Surface Modification Of Bacterialinfection-responsivematerials Andcharacterization Ofits Antibacterial Properties

With the development of science and technology,more and more people have gradually accepted implanted materials in the body.Among the materials implanted in the body,bone implant materials are widely used in the treatment of fractures,nonunion,bone column fractures and deformities,and arthritis.Implanted biomaterials have two major problems:1.The surface of bacterial biofilm causes infection and hardly been removed well;2.The surface has poor biocompatibility.For artificial joints,a serious infection leads to reoperation,arthritis,amputation,or even death.It is quite large that the number of people affected by implant infection in the world every year.Therefore,the anti-infective treatment on the implanted material surface is an urgent problem to be solved.At present,the design of surface-loaded antibiotics on titanium alloys cannot meet the actual needs of clinical Total Joint Replacement(TJA)infections.The ideal release of antibiotics on the surface of artificial joints should be the specific release of an infection-responsive type:When infection does not occur,the antibiotic does not release substantially;in the event of infection,antibiotics can quickly fall off from the surface of the prosthesis.In this project,an antibiotic drug was attached to the surface of a titanium alloy prosthesis by a protease-sensitive peptide chain.It can use the protease produced by aggregation of Staphylococcus aureus to cut the peptide chain and release the drug around the prosthesis so as to achieve the purpose of releasing the antibiotic in response to infection on the surface of the titanium alloy prosthesis.In this study,we firstly examined two different methods that for introducing amino groups on the surface of medical titanium alloys:the use of N'N-carbonyldiimidazole/polyethyleneimine(CDI/PEI)to introduce the amino group to the titanium alloy(TC4)substrate and the use of aminopropyltriethoxysilane(KH550)to introduce the amino group to the titanium metal.The best method conditions for the introduction of amino groups was determined.At the same time,the characterization methods suitable for this substrate and this experimental scheme were selected.The connection scheme between the drug and the peptide end group was investigated.The results of mass spectrometry and other characterizations indicated that the peptide was difficult to react with the polypeptide due to the structure of the peptide.Therefore,we review the literature and re-selected the peptide sequence which are sensitive to the splB enzyme secreted byStaphylococcus aureus;Finally,the program for determining the modification of the titanium alloy surface is using KH550 to introduce amino groups into the surface of titanium metal,using 4-(N-Maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt(Sulfo-SMCC)to link the polypeptide to the surface of the titanium;Using an amide bond linking the drug at the end of the polypeptide,thereby completing the construction of the infection responsive function of the titanium alloy surface.The physicochemical structure of the surface was analyzed by X-ray photoelectron spectroscopy(XPS),energy dispersive spectroscopy(EDS)and other major characterization methods.The results showed that the drug was successfully linked to the titanium alloy surface through a bacterial-sensitive peptide chain.In addition,the surface functionalized titanium alloys were subjected to in vitro enzyme-clearing drug release assays,cytotoxicity,and responsive bacteriostatic efficacy tests.The enzyme digestion experiments showed that the peptide could be successfully released by splB cleavage.Cytotoxicity experiments showed that the surface of the modified medical titanium alloy had good biocompatibility,bacterial experiments further demonstrated that surface-modified titanium metal has a reactive inhibitory effect on staphylococcus aureus.