The Surface Construction And Biological Property Study Of Thermo-responsive Multifunctional Titanium Implants Based On Bioactive Peptides

Bacterial infection is a common problem in the applications of titanium implants.Theconstruction of bacterial anti-adhesion and bactericidal surfaces are two important strategies to resist this problem.However,previous studies have found that bacterial anti-adhesion surfaces are not conductive for cell adhesion and proliferation,while bactericidal surfaces present cytotoxicity to the body,thus limiting their application.And some hydrophilic polymers that can resist bacterial adhesion will produce toxic amines.It is still a huge challenge to construct ideal antibacterial infection surfaces.Based on the different stages during implantation,this thesis constructed responsive intelligent surfaces with thermo-responsive polymer(P(MEO₂MA-co-OEGMA))combining with RGD(or AMP),which could selectively express different biological functions in response to temperature changes of the surrounding microenvironment during surgery.The surfaces can achieve controlled exposure and hide of RGD(or AMP)by utilizing a reversible conformational extension-collapse change of the polymer at different temperatures,preventing bacteria from adhering to the surface of the implants,or to kill bacteria on the surface.Meanwhile,this implant also presented good biocompatibility to the body.Firstly,the temperature-responsive characteristics of Ti-A-MPEG_n-RGD and Ti-A-MPEG_n-AMP(n=1.5,3.0 and 4.3)titanium implant surface were studied.The two functionalized surfaces selectively hided and exposed surface peptides in response to the temperature changes.Ti-A-MPEG_n-RGD responds to the temperature changes of 25?and 37?,while Ti-A-MPEG_n-AMP responds to changes in temperature 25?,37?and 42?.Secondly,the biological function in vitro of titanium implant surface was studied.During surgery temperature(25?),the inhibition rates of Ti-A-MPEG_n-RGD and Ti-A-MPEG_n-AMP on Staphylococcus aureus adhesion in vitro were more than 90%.At physiological temperature(37?),the adherence and proliferation of human bone marrow mesenchymal stem cells(h BMSC)could be enhanced with these implant surface by 20%.And these implant surfaces also promoted h BMSC osteogenic differentiation.When local infection occurred(42?),the surface of Ti-A-MPEG_n-AMP killed more than 93%of the common clinical pathogens.Finally,the biological characteristics of the implants in vivo were studied by using the bacterial adhesion infection and bacterial implantation infection models of New Zealand rabbits.The results showed that Ti-A-MPEG_3.0-RGD effectively inhibited more than 95%bacterial adhesion to the surface of the implant in the model of bacterial adhesion infection.Ti-A-MPEG_3.0-AMP killed more than 95%of bacteria in the model of bacterial implantation infection.These implants also reduced the inflammatory response of the skin tissue around the implant site,facilitated tissue repair and healing,and presented anti-inflammatory effects.The above studies provide strategies for solving the problems such as the inhibition ofadhesion and proliferation of normal cells by bacterial anti-adhesion surface and the toxic and side effects of bactericidal surface on the body.