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

Description du projet

Des implants articulaires avancés dotés de propriétés antimicrobiennes uniques

Les arthroplasties de la hanche et du genou sont des traitements chirurgicaux courants en chirurgie orthopédique pour restaurer la fonction d’une articulation blessée ou malade. Ces procédures reposent fortement sur des prothèses de remplacement, qui peuvent toutefois accumuler des bactéries, entraînant une infection articulaire périprothétique. Pour résoudre ce grave problème médical, le projet NanoBioRS, financé par l’UE, propose de développer un revêtement moléculaire intelligent qui combine des facteurs de croissance tissulaire avec des antimicrobiens. Il contiendra en outre des enzymes qui empêchent la formation de biofilm sur les prothèses articulaires ainsi que la propagation de la résistance antimicrobienne. La solution NanoBioRS pourrait être utilisée pour revêtir divers matériaux implantables, traitant ainsi la menace pour la santé que représentent les bactéries résistantes aux staphylocoques.

Objectif

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.