NanoBioRS · Nano bio-responsive systems designed to avoid staphylococcal colonization of implant interfaces
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2022-04-01 → 2026-07-31
- EU contribution
- €279,251
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Nano bio-responsive systems designed to avoid staphylococcal colonization of implant interfaces
Biomaterial-centered infections involving Staphylococcus aureus and S. epidermidis can be visualized as a race between bacteria and mammalian cells for the implant surface. If bacteria dominate, biofilm is formed, often leading to persistent infection. However, if mammalian cells colonize the implant, they are able to defend the surface. To tip the balance in favor of host cells, we present and dissect the functioning of a nano bio-responsive system (NanoBioRS) engineered to deploy two synergistic nanostructured defense lines, each targeting key aspects of this competitive colonization process. The first defense line is a bio-adhesive implant surface, created by functionalizing the implant with polymer brushes that act as mammalian cell recruiters. The second includes nano bio-responsive pharmaceutical formulations containing chimeric phage endolysins (lytic antimicrobials), whose efficacy relies on enzymes that play a key role in bone development and the staphylococcal biofilm lifecycle. The success of NanoBioRS approach was demonstrated by the eradication of staphylococci in competition with mammalian cells. This was achieved using liquid formulations containing enzyme-responsive nanoparticles that encapsulated the lytic antimicrobials, or by modifying the bio-adhesive implant surface with the nanoparticles developed. It was concluded that an effective NanoBioRS implant modification comprises enzyme-responsive nanoparticles that rapidly release lytic antimicrobials. Additionally, the results of this approach could be enhanced by incorporating lytic antimicrobials that target bacteria internalized within mammalian cells. The use of the enzyme-responsive liquid pharmaceutical formulations developed here was proposed as a reinforcement of the current practices offering an added layer of protection against the ongoing challenge of implant-associated infections. This approach may help reduce the development of antibiotic resistance, as the formulation is released only in the presence of target bacteria, thereby avoiding the overexposure to antibiotics that drives resistance. All the results generated in NanoBioRS project and the knowledge transfer activities involved as part of this action were communicated, published and submitted for publication. NanoBioRS development strongly contributes to the advance in knowledge to combat the growing problem of antibiotic resistance, as well as the patient health issues and strain on the healthcare system caused by implant-related infections from S. epidermidis and S. aureus, including methicillin-resistant S. aureus (MRSA).
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- UNIVERSITAET INNSBRUCK · InnsbruckCoordinatorAustria
Links
Data: CORDIS, © European Union