Assoc. Prof. Rikke L Meyer, Prof. Jørgen Kjems, Prof. Peter Nejsum, Prof. Lars Østergaard og MD PhD Nis Pedersen Jørgensen

Background: Medical advances and a demographic shift towards an older population has led to a dramatic increase in the use of biomedical implants in the western world. However, implants are also hotspots for some of the most serious bacterial infections that challenge clinicians today. The bacteria form multicellular aggregates contained in a protective layer (a biofilm) at or near the implant surface, and thereby evade the immune system. Furthermore, bacterial “persisters” residing in the biofilm tolerate antibiotics and cause the infection to relapse when treatment is completed. Furthermore, prolonged and repeated antibiotic treatments lead to development of resistant strains that deliver the final blow to treatment options. Therefore, the mortality rate for some implant-associated infections is similar to severe cancers.

Aim 1: The success of antibiotic treatment of any type of implant-associated infection relies heavily on early diagnosis of the infection. However, diagnosis is problematic because the infection is confined and the bacteria do not circulate in the bloodstream. Existing inflammatory biomarkers and radiological methods are not sensitive enough to detect the infection. We propose to identify biomarkers that can be used for early detection of biofilm infections from blood samples. Such biomarkers will be a valuable and potentially life-saving tool.

Aim 2: It remains unknown why some patients develop infections after insertion of an implant and others do not. It is assumed that bacteria attach to the implant surface to form the biofilm. However, recent research shows that this assumption is wrong, as biofilms also form in the local environment around the implant. We hypothesize that biofilms form as a response to an inappropriate immune response to the implant, which is driven in part by differences in macrophage differentiation and/or difference in T-cell response. We therefore propose that implant-associated infections can be prevented, not by designing antimicrobial implant materials, but by illuminating how the immune system responds to the implant in a way that promotes biofilm infections. Biomarkers for the immune response to an implant are therefore potential targets for i) predicting a patient’s risk of infection and ii) modulating the immune system towards a more appropriate response. We will identify these biomarkers in the proposed project. Method: We intend to identify the biomarkers by studying the composition of the blood (RNA and protein content of extracellular vesicles and plasma as well as circulating bacterial DNA) obtained from patients before and after implantation by novel high-throughput technologies. Changes in the blood will be correlated with complications suffered by the patient post implantation and used to build predictive models using artificial intelligence (AI). .