## 1 Introduction  
Dental implants are medical-surgical devices placed in the jaw bones in order to replace one or more missing teeth by prosthetics [1]. The process that leads to integration of dental implants into the bone was described by [PERSON] in the 1960s and is called osseeintegration, which is a direct connection, both structural and functional, between the vital bone and the surface of a loaded (i.e., prosthetic) implant [2]. Peri-implant infections are the most common complications related to the placement of dental implants: they are classified into peri-implant mucositis and peri-implantitis [3]. According to the most recent guidelines, the diagnosis of peri-implant mucositis can be made if bleeding on probing (BOP) or supuration is present in the absence of radiographic crestal bone loss (beyond initial remodeling); peri-implantitis also involves bone resorption (beyond initial remodeling) and, consequently, an increase in probing pocket depth (PPD) [4]. The prevalence of peri-implant mucositis and peri-implantitis can be as high as 80% and 56%, respectively [5]. Risk factors related to the development of peri-implant disease reported in the literature are: smoking [6], genetic factors such as a combined IL-1 genotype positivity [7], history of periodontitis [8], poor oral hygiene [9], systemic diseases (uncontrolled diabetes mellitus, cardiovascular and immunodepressive diseases) [10], atrogenic causes (such as extra cement) [11], poor peri-implant soft tissue quality (keratinized gingiva thickness \(<\) 2 mm) [12], history of one or more implant losses [13], excessive occlusal loading [14], and titanium particles [15]. The primary etiological factor in the development of peri-implant diseases is the biofilm, which is a complex microbial community consisting of numerous micro-organisms that can communicate with each other through fine molecular processes (known as \"quorum sensing\") [16]. The oral microbiota consists of more than 700 different species, which rarely live in planktonic form but aggregate in communities to form the biofilm; it can grow both on mineralized tooth surfaces, leading to periodontitis, and on titanium implant surfaces, leading to peri-implant mucositis and, in the long term, peri-implantitis [17]. Salivary film, termed \"acquired pellicle\", is a bacteria-free biofilm that covers dental and implant surfaces exposed to the oral cavity due to the presence of saliva; different surface receptors are expressed in order to set up molecular links with late bacterial colonizers [18]. Salivary film on titanium surfaces does not include low molecular weight cystatins and mucins, in contrast to biofilms adherent to enamel surfaces [19]. However, the underlying differences in the composition of films formed on titanium does not appear to represent a risk factor that can increase initial bacterial adhesion to implant surfaces [20]. It has been shown that only 30 min after implant insertion, there is a conspicuous bacterial colonization able to develop a well-organized biofilm in the peri-implant space after 2 weeks [17]. In the following months, the peri-implant biofilm that has formed appears to be qualitatively less diversified in micro-organisms than that present on neighboring teeth, if present [21]. There are many similarities in the microbial composition and immunological processes underlying the pathogenesis of periodontitis and peri-implantitis, but there are some significant differences that have to be considered [22]. From a histological and immunophysiological point of view, there are some important differences that make dental implants more susceptible to oral infections [23]. Whereas natural teeth are placed in the alveoli by the periodontal ligament (PDL), osseointegrated implants have a direct connection to the bone: the absence of the PDL reduces the blood flow to the supraperiosteal vessels and, consequently, limits the amount of nutrients and immunity cells that can come out of the vessels to deal with the ongoing bacterial infection [24].