Implant Associated Infection

Infections caused by bacterial biofilms play an important role in all areas of medicine. Implants such as dental implants, hip-joint and knee prostheses, pacemakers, artificial heart valves, or Cochlear implants are made of artificial material. Bacteria can adhere to them and form complex antibiotic-resistant biofilm communities. This initiates inflammation and the resulting progressive destructive processes lead to loss of implant function and to considerable problems for the patient. It can even lead to life threatening complications. The costly and risky treatments that often end in the complete removal of the implant material not only restrict the patient but are also a burden for the health care system. At this time, the complexity and diversity of different human biofilms and their pathogenic mechanisms and interactions with tissue have not been sufficiently studied. In view of this fact, a research field is evolving that aside from having high clinical and health economic relevance also has to meet highest scientific standards of originality and novelty.

Many scientists in the metropolitan area of Hannover are working together to fight implant infections. In their corresponding medical fields, they have many years of experience with implants, implant infections, and great basic science expertise. Together, they are developing biomaterials that reduce adverse side effects. Despite different functionalities of the studied organs, congruent issues apply for studies on biofilm associated diseases. These diseases can only be successfully investigated with long term cooperative solution strategies. One of the two main research goals in the focus Biomaterial-Associated Infections is the development of new diagnostic and therapeutic strategies. They will be based on the systematic characterization of biofilms on implant surfaces and of the resulting implant-associated diseases. Here, the focus is on the identification of bacterial diversity, of structural and pathogenic characteristics for different clinically relevant implant and organ systems, and on the congruency between bacterial consortium and diverse clinically pathogenic phenotypes. This information will be used to develop modern biomarkers. A basis will be the Biobank BIT in NIFE. Through the defined collection focus (implants, biofilms, and associated tissue), specimens can be provided for the various infection-biology relevant areas. Based thereupon, it is possible to identify the bacterial culprits of implant infections. Furthermore, it will lead to a basic understanding of their adhesion behavior, their growth, and the pathogenic mechanisms of complex biofilms and also individual species. Modern molecular biological (NGS-sequencing, DNA-microarrays) and microscopic methods (confocal laser scanning microscopy, atomic force microscopy) can unfold valuable information on the structure and dynamics of bacteria in the protective extracellular biofilm matrix. Beyond the diversity of biofilm communities, the influence of environmental factors on the development, texture, composition, and distribution of biofilms will be studied. This will be done using expression profiles and image supported evaluations. Furthermore, the host’s chemical immune response mechanisms involved in inflammatory reactions as well as the proinflammatory reactions and the signal cascades involved will be analyzed. The aim is to switch off irreversible inflammatory processes, which are an important aspect in the failure of permanent implant treatments. In the future, targeting pathogen-associated molecules or unwanted host signals can be used for prevention and treatment.

The second research focus is on the development of strategies for the permanent effective prevention of bacterial colonization or biofilm development on a broad range of materials. This will be done using innovative surface functionalization. In the interdisciplinary research project, ultrastructural and molecular biological analyses will be done on biofilms to evaluate the antibacterial efficacy and biocompatibility of different implant surfaces in vitro and in situ. In addition, approval relevant standardized test systems will be implemented. A particular challenge is selectively fighting biofilms and individual bacterial species with the help of innovative implant systems without impairing the biocompatibility of the different implant materials. This compatibility is required by the individual surgical disciplines. To develop these antibacterial implant surfaces, materials will be physically and/or chemically functionalized. This will be achieved by changing the structure and composition of the bacterial biofilms and by specifically inhibiting pathological processes. Furthermore, current trends in biomaterial research such as biomimetic structuring, implant previtalization, molding extracellular matrices with surface structures, and regulation of the biological response will be included in the application-oriented biomaterial development. A number of established in vitro and in vivo models are available to test innovative biomaterials. These include a bacterial multi-species biofilm model, a co-culture system to study interactions between human cells and bacteria on surfaces, as well as an atraumatic in vivo model to test native oral biofilms.

The research focus Implant-Associated Infections is one of the group’s research foci that strongly collaborates with all groups of NIFE. This is because important issues of biomedical technology and the application of biological and artificial implants are always associated with prevention and therapy of bacterial infections. The knowledge won in this research focus on interactions between implant surfaces, biofilms, and human tissue as well as the established standardized test systems will also be of elementary importance to other medical disciplines. They offer an excellent basis to develop strategies to prevent early implant loss due to bacterial infections.