RESUMO
Catheter-associated urinary tract infections represent a major share of nosocomial infections, and are associated with longer periods of hospitalization and a huge financial burden. Currently, there are only a handful of commercial materials that reduce biofilm formation on urinary catheters, mostly relying on silver alloys. Therefore, we combined silver-phenolated lignin nanoparticles with poly(carboxybetaine) zwitterions to build a composite antibiotic-free coating with bactericidal and antifouling properties. Importantly, the versatile lignin chemistry enabled the formation of the coating in situ, enabling both the nanoparticle grafting and the radical polymerization by using only the oxidative activity of laccase. The resulting surface efficiently prevented nonspecific protein adsorption and reduced the bacterial viability on the catheter surface by more than 2 logs under hydrodynamic flow, without exhibiting any apparent signs of cytotoxicity. Moreover, the said functionality was maintained over a week both in vitro and in vivo, whereby the animal models showed excellent biocompatibility.
Assuntos
Lacase , Cateteres Urinários , Cateteres Urinários/microbiologia , Animais , Lacase/química , Prata/química , Prata/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Lignina/química , Camundongos , Humanos , Biofilmes/efeitos dos fármacos , Infecções Urinárias/prevenção & controle , Infecções Urinárias/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Nanopartículas/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
Catheter-associated urinary tract infections are the most common hospital-acquired infections and cause patient discomfort, increased morbidity, and prolonged stays, altogether posing a huge burden on healthcare services. Colonization occurs upon insertion, or later by ascending microbes from the rich periurethral flora, and is therefore virtually unavoidable by medical procedures. Importantly, the dwell time is a significant risk factor for bacteriuria because it gives biofilms time to develop and mature. This is why we engineer antibacterial and antibiofilm coating through ultrasound- and nanoparticle-assisted self-assembly on silicone surfaces and validate it thoroughly in vitro and in vivo. To this end, we combine bimetallic silver/gold nanoparticles, which exercise both biocidal and structural roles, with dopamine-modified gelatin in a facile and substrate-independent sonochemical coating process. The latter mussel-inspired bioadhesive potentiates the activity and durability of the coating while attenuating the intrinsic toxicity of silver. As a result, our approach effectively reduces biofilm formation in a hydrodynamic model of the human bladder and prevents bacteriuria in catheterized rabbits during a week of placement, outperforming conventional silicone catheters. These results substantiate the practical use of nanoparticle-biopolymer composites in combination with ultrasound for the antimicrobial functionalization of indwelling medical devices.