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Dental implants are nowadays a standard treatment to replace missing teeth and restore function and aesthetics. However, biological complications associated with implants, e.g., peri-implant infections, are common and jeopardize the success of treatment. The main aim of this thesis was to explore strontium (Sr) as a possible prevention strategy against peri-implant infections, since Sr has been shown to have antibacterial action and also to promote titanium (Ti) implant osseointegration. In this thesis, a systematic appraisal of the literature about the antimicrobial potential of Sr-functionalized Ti surfaces for oral applications was performed, and was followed by a series of in vitro studies assessing the antimicrobial potential of Sr against micro-organisms associated with peri-implantitis. In Study I, the systematic appraisal of the literature resulted in an initial list of 1081 potentially relevant publications, where from nine publications from in vitro studies met the inclusion criteria. Most of the included studies showed that Sr-functionalized Ti exerted a limited immediate (i.e., 24 h) antimicrobial effect, likely due to a low Sr ion release; a relevant antimicrobial effect and biofilm inhibition potential against Streptococcus aureus was observed at both early and late timepoints, with an adequate Sr ion release. Study II assessed, in vitro, five different concentrations of soluble Sr(OH)2 (100, 10, 1, 0.1, and 0.01 mM) against 6 different mono-species bacteria (Streptococcusmitis, Staphylococcus epidermidis, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Escherichia coli, and Fusobacterium nucleatum) in terms of cell growth, minimal inhibitory concentration (MIC), and biofilm viability. In the agar diffusion test, zones of inhibition were only observed for 0.01, 0.1, and 1 mM of Sr(OH)2 against P. gingivalis. Growth inhibition in planktonic cultures was achieved at 10 mM for all species tested. In the biofilm viability assay, 10 and 100, Paper III and IV in dissertation as manuscript

The aim of this systematic review was to assess the current scientific evidence of the antimicrobial potential of strontium (Sr) when used to functionalize titanium (Ti) for oral applications. Out of an initial list of 1081 potentially relevant publications identified in three electronic databases (MEDLINE via PubMed, Scopus, and Cochrane) up to 1 February 2021, nine publications based on in vitro studies met the inclusion criteria. The antimicrobial potential of Sr was investigated on different types of functionalized Ti substrates, employing different application methods. Nine studies reported on the early, i.e., 6-24 h, and two studies on the late, i.e., 7-28 days, antimicrobial effect of Sr, primarily against Staphylococcus aureus (S. aureus) and/or Escherichia coli (E. coli). Sr-modified samples demonstrated relevant early antimicrobial potential against S. aureus in three studies; only one of which presented statistical significance values, while the other two presented only the percentage of antimicrobial rate and biofilm inhibition. A relevant late biofilm inhibition potential against S. aureus of 40% and 10%-after 7 and 14 days, respectively-was reported in one study. Combining Sr with other metal ions, i.e., silver (Ag), zinc (Zn), and fluorine (F), demonstrated a significant antimicrobial effect and biofilm inhibition against both S. aureus and E. coli. Sr ion release within the first 24 h was generally low, i.e., below 50 mu g/L and 0.6 ppm; however, sustained Sr ion release for up to 30 days, while maintaining up to 90% of its original content, was also demonstrated. Thus, in most studies included herein, Sr-functionalized Ti showed a limited immediate (i.e., 24 h) antimicrobial effect, likely due to a low Sr ion release; however, with an adequate Sr ion release, a relevant antimicrobial effect, as well as a biofilm inhibition potential against S. aureus-but not E. coli-was observed at both early and late timepoints. Future studies should assess the ant