Diederik Hentenaar

144 Chapter 7 At the start of this PhD thesis 6 years ago, clinical research on potential interventions for treating peri-implantitis was highly needed considering the absence of a gold standard protocol. Back then, a wide variation of in-vitro and preclinical studies had been published, evaluating different implant surface decontaminating agents/ methods or combination of methods in different situations/conditions, making it difficult to discriminate between effective and ineffective interventions (Ntrouka et al. 2011, Meyle 2012, Mellado-Valero et al. 2013, Louropoulou 2014). Clinical studies to put these non-clinical data into perspective remained scarce (Esposito et al. 2012, Heitz-Mayfield & Mombelli 2014). Therefore, in line with previous research performed by the current research group on the treatment of peri-implantitis (de Waal et al. 2013, de Waal et al. 2015), the aim of the research presented in this thesis was to perform randomized clinical trials to clinically, radiographically, microbiologically and immunologically evaluate the influence of a single implant surface decontaminating/ peri-implant debridement intervention. In addition, the aim was to add knowledge on the peri-implant diagnosis and on the influence of the implant supported crown contour with regard to the peri-implant condition. Biomarkers in peri-implant diagnostics Dental implants are foreign bodies and can initiate inflammation in the surrounding tissues due to infection or a foreign body reaction. Inflammation is characterized by the production of an array of pro- and anti- inflammatory proteins. To assess whether implants with peri-implantitis and implants in healthy state are accompanied by different inflammatory biomarker levels in peri-implant crevicular fluid (PICF), a comparative study was conducted ( chapter 2 ) in which several potentially diagnostic biomarker candidates were evaluated (Duarte et al. 2016). The results of this study revealed that PICF of implants with peri-implantitis contains significantly higher levels of IL-1β and MMP-8 compared to PICF obtained from healthy peri-implant sites. Other inflammatory markers including IL-6, TNF-α, MIP-1α/CCL3, MCP-1, OPG and G-CSF showed no difference between both conditions. Levels of sRANKL and INF-γ appeared to be under limit of detection. Up to date, IL-1β belongs to the most investigated pro-inflammatory cytokines in PICF (Duarte et al. 2016). Evidence suggests that IL-1β acts synergistically with TNF-α to initiate and propagate inflammation (Dinarello 2000). Also, when IL-1β is inhibited, reduced tissue breakdown and progression of tissue inflammation has been reported (Delima et al. 2001). The enhanced levels of IL-1β found in our study corroborate the majority of previous studies on IL-1β, strengthening the evidence that IL-1β is currently one of the most promising proteins to be used as marker in PICF to distinguish peri- implantitis from peri-implant health (Ghassib et al. 2019). Whether this marker also