# Optimizing CNT Loading in Antimicrobial Composites for Urinary Tract Application
## 1 Introduction  
Urinary tract devices (UTDs), namely urinary catheters and ureteral stents, are commonly used in the treatment and mitigation of urinary tract diseases, improving the patients' quality of life. However, the use of these devices is associated with serious complications, including the development of urinary tract infections (UTIs). UTIs account for 36 and 27% of the healthcare-associated infections reported in the United States and Europe, respectively [1; 2], resulting in increased mortality rates and hospital costs [2; 3; 4; 5; 6]. Among hospital-acquired UTIs, 75% of cases have emerged from the insertion of urinary catheters (catheter-associated urinary tract infections) [7; 8], and 31% from ureteral stents [9]. The insertion of these medical devices disturbs the local host defence mechanisms of patients, facilitating the access of microorganisms to the urinary tract and allowing their colonization [5]. Most UTDs are fabricated with silicone-based polymers such as poly(dimethylsiloxane) (PDMS) [10]. Despite its attractive properties, including the high mechanical and chemical stability and low toxicity, PDMS is extremely hydrophobic and, like the majority of the coating materials, is susceptible to bacteria and fungi adhesion [11; 12]. In fact, UTDs are very prone to microbial adhesion and, consequently, biofilm formation, which is the leading cause for most UTIs. Different microorganisms have been identified as colonizers of UTDs, including _Escherichia coli_, _Staphylococcus aureus_, _Pseudomonas aeruginosa_, _Proteus_ spp., _Klebsiella pneumoniae_, _Staphylococcus epidermidis_, _Enterococcus_ spp. and _Candida_ spp. [13; 14]. Following microbial adhesion and colonization on UTD surfaces, microorganisms form biofilms, which protect them from the host immune system as well as from the action of antimicrobial agents, contributing to the persistence and spread of infection [15; 16; 17]. To date, different alternative materials with antimicrobial and antib Biofilm properties have been developed to inhibit, or at least delay, biofilm formation. These strategies include the release of antimicrobial agents, contact-killing and anti-adhesive coatings, as well as surfaces that cause disruption of biofilm architecture by quorum sensing disturbance or matrix degradation [10]. However, although several preventive strategies having been proposed to reduce the incidence of UTIs, their application for coating UTDs is still questionable due to the resistance phenomena, low biocompatibility, and toxicity that derives from the use of some of these coatings [18]. In recent decades, carbon nanotubes (CNTs) have gained much attention in the industrial, environmental and biomedical fields. Described as sheets of graphene rolled up into cylinders (with several micrometres in length and nanometres in diameter), they can be classified as single- (SWCNTs) and multi-walled CNTs (MWCNTs), accordingly to the number of graphene layers [19; 20]. Because of their outstanding properties, such as electrical conductivity, high aspect ratio and mechanical strength, flexibility, high surface energy density, chemical stability, and the possibility of functionalization with a wide variety of moieties (antimicrobial drugs and other bioactive molecules), CNT-based surfaces have been widely applied in the medical field, and in particular for the manufacture of medical devices [18; 21]. Although there is still little consensus regarding the mechanisms behind the CNTs' antimicrobial activity, different influencing factors have been described, including CNT diameter and length, purity, electronic structure, CNT aggregation and surface functional groups, as well as CNT type (SWCNT or MWCNT) [22]. CNT activity is related not only to the mechanical damage (by the direct piercing of the microorganisms' outer membranes) and consequent cell disruption and release of intracellular content but also to the generation of oxidative stress [22].