Nano bio-responsive systems designed to avoid staphylococcal colonization of implant interfaces

Descripción del proyecto

Implantes articulares avanzados con propiedades antimicrobianas únicas

La artroplastia de cadera y rodilla constituyen intervenciones quirúrgicas frecuentes en cirugía ortopédica para restaurar la función de una articulación lesionada o enferma. Estos procedimientos dependen sobremanera de las prótesis de reemplazo que, sin embargo, pueden acumular bacterias, lo que puede producir una infección articular periprotésica. Para abordar este grave problema médico, el equipo del proyecto NanoBioRS, financiado con fondos europeos, se propone desarrollar un material de recubrimiento molecular inteligente que combine factores de crecimiento tisular con antibióticos. Además, contendrá enzimas que previenen la formación de biopelículas en las prótesis articulares, así como la propagación de la resistencia a los antimicrobianos. La innovación de NanoBioRS podría emplearse para recubrir distintos materiales implantables, lo que permitiría abordar la amenaza sanitaria que suponen los estafilococos resistentes a antibióticos.

Objetivo

Antimicrobial resistance (AMR) is responsible for 25,000 deaths per year in the EU and costs EUR 1.5 billion annually. Methicillin-sensitive Staphylococcus aureus (MSSA), Methicillin-resistant S. aureus (MRSA) and S. epidermidis remain a serious problem in the treatment of periprosthetic joint infection (PJI).
After surgery, bacteria may attach to the surface of prosthetic joints to form biofilms. The fate of an available surface can be conceptualized as a race between tissue cell integration and bacterial adhesion to that same surface. If the race is won by tissue, then the surface is occupied and defended and is thus less available for bacterial colonization.
The integration of the synthetic routes for smart molecular coatings doped with anti-staphylococcal agents that promote tissue growth, their biological responses and biointerface interactions into functional nano bio-responsive systems (NanoBioRS) able to avoid PJI is an unexplored opportunity for innovation.
In order to tackle PJI and to contribute to avoid the development and spread of antimicrobial resistance, NanoBioRS aims to engineer smart coatings equipped with three frontlines: (i) Increased adhesiveness of their interface to favour tissue cell integration. (ii) Smart responses to eradicate MSSA, MRSA and S. epidermidis using antimicrobials that are not prompt to resistance development. (iii) Means of avoiding biofilm and horizontal gene transfer (HGT) of AMR.
Thiol-modified polymers, surface-tethered stimuli-responsive polymer brushes and antimicrobial/antifouling agents will render coatings with eukaryotic cell adhesive, smart bacterial contact-kill and anti-biofilm properties, respectively. Endonucleases will be used to avoid biofilm and HGT of AMR. Implant surfaces will be modified with NanoBioRS. Nanoscale characterization will allow for the understanding of biointerface interactions taking place during eukaryotic cell colonization and bacterial invasion of implants.