## 4 Discussion  
The insertion of a dental implant implies the introduction of a foreign body into a living host and leads to immediate tissue damage and cell disruption resulting from the surgical procedure [16]. Blood protein adsorption onto the surface of the implant initiates tissue healing by activating the immune response [17]. To promote proper tissue regeneration, suitable fibroblast activity without chronic inflammation is required. The collagen produced by fibroblasts is crucial to form a correct extracellular matrix (ECM), and acute proinflammatory environments adversely affect the ECM quality required for tissue regeneration [18]. The in vivo biocompatibility of the biomaterial and its tissue regeneration capacity depend on the modulation of immune cells, which are driven by complement system proteins [19]. In this sense, the composition, conformation and number of proteins bound onto the abutment surfaces can lead to distinct biological responses depending on the specific surface characteristics. In this study, two distinct anodized Ti treatments (YA and PA) were studied. The anodization process led to morphological differences between the YA and PA surfaces versus the control (MC), as the oxidation attenuated the initial grooves typical of the machining process. This fact was supported by the roughness measurements, since a mild decrease in the Ra parameter was observed for the anodized surfaces versus MC. [PERSON] et al. [20] found gingival connective tissue compatibility to be constant within the smooth-classified surface roughness category, as different Ti-treated surfaces with distinct Ra values (0.075, 0.217, 0.671 and 1.024 \(\upmu\)m) showed no significant differences in human oral fibroblast attachment. In concordance with the present study, the measured decrease in Ra within this range did not impair hGF adhesion onto the Ti anodized surface. The proteomic characterization of the protein layers adsorbed onto the anodized surfaces identified 26 proteins differentially attached onto these treated surfaces versus the control (MC). A total of 14 proteins increased their adsorption after anodization (UP), while another 12 reduced their adsorption (DOWN). It should be highlighted that the anodization of the Ti abutment implied a significant change in the adsorption of proteins associated with coagulation functions. In fact, the protein that showed the greatest increase in adsorption was coagulation factor X (FA10), which was the first factor of the common coagulation pathway [21]. During hemostasis, FA10 was converted into factor Xa (FA10a), which finally led to the conversion of prothrombin into thrombin, following the formation of fibrin and the blood clot [22]. FA10a stimulated fibroblast procollagen production, proliferation and calcium signaling [23]. In this sense, the in vitro evaluation of collagen synthesis by human fibroblasts cultured onto the anodized surfaces showed a significant increase for PA after 7 days--this being the treatment showing the highest affinity for FA10 versus MC (7.7-fold higher). The anodized surfaces, in addition to having a greater adsorption of FA10, showed an increased affinity for other coagulation-related proteins such as KLKB1, ZPI, HRG and PLMN, as well as a decrease for coagulation pathway factors FA5 and FA11. KLKB1 played a role in the activation of the intrinsic coagulation pathway through the surface-activating coagulation system [24]. On the other hand, HRG and ZPI were associated with a regulatory role during blood clot formation. HRG was related to both anticoagulant and antifibrinolytic functions, being able to regulate platelet function in vivo [25]. ZPI is a serpin family protein protease inhibitor with anticoagulant functions, which, in conjunction with its cofactor (protein Z), can inhibit prothrombinase-bound FA10a during prothrombin activation [26]. After clot formation, fibrinolysis causes fibrin degradation, leading proper tissue repair.