Pivotal roles of Ta natural oxide layer in cell-driven protein remodeling and osteogenesis

3D-printed porous tantalum (Ta) and porous titanium (Ti) are extensively utilized; nevertheless, the use of pure porous tantalum in orthopedics is constrained by its high density and cost. Consequently, the deposition of Ta-coating onto the surface of porous Ti to combine the lightweight property of Ti with the superior bone integration capability of Ta has been widely reported and adopted. Upon exposure to air, the Ta surfaces rapidly form a natural oxide layer. This oxide layer promptly adsorbs proteins within seconds of implantation, acting as a crucial bridge to mediate cell-material interactions. However, few researches have focused on this natural oxide layer, and even fewer on its impact on protein adsorption. This work aims to bridge the gap between Ta and cell responses by using Ti as the control. To this end, Ta- and Ti-coating were prepared via magnetron sputtering on monocrystalline silicon and subjected to natural oxidization. Both were found to form a dense amorphous oxide layer (Ta-coating: Ta₂O₅, Ti-coating: TiO₂) with hydroxylation. Ta-coating had a higher bridging/terminal OH ratio and more negative surface potential, leading to stronger fibronectin (FN) adsorption, more RGD (Arginine-Glycine-Aspartic) exposure and lower modulus of FN layer. These differences led to varied cell traction force, driving divergent FN remodeling by osteoblasts, resulting in better mineralization, osteogenic differentiation, and in vivo bone ingrowth for Ta-coating. This work introduces a new viewpoint of "material-protein-cell" axis to uncovers the osteogenic mechanisms of Ta and provides mechanistic support to the strategy of coating Ta onto the 3D-printed Ti-based scaffolds.