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

Projektbeschreibung

Moderne Gelenkimplantate mit einzigartigen antimikrobiellen Eigenschaften

Hüft- und Knie-Endoprothesen sind in der orthopädischen Chirurgie gängige chirurgische Behandlungen zur Wiederherstellung der Funktion eines verletzten oder erkrankten Gelenks. Bei diesen Eingriffen kommen in hohem Maße Ersatzprothesen zum Einsatz, in denen sich jedoch Bakterien ansammeln können, die zu einer periprothetischen Gelenkinfektion führen. Um dieses ernste medizinische Problem anzugehen, schlägt das EU-finanzierte Projekt NanoBioRS vor, eine intelligente molekulare Beschichtung zu entwickeln, die Wachstumsfaktoren des Gewebes mit antimikrobiellen Mitteln kombiniert. Außerdem soll sie Enzyme enthalten, die der Bildung von Biofilmen auf Gelenkprothesen und der Ausbreitung antimikrobieller Resistenzen entgegenwirken. Die NanoBioRS-Lösung könnte zur Beschichtung verschiedener implantierbarer Materialien verwendet werden und so der gesundheitlichen Gefahr durch Staphylokokken-resistente Bakterien vorbeugen.

Ziel

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.