Kyser Anthony J, Greiner Arielle, Harris Victoria, Patel Rudra, Frieboes Hermann B, Gilbert Nicole M
Department of Bioengineering, University of Louisville Speed School of Engineering, Louisville, KY, 40292, USA.
Center for Predictive Medicine, University of Louisville, Louisville, KY, 40292, USA.
Probiotics Antimicrob Proteins. 2025 Jan 6. doi: 10.1007/s12602-024-10428-8.
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.
导尿管相关尿路感染（CAUTIs）在医疗保健相关感染中占很大比例。CAUTIs由尿路病原体在导尿管表面定植引起，治疗具有挑战性，尤其是当合并抗生素耐药性时。一种可以减少病原体定植的预防策略是细菌干扰，即导尿管表面涂覆非致病性细菌。当前的挑战包括识别与导尿管保持稳定关联且在尿路环境中存活但无致病性的合适细菌干扰菌株。本研究评估了益生菌鼠李糖乳杆菌在模拟尿液流动下的导尿管管材的3D生物打印物中的稳定性，并在体内小鼠模型中评估了其活力和安全性。生物打印物在体外用人造尿液培养基（AUM）进行水力流动测试，随后评估导管结构、鼠李糖乳杆菌回收率和生物膜形成。给小鼠接种游离的鼠李糖乳杆菌细菌或植入含鼠李糖乳杆菌的生物打印物，以测量尿路定植情况并评估对膀胱组织的影响。生物打印段在保持完整形状的同时质量变化最小，并在7天内均显示出可存活的鼠李糖乳杆菌回收率。鼠李糖乳杆菌在生物打印表面形成生物膜，且不受尿液流动条件的破坏。令人鼓舞的是，在小鼠尿路插管模型中，生物打印物中的鼠李糖乳杆菌活力得以维持。生物打印物在体内释放鼠李糖乳杆菌，且不会引起超过标准硅胶导管所产生的组织学炎症。总之，鼠李糖乳杆菌生物打印物表现出关键的理想特性，包括维持益生菌活力、在导管表面生长益生菌以及增强膀胱中的益生菌定植。本研究支持开发生物打印益生菌导管作为预防CAUTI的新策略。
