Construction Of Multifaceted Bioactive Coatings On Titanium Dental Implants And The Underlying Mechanism As Regards Advanced Osseointegration

Titanium and its alloys have been widely used clinically as hard tissue implants due to their satisfying mechanical properties,corrosion resistance,and biocompatibility.However,the surface of the titanium implant is bio-inert and leads to loosening and infection,which are two major complications after implantation.This poor osseointegration will ultimately result in failure of the implant.Surface modification of titanium can confer it ideal biological activity,thus has been regarded as an effective and promising approach to solve the loosening and infection.However,most studies performed currently have inconsistent results in vitro/vivo,which indicated that multiple factors need to be considered in mediation of osseointegration.Osseointegration is a long-term physiological process that changes dynamically over time,which in turn undergoes the formation of blood clots,immune responses,angiogenesis,and osteogenesis.The process involves the synergistic action of various cells such as platelets,macrophages,endothelial cells,and osteoblasts.Most studies only focus on stimulating osteogenesis or angiogenesis while neglecting the interactions among each stage in osseointegration.Therefore,a multifaceted surface coating that will mediate the above-mentioned various cell behaviors has raised us intense interest.In this study,physical and chemical modification methods were used to design five different surface structures on the surface of pure titanium implants.The effect of the coatings on at least two stages involved in osseointegration were systematically investigated.The results showed that the five surface coatings possessed reliable multifunctionality,and some of the In vivo results were consistent with the In vitro one.Based on the work,the research results obtained are as follows:?1?Five Ti-Ag coatings with different Ag contents were obtained on the pure titanium substrate through one-step magnetron sputtering process.Ti-Ag coatings can not only inhibit the proliferation of the bacteria as the content of Ag increased from1.2 at.%to 21.6 at.%,but also promote the proliferation and differentiation of osteoblasts by the sustained release of Ag ions.Additionally,this study indicates that various active elements can be loaded on the surface of titanium through the facile and economical magnetron sputtering.?2?Based on the above studies,five Ti-Si coatings with different Si content were prepared on the titanium substrate by magnetron sputtering.Anodic oxidation was then employed to obtain Si-containing TiO₂ nanotubes.It was found that Ti-Si nanotubes can not only promote the proliferation and differentiation of osteoblasts,as the content of Si increased from 1.2 wt.%to 10.7 wt.%,but also enhance the function of endothelial cells osteoblasts by the sustained release of Si ions.To the best of our knowledge,this project firstly solved the loading problem of non-metallic Si elements in nanotube arrays.The combination of topological cues and the chemical cues?Si?confers titanium implants with the capacity for inducing the osteogenesis and angiogenesis;?3?The microporous coating was obtained on pure titanium by one-step micro-arc oxidation.Following steam-hydrothermal treatment enabled micro/nano hybrid structures with nano-sized hydroxyapatite?HA?particles/rods on the surfaces.The hybrid structures can not only stimulate macrophages to suppress the inflammatory but also manipulate a favorable immune microenvironment to promote the proliferation and differentiation of osteoblasts and endothelial cells through multiple signaling pathways?TGF-?,OPG/RANKL,and VEGF?.Additionally,in combination with the favorable osteoimmunomodulation,the synergistic surface physiochemical properties further promoted the function of osteoblasts and endothelial cells,ultimatelyacceleratedtheosseointegration.Incontrast,thenano-rods micro/nanostructure inhibits the function of the aforementioned cells,thereby inhibited the osseointegration;?4?Based on the above studies,we found that nano-HA particles on titanium had a positive impact on a variety of cells and subsequent osseointegration.Therefore,we further explored the effect of the size of nano-HA particles on osseointegration.Similarly,a microporous coating was obtained on titanium by micro-arc oxidation.Annealing treatment was then used to obtain the micro-nano hybrid structures with HA particles in different nano-size.It was found that the hybrid structures can not only stimulate macrophages to suppress the inflammatory,but also manipulate a favorable immune microenvironment to promote the proliferation and differentiation of osteoblasts and endothelial cells through multiple signaling pathways?TGF-?,OPG/RANKL,and VEGF?.Noteworthy,the effect is positively correlated with the size of the HA particles.Additionally,in combination with the favorable osteoimmunmodulation,the synergistic surface physiochemical properties further promoted the function of osteogenic/endothelial cells through multiple signaling pathways and ultimately promoted osseointegration;?5?Different diameters?15 nm,60 nm,120 nm?of TiO₂ nanotube arrays were prepared on pure titanium by one-step anodization.It is found that nanotubes of 15nm can upregulate the platelet activation and manipulate the clot fiber structure?fiber thickness and porosity?.Additionally,the physical structure and the released active factors?PDGF-AB and TGF-?1?from the clot can also manipulate a favorable immune response by macrophages.The beneficial immune microenvironment further promotes osseointegration through osteoimmunmodulation.