作为稳定剂，直接将银离子还原成银纳米粒子与二者的复合物，使导管同时具有抗菌、抗凝血和润滑功能，整个过程简单且“绿色”。探索银纳米粒子形貌、结构、含量和肝素透明质酸覆盖层厚度及配比与抗菌抗凝血亲水性能的关系；揭示细菌和血液蛋白及血小板在导管表面的粘附机制，揭示复合物中银纳米粒子与天然多糖的协同抗菌作用机制，为多功能生物医用表面涂层材料的设计制备及进一步深入研究提供依据。

项目研究的前期，首先按照原计划研究集抗菌抗凝血润滑三功能于一体的导管表面涂层的制备并对结构进行了表征，初步研究了材料的抗菌性能和亲水性。但后面阶段在抗凝血测试部分遇到了障碍。最后根据现有实验条件，改变研究计划，在壳聚糖多元复合骨修复材料、掺氮石墨烯量子点癌细胞诊断材料和纳米复合光催化材料三个方面有较大的进展和取得不错的成果。发表学术论文20篇，其中SCI收录17篇，EI收录会议论文1篇。还有一篇文章已经被Nanotechnology接收。培养硕士研究生8名。.通过对聚乙烯导管表面进行银纳米粒子、肝素和透明质酸的改性及调控，建立了集抗菌抗凝血润滑三功能于一体的导管表面涂层的绿色制备方法，修饰后的导管具有超强的广谱杀菌性能，亲水性能亦增加。为多功能生物医用表面涂层材料的设计制备及进一步深入研究提供了依据。.以自然骨的成分和微结构为依据，构造了三维多孔核壳结构的壳聚糖仿生骨修复纳米纤维支架，进行形貌表征、结构与组成分析以及细胞活性测试，探究制备条件与其生物相容性的关联。并有效引入活性离子氧化锌、锶磷灰石，进一步提高骨修复能力。为骨修复材料的设计提供了依据和方法。.制备了氮掺杂石墨烯量子点，并将其作为基底材料，与叶酸、透明质酸以及吲哚美辛等靶向基团相结合。对分子结构、微观结构以及光学性能等深入分析。作为荧光诊断材料与癌细胞培养后，验证该类结合物能够精准识别癌细胞。探究培育时间、氮掺杂含量、pH值等因素对荧光诊断的影响。为癌症荧光诊断材料的制备奠定了基础。.制备了各种结构和各种材料的具有优异的光催化或光催化制氢性能的有机-无机复合材料体系。研究材料的形貌，结构，以及提高光催化性能以及光催化制氢性能的方法，并阐明了性能提高的原理及机制。这些材料提供了新型光催化剂有效的设计方法，有望在能源和环境领域获得应用。