Research Project
8248936
DESCRIPTION (provided by applicant): Novel Polymer Coatings to Prevent Biofilms on Urinary Stents and Catheters Bacterial infection and subsequent encrustation of urinary stents and catheters is a persistent problem in clinical urology and leads to significant patient morbidity and mortality. Most implanted stents become infected at some point, requiring retrieval and re-implantation if the initial treatment duration did not correct the underlying condition. Indeed, more than 90% of patients who have a long-term catheter develop bacteriuria within a month. Considering that about 100 million urethral catheters and urinary stents are inserted each year, millions of device-associated infections occur annually. Various surface modifications to urinary devices have been developed to prevent bacterial adhesion, such as silver-coated surfaces, control-release antibiotics, and surface modification to change hydrophobicity. These approaches have enjoyed varying degrees of success, but all suffer from numerous limitations. Clearly, development of a highly efficacious, long-lasting technology for preventing bacterial infections of urinary stents and catheters would dramatically benefit patients'well-being and quality of life and substantially reduce health care costs. A novel biomimetic strategy to produce surface coatings that repel cells and macromolecules has recently been developed. This strategy was inspired by the unique protein glues that marine mussels secrete for adhesion to various underwater substrates. In brief, antifouling polymers have been coupled to the amino acid L-3,4-dihydroxyphenylalanine (DOPA), a key component of so-called mussel adhesive proteins (MAPs). The resulting constructs have greatly reduced protein adsorption, mammalian cell attachment, and microbial attachment to metal and metal oxide surfaces. DOPA is believed to be responsible for anchoring the antifouling polymer to the substrates. In the research conducted in our Phase I feasibility study, we have demonstrated that DOPA-mimic polymers can be successfully synthesized and applied to urinary stent and catheter material surfaces and that the polymer-coated surfaces exhibited a significant reduction in bacterial adhesion compared to uncoated controls. This proposal outlines the synthesis, characterization, and evaluation of two polymers selected from the Phase I study. The two candidate coating polymers will be synthesized in a larger scale to provide sufficient material for the testing, and to determine manufacturability. Application conditions for the coatings will be adjusted to optimize their ability to reduce bacterial adhesion. Long-term, the in vitro efficacy of the candidate coatings will be determined by incubating coated samples with bacterial inoculums for extended periods. Additional experiments will be performed to determine the biocompatibility of these coatings and to test the efficacy of coated urinary stents and catheters in pilot animal models. PUBLIC HEALTH RELEVANCE: Bacterial contamination and encrustation of urinary stents and catheters is a persistent problem in urology, and often leads to urinary tract infection and retrieval and replacement of the implanted devices. Coatings that are designed to prevent bacterial adherent will largely prevent this problem, improving the quality of life for patients and reducing healthcare-related costs.
