Structural Regulation Of Titanium By Adding Oxygen Atoms To Improve Implant Strength And Promote Osseointegration

Pure titanium（CP-Ti）has become the preferred material for implants owning to its good biocompatibility.However,CP-Ti implants are limited in clinical use due to its low strength.For example,the diameter of the implants is generally larger than 3.5 mm,or some implants may crack or even fracture sometimes.With the wide application of implant restoration technology,higher requirements are putting forward for the mechanical properties of implant materials.In recent years,the structure regulation method is an important method to change the mechanical properties of metal materials.Through the change of the macro composition and microstructure,such as grain size,grain orientation and grain morphology,the strength of materials could be improved significantly.The previous research showed that the mechanical properties of ultrafine grained materials formed by grain refinement of CP-Ti have been greatly improved,while retaining the good biocompatibility of CP-Ti.However,simply adjusting the grain structure will reduce the ductility and fracture toughness of the material during use,which will affect its service life.Nowadays,some studies have shown that by embedding oxygen atoms into the lattice could regulate the composition and grain size of the material.And the regulation of the internal structure could achieve the purpose of improving the mechanical strength and maintaining the plasticity of the material.However,whether the high oxygen concentration pure titanium formed by oxygen atom solid solution regulation could retain the good biocompatibility of CP-Ti both in vivo and vitro while improving the mechanical properties are not clear and need to be further investigated.Therefore,in this study,in cooperation with Northwestern Polytechnic University and Osaka University,our group tried to use powder metallurgy methods（PM）to prepare high oxygen concentration titanium material（HOC-Ti）.The internal changes in the material preparation process,as well as the structural characteristics,mechanical properties,and electrochemical properties of the prepared HOC-Ti were investigated to clarify the relationship between the increased oxygen concentration and the changes in structure,as well as phychemical properties.Then,a special micro-nanocomposite morphology was constructed on the HOC-Ti surface,and the surface properties were investigated.After evaluating the biosafety of HOC-Ti,the ability of promoting bone formation of HOC-Ti which loaded with micro-nano composite structure was systematically investigated and the potential biological mechanism was explored.Finally,HOC-Ti implant was processed and implanted into New Zealand White rabbits after surface treatment to construct the in vivo experimental model.Then the remodeling speed of bone tissue around the implants and the osseointegration quality were analyzed.All above results laid the foundation for the potential clinical application of HOC-Ti.This study is divided into five parts.Part Ⅰ Preparation and the structure regulation of HOC-Ti1.Preparation and compositional analysis of HOC-Ti.In the process of powder metallurgy,titanium dioxide in the mixed powder decomposes into pure titanium,and its internal oxygen atoms overflow into the surrounding materials.The internal oxygen concentration of the HOC-Ti prepared in this study is up to 0.8 wt%,which significantly higher than that of ordinary pure titanium（0.4 wt%）,and is consistent with the oxygen concentration in the mixed powder before the experiment.The crystal structure of Ti shows that the TiO₂ powder inside the HOC-Ti is completely decomposed during the preparation process,and the oxygen atoms exist in the crystal of the material in the form of solid solution elements,and no titanium oxide and other substances are formed.2.Structure analysis of HOC-TiHOC-Ti with different oxygen concentration has characteristic diffraction pattern ofα-Ti.The increase of oxygen concentration makes the two characteristic diffraction peaks of HOC-Ti（2θ={10（?）0}and{0002}）shift to smaller orientation,and the lattice constant C of HOC-Ti also had an upward trend with the increased oxygen concentration,indicating that the lattice of the material expanded significantly along the c axis after oxygen entered the material.At the same time,the grain size of HOC-Ti is also refined,and has higher grain boundaries and dislocation densityIn general,HOC-Ti still maintains the crystallographic characteristics of pure titanium,and the increase of oxygen concentration effectively regulates the internal structure of HOC-Ti.Part Ⅱ Mechanical properties and electrochemical study of HOC-Ti1 Study on mechanical properties of HOC-TiThe mechanical properties of the HOC-Ti prepared in this study are significantly improved compared with CP-Ti.The tensile yield strength of HOC-Ti shows a trend of synchronous increase with the oxygen concentration.Ti-0.79wt%HOC-Ti shows the highest yield strength,reaching about 1200MPa,which is much higher than 500MPa of CP-Ti.The fracture toughness of HOC-Ti has different trends with the increase of oxygen concentration,which shows a trend of increasing first and then decreasing.The fracture toughness of HOC-Ti in the Ti-0.52wt%group is the best.Therefore,the Ti-0.52wt%group of HOC-Ti has the most suitable mechanical properties for subsequent experiments2.Study on the electrochemical properties of HOC TiHOC-Ti has higher open circuit potential（OCP）,polarization potential and lower polarization current density than CP-Ti in 0.5%HF electrolyte,indicating that HOC-Ti has better corrosion resistance.The performance changes of HOC-Ti in electrochemical performance will provide new ideas for subsequent material surface treatmentThis part of research shows that the structural changes of HOC-Ti caused by the increase of internal oxygen concentration will further affect the physical and electrochemical properties.Part Ⅲ Fabrication and study of micro-nano composite structure on HOC-Ti surface1.Construction and characterization of the composite structure on the surface of HOC-TiAfter the surface treatment of HOC-Ti using anodic oxidation method,the morphology composite of micron sized crater like structures（about 20μm in diameter）and nanotube（about 100nm in diameter）was formed on the surface of HOC-Ti（HOC-NT）.XRD results suggested that the composition of the composite structure was Ti O₂ only.2.The surface properties of the composite structure on the HOC-TiThe micro-nano composite morphology constructed on the surface of HOC-Ti has good hydrophilic properties,and its water contact angle is 35.78±0.21°,which is significantly lower than that of the polished surface（68.03±1.45°）,and lower than that of CP-Ti with simple nanotube array structure on the surface（45.87±0.36°）.The surface roughness of HOC-Ti with micro-nano composite structure is also in the favorable position for bone remodeling.The surface hardness and Young’s modulus of HOC-Ti with micro-nano-composite morphology on the surface are reduced compared to the polished surface morphology,which is closer to the mechanical properties of natural bone and may prevent the potential stress shielding phenomena in subsequent clinical use.The better corrosion resistance and stronger bonding force of HOC-NT also laid the foundation for the long-term service of HOC-Ti implants in the oral.This part of the research shows that anodic oxidation method magnifies the difference in electrochemical performance of HOC-Ti.The micro nano composite morphology constructed on the HOC-Ti surface in the form of one-step method exhibited good surface performance,which has a potential role in promoting the biological performance of HOC-Ti.Part Ⅳ The bone formation promoting ability of HOC-Ti and its potential mechanism1.Biocompatibility experiment of HOC TiAfter treated with anodic oxidation,the biocompatibility of HOC-Ti loaded with micro nano composite morphology（HOC-NT）was studied.The results show that the HOC-NT group has better hydrophilicity and suitable roughness compared with the conventional SLA treatment surface,and shows excellent protein adsorption capacity.The osteocytes and osteoblasts adhered to the surface of HOC-NT also showed better adhesion,proliferation,migration ability and higher cell activity.The results indicated that HOC-NT has good biocompatibility,which could be used for the further study of osseointegration promotion.2.The bone formation promoting ability of HOC TiThe micro nano composite structure on HOC-Ti surface has a well-behaved biocompatibility,as well as has a clear regulatory effect on the adhesion cells.In specific,the micro nano composite structure could guide macrophages transform into M2 subtype with anti-inflammatory functions,inhibit the expression of osteoclast related proteins（sclerostin）in osteocytes and promote the differentiation of osteoblasts.All above ability indicate a better bone formation promoting effect.RNA-sequence analysis revealed that the micro-nano composite morphology may affect the osteogenic differentiation of osteoblasts through MAPK pathway by changing the adhesion state of osteoblasts on the surface of HOC-Ti.At the same time,it may change the physiological function of osteocyte cells by causing endoplasmic reticulum stress.This part of the research has proved that HOC-Ti has good biocompatibility.After formed the micro nano composite structure on surface,HOC-Ti shows a better bone formation promoting properties in vitro.Part Ⅴ Osseointegration performance of HOC-Ti implant in vivoThe HOC-Ti material was processed into implant and the micro nano composite structure was loaded on its surface.The New Zealand white rabbits was selected to construct the animal experimental model.The HOC-Ti implants loaded with micro nano composite surface morphology showed a faster bone remodeling rate.And there was also a denser peri implant bone at the 5th and 9th weeks after implantation.After the formation of osseointegration,the HOC-Ti implant showed the highest vibration frequency,representing the best implant stability and the most perfect formation of osseointegrationThe results of the in vivo experimental study of the HOC-Ti implant are consistent with the in vitro study.All above research indicated the effect of promoting osseointegration formation of HOC-Ti.This part of the study also laid the foundation for the clinical application of HOC-Ti.