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Bingfeng Wu,1,* Yufei Tang,1,2,* Kai Wang,3 Xuemei Zhou,3 Lin Xiang1,4 1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, Peopleâs Republic of China; 2Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, Peopleâs Republic of China; 3School of Chemical Engineering, Sichuan University, Chengdu, Sichuan, Peopleâs Republic of China; 4Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, Peopleâs Republic of China*These authors contributed equally to this workCorrespondence: Xuemei Zhou, School of Chemical Engineering, Sichuan University, No. 24th, South Section 1, Yihuan Road, Chengdu, 610065, Peopleâs Republic of China, Email xuemeizhou@scu.edu.cn Lin Xiang, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases Sichuan University, No. 14th, 3rd Section, Renmin South Road, Chengdu, 610041, Peopleâs Republic of China, Tel +86 28 85503579, Email dentistxiang@126.comAbstract: 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.Keywords: nanostructure, TiO2 nanotube arrays, titanium implant, osseointegration, anodization |
