## 4 Discussion
In this regard, a more interesting finding of our study shows that 40% CA had similar antibacterial activity to the 5.25% NaOCl as well as the 37% OPA formulations. This evidence is of especial clinical importance as CA has been demonstrated to be well tolerated by host cells. One study also observed that 50% CA favored the adhesion and proliferation of pre-osteoblastic cells on bone as a result of the demineralization and consequent formation of a micro-rough substrate similar to that produced by osteoclasts [32]. In addition to the antibacterial activity toward biofilm contaminated implants, our results also evidenced that NaOCl, OPA, CA, and CHX did not produce significant alterations in surface chemical properties, avoiding potential detrimental effects on surrounding tissues [20]. Indeed, NaOCl, CA and CHX have not altered the chemical structure of the titanium oxide surface layer as evidenced by spectroscopic analysis. However, titanium could not be detected on the sample treated with OPA, suggesting the formation of a layer of corrosion products consisting of titanium oxide phosphate [33], and this deserves further investigation. Moreover, multiple elements such as carbon, chlorine, sodium, and phosphorus were detected on treated titanium disks, suggesting adsorption and/or residual traces of decontaminating substances on the surface. Titanium disk surfaces can be altered by either a direct action of the substance on the surface or, more likely, by the adsorption and permanence of the chemical agent. Our results point to a potential chemical contamination of the surface, which may be due to inadequate washing of decontaminated titanium disks. Prolonged rinsing of the treated surfaces might then be required in clinical practice. Also, we cannot exclude that the chemical surface contamination of treated titanium disks might compromise their biocompatibility with host tissues. In fact, [PERSON] et al. showed the presence of elemental contaminants of NaOCl and CHX on decontaminated surfaces that lead to a cytotoxic effect of the host tissues, potentially compromising the biocompatibility of treated surfaces [20]. In addition to chemical surface contamination by antiseptic agents, chemical alterations of the titanium oxide layer can be also caused by the peri-implantitis environment, the inflammatory process and acids originated by the bacterial metabolism [34; 35; 36; 37; 38]. It is not clear, however, whether local corrosion phenomena affect re-osseointegration. On this, a protocol aimed at restoring the atomic composition of the titanium oxide surface layer, based on the combined use of hydrogen peroxide and CO\({}_{2}\) laser, was also investigated, although with controversial results [39; 40]. The main limitation of this study is that it utilizes an in vitro system that warrants caution in translating results to clinical practice as host defense mechanisms and local tissue detoxification, and the influence of blood flow should also be considered. In our study we set up a biofilm model grown on a titanium surface better to simulate the oral microenvironment, which uses human saliva-coated surfaces, the most common periodontal pathogens, anaerobic conditions during biofilm formation and routine exposure time. In the future, ex vivo studies with multispecies biofilm will be of great help to identify the most promising antiseptic agent, in terms of antibacterial, anti-biofilm, and biocompatibility properties, for the standardization of peri-implantitis treatment.