<p>There are over 30 million Foley urinary catheters used annually, and the greatest problem with Foley catheters is catheter-associated urinary tract infections (CAUTIs). CAUTIs are the number one cause of hospital-acquired infections and make up to 40% of nosocomial infections. Biofilms on urinary catheters are critical to the progression of symptomatic CAUTIs, but are difficult to treat due to the protective effect of the biofilm matrix against antibiotics. The anti-fouling catheter technology proposed and demonstrated herein uses a mechanical, non-antibiotic approach to physically remove biofilms and thereby provide an appealing option for potentially stopping the progression of symptomatic infections. Additionally, because the anti-fouling technology is mechanical, it can circumvent the persistent failings of chemical and biological approaches that have failed to address catheter-associated urinary tract infections for the last 50+ years since Foley catheters were introduced. </p><p>We designed and optimized urinary catheter prototypes capable of on-demand removal of biofilms from the previously-inaccessible main drainage lumen of catheters. The concept uses pressure-actuated chambers in elastomer constructs to generate regio-selective strain and thereby remove biofilms. We first grew mature Proteus mirabilis crystalline biofilms on flat silicone elastomer substrates, and showed that application of strain to the substrate debonded the biofilm, and that increasing the strain rate increased biofilm detachment. A quantitative relationship between the applied strain rate and biofilm debonding was found through an analysis of the biofilm segment length and the calculated driving force for debonding. We then constructed proof-of-concept prototypes of sections of anti-fouling catheter shafts using silicone and 3D printed reverse molding in methods akin to those used for soft robotics. The proof-of-concept prototypes demonstrated release of mature P. mirabilis crystalline biofilms from their strained surfaces, and prompted our development of more advanced multi-lumen prototypes. The multi-lumen prototypes were designed and optimized using successive rounds of finite element modeling to adjust the number and postion of intra-wall inflation lumens. We then constructed prototypes based on the optimized design with clinically relevant dimensions and showed they were able to generate greater than 30% strain on the majority of the luminal surface, and along their full length. Those catheter prototypes were able to on-demand, and repeatedly, remove greater than 80% of a mixed community biofilm of P. mirabilis and E. coli. In summary, this study shows (1) strain in the elastomeric substrate actively debonds crystalline biofilms in vitro (2) modeling based on characterization of biofilm properties and understanding of substrate strain informs and facilitates prototype catheter design (3) urinary catheter prototypes utilizing inflation-induced substrate strain are capable of on-demand and repeatedly removing biofilms in vitro.</p> / Dissertation
| Identifer | oai:union.ndltd.org:DUKE/oai:dukespace.lib.duke.edu:10161/10473 |
| Date | 1 January 2015 |
| Creators | Levering, Vrad Wilson |
| Contributors | López, Gabriel P |
| Source Sets | Duke University |
| Detected Language | English |
| Type | Dissertation |
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