Periodic Reporting for period 4 - PROMETHEUS (Flame nanoengineering for antibacterial medical devices)
Reporting period: 2022-09-01 to 2023-08-31
Bacterial skin infections from drug-resistant bacteria in hospitals can be fatal. This is because such infections typically occur in patients with already compromised immune system (e.g. diabetic, cancer chemotherapy, HIV patients), and can rapidly progress within the body causing life-threatening sepsis. Current treatments involve continuous and high-dosage systemic administration of a mixture of potent antibiotics. However, such treatments are often not effective with detrimental side-effects to patients. Other conventional delivery systems, such as gels and creams often struggle to overcome the necrotic tissue barrier with minimal drug penetration to infected site. Thus, there is a need for novel treatments of such infections.
Infections are the leading cause of implant failure that lead to increased patient pain and functional loss affecting thousands of people with enormous costs. The ideal surface of an implant should serve two functions: promote osseointegration (connection between bone and implant) and prevent infection. Although osseointegration can be achieved today and has been optimized over the years since the introduction of 45S5 bioglass in 1960’s, infection control has not been resolved, yet. Bacterial growth on implant surface forms biofilms, in which bacteria produce a protective polymeric extracellular substance. Such bacteria are more difficult to kill than individual ones floating around the body. The poor vascularity in implant sites inhibits the effective antibiotic delivery there when administered systemically. Today, there is no commercial implant that combines both osseointegration and anti-infection properties.
This project addresses both urgent societal and industrial needs in the field: Our target is to develop the next generation of smart medical devices that fight and prevent the most prevalent public health threat today, infections from drug-resistant bacteria. This is done while employing a nanomanufacturing process with proven scalability and reproducibility, flame aerosol technology, to assist rapid technology transfer to industry. We employ flame direct nanoparticle deposition on substrates and combine nanoparticle production and functional layer deposition in a single-step with close attention to product nanoparticle properties and assembly of devices. Specific focus lies on two smart medical products; a) hybrid polymer microneedle patch to fight life-threatening skin infections from drug-resistant bacteria and b) nanocoatings on medical implant surfaces providing both osteogenic as well as self-triggered antibacterial properties.
Infections are the leading cause of implant failure that lead to increased patient pain and functional loss affecting thousands of people with enormous costs. The ideal surface of an implant should serve two functions: promote osseointegration (connection between bone and implant) and prevent infection. Although osseointegration can be achieved today and has been optimized over the years since the introduction of 45S5 bioglass in 1960’s, infection control has not been resolved, yet. Bacterial growth on implant surface forms biofilms, in which bacteria produce a protective polymeric extracellular substance. Such bacteria are more difficult to kill than individual ones floating around the body. The poor vascularity in implant sites inhibits the effective antibiotic delivery there when administered systemically. Today, there is no commercial implant that combines both osseointegration and anti-infection properties.
This project addresses both urgent societal and industrial needs in the field: Our target is to develop the next generation of smart medical devices that fight and prevent the most prevalent public health threat today, infections from drug-resistant bacteria. This is done while employing a nanomanufacturing process with proven scalability and reproducibility, flame aerosol technology, to assist rapid technology transfer to industry. We employ flame direct nanoparticle deposition on substrates and combine nanoparticle production and functional layer deposition in a single-step with close attention to product nanoparticle properties and assembly of devices. Specific focus lies on two smart medical products; a) hybrid polymer microneedle patch to fight life-threatening skin infections from drug-resistant bacteria and b) nanocoatings on medical implant surfaces providing both osteogenic as well as self-triggered antibacterial properties.
Regarding the hybrid microneedle patches, we have developed for the first time a microneedle array that enables the local vancomycin administration into the skin to fight methicillin resistant s. aureus. Vancomycin is the first line of treatment against MRSA however it is only administered to-date intravenously that limits its biodistribution and elicits adverse side-effects. We have been able to show that such a patch is effective both in vitro and ex vivo against MRSA. We have further advanced the knowledge on plasmonic photothermal MN patches that heat up upon the application of light irradiation. That makes it possible to achieve a local temperature increase in the skin with laser irradiation. We have finally also combined the two functionalities in a single MN array in which we have the plasmonic photothermal insoluble core in the tips, coated with a soluble polymer that contains the drug. That way it is possible to eradicate bacteria in a synergistic way upon the application of an external stimulus (light).
Regarding the smart implant coatings., we have managed to establish a good understanding on the coating deposition properties and we have focused so far on antimicrobial nanosilver as the active compound. We have managed to elicit a 5-log reduction in S. aureus biofilm formation when using nanosilver as a coating. We have also further advanced the multifunctionality of the developed coatings by adding an osteogenic support material, bioglass, in the composition of the nanocoating. That make sit possible to have a coating with both the antibiofilm activity, as well as osseointegrative properties.
We have disseminated the results in publications and conferences. We are currently in the process of trying to explore the exploitation of the results through our Proof of concept grant, with which we have protected the IP of two inventions (one we continued to the international phase), and we are in the process of licensing this technology to an industrial partner, or make a new company and assign the rights of the patent to that one. The ultimate target is to attract additional funding – perhaps through the European Innovation Council – to promote the translation of the developed product to the clinics.
Regarding the smart implant coatings., we have managed to establish a good understanding on the coating deposition properties and we have focused so far on antimicrobial nanosilver as the active compound. We have managed to elicit a 5-log reduction in S. aureus biofilm formation when using nanosilver as a coating. We have also further advanced the multifunctionality of the developed coatings by adding an osteogenic support material, bioglass, in the composition of the nanocoating. That make sit possible to have a coating with both the antibiofilm activity, as well as osseointegrative properties.
We have disseminated the results in publications and conferences. We are currently in the process of trying to explore the exploitation of the results through our Proof of concept grant, with which we have protected the IP of two inventions (one we continued to the international phase), and we are in the process of licensing this technology to an industrial partner, or make a new company and assign the rights of the patent to that one. The ultimate target is to attract additional funding – perhaps through the European Innovation Council – to promote the translation of the developed product to the clinics.
We are in line with the planned activities of the project and we have managed to contribute decisively to the manufacturing of sophisticated and novel, nanoscale revolutionary devices to fight drug-resistant infections. A scalable nanomanufacture process has been utilized to systematically study the process parameters that dictate device performance. The engineering approach for development of antibacterial medical devices will provide insight into the basic physicochemical and biological principles to assist in process scale up and industrial utilization. The outcome of this research will help the fight against antibiotic resistance improving the public health worldwide and guiding the healthcare industry towards the responsible and efficient use of nano-enabled medical devices.