The development of a novel universal coating for urological implants

Abstract

Urology employs various implants, such as urinary catheters, ureteral stents, and ureteral access sheaths (UASs), to manage diseases associated with the urinary tract system. These implants serve different purposes. For example, urinary catheters are primarily used to drain urine from the bladder, ureteral stents are used to keep the ureteral cavity open for urine passage, and UASs are used in expanding the ureteral cavity to facilitate the introduction of other devices. However, these implants pose challenges due to their invasive nature and inadequate biocompatibility, which can lead to uroepithelial tissue damage (caused by friction) and an increase in the risk of urinary tract infections (UTIs). Urinary tract infections, in turn, can cause blockages that limit the effectiveness of these implants. Therefore, several strategies are currently employed to address these challenges, mainly the use of lubricious hydrophilic polymeric coatings and antimicrobial agents. While some success has been achieved, uroepithelial tissue damage and UTIs remain significant concerns. Furthermore, most of these strategies are tailored to specific urological fabricating materials, limiting their scope. In light of these challenges, this study developed a universal coating technology using polydopamine (PDA) as a versatile primer and polyvinyl pyrrolidone (PVP) as a hydrophilic polymeric top layer loaded with iodine (I2) as an antibacterial agent to improve properties of urological implants. Urological implant fabricating biopolymers including polyurethane (PU) and polydimethylsiloxane (PDMS) were modified with a PDA/PVP coating technology and loaded with various concentrations of I2 (0.1%, 0.5% and 1% w/v). The ability of the coating technology to reduce the friction coefficient of urological biomaterials was evaluated by assessing its ability to introduce lubricity. Other biological effects that characterize the biocompatibility and antimicrobial activity of the coated samples were assessed using relevant standard ISO (International Organization for Standardization) and EUCAST (European Committee on Antimicrobial Susceptibility Testing) In vitro methods. The biocompatibility of the coating technology was assessed by determining their cytotoxicity with the XTT cytotoxicity assay using L292 cells while the brine shrimp lethality assay (BSLA) was carried out as a preliminary animal model study. Their genotoxicity was assessed with the Ames mutachromo assay carried out with Salmonella typhimurium T100 to detect base shift mutation. The antimicrobial activity of the coated technology was determined using the IS0 22196 assay with Escherichia coli (ATCC 25922), the EUCAST disk diffusion and broth microdilution assays with E. coli (ATCC 25922), Proteus mirabilis and the urinary catheter bridge microbial migration assay with E. coli (ATCC 43888). The novel coating technology was adaptable to urological implant fabricating biomaterials with different surface polarities including PDMS and PU. The polydopamine/polyvinyl pyrrolidonecoated biomaterials were observed to have improved lubricity (slipperiness rate of 5 s per 10 mm biomaterial-agar interaction) and the ability to absorb and trap fluids (0.088 ± 0.009 mg/cm2). The concentration of iodine solution (0.1%, 0.5% and 1% w/v) loaded in the coatings significantly influenced their biocompatibility and antimicrobial efficacy. The biocompatibility observations made in the BSLA were mostly in line with the XTT cytotoxicity assay. When an iodine concentration of 0.1% and 0.5% w/v was incorporated, the PDA/PVP-coated biomaterials were not toxic towards L292 cells and not lethal towards brine shrimp larvae after a 24 h exposure period. However, potential lethality towards brine shrimp larvae was only observed in the biomaterial loaded with 0.5% w/v after an exposure period of 48 h. The coated biomaterials without iodine were not toxic while those that were loaded with a concentration of 1% w/v iodine were toxic according to both the XTT assay and BSLA. All the PDA/PVP-coated biomaterial loaded with iodine (0.1%, 0.5% and 1% w/v) did not demonstrate base shift mutations in Ames muta-chrome assay. The ISO 22196 method demonstrated that the PDA/PVP-coated biomaterials loaded with at least 0.1% (w/v) iodine reduced E. coli (ATCC 43888) by at least 2 growth logs. The minimum inhibitory concentration (MIC) for the PU-PDA/PVP (0.1% I2) surfaces was determined to be 40 mm2/ml for E. coli (ATCC 2592) 0.5 McFarland standard. The broth microdilution showed that the MIC of extracts of the PU-PDA/PVP (0.5% I2) to be 3 cm2/ml and of PU-PDA/PVP (1% I2) to be 1.5 cm2/ml for E. coli (25922). However, only the extract of PU-PDA/PVP (1% I2) was effective against P. mirabilis at 3 cm2/ml. In the disk diffusion assay, the PU-PDA/PVP (0.1% I2) was only effective against E. coli (ATCC 25922) with a 1 mm zone of inhibition. The PU-PDA/PVP (0.5% I2) was effective against both E. coli (ATCC 25922) and P. mirabilis with 12.13 ± 1.53 mm and 8.5 ± 0.5 mm zones of inhibition, respectively. PU-PDA/PVP (1% I2) showed the highest zone of inhibition (16.25 ± 1.77 mm) against E. coli (ATCC 25922) and 13 ± 1 mm against P. mirabilis. In the catheter bridge microbial migration assay, E. coli (ATCC 43888) growth across the bridge was observed after 24 h for PDMS and PDMS-PDA/PVP without iodine incorporation, after 48 h for PDMS-PDA/PVP (0.1% I2) and PDMS-PDA/PVP (0.5% I2), and after 72 h for PDMS-PDA/PVP (1% I2). In addition, there was a positive correlation (P<0.05) between the concentration of iodine loaded in the PDA/PVP coated biomaterials and antimicrobial activity (disk diffusion assay) while a negative correlation with biocompatibility (XTT cytotoxicity assay) was observed. Overall, the research demonstrated that a PDA/PVP-coating technology is adaptable for urological biomaterials including PU and PDMS, introduces lubricity on the surface of the biomaterials, and when it is loaded with 0.5% w/v I2, the coating can inhibit the growth of bacteria that cause UTI without causing toxicity in model eukaryotic cells. Therefore, the PDA/PVP (0.5% w/v I2) coating is a promising strategy for improving us.