Surface modification of urinary catheters

Abstract

Catheters have been an indispensable tool in medical practice since ancient times, their use dating back to the sixth century BC by the Indian surgeon Sushruta [1]. Originally made using materials like gold, silver, iron, and wood, catheters have evolved into advanced designs over the centuries across the world. Benjamin Franklin’s 1752 invention of a silver catheter made of hinged segments of tubes may be considered the first flexible catheter in recorded history [Figure 1]. The modern balloon-based self-retaining catheter, introduced in 1933, marked a turning point in catheter design and development. Today, three main types of catheters are used: indwelling, external, and short-term catheters, which are available in various sizes, materials (including latex, silicone, Teflon, PVC, etc.), and types (straight or coude tip). The invasive nature of catheters comes with risks of microbial growth and incompatibility with the human system, leading to infection, inflammation and device rejection and the need to change them frequently especially in the elderly. Catheter-associated urinary infections (CAUTIs) pose a significant concern, contributing to increased mortality rates and substantial economic burdens. UTIs account for 20 to 40% of hospital-associated infections, with an estimated 80% linked to urinary catheters [3]. There has been increasing interest in developing surface modification techniques to afford microbicidal properties and biocompatibility to catheter surfaces, as seen in the increasing number of publications in the area [Figure 2]. These surface modification methods involve the use of coatings or physical microand nano-dimensional surface modifications [4]. Coatings can be classified based on their mechanism of action: passive strategies include antifouling surfaces, while active approaches involve antimicrobial coatings that disrupt biological pathways. Antifouling coatings, especially hydrogels [5], poly (tetrafluoroethylene) [6], polyzwitterions [7], and poly (ethylene glycol) [8] are being explored. These coatings are often loaded with antimicrobial agents such as antibiotics, biocidal enzymes, and bacteriophages [9]. The agents prevent CAUTIs through mechanisms such as the slow release of microbicidal chemicals, modifying catheter surfaces to prevent microbial adherence, and disrupting biofilms that allow pathogen colonization. For example, researchers developed a poly(sulfobetaine methacrylate)-tannic acid hydrogel coating loaded with antimicrobials (poly(vinylpyrrolidone)-iodine, copper ions, and nitrofurazone) through non-covalent interactions. The coating exhibited pH-responsive release of the antibacterial agents under alkaline conditions, offering improved antibacterial activity against urease-producing bacteria [10]. Urinary catheters have been coated with thin layers of silver in the form of silver oxide or silver alloy, as well as noble metal alloys (gold, silver, and palladium), to reduce bacterial adherence to their surfaces [Figure 3]. Polymeric coatings have been loaded with these noble metal species as well [11]. Diamond-like coatings (DLC) are biocompatible and offer advantageous properties like low friction, smoothness, and abrasion resistance, making them ideal for medical devices. In a recent study, DLC was deposited into 2 mm inner diameter silicon catheter tubes. Bacterial adhesion and biofilm formation were evaluated using clinical isolates. Results showed reduced adherence and biofilm formation on the DLC-coated samples compared to uncoated ones, indicating their potential for medical applications [13]. Antibiotics such as nitrofurazoneon [14] and minocycline–rifampicin [15] have been immobilized on catheter surfaces. Two approaches have been used for the immobilization. In the first approach, a layer of antibiotic is applied to cover the surface, leading to rapid drug elution. Alternatively, the antibiotic can be directly impregnated into the device polymer during production, either with or without excipients to control the drug release rate. A successful two-step polydopamine-based surface modification strategy has been reported to coimmobilize an antimicrobial peptide (Palm) and an enzyme targeting a crucial component of biofilm matrix (DNase I) on polydimethylsiloxane surfaces. This approach provided the surfaces with both antiadhesive and antimicrobial properties against relevant bacteria, both in single and dual-species scenarios. The modified surfaces demonstrated excellent stability, biocompatibility, and anti-biofilm capabilities. [16] More recently, catheter surfaces were modified with Lactobacilli probiotics using a ‘bacterial interference’