Periodic Reporting for period 2 - STIMULUS (Stimuli Responsive Materials for the Rapid Detection and Treatment of Healthcare Associated Infections)
Berichtszeitraum: 2022-10-01 bis 2025-03-31
Healthcare-Associated Infections (HAIs) are bacterial infections obtained from clinical treatment, e.g. following medical intervention. HAIs are a problem of tremendous proportions, as more than 4 million EC citizens get infected annually. The ECDC estimates ~150,000 HAI-related deaths in Europe each year, mainly stemming from wound infections. These alarming facts motivate the urgent need to develop novel medical devices, particularly wound dressings, which rapidly signal and prevent or eradicate invasive bacterial colonization following a stimulus. Current antimicrobial coatings rely on slow, passive diffusion of antimicrobials. Hence, the antimicrobial may not be sufficiently concentrated to eradicate the infection or delivered when there is no need; such low-concentration zones or unnecessary antibiotic treatments promote the evolution of resistance.
In response, STIMULUS has successfully delivered a new class of theranostic wound dressings—multifunctional materials that combine early detection of infection with immediate, localized treatment. These dressings represent a breakthrough in infection management by autonomously responding to infection-specific triggers, such as bacterial enzymes or pH shifts, without requiring the wound to be opened or systemic antibiotics to be used. A defining achievement of the project was the integration of alternative antimicrobial strategies into these materials. For example, STIMULUS showed that responsive systems that could release reactive oxygen species (ROS) upon exposure to light or specific microbial signals, as well as antimicrobial peptides, powerful molecules modeled on the body's natural defenses, incorporated into hydrogels, could be used for antimicrobial therapy on demand without risking antibiotic resistance. STIMULUS also advanced infection models and testing systems that better mimic clinical conditions, ensuring more predictive evaluation of wound dressings with reduced animal testing.
The completion of STIMULUS marks a substantial step forward in creating effective, targeted, and sustainable solutions for wound care, addressing both the medical and societal challenges of antimicrobial resistance and healthcare-associated infections.
In response, STIMULUS has successfully delivered a new class of theranostic wound dressings—multifunctional materials that combine early detection of infection with immediate, localized treatment. These dressings represent a breakthrough in infection management by autonomously responding to infection-specific triggers, such as bacterial enzymes or pH shifts, without requiring the wound to be opened or systemic antibiotics to be used. A defining achievement of the project was the integration of alternative antimicrobial strategies into these materials. For example, STIMULUS showed that responsive systems that could release reactive oxygen species (ROS) upon exposure to light or specific microbial signals, as well as antimicrobial peptides, powerful molecules modeled on the body's natural defenses, incorporated into hydrogels, could be used for antimicrobial therapy on demand without risking antibiotic resistance. STIMULUS also advanced infection models and testing systems that better mimic clinical conditions, ensuring more predictive evaluation of wound dressings with reduced animal testing.
The completion of STIMULUS marks a substantial step forward in creating effective, targeted, and sustainable solutions for wound care, addressing both the medical and societal challenges of antimicrobial resistance and healthcare-associated infections.
The STIMULUS project developed intelligent wound dressing materials to detect infections and respond by delivering treatment. Over the course of the project, 15 Early-Stage Researchers (ESRs) trained within STIMULUS created new materials that react to infection-specific signals, such as changes in pH or the presence of bacterial enzymes, by changing color or emitting light. These materials were integrated into hydrogels, films, and vesicles that could be applied directly to wounds.
The ESRs engineered several systems capable of releasing antimicrobial agents only when needed. These included enzyme-responsive hydrogels, light-activated nanoparticles that produce bacteria-killing reactive oxygen species, and materials that release treatment agents when bacterial activity is detected. The antimicrobial agents used included synthetic peptides, photosensitizers, and bacteriophages. Some systems allowed controlled release by external triggers like green or blue light, while others responded to local infection conditions.
Multiple materials were designed by the ESRs to combine detection and treatment in a single platform. These theranostic systems could signal infection and simultaneously eliminate bacteria, including drug-resistant strains. Prototypes were tested in realistic lab-grown skin models and complex biofilms that mimic chronic wounds. Materials were also incorporated into hydrogel foams and dressings suitable for real-world application.
The ESRs created advanced testing models to support these developments, including three-dimensional human skin equivalents and polymicrobial biofilms containing bacteria and fungi. These models allowed precise assessments of how well the new dressings work in realistic wound conditions. The models developed and tested in STIMULUS also aim to reduce animal testing. The effectiveness of new antimicrobial peptides and vesicle-based diagnostic tools was confirmed through standardized testing on these and other established models.
Our ESRs disseminated their work at national and international conferences, including two STIMULUS-led scientific events, scientific publications, and online and real-world outreach activities. Four patent applications were filed covering antimicrobial materials, diagnostic systems, and responsive delivery platforms, with more expected. Clinical and industrial partners supported the potential commercialization of selected prototypes. Particularly advanced were the developments around the GBS diagnostic test, which underwent pilot-scale production and clinical validation in collaboration with an industry partner. Some systems, such as a diagnostic test for Group B Streptococcus, were clinically validated and scaled up for production. Other inventions already applied for patent protection included, e.g. hydrogel wound dressings incorporating antimicrobial peptides, super-absorbent wound dressings, and indicators for wound dressings. Additionally, a holography-based imaging method studied by one of the ESRs to monitor bacteria led to the creation of a spin-off company.
These efforts helped maximize the impact of STIMULUS, positioning its results for continued development beyond the project’s lifetime and paving the way for future innovation in infection-responsive wound care technologies. The training and hands-on experience received by the ESRs throughout STIMULUS not only contributed to the project’s success but also prepared them to become future leaders in healthcare materials and innovation.
The ESRs engineered several systems capable of releasing antimicrobial agents only when needed. These included enzyme-responsive hydrogels, light-activated nanoparticles that produce bacteria-killing reactive oxygen species, and materials that release treatment agents when bacterial activity is detected. The antimicrobial agents used included synthetic peptides, photosensitizers, and bacteriophages. Some systems allowed controlled release by external triggers like green or blue light, while others responded to local infection conditions.
Multiple materials were designed by the ESRs to combine detection and treatment in a single platform. These theranostic systems could signal infection and simultaneously eliminate bacteria, including drug-resistant strains. Prototypes were tested in realistic lab-grown skin models and complex biofilms that mimic chronic wounds. Materials were also incorporated into hydrogel foams and dressings suitable for real-world application.
The ESRs created advanced testing models to support these developments, including three-dimensional human skin equivalents and polymicrobial biofilms containing bacteria and fungi. These models allowed precise assessments of how well the new dressings work in realistic wound conditions. The models developed and tested in STIMULUS also aim to reduce animal testing. The effectiveness of new antimicrobial peptides and vesicle-based diagnostic tools was confirmed through standardized testing on these and other established models.
Our ESRs disseminated their work at national and international conferences, including two STIMULUS-led scientific events, scientific publications, and online and real-world outreach activities. Four patent applications were filed covering antimicrobial materials, diagnostic systems, and responsive delivery platforms, with more expected. Clinical and industrial partners supported the potential commercialization of selected prototypes. Particularly advanced were the developments around the GBS diagnostic test, which underwent pilot-scale production and clinical validation in collaboration with an industry partner. Some systems, such as a diagnostic test for Group B Streptococcus, were clinically validated and scaled up for production. Other inventions already applied for patent protection included, e.g. hydrogel wound dressings incorporating antimicrobial peptides, super-absorbent wound dressings, and indicators for wound dressings. Additionally, a holography-based imaging method studied by one of the ESRs to monitor bacteria led to the creation of a spin-off company.
These efforts helped maximize the impact of STIMULUS, positioning its results for continued development beyond the project’s lifetime and paving the way for future innovation in infection-responsive wound care technologies. The training and hands-on experience received by the ESRs throughout STIMULUS not only contributed to the project’s success but also prepared them to become future leaders in healthcare materials and innovation.
STIMULUS has moved significantly beyond the state of the art in infection-responsive wound care. The project introduced a new generation of wound dressings that combine autonomous detection of infection with targeted therapeutic response—technologies that did not previously exist in integrated, scalable forms. These materials respond to specific signals produced by pathogenic bacteria, such as enzymatic activity and local pH changes, without requiring the dressing to be removed. This allows for earlier, safer, and more accurate intervention in wound management.
Among the most advanced innovations were hybrid theranostic systems capable of changing color to visibly indicate infection while simultaneously releasing antimicrobial agents only when needed. Novel light-activated nanoparticles were developed that eradicate bacteria on demand, offering a potent, non-antibiotic alternative to treat infections. Diagnostic vesicles specific to critical pathogens, such as Group B Streptococcus, were clinically validated and scaled up for industrial production. Altogether, these systems represent a step-change in wound care materials' functionality, precision, and responsiveness.
The societal impact of these advances is far-reaching. By reducing the unnecessary use of antibiotics, STIMULUS technologies directly contribute to the fight against antimicrobial resistance. The ability to detect infections non-invasively will prevent unnecessary dressing changes, reduce exposure of wounds to new pathogens, and minimize patient discomfort. As these technologies move toward clinical translation, they are expected to reduce healthcare costs, hospital stays, and treatment failures.
Among the most advanced innovations were hybrid theranostic systems capable of changing color to visibly indicate infection while simultaneously releasing antimicrobial agents only when needed. Novel light-activated nanoparticles were developed that eradicate bacteria on demand, offering a potent, non-antibiotic alternative to treat infections. Diagnostic vesicles specific to critical pathogens, such as Group B Streptococcus, were clinically validated and scaled up for industrial production. Altogether, these systems represent a step-change in wound care materials' functionality, precision, and responsiveness.
The societal impact of these advances is far-reaching. By reducing the unnecessary use of antibiotics, STIMULUS technologies directly contribute to the fight against antimicrobial resistance. The ability to detect infections non-invasively will prevent unnecessary dressing changes, reduce exposure of wounds to new pathogens, and minimize patient discomfort. As these technologies move toward clinical translation, they are expected to reduce healthcare costs, hospital stays, and treatment failures.