Catheter‐associated urinary tract infections (CAUTIs) are one of the most commonly occurring hospital‐acquired infections. Current coating strategies to prevent catheter‐associated biofilm formation are limited by their poor long‐term efficiency and limited applicability to diverse materials. Here, the authors report a highly effective non‐fouling coating with long‐term biofilm prevention activity and is applicable to diverse catheters. The thin coating is lubricous, stable, highly uniform, and shows broad spectrum prevention of biofilm formation of nine different bacterial strains and prevents the migration of bacteria on catheter surface. The coating method is adapted to human‐sized catheters (both intraluminal and extraluminal) and demonstrates long‐term biofilm prevention activity over 30 days in challenging conditions. The coated catheters are tested in a mouse CAUTI model and demonstrate high efficiency in preventing bacterial colonization of both Gram‐positive and Gram‐negative bacteria. Furthermore, the coated human‐sized Foley catheters are evaluated in a porcine CAUTI model and show consistent efficiency in reducing biofilm formation by Escherichia coli (E. coli) over 95%. The simplicity of the coating method, the ability to apply this coating on diverse materials, and the high efficiency in preventing bacterial adhesion increase the potential of this method for the development of next generation infection resistant medical devices.
Bacterial adhesion and the succeeding biofilm formation onto surfaces are responsible for implant-and deviceassociated infections. Bifunctional coatings integrating both nonfouling components and antimicrobial peptides (AMPs) are a promising approach to develop potent antibiofilm coatings. However, the current approaches and chemistry for such coatings are time-consuming and dependent on substrates and involve a multistep process. Also, the information is limited on the influence of the coating structure or its components on the antibiofilm activity of such AMP-based coatings. Here, we report a new strategy to rapidly assemble a stable, potent, and substrate-independent AMP-based antibiofilm coating in a nonfouling background. The coating structure allowed for the screening of AMPs in a relevant nonfouling background to identify optimal peptide combinations that work in cooperation to generate potent antibiofilm activity. The structure of the coating was changed by altering the organization of the hydrophilic polymer chains within the coatings. The coatings were thoroughly characterized using various surface analytical techniques and correlated with the efficiency to prevent biofilm formation against diverse bacteria. The coating method that allowed the conjugation of AMPs without altering the steric protection ability of hydrophilic polymer structure results in a bifunctional surface coating with excellent antibiofilm activity. In contrast, the conjugation of AMPs directly to the hydrophilic polymer chains resulted in a surface with poor antibiofilm activity and increased adhesion of bacteria. Using this coating approach, we further established a new screening method and identified a set of potent surface-tethered AMPs with high activity. The success of this new peptide screening and coating method is demonstrated using a clinically relevant mouse infection model to prevent catheterassociated urinary tract infection (CAUTI).
The long-term prevention
of biofilm formation on the surface of
indwelling medical devices remains a challenge. Silver has been reutilized
in recent years for combating biofilm formation due to its indisputable
bactericidal potency; however, the toxicity, low stability, and short-term
activity of the current silver coatings have limited their use. Here,
we report the development of silver-based film-forming antibacterial
engineered (SAFE) assemblies for the generation of durable lubricous
antibiofilm surface long-term activity without silver toxicity that
was applicable to diverse materials via a highly scalable dip/spray/solution-skinning
process. The SAFE coating was obtained through a large-scale screening,
resulting in effective incorporation of silver nanoparticles (∼10
nm) into a stable nonsticky coating with high surface hierarchy and
coverage, which guaranteed sustained silver release. The lead coating
showed zero bacterial adhesion over a 1 month experiment in the presence
of a high load of diverse bacteria, including difficult-to-kill and
stone-forming strains. The SAFE coating showed high biocompatibility
and excellent antibiofilm activity in vivo.
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