Layer by layer (LbL) coating on urological devices to prevent biofilm formation

Abstract

Urological devices, such as indwelling catheters and stents, are widely used to maintain urinary drainage when this is impaired by obstructions. However, the important function of these devices is frequently compromised by the formation of encrustation, which can lead to complications such as blockages, urinary tract infections (UTIs), and retained devices that are difficult to remove. Encrustation occurs by precipitation of solid crystals from urine onto the surface of a device and is frequently promoted and mediated by urease-producing bacteria (such as Proteus mirabilis). The net result is the formation of crystalline biofilms, i.e., bacterial biofilms embedding crystalline structures, showing enhanced resistance against antibiotic treatment. Complications due to encrustation negatively impact on a patient’s quality of life and cause significant financial burden on healthcare providers. Various approaches have been investigated to address these challenges, including the development of new device geometries and the use of different types of materials and surface coatings. However, a comprehensive solution that prevents the formation of crystalline biofilms and avoids device failure remains elusive. The formation of crystalline biofilms is influenced by a range of conditions, including the urinary flow field and the chemical and micro-biological composition of urine, which may differ between patients and depend upon where the device is placed within the urinary tract. Devices that can be customized to resist crystalline biofilm formation for a set of specific environmental conditions, or that address multiple causative mechanisms governing the development of encrustation, are a potential solution to this ongoing challenge. Layer-by-layer (LbL) assembly is a technique for depositing multilayer coatings that is capable of nano-scale control over the layer’s composition and thickness. Individual layers are typically deposited from a solution or suspension onto a charged substrate via electrostatic attraction, leading to charge reversal of the coated surface, and enabling subsequent deposition of an oppositely charged moiety. A wide range of polyelectrolytes, other molecules, and particles can be deposited via LbL assembly, leading to multilayer coatings with many different potential combinations of materials, properties, and functions. LbL-assembled coatings with different surface chemistry, mechanical stiffness, and drug delivery capability have been reported with proven or potential infection-resistant functionality based on bactericidal or anti-adhesion effects. The high degree of control and flexibility that LbL assembly can achieve provides the opportunity to produce customized and multifunctional coatings for combatting crystalline biofilms and associated failures of urological devices. In this project, LbL assembly is used to produce multilayer coatings of Polyethyleneimine (PEI) and Polyacrylicacid (PAA) with different thickness and composition of the last deposited layer. The coatings were deposited onto Polydimethylsiloxane (PDMS) substrates, which is representative of materials commonly used for urinary catheters and stents. The coatings were characterized by microscopy for thickness and morphology, by nanoindentation for mechanical stiffness, and using bacterial cultures to assess microbiological properties. Results show that the proposed coatings can significantly prevent biofilm formation against common UTI bacteria P. aeruginosa, and the antimicrobial behaviour can improve by increasing the thickness of coating.

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ORCID for Andrew Hamilton: orcid.org/0000-0003-4627-849X

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