Abstract

Microbial biofilm formation on indwelling medical devices causes persistent infections that cannot be cured with conventional antibiotics. To address this unmet challenge, we engineer tunable active surface topographies with micron-sized pillars that can beat at a programmable frequency and force level in an electromagnetic field. Compared to the flat and static controls, active topographies with the optimized design prevent biofilm formation and remove established biofilms of uropathogenic Escherichia coli (UPEC), Pseudomonas aeruginosa, and Staphylococcus aureus, with up to 3.7 logs of biomass reduction. In addition, the detached biofilm cells are found sensitized to bactericidal antibiotics to the level comparable to exponential-phase planktonic cells. Based on these findings, a prototype catheter is engineered and found to remain clean for at least 30 days under the flow of artificial urine medium, while the control catheters are blocked by UPEC biofilms within 5 days.

Highlights

  • Microbial biofilm formation on indwelling medical devices causes persistent infections that cannot be cured with conventional antibiotics

  • We evaluated the antibiotic susceptibility of biofilm cells detached during on-demand actuation of pillars; and compared it with that of cells remained on the surface, cells dispersed by bead beating, and those in intact biofilms

  • The results showed that the expression of these three genes increased over time in uropathogenic Escherichia coli (UPEC) biofilm cells detached by ondemand actuation (p < 0.0004, two-way ANOVA adjusted by Tukey test), but not in the cells that remained on the surface and detached by bead beating (p > 0.05, two-way ANOVA adjusted by Tukey test; Supplementary Fig. 12)

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Summary

Introduction

Microbial biofilm formation on indwelling medical devices causes persistent infections that cannot be cured with conventional antibiotics To address this unmet challenge, we engineer tunable active surface topographies with micron-sized pillars that can beat at a programmable frequency and force level in an electromagnetic field. Static topographies have limitations in long-term fouling control, because the small number of cells that attach can grow and gradually overcome the unfavorable topographies[29] Motivated by these challenges, we aim to develop strategies with sustained antifouling activities. Human motile cilia propel a superficial mucus layer that entraps foreign particles and pathogens to remove them out of the airway by beating in an underlying periciliary layer[30] Both the mucus and periciliary layers are essential for the antifouling effects of cilia[30], but missing in the application environments of most medical devices, e.g., urinary catheters

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