## 1 Introduction  
Following the spread of the use of titanium implants and patients' high expectations, dental implants improved with new surface treatments are continuously delivered on the market, providing implants with different chemical compositions and topographies of their surface. Such intrinsic characteristics of the implant surface (chemical composition, wettability, topography) and the possible presence of endotoxins or other contaminants on their surface, as a result of environmental influence or manufacturing and packaging processes, affect the bone-implant interface and cause an inflammatory response, which has been traditionally defined by the evaluation of pyrogenicity. This feature has always been taken into consideration in the qualification of medical devices to prevent pyrogenic effects, and in recent years it has become particularly relevant for devices in contact with bone. In fact, there is evidence of the stimulation of osteoclastogenesis, and therefore of potential bone resorption induced by cytokines developed in the inflammatory response at the tissue-device interface [1, 2]. Recent work from [PERSON] et al. [3] has described the dynamic phenomenon of osseointegration of titanium dental implants as an immune-mediated foreign body reaction (FBR), that is concomitant to the wound-healing process consequent to surgical trauma. The authors thus introduced the concept of foreign body equilibrium (FBE) applied to osseointegration of dental implants [4]. This notion relies on the fact that dental implants, although biocompatible, are not completely inert materials. Indeed, the concept of biocompatibility should not be translated into that of biological inertia. In fact, once dental implants are inserted, a cascade of biological phenomena starts at the host-implant interface, and the crosstalk between cells of the immune and the musculoskeletal systems plays a pivotal role in the process of osseointegration [2]. However, while the effect of dental implants in contact with cells such as osteoblasts and fibroblasts has been widely investigated [5,6], their influence on cells of the immune system has been neglected [7]. In particular, monocyte/macrophages play a central role in bone homeostasis; they can have a direct osteolytic role, and they are fundamental in bone/biomaterial integration around dental implants and in the bone loss pathway during FBR [4,7, 7, 8]. Once the implant is inserted, after plasma proteins adhesion to the implant surface and a considerable recruitment of neutrophils in the implantation site, the first cells to come into contact with the biomaterial are those derived from the monocyte/macrophage lineage [10]. The last are considered mainly responsible for the host response toward the foreign biomaterial, based on their behavior during the chronic inflammation stage of implantation. The lymphocyte Th1 response generally promotes the polarization of circulant monocytes recruited in the peri-implant site, into \"classically activated\" or \"pro-inflammatory\" M1 macrophages ([PERSON] et al., 2018). This type of macrophage releases proinflammatory cytokines (such as TNF\(\alpha\), IL-6 e IL-1\(\beta\)), which promote osteoclastogenesis and bone resorption, but also secrete the pro-osteogenic oncostatin-M, in addition to help in debris and dead cells cleaning [11]. On the other hand, Th2 response promotes resident macrophage polarization into \"alternative activated\" or \"wound-healing\" M2 macrophages, which release a set of anti-inflammatory/regulatory molecules, such as IL-4, IL-10 and TGF-\(\beta\), that mitigates the host inflammatory reaction [12]. In physiological conditions, both macrophage phenotypes are essential for a proper wound repair, and if a balance among them is obtained, the implantation process will result in successful tissue integration. However, possible cellular shifts at the implant interface are influenced by several factors (e.g., features of the tissues, local microenvironment, physio-pathological conditions of the patient).