SBIR-STTR Award

Novel Polymer Coatings to Prevent Biofilms on Urinary Stents and Catheters Nearly all patients with indwelling urinary stents or catheters experience bacterial infections and problems with encrustation. For stents, these problems are so common and so severe that stents are replaced at least every six months. Considering that about 100 million urethral catheters and urinary stents are placed in patients each year, millions of device-associated infections occur annually. Biofilms formed on the surface of these urinary devices are the source of most infections and encrustations, because pathogenic bacteria thrive within the protective environment biofilms create. Biofilm formation starts within minutes of implantation when soluble proteins and other macromolecules from the urine non-specifically adsorb to the device surface. These macromolecules provide an anchor for pathogenic bacteria, which then recruit other bacteria. Eventually a colony of multiple pathogenic bacteria, protected by a "slime layer" of secreted exopolymers, develops. Many attempts have been made to combat bacterial infection and biofilm formation on urological devices, and have met with varied success. The proposed Phase I research is a new approach to prevent biofilm formation on urinary stents and catheters which exploits key components of the adhesive proteins that marine mussels secrete to tether themselves to underwater surfaces. This long-lasting, cost-effective approach is non-leaching (i.e. does not release any biocides or antibiotics), biocompatible, simple to process, and easy to apply to urinary device surfaces. The primary objectives of this research are to establish the feasibility of (1) chemically synthesizing new antifouling polymers that are durable and long-lasting, (2) modifying the surfaces of urinary devices, and (3) preventing biofilm formation under static and dynamic conditions. In this Phase I study, we will establish the proof of principle that the polymers described above will adsorb to and then inhibit bacterial attachment and encrustation on the types of materials used to manufacture urinary devices. Project Narrative Novel Polymer Coatings to Prevent Biofilms on Urinary Stents and Catheters Urinary catheters and stents can be life-saving medical devices, but bacterial biofilm growth on the device can cause dangerous infections. Current methods to prevent biofilms are expensive, often ineffective, and can promote antibiotic resistance. Our proposed coating technology will, without antibiotics or biocides, potentially block biofilm formation reliably and inexpensively.

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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.

Thesaurus Terms:
(--)-2amino-3-)3,4-Dihydroxyphenyl)Propanoic Acid;(--)-3-(3,4-Dihydroxyphenyl)-L-Alanine;3,4-Dihydroxyphenylalanine;3-Hydroxy-Dl-Tyrosine;3-Hydroxy-L-Tyrosine;Address;Adhesions;Adsorption;Ag Element;Amino Acids;Amla;Animal Model;Animal Models And Related Studies;Antibiotic Agents;Antibiotic Drugs;Antibiotics;Bacterial Adhesion;Bacterial Infections;Bacteriuria;Benzamide, N,N-Diethyl-3-Methyl-;Biomimetics;Care, Health;Catheters;Cell Attachment;Cell-Matrix Adhesions;Cell-Matrix Junction;Cells;Clinical;Complex;Coupled;Deta;Deet;Development;Devices;Dihydroxyphenylalanine;Dopa;Emblica Officinalis;Environment;Evaluation;Exhibits;Face;Feasibility Studies;Glues;Health Care Costs;Health Costs;Healthcare;Healthcare Costs;Hydrophobicity;Implant;In Vitro;Incubated;Infection;L-3,4-Dihydroxyphenylalanine;L-Dopa;Levodopa;Mammalian Cell;Marines;Materials Testing;Metals;Methods;Microbial Biofilms;Mimetics, Biological;Mirobalanus Embilica;Miscellaneous Antibiotic;Modification;Morbidity;Morbidity - Disease Rate;Mortality;Mortality Vital Statistics;Mussels;N,N-Diethyl-3-Methylbenzamide;N,N-Diethyl-M-Toluamide;N,N-Diethyltoluamide;Patients;Personal Satisfaction;Phase;Phyllanthus Emblica;Polymers;Process;Property;Property, Loinc Axis 2;Proteins;Qol;Quality Of Life;Research;Retrieval;Saline;Saline Solution;Sampling;Series;Silver;Stents;Surface;Technology;Testing;Treatment Period;Uti;Urethra;Urinary Tract Infection;Urinary Tract Infectious Disease;Urology;Adhesive Protein (Mussel);Aminoacid;Bacterial Disease;Beta-(3,4-Dihydroxyphenyl)-L-Alanine;Beta-Hydroxytyrosine;Biocompatibility;Biofilm;Biomaterial Compatibility;Biomedical Implant;Clinical Applicability;Clinical Application;Controlled Release;Cost;Design;Designing;Efficacy Testing;Experiment;Experimental Research;Experimental Study;Facial;Gene Product;Implant Device;Implantable Device;Implantation;Improved;In Vivo;Indwelling Device;Macromolecule;Metal Oxide;Microbial;Mimetics;Model Organism;Mussel Glue Protein;Novel;Phase 1 Study;Phase 2 Study;Polyphenolic Protein;Prevent;Preventing;Public Health Relevance;Research Study;Success;Surface Coating;Treatment Days;Treatment Duration;Urethral;Urinary;Well-Being