Diederik Hentenaar

32 Chapter 2 biomarkers, mainly including only 1 or 2 classical pro-inflammatory cytokines (i.e., IL-1β, TNF-α and/or IL-6). These markers are commonly chosen since they exert synergistic properties in the initiation of inflammatory marker cascade and are produced at local sites with inflammation. In addition, they probably play an important role in osteoclast formation and hence, resorption of bone structures (Hirano et al. 1990, Dinarello 2000, Tanaka et al. 2014). Studies on several important anti-inflammatory biomarkers, collagen degradation enzymes, osteoclastogenis-related cytokines, and chemokines (e.g., granulocyte-colony stimulating factor (G-CSF), matrix metalloproteinase-8 (MMP- 8), monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP- 1α/CCL3), bonemarkers (OPG & sRANKL) and interferon-γ) have, however, never been performed properly (Duarte et al. 2016). Also, whether these biomarker levels in PICF could be helpful to evaluate the outcome of peri-implantitis therapy, has scarcely been evaluated in previous studies (Bassetti et al. 2014, Renvert et al. 2016). Considering that cytokines are involved in broad networks, which to a large extent orchestrate the immuno-inflammatory process, an expanded approach of biomarker evaluation is necessary to increase the chance to find biomarkers that could help to distinguish between healthy and diseased implants (Feghali & Wright 1997, Duarte et al. 2016). Therefore, the aim of the present study was to assess scarcely investigated or priorly not investigated biomarkers next to the commonly studied classical pro-inflammatory biomarkers in PICF of healthy implants and implants with peri-implantitis (before and after non-surgical treatment). MATERIALS AND METHODS Study design A combined cross-sectional and intervention study was conducted. The SPIRIT guidelines for reporting a clinical trial were followed (Chan et al. 2013). Study population Patients with implants with peri-implantitis from the Center of Dentistry and Oral Hygiene and the Department of Oral and Maxillofacial Surgery of the University Medical Center Groningen (UMCG), Groningen, The Netherlands were consecutively recruited to participate in the study, according to specific in- and exclusion criteria (see Table 1). The study was executed at the Department of Oral and Maxillofacial Surgery of the University Medical Center Groningen between September 2017 and November 2019. The study was conducted in accordance with the Medical Research Involving Human Subjects Act (WMO) and in full accordance with the principles of the Declaration of Helsinki as stated in 64th WMA General Assembly, Fortaleza, Brazil,