Antimicrobial-Loaded Polyacrylamide Hydrogels Supported on Titanium as Reservoir for Local Drug Delivery

Arthroplasty is a highly successful treatment to restore the function of a joint. The contamination of the implant via bacterial adhesion is the first step toward the development of device-associated infections. The emerging concern about antimicrobial resistance resulted in a growing interest to de...

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Main Authors: Irene E. Sille, Diego E. Pissinis, Natalia S. Fagali, Fiorela Ghilini, María Noel Urrutia, Patricia L. Schilardi
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Pathogens
Subjects:
Online Access:https://www.mdpi.com/2076-0817/12/2/202
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author Irene E. Sille
Diego E. Pissinis
Natalia S. Fagali
Fiorela Ghilini
María Noel Urrutia
Patricia L. Schilardi
author_facet Irene E. Sille
Diego E. Pissinis
Natalia S. Fagali
Fiorela Ghilini
María Noel Urrutia
Patricia L. Schilardi
author_sort Irene E. Sille
collection DOAJ
description Arthroplasty is a highly successful treatment to restore the function of a joint. The contamination of the implant via bacterial adhesion is the first step toward the development of device-associated infections. The emerging concern about antimicrobial resistance resulted in a growing interest to develop alternative therapeutic strategies. Thus, the increment in the incidence of bacterial periprosthetic infections, the complexity of treating infections caused by organisms growing in biofilms, together with the rise in antibiotic resistant bacteria, expose the need to design novel surfaces that provide innovative solutions to these rising problems. The aim of this work is to develop a coating on titanium (Ti) suitable for inhibiting bacterial adhesion and proliferation, and hence, biofilm formation on the surface. We have successfully prepared polyacrylamide hydrogels containing the conventional antibiotic ampicillin (AMP), silver nanoparticles (AgNPs), and both, AMP and AgNPs. The release of the antibacterial agents from the gelled to aqueous media resulted in an excellent antibacterial action of the loaded hydrogels against sessile <i>S. aureus</i>. Moreover, a synergic effect was achieved with the incorporation of both AMP and AgNPs in the hydrogel, which highlights the importance of combining antimicrobial agents having different targets. The polyacrylamide hydrogel coating on the Ti surface was successfully achieved, as it was demonstrated by FTIR, contact angle, and AFM measurements. The modified Ti surfaces having the polyacrylamide hydrogel film containing AgNPs and AMP retained the highest antibacterial effect against <i>S. aureus</i> as it was found for the unsupported hydrogels. The modified surfaces exhibit an excellent cytocompatibility, since healthy, flattened MC3T3-E1 cells spread on the surfaces were observed. In addition, similar macrophage RAW 264.7 adhesion was found on all the surfaces, which could be related to a low macrophage activation. Our results indicate that AMP and AgNP-loaded polyacrylamide hydrogel films on Ti are a good alternative for designing efficient antibacterial surfaces having an excellent cytocompatibility without inducing an exacerbated immune response. The approach emerges as a superior alternative to the widely used direct adsorption of therapeutic agents on surfaces, since the antimicrobial-loaded hydrogel coatings open the possibility of modulating the concentration of the antimicrobial agents to enhance bacterial killing, and then, reducing the risk of infections in implantable materials.
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spelling doaj.art-c7d0ed7de49d4f59be119f7d75bf3b542023-11-16T22:33:25ZengMDPI AGPathogens2076-08172023-01-0112220210.3390/pathogens12020202Antimicrobial-Loaded Polyacrylamide Hydrogels Supported on Titanium as Reservoir for Local Drug DeliveryIrene E. Sille0Diego E. Pissinis1Natalia S. Fagali2Fiorela Ghilini3María Noel Urrutia4Patricia L. Schilardi5Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), CONICET-Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4, La Plata 1900, ArgentinaInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), CONICET-Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4, La Plata 1900, ArgentinaInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), CONICET-Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4, La Plata 1900, ArgentinaInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), CONICET-Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4, La Plata 1900, ArgentinaInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), CONICET-Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4, La Plata 1900, ArgentinaInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), CONICET-Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4, La Plata 1900, ArgentinaArthroplasty is a highly successful treatment to restore the function of a joint. The contamination of the implant via bacterial adhesion is the first step toward the development of device-associated infections. The emerging concern about antimicrobial resistance resulted in a growing interest to develop alternative therapeutic strategies. Thus, the increment in the incidence of bacterial periprosthetic infections, the complexity of treating infections caused by organisms growing in biofilms, together with the rise in antibiotic resistant bacteria, expose the need to design novel surfaces that provide innovative solutions to these rising problems. The aim of this work is to develop a coating on titanium (Ti) suitable for inhibiting bacterial adhesion and proliferation, and hence, biofilm formation on the surface. We have successfully prepared polyacrylamide hydrogels containing the conventional antibiotic ampicillin (AMP), silver nanoparticles (AgNPs), and both, AMP and AgNPs. The release of the antibacterial agents from the gelled to aqueous media resulted in an excellent antibacterial action of the loaded hydrogels against sessile <i>S. aureus</i>. Moreover, a synergic effect was achieved with the incorporation of both AMP and AgNPs in the hydrogel, which highlights the importance of combining antimicrobial agents having different targets. The polyacrylamide hydrogel coating on the Ti surface was successfully achieved, as it was demonstrated by FTIR, contact angle, and AFM measurements. The modified Ti surfaces having the polyacrylamide hydrogel film containing AgNPs and AMP retained the highest antibacterial effect against <i>S. aureus</i> as it was found for the unsupported hydrogels. The modified surfaces exhibit an excellent cytocompatibility, since healthy, flattened MC3T3-E1 cells spread on the surfaces were observed. In addition, similar macrophage RAW 264.7 adhesion was found on all the surfaces, which could be related to a low macrophage activation. Our results indicate that AMP and AgNP-loaded polyacrylamide hydrogel films on Ti are a good alternative for designing efficient antibacterial surfaces having an excellent cytocompatibility without inducing an exacerbated immune response. The approach emerges as a superior alternative to the widely used direct adsorption of therapeutic agents on surfaces, since the antimicrobial-loaded hydrogel coatings open the possibility of modulating the concentration of the antimicrobial agents to enhance bacterial killing, and then, reducing the risk of infections in implantable materials.https://www.mdpi.com/2076-0817/12/2/202antibacterialsurface functionalizationhydrogelsilver nanoparticlesampicillin
spellingShingle Irene E. Sille
Diego E. Pissinis
Natalia S. Fagali
Fiorela Ghilini
María Noel Urrutia
Patricia L. Schilardi
Antimicrobial-Loaded Polyacrylamide Hydrogels Supported on Titanium as Reservoir for Local Drug Delivery
Pathogens
antibacterial
surface functionalization
hydrogel
silver nanoparticles
ampicillin
title Antimicrobial-Loaded Polyacrylamide Hydrogels Supported on Titanium as Reservoir for Local Drug Delivery
title_full Antimicrobial-Loaded Polyacrylamide Hydrogels Supported on Titanium as Reservoir for Local Drug Delivery
title_fullStr Antimicrobial-Loaded Polyacrylamide Hydrogels Supported on Titanium as Reservoir for Local Drug Delivery
title_full_unstemmed Antimicrobial-Loaded Polyacrylamide Hydrogels Supported on Titanium as Reservoir for Local Drug Delivery
title_short Antimicrobial-Loaded Polyacrylamide Hydrogels Supported on Titanium as Reservoir for Local Drug Delivery
title_sort antimicrobial loaded polyacrylamide hydrogels supported on titanium as reservoir for local drug delivery
topic antibacterial
surface functionalization
hydrogel
silver nanoparticles
ampicillin
url https://www.mdpi.com/2076-0817/12/2/202
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AT fiorelaghilini antimicrobialloadedpolyacrylamidehydrogelssupportedontitaniumasreservoirforlocaldrugdelivery
AT marianoelurrutia antimicrobialloadedpolyacrylamidehydrogelssupportedontitaniumasreservoirforlocaldrugdelivery
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