Nanostructured Titanium Implant Surface Facilitating Osseointegration from Protein Adsorption to Osteogenesis: The Example of TiO2 NTAs

Titanium implants have been widely applied in dentistry and orthopedics due to their biocompatibility and resistance to mechanical fatigue. TiO₂ nanotube arrays (TiO₂ NTAs) on titanium implant surfaces have exhibited excellent biocompatibility, bioactivity, and adjustability, which can significantly promote osseointegration and participate in its entire path. In this review, to give a comprehensive understanding of the osseointegration process, four stages have been divided according to pivotal biological processes, including protein adsorption, inflammatory cell adhesion/inflammatory response, additional relevant cell adhesion and angiogenesis/osteogenesis. The impact of TiO₂ NTAs on osseointegration is clarified in detail from the four stages. The nanotubular layer can manipulate the quantity, the species and the conformation of adsorbed protein. For inflammatory cells adhesion and inflammatory response, TiO₂ NTAs improve macrophage adhesion on the surface and induce M2-polarization. TiO₂ NTAs also facilitate the repairment-related cells adhesion and filopodia formation for additional relevant cells adhesion. In the angiogenesis and osteogenesis stage, TiO₂ NTAs show the ability to induce osteogenic differentiation and the potential for blood vessel formation. In the end, we propose the multi-dimensional regulation of TiO₂ NTAs on titanium implants to achieve highly efficient manipulation of osseointegration, which may provide views on the rational design and development of titanium implants.