3D-Bioprinted Urinary Catheters Enable Sustained Probiotic Recovery Under Flow and Improve Bladder Colonization In Vivo.

Abstract

Catheter-associated urinary tract infections (CAUTIs) account for a large proportion of healthcare-associated infections. CAUTIs, caused by colonization of the catheter surface by uropathogens, are challenging to treat, especially when compounded by antibiotic resistance. One prophylactic strategy that could reduce pathogen colonization is bacterial interference, whereby the catheter surface is coated with non-pathogenic bacteria. Current challenges include identifying appropriate bacterial interference strains that maintain stable association with the catheter and are viable, but not pathogenic, in the urinary tract environment. This study evaluated the stability of probiotic Lactobacillus rhamnosus in 3D bioprints mimicking urinary catheter tubing under urine flow and assessed viability and safety in an in vivo mouse model. Bioprints underwent hydraulic flow testing in vitro with artificial urine media (AUM), followed by evaluation of catheter structure, L. rhamnosus recovery, and biofilm formation. Mice were inoculated with free L. rhamnosus bacteria or implanted with L. rhamnosus-containing bioprints to measure urinary tract colonization and assess effects on the bladder tissue. Bioprinted segments exhibited minimal mass change while maintaining an intact shape and demonstrated viable L. rhamnosus recovery throughout 7 days. L. rhamnosus formed biofilms on the bioprint surface that were not disrupted by urinary flow conditions. Encouragingly, L. rhamnosus viability was maintained in bioprints in a mouse urinary tract catheterization model. Bioprints released L. rhamnosus in vivo and did not cause histological inflammation beyond that generated by standard silicone catheters. In summary, L. rhamnosus bioprints exhibited key desirable characteristics, including maintenance of probiotic viability, probiotic growth on the catheter surface, and enhanced probiotic colonization of the bladder. This study supports the development of bioprinted probiotic catheters as a new strategy to prevent CAUTI.