## 4 Discussion  
Replacement of body components must respect several functional properties, with one of the basic features being restoration of the removed organ in terms of strength and biofunctional and biomechanical properties. For this purpose, materials with complex chemical properties characterized by a controlled effect on the immune system of the body and biocompatibility have been used. The most important feature of the biomaterial is biocompatibility, which is the ability of the material to show proper reaction during contact with tissue, blood or plasma for a specific time period, either inside or outside the body. For such reasons the dental implants marketed by companies must meet stringent requirements in terms of chemical purity and strength of materials as well as their biocompatibility. The development of inflammatory reactions after insertion of the implant may result from the body's reaction to the inserted implant and the bacterial microflora in the oral cavity. In the present study, for the evaluation of the inflammatory response next to different implant types, a direct contact method was adopted. Inflammatory cells (macrophages) were placed in contact with the devices to be evaluated, and the effects on the expression of genes that code for typical proteins of the inflammatory processes (cytokines and chemokines) were measured. The measurement of pro-inflammatory cytokines produced by macrophages provides the evaluation of an eventual inflammatory response of such cells in contact with the implant surface or with eventual particles released in the surrounding environment. The analysis at 4 h of incubation allowed evaluating pro-inflammatory genes during the early inflammatory response. In fact, macrophages release inflammatory mediators during a FBR and in the presence of bacterial endotoxins, which can adhere to the implant surface and promote a cascade of events that include the recall of other inflammatory cells, leading to progressive destruction of peri-implant tissues, up to bone tissue resorption and, ultimately, implant failure. In order to carry out their functions, macrophages must recognize the pro-inflammatory stimulus, which will determine a modification of their state of quiescence (M0) to an activated state that, based on the specific requested function, can be a \"classical\" or an \"alternative\" activation [7; 18; 19]. This modification, from phenotypical and functional viewpoints, is defined as \"macrophagic polarization\" and includes different macrophage subtypes that are able to express a specific set of inflammatory cytokines, and several types of other molecules. Namely, M1 macrophages promote and lead the pro-inflammatory response and produce high levels of IL-18, IL-6 and TNF-\(\alpha\), in addition to the enzyme NOS, while M2 macrophages are defined as \"anti-inflammatory\" because they mitigate the pro-inflammatory response during tissue repair and tissue remodeling processes, and they produce high levels of IL-4, IL-10 and TGF-\(\beta\)[7; 15; 16; 18; 19]. [PERSON] et al., applying the same research methods herein used, reports that after 4 h of contact, the expression of the gene that codes for IL-6 is highly sensitive to the presence of adherent endotoxins on the implant surfaces regardless of their specific topography. Endotoxins are molecular species typical of the walls of bacteria. When our immune system senses their presence, it triggers the inflammatory reaction. Adherent endotoxins can be present on the surfaces of medical devices, including implant surfaces, as a consequence of the presence of bacteria that are no longer active following sterilization, but whose \"corpses\" can still trigger pyrogenic reactions through the molecular structures of their walls, promoting osteoclastistic activity. A poor awareness of the production processes, for example the use of non-sterile washing water or the handling of the implants packaging with gloves that are not perfectly clean, can lead to the accumulation of endotoxins that adhere to the implant surfaces.