Diederik Hentenaar

31 Biomarkers in crevicular peri-implant fluid Clinical relevance Scientific rationale for study To assess whether peri-implant health and disease is accompanied by different biomarker levels in PICF as well as to evaluate the effect of non-surgical peri-implantitis treatment on these levels. Principal findings Peri-implantitis implants showed higher levels of IL-1β and MMP-8 in PICF compared to healthy implants. Immune response seemed not to change by a single non-surgical peri-implantitis intervention. sRANKL and INF-γ appeared under level of detection using a customized Luminex™ assay. Practical implications PICF collection, in addition to clinical and radiographical examination, helps to understand peri-implant health. Evaluation of non-surgical peri-implantitis therapy outcome using PICF diagnostics did not show to be helpful. INTRODUCTION AND RATIONAL Peri-implant infections are characterized by an inflammatory response to a bacterial imbalance leading to soft tissue inflammation with or without progressive loss of supporting bone (i.e., peri-implantitis or peri-implant mucositis, respectively) (Schwarz et al. 2018). Objective methods to differentiate between peri-implant health and disease, and to evaluate the effect of therapeutic intervention are lacking since traditional clinical diagnostic methods, such as pocket probing, bleeding on probing and radiographic assessment exert a weak sensitivity/specificity (Heitz-Mayfield 2008, Hashim et al. 2018). It is thought that immunological host-derived molecules, such as cytokines, chemokines, proteolytic and tissue breakdown enzymes, could serve as adjunctive parameters to ameliorate the diagnosis, prediction and management of peri-implant disease (Ramseier et al. 2009, Sexton et al. 2011, Syndergaard et al. 2014, Kinney et al. 2014, Carinci et al. 2019). Since 1989, when Apse et al. (1989) demonstrated the presence of fluid in the osseointegrated implant pocket (i.e., peri-implant crevicular fluid (PICF)), a broad research effort has been spent to analyse host-derived immunological biomarkers present in this fluid (Aspe et al. 1989, Armitage 2004, Lamster & Ahlo 2007). Ideally, with the idea that this could lead to PICF diagnostics (e.g., point-of-care testing), to flank clinical and radiographical examination in the monitoring of peri-implant tissue health (Carinci et al. 2019). To date, most studies have focused only on a limited number of 2