Periodic Reporting for period 1 - NanoBioRS (Nano bio-responsive systems designed to avoid staphylococcal colonization of implant interfaces)
Reporting period: 2022-04-01 to 2025-03-31
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).
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).
NanoBioRS work focused on the development of advanced coatings that promote cell adhesion and bone tissue formation, utilizing state-of-the-art synthetic methods to produce polymer brushes functionalized with adhesive moieties. The characterization of enzymes central in biofilm lifecycle allowed the design of enzyme-responsive delivery systems for the targeting of staphylococcal biofilm. Innovative approaches were applied to characterize the competition between staphylococci and mammalian cells for the implant surface, ultimately leading to the creation of new methodologies.
As a result, four different pharmaceutical formulations comprising two chimeric phage endolysins were developed and applied in a liquid form or attached to the surface of the bio-adhesive polymer brushes. The nano bio-responsive delivery systems obtained were able to eradicate S. aureus biofilm and avoid implant colonization with staphylococci in competence with mammalian cells.
The results of NanoBioRS project led to four scientific articles with associated data (one published, one accepted for publication, and two under review), three protocols deposited in public repositories for use by the scientific community, and four conference presentations. Knowledge transfer between the ER and the host generated three additional papers. Finally, two workshops were delivered by the ER, with support from host collaborators, to encourage younger generations to pursue careers in science.
All outcomes of NanoBioRS were disseminated and communicated through social media to maximize their impact on the scientific community and the general public.
As a result, four different pharmaceutical formulations comprising two chimeric phage endolysins were developed and applied in a liquid form or attached to the surface of the bio-adhesive polymer brushes. The nano bio-responsive delivery systems obtained were able to eradicate S. aureus biofilm and avoid implant colonization with staphylococci in competence with mammalian cells.
The results of NanoBioRS project led to four scientific articles with associated data (one published, one accepted for publication, and two under review), three protocols deposited in public repositories for use by the scientific community, and four conference presentations. Knowledge transfer between the ER and the host generated three additional papers. Finally, two workshops were delivered by the ER, with support from host collaborators, to encourage younger generations to pursue careers in science.
All outcomes of NanoBioRS were disseminated and communicated through social media to maximize their impact on the scientific community and the general public.
The work performed on the frame of NanoBioRS increased the understanding of delivery systems adapted for chimeric phage endolysins which are of great interest for the pharmaceutical industry at the moment. The results obtained were not patentable due to the prior disclosure of specific components of the delivery systems in the literature, as well as certain limitations in efficacy. However, adapting these systems to chimeric endolysins able to kill bacteria intracellularly holds substantial promise for the application of this technology.
The knowledge generated throughout NanoBioRS will probably be exploited for delivery and future application of chimeric phage endolysins as next generation antimicrobials. This is expected to significantly influence both the social and economic aspects of healthcare systems by targeting antibiotic resistance and implant-associated infections.
The scientific methods developed on the frame of NanoBioRS can be applied by a broad audience in the biomedical field. They were deposited in several repositories and made immediately available to the collaborators of NanoBioRS project. Public access will be granted after the final publication of the project’s findings.
The knowledge generated throughout NanoBioRS will probably be exploited for delivery and future application of chimeric phage endolysins as next generation antimicrobials. This is expected to significantly influence both the social and economic aspects of healthcare systems by targeting antibiotic resistance and implant-associated infections.
The scientific methods developed on the frame of NanoBioRS can be applied by a broad audience in the biomedical field. They were deposited in several repositories and made immediately available to the collaborators of NanoBioRS project. Public access will be granted after the final publication of the project’s findings.