Titanium dental implants hydrophilicity promotes preferential serum fibronectin over albumin competitive adsorption modulating early cell response

In vitro studies have consistently shown that titanium surface wettability affects the response of osteoprogenitors, leading to important advances in the clinical osseointegration of dental implants. However, the underlying molecular mechanisms remain unknown. Since surface conditioning by blood components initiates within milliseconds after insertion, it is reasonable to hypothesize that the amount and the type of blood proteins adsorbed influences the interaction between the implant surface and osteoprogenitors. To test this hypothesis, titanium implant surfaces with different characteristics, in terms of topography and wettability, have been conditioned with selected plasma proteins. Pure fibronectin (HFN) and albumin (HSA) solutions, or their mixture at the relative plasma concentrations were allowed to adsorb on titanium surfaces for 60 min. Protein adsorption was monitored by Bradford assay, while the contribution of HSA and HFN in forming the microfilm layer at the interface was studied by Western Blot. Subsequently, the same protein-conditioned surfaces were used to culture C2C12 cells, thus studying their capacity to adhere and to spread after 3 h. Cell viability was evaluated up to 7 days, while the expression of osteogenic genes was assessed after 3 days. Under competitive adsorption conditions, hydrophilicity promotes the selectivity of titanium for HFN regardless of the surface microtopography. As a consequence of selective HFN adsorption, cells on hydrophilic surfaces displayed enhanced adhesion and spreading, as well as increased proliferation. On the other hand, selective HFN adsorption did not appreciably affect cell differentiation. These data suggest that implant surface hydrophilicity plays a key role in guiding the selective adsorption of specific proteins from blood plasma. Moreover, the selective adsorption of HFN, as a consequence of surface hydrophilicity, was found to account for early cell responses amelioration. Thus, titanium surface hydrophilicity contributes to the clinical success of dental implant by selectively controlling protein adsorption at the interface.