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).
