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

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.

The high incidence of infections caused by the use of implanted biomedical devices, including catheters, bone fracture fixation pins and heart valves etc. has a considerable impact on human health and health care costs. For example, catheter-associated urinary tract infections alone account for up to one third of all hospital-acquired infections and cost the UK NHS ~£100M per annum, and result in increased morbidity and mortality. Over 39 million urinary catheters are used each year in the EU and 400 million world-wide. The catheter market as a whole is currently growing by over 10% each year. To date only a few types of antimicrobial coated catheters have come into clinical use, including a nitrofural-impregnated silicone catheter, a silver alloy-hydrogel coated latex catheter, and a PTFE-coated latex catheter. Clinical trials have shown that the use of these coated catheters has resulted in an insignificant reduction in CAUTIs or encrustation formation.

Our new idea for preventing CAUTIs and encrustation is to develop Ag@TiO2-PTFE and Ag/TiO2-PTFE coatings for urinary catheters that combine the excellent antibacterial properties of Ag@TiO2 and Ag/TiO2 nanoparticles and the non-stick properties of PTFE nanoparticles using a cost-effective so-gel technique. We anticipate the generation of new IP from the proposed research. Clinical trials will be required after the project as further work to proved the effectiveness. The successful application of the new coatings to catheters and other medical devices would improve patient care and quality of life by significantly reducing the morbidity and mortality caused by infection and would also significantly reduce costs to the NHS incurred treating catheter-associated infections by reducing hospital stays and delay in rehabilitation.

In order to protect our new IP, ensuring that any discoveries can be developed and exploited so as to maximise future benefits both to healthcare and research, we shall hold IP and potential commercialization meetings every six months during the course of the project. All the investigators will attend the meetings. We will also invite the Head of Knowledge Transfer and/or the Research Business Development Manager from the Research and Innovation Services (RIS) at Dundee to attend the meetings. Three workshops will be run during the course of the project: months 3, 18, and 36, which open to relevant industries (e.g. catheter manufacturers, biomaterials and coating companies), interested researchers, clinicians and the public. Workshop 1 will identify with the beneficiaries/end users the major issues they have with CATUIs and encrustation; Workshop 2 will update the main stakeholders on the progress of the research and Workshop 3 will present the final results of the project to the key stakeholders.

The dissemination of the results from the project will have three main thrusts providing additional detail and information at each level:
i) The first will be the dissemination of information about the project and the achievements towards a larger lay public, ensuring the awareness of results and the use of EPSRC funding in this important research area.
ii) The second will be aimed at industrial end users who can benefit from the use of the results, including medical device manufactures and hospitals.
iii) The third will be towards the scientific community through specialised media such as selected scientific journals, magazines, conferences and web sites, etc. to ensure that all these potential impacts are realised. We plan to attend one international conference on Biomaterials per year and to submit/publish 6 journal papers.