SummaryPeriodontitis is a complex multifactorial inflammatory disease, which is characterized by the destruction of tooth-supporting tissues. Periodontitis not only reduces the quality of life and increases the risk of systemic diseases but also poses an enormous problem as regards health economics. However, the exact aetiopathogenetic mechanisms for periodontitis are still largely unknown. Therefore, the major goal of the Clinical Research Unit (CRU) 208 “Aetiology and Sequelae of Periodontal Diseases - Genetic, Cell Biological and Biomechanical Aspects” was to improve the prevention, disease control and therapy of periodontal diseases and to minimize health risks for the entire organism through a better understanding of the aetiopathogenetic and regenerative processes. The CRU 208 was an interdisciplinary and multicenter research unit funded by the German Research Foundation and the Medical Faculty of the Universtity of Bonn. The scientists of the Clinical Research Unit were from the Dept. of Periodontology, Operative and Preventive Dentistry, the Dept. of Orthodontics, the Dept. of Oral and Maxillofacial Plastic Surgery, the Section of Oral Technology, the Dept. of Dermatology and Allergy, and the Dept. of Internal Medicine II, Cardiology, Pneumology, and Angiology (all from University of Bonn), the Institute for Clinical Molecular Biology and the 1st Dept. of General Internal Medicine of the University Hospital Schleswig-Holstein (University of Kiel), and the Institute of Computational Science (University of Lugano). During the first funding period, the nine projects examined the immunoinflammatory processes in periodontal tissues, the regulation of the inflammatory and tissue-destructive processes by various intrinsic and extrinsic factors, the mechanisms how local periodontal inflammation and destructive processes cause systematic vascular damage and how an improvement of the vascular regeneration processes affects periodontal diseases and, finally, how the regeneration of lost periodontal structures is initiated or supported by growth and differentiation factors. The great efforts and strides by the CRU 208 were evidenced by the significant number of publications, awards and presentations at international conferences. Furthermore, the design principle of a cell strain device was successfully applied for national and international patents. Close collaborations among the projects of the CRU 208 as well as fruitful intra- and extramural collaborations were successfully established, strengthened or expanded. In order to support the exchange of scientific knowledge and expertise, an international symposia, six workshops and monthly seminars were organized. Moreover, the research structure at the Center of Dento-Maxillo-Facial Dentstry in terms of personnel, equipment and available space was considerably improved. It was a strong concern of the CRU 208 to involve the younger generation of researchers with a doctoral and postdoctoral qualification as well as students into the projects. Therefore, one project was entirely dedicated to this purpose. In the second funding period, the CRU 208 further explored the innate and adaptive immune responses to bacterial infections (Aim #1). These projects helped further identify immunological mechanisms critical not only for the initiation, but also for the chronic manifestation as well as the induction of autoimmunity in periodontitis. Furthermore, they will serve to obtain a rational basis for specific therapeutic interventions. Although periodontopathogenic microorganisms represent a necessary prerequisite for the initiation and progression of periodontitis, additional factors, such as genetic factors and systemic diseases, contribute to the development of periodontitis. On the other side, the infectious and inflammatory burden of periodontitis has also an important systemic impact. The CRU 208 therefore focused on the underlying mechanisms for the association of periodontitis with systemic diseases and conditions, such as cardiovascular diseases, obesity, neoplasia, age and oxidative stress (Aim #2). These projects contributed to a better understanding of the interactions of systemic diseases and factors with periodontal homeostasis, destruction and regeneration. Moreover, the projects also guided the development of prognostic and diagnostic markers and paved the way for future therapeutic applications. Another focus (Aim #3) of the CRU 208 was the development of mathematical models and efficient algorithms to simulate the loading conditions of the periodontium and the subsequent experimental and clinical validation. These studies allowed to better predict the course of periodontitis with respect to the biomechanical function of the tooth and periodontium. We expected that the findings of the proposed projects of CRU 208 will have a decisive influence on the prevention, diagnostics and therapy of periodontal diseases and may also help minimize health risks for the entire organism. In addition, the integration of dental medicine into the research focus areas of the Medical faculty of Bonn was further strengthened.