The Construction And Biological Behavior Of Antibacterial Micro/Nano Bionic Coatings On Pure Titanium Implant Surface

Biomedical metal titanium?Ti?has a broad application prospect in the field of hard bone tissue replacement due to its low density,close elastic modulus to human bone and superior biocompatibility to stainless steel and cobalt-based alloy.However,Ti is a kind of biologically inert materials with low biological activity.It can only be combined with bone in a mechanically interlocking manner instead of synostosis.Moreover,Ti itself has no antibacterial ability,which can easily cause bacterial adhesion,resulting in a series of complications such as implant infection and loosening.Since the interaction between the Ti implant and the surrounding tissue environment mainly occurs on the surface of the implant,the proper surface modification of Ti implant is carried out to improve its biocompatibility,antimicrobial properties,corrosion resistance,thus promoting the bone integration,which has important clinical research significance.The common surface modification methods include surface morphology and chemical modification.Since the micro/nano morphology is capable of mimicking the structure of human bone tissue and the release of surface chemical components can promote cell response,this study combines the two kinds of surface modification approaches to form a bioactive coating on the surface of inert Ti by simultaneously introducing both the antibacterial elements and bone-philic elements,as well as being endowed with micro/nano surface topography with bionic effects.The surface characteristics,antimicrobial properties,corrosion resistance,biocompatibility,osteoblast differentiation,angiogenesis and in vivo osseointegration performance of the modified bioactive coatings were evaluated.The main research contents and research results of this paper are as follows:?1?Silver?Ag?-containing antibacterial film was firstly deposited on Ti surface by magnetron sputtering technique and then strontium?Sr?elements were successfully loaded onto antibacterial film by micro-arc oxidation technique to form Ag/Sr-TiO₂ porous coatings.The results showed that the coatings were mainly composed of anatase Ti O₂ and rutile TiO₂.The content of Ag in the micropores on the coating surface was significantly higher than that surrounding the micropores,which avoid the direct contact between Ag and body tissues,to produce cytotoxicity.Besides,the rapid release in the early stage and the sustained and stable release in the later period of Ag⁺make the coating exhibit effective and long-term antibacterial activity against both Escherichia coli?E.coli?and Staphylococcus aureus?S.aureus?.When the release amount of Sr²⁺and Ag⁺of the coating were within the safety threshold,it would not be toxic to cells.Further,the incorporation of Sr promote the osteoblast adhesion,spreading,proliferation and differentiation.?2?Copper?Cu?-containing antibacterial film was firstly deposited on Ti surface by magnetron sputtering technique and then Cu-TiO₂ coating was successfully prepared after annealing treatment technology.The results show that the coating was mainly composed of TiO₂ and CuO.The Cu elements on the surface of coating showed strong bactericidal effect on S.aureus,and the Cu content was within the safety threshold,which not only produce no toxic to osteoblast,but also can obviously promote the osteoblast adhesion,spreading and proliferation.Due to the dense structure of the coating and the presence of insulating CuO,the corrosion resistance of the coating was significantly improved,which can effectively protect the substrate from the erosion of body fluids.?3?Cu/Si-TiO₂ porous coatings were successfully prepared on Ti surface by one-step micro-arc oxidation technique.The single Cu doping resulted in the formation of micrometer-sized large particles on coating surface,while the further doping of Si resulted in the disappearance of micrometer-sized particles.With the increase of Si doping amount,the nanoparticles produced on the coating surface and gradually became larger.The Cu/Si-TiO₂ coating is mainly composed of TiO₂,Cu O,Ca₃?PO₄?₂ and CaSiO₃.The long-term controlled release of Cu²⁺on the coating surface gives the material a long-lasting antibacterial effect,which can effectively reduce the postoperative infection of the implant.The coating doped with single Cu element showed osteogenic and endothelial cell toxicity due to the higher Cu content and Cu²⁺release.However,the Cu/Si-TiO₂ coatings produce no toxicity by introduction of Si elements on the coating surface.When the release amounts of Cu²⁺and Si²⁺were within the safety threshold,the coating can not only obviously promote the cell adhesion,spreading,proliferation and differentiation of osteoblasts,but also improve the secretion of vascular endothelial growth factor?VEGF?and the formation of blood vessels of endothelial cells and the osseointegration.?4?The porous Si doping TiO₂ coatings were firstly prepared on Ti surface by micro-arc oxidation technology,and then the different nano-beam,nano-rod or nano-leaf structure were constructed by hydrothermal treatment technology to form a gradient micro/nanoscale Si-TiO₂ porous coating.The coating was mainly composed of TiO₂,Ca₃?PO₄?₂ and CaSi O₃,but the hydrothermal treatment leads to the improvement of TiO₂ crystallinity and the phase transformation from CaSiO₃ to Ca₃?PO₄?₂.Si mainly existed on the porous structure surface at the bottom of the nanostructure,and the hydrothermal treatment resulted in a significant decrease in the Si content on the coating surface,but there was no significant reduction in the release amount of Si²⁺.The combination of the safe and controllable Si²⁺release from coating and the nanostructure on the coating surface,especially the nano-leaf structure surface,can not only obviously promote the cell adhesion,spreading,proliferation and differentiation of osteoblasts,but also improve the secretion of VEGF and the formation of blood vessels of endothelial cells and the osseointegration.In summary,surface modification of bio-inert materials endow coating with specific micro-nano surface morphology and suitable reactive ion release.The modified coating exhibits the best long-lasting antibacterial property,osteogenic activity and vascularization in vitro,and can be used as hard tissue implant coating material that has a broad application prospect.