Study On The Immune Response Of Nanostructures And Functional Elements On Titanium Surface

Titanium and its alloys are the preferred materials for surgical implants due to their good biocompatibility and physical properties.However,the failure of biomaterial implantation occurs due to the delayed bone formation around the implants and the impaired bone-biomaterial interface in the clinic.With the development of the research on biomaterials,the host innate immune response caused by biomaterials,especially the polarization（M1/M2 phenotype）and inflammatory secretion of macrophages,will directly affect the osseointegration.Therefore,it is of great scientific significance to regulate the immune response of macrophages by the surface modification of biomaterials to promote the rapid and stable bone-biomaterials integration.In this work,the different nanostructures were constructed on the surface of titanium by the hydrothermal method to study the effects of nanostructures on the immune response of macrophages and the molecular mechanism.The ds-block elements copper,zinc,and silver were introduced onto the titanium substrate by plasma immersion ion implantation（PIII）method to investigate the immune responses of macrophages and the molecular mechanism.Additionally,the interaction and mechanism between macrophages and mouse bone marrow mesenchymal stem cells（m BMSCs,referred to as stem cells）on the modified biomaterials were also explored.The main results obtained are described as follows:1.The different nanostructures were constructed on the surface of titanium by hydrothermal method,and they with the same composition are of various elastic modulus:the average elastic modulus of the nanostructural surface was inversely proportional to the third power of the nanostructure aspect ratio（h/d）and proportional to the density（n）of nanostructure bundles.The nanostructures with different surface elastic modulus would bend to a different extent under the action of cellular force and cause cells to adhere to them being stretched.The pulling effect was proportional to the surface elastic modulus of nanostructures and influenced the adhesion and spread of macrophages on the nanostructures,and further regulated the immunological response of macrophages through the FAK-NF-κB signaling pathway.2.Three most used ds-block elements,copper,zinc,and silver were introduced onto titanium substrate by plasma immersion ion implantation method（PIII）.The PIII samples exhibited good antibacterial and anti-inflammatory effects.The trend of anti-inflammatory effects of macrophages on samples was in the correlation with cellular ROS levels through the PGE2 signaling pathway,which was induced by samples and positively correlated with the number of valence electrons of ds-block elements in their steady states(Cu²⁺,Zn²⁺,and Ag).Additionally,macrophages and stem cells（m BMSCs）regulate each other biological responses through the paracrine action of PGE2 to further improve the anti-inflammatory effect and bone differentiation effect of the sample surface.3.The different contents of silver were loaded on the titanium surface by the PIII method.There formed the micro-galvanic couple between the embedded Ag NPs and Ti matrix on Ag-PIII samples and the number increased with the increase of silver content,which could consume protons（H⁺）in the intercellular membrane of bacteria and cells.On the one hand,it interfered with the synthesis of ATP in bacterial to kill them.On the other hand,it stimulated macrophages to produce ROS and promote macrophage polarization toward M2 phenotype by activating PGE2 signaling pathway,and improve the anti-inflammatory effect of samples.Additionally,macrophages and stem cells（m BMSCs）regulated each other through paracrine of PGE2 to further improve the anti-inflammatory response of macrophages,and the osteogenic differentiation of stem cells（m BMSCs）on samples.