| In daily life,people lack the awareness of health,safety and protection,resulting in the emergence of many infectious diseases caused by new bacteria,fungi,virus and other microorganisms,posing a great threat to human life and health as well as property safety.Although antibiotics have been widely used to treat microbial-infected wounds,chronic misuse of antibiotics have provoked the development of antibiotic resistant bacteria,gradually increasing the mortality rate caused by multidrug-resistant bacterial infections.However,natural antimicrobials such as chitosan,polyphenols and antimicrobial peptides have some problems,such as weak antibacterial activity and poor stability.At the same time,inorganic antibacterial agents such as gold,silver and other antibacterial agents have a certain antibacterial effect on infected wounds by organisms,but there are still biological safety problems.N-halamine compounds have drawn increasing research interest due to the unique properties,such as wide antimicrobial properties,fast sterilization and no drug resistance,regenerability and safety to human beings and the environment.At present,domestic scholars mainly focus on the research of antibacterial textiles,and the research in the medical field is insufficient.Foreign scholars mainly focus on small molecular N-halamines in biomedicine field,while few studies on macromolecules N-halamines.Natural macromolecules have attracted extensive attention due to their abundant resources,low cost,bioactivity and biocompatibility.Protein,as a very important class of natural macromolecules,contains a lot of amide bonds and amine groups,which makes it possible for halogenation to give it certain antibacterial properties.Therefore,this thesis mainly halogenated protein molecules,and further studied the antibacterial properties of the prepared samples in vivo and in vitro.(1)Using a convenient and simple strategy,taking gelatin sponge as the base skeleton material,a series of N-halogenated gelatine sponge(GS-Cl)samples with different active chlorine contents were prepared by changing the concentration of halogenated agent(sodium hypochlorite),and the antibacterial properties of GS-Cl samples in vitro and in vivo were studied.In vitro antibacterial experiments showed that GS-Cl had excellent antibacterial effect on Gram-positive bacteria(E.coli)and Gram-negative bacteria(S.aureus).The antibacterial property of GS-Cl-0.3 sample prepared under the condition of 0.3 % halogen concentration is optimal.The results of plate counting experiment showed that the antibacterial rate of GS-Cl-0.3 sample against two kinds of bacteria reached 100 %.The results of cytotoxicity test showed that the GS-Cl had good biocompatibility.In vivo experiments showed that GS-Cl sample could effectively promote the healing of skin wounds in a mouse E.coli and S.aureus infection models and,the GS-Cl-0.3 samples had the best antibacterial performance in vivo.(2)Firstly,homogeneous gelatin microspheres(GM)were prepared by emulsion crosslinking method.Then,GM,collagen(CG)and gelatin(Ge)with different protein structure and morphology were halogenated by halogenated agent(sodium hypochlorite).Samples of halogenated gelatin microspheres(GM-Cl),halogenated collagen(CG-Cl)and halogenated gelatin(Ge-Cl)were prepared respectively,and their antibacterial properties were studied.The results of minimum bacteriostatic concentration(MIC)and minimum bactericidal concentration(MBC)showed that under the same active chlorine content,the antibacterial performance of CG-Cl sample was the best,and GM-Cl sample was the lowest.The biocompatibility and hemolysis properties of CG-Cl,Ge-Cl and GM-Cl samples were evaluated.The results showed that the three samples have excellent biocompatibility.Subsequently,we studied the application of the GS-Cl sample in the treatment of bacterial keratitis by establishing the model of bacterial infectious keratitis.The results showed that GS-Cl sample had a good therapeutic effect on keratitis. |
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