Influence of Surface Properties of New Biomaterials for Catheters on Bacterial Adhesion in Urine

导尿管相关性尿路感染（CAUTIs）和结痂对人类健康和卫生保健成本产生严重影响。迄今为止，只有几种类型的抗菌涂层导管已进入临床使用，包括硝基呋喃浸渍导管，银合金水凝胶涂层导管和聚四氟乙烯涂层导管。临床试验表明，这些包覆导管仅能显著减少CAUTIs或结皮的形成。众所周知，TiO2和Ag纳米粒子都具有杀菌性能。然而，直径小于200nm的银纳米粒子容易自发聚集，在空气、水或阳光下的稳定性不够好，不利于长期应用，从而降低了其抗菌性能。为了解决这些问题，一系列不同的无聚集的Ag-TiO2复合纳米颗粒被开发出来。研究表明，与Ag和TiO2纳米粒子相比，核壳纳米粒子Ag@TiO2 （Ag纳米粒子包覆一层薄薄的TiO2）和球形Ag/TiO2纳米粒子（TiO2纳米粒子包覆Ag纳米粒子）在光照和黑暗条件下均表现出协同杀菌活性，且作用期长。Ag@TiO2或Ag/TiO2纳米复合材料中的Ag纳米粒子能够激活TiO2的可见光激发，并能极大地提高细菌的光催化失活能力。在本提案中，两种不同类型的Ag@TiO2-PTFE涂层和Ag/TiO2-PTFE涂层导管将通过凝胶技术开发。这两种新型涂层结合了Ag@TiO2和Ag/TiO2纳米粒子的优异抗菌性能和聚四氟乙烯纳米粒子的不粘附性能。计算和测量所选细菌与尿中包被导管之间的相互作用，以找出包被的最佳表面条件。采用膀胱模型模拟人体膀胱的体内环境，并与现有的银水凝胶包覆导管、聚四氟乙烯包覆导管和未包覆硅胶包覆导管进行比较，评估包覆全长导尿管在尿液中的抗菌和抗结痂性能。涂布导管的细胞毒性测定也将进行。项目结束后，我们将与当地医院和一家导管制造商合作进行临床试验。

Catheter-associated urinary tract infection (CAUTIs) and encrustation have a severe impact on human health and health care costs. To date only a few types of antimicrobial coated catheters have come into clinical use, including a nitrofural-impregnated catheter, a silver alloy-hydrogel coated catheter, and a PTFE-coated catheter. Clinical trials show that these coated catheters give only an insignificant reduction in CAUTIs or encrustation formation. It is well known that both TiO2 and Ag nanoparticles exhibit bactericidal properties. However Ag nanoparticles with diameters less than 200 nm tend to aggregate spontaneously, and their stability in air, water or sunlight is not good enough for long-term application, which decreases their antibacterial performance. To solve these problems, a range of different Ag-TiO2 composite nanoparticles have been developed without aggregation. It has been demonstrated that both core-shell Ag@TiO2 nanoparticles (Ag nanoparticles coated with a thin shell of TiO2) and spherical Ag/TiO2 nanoparticles (TiO2 nanoparticles coated with Ag nanoparticles) exhibit synergistic bactericidal activities with long lasting action period in both light and dark conditions, compared with Ag and TiO2 nanoparticles. The Ag nanoparticles in Ag@TiO2 or Ag/TiO2 nanocomposites enable to active visible light excitation of TiO2, and can highly improve photocatalytic inactivation of bacteria. In this proposal two different types of Ag@TiO2-PTFE coated and Ag/TiO2-PTFE coated catheters will be developed by a so-gel technique. The two new types of coatings combine the excellent antibacterial properties of Ag@TiO2 and Ag/TiO2 nanoparticles and the non-stick properties of PTFE nanoparticles. The interactions between selected bacteria and the coated catheters in urine will be calculated and measured in order to find out optimum surface conditions of the coatings. The anti-bacterial and anti-encrustation performance of the coated full-length catheters in urine will be evaluated using bladder models that mimic in vivo environments of the human bladder for a catheter, and compared with existing silver-hydrogel coated catheter, PTFE coated catheter and uncoated silicone catheter. The cytotoxicity assays of the coated catheters will also be performed. After the project we will collaborate with local hospitals and a catheter manufacture to undertake clinical trials.