Preparation And Properties Of Photocrosslinked Antibacterial Materials Based On Modified Gelatin GelMA

As the largest organ of the human body,skin is an essential and indispensable barrier to protect the human body from bacteria and pathogens.Once the skin is broken,bacterial infection was accompanied,which can lead to festering wounds,in severe cases,general malaise.Therefore,the research and development of antibacterial medical materials is extraordinarily crucial.As a kind of clinical medical materials,gelatin has excellent characteristics of non-toxicity and degradability,which is a hot spot in clinical medical materials.Materials prepared by gelatin are not only popular in clinical medicine,but also a hot spot in current scientific research.However,gelatin itself does not have antibacterial properties,which need to be modified by other components.In this thesis,gelatin was selected as the substrate,methacrylic anhydride（MA）was introduced for photo-crosslinking properties,combining with a variety of functional components.A series of antibacterial materials including gelatin/quaternary ammonium salt,gelatin/chitosan quaternary ammonium salt,gelatin/chitosan/N-halamine were successfully prepared by mixing different functional components,which made up for the defect that gelatin material does not have antibacterial function.The application properties of the materials were further investigated,the specific research contents of this thesis are as follows:Firstly,gelatin methacrylate（Gel MA）was prepared by grafting gelatin with MA as functional monomer.Its chemical structure was analyzed by infrared spectroscopy and nuclear magnetic resonance hydrogen spectroscopy.By mixing phenyl-2,4,6-trimethylbenzoylphosphinate（LAP）,poly（ethylene glycol）diacrylate and Gel MA,the mixture could form a hydrogel（DMC）within 1 min under 405 nm light.The blood compatibility test results show that the hemolysis rate of all hydrogels is below 2%,which will not cause damage to red blood cells,and has reliable blood safety.The results of biocompatibility test show that the survival rate of L929 mouse fibroblasts was above 92%.As the hydrogel with the highest concentration of DMC,DMC₃hydrogel could inactivate 83.23%of E.coli within 24 hours.The hydrogel can effectively reduce tail bleeding in mice within 1 min.The results of liver hemostasis experiment in rats showed that the DMC₃ hydrogel could effectively stop the bleeding of irregular and non-deformable wounds.Swelling property and porosity test results showed that all hydrogels have good fluid absorption effect and suitable porosity,which can provide a clean environment and a certain gas exchange environment for the wound.In order to further improve the antibacterial activity,chitosan quaternary ammonium salt hydroxypropyl trimethyl ammonium chloride chitosan（QCS）was selected as antibacterial component in the part.Gelatin/chitosan quaternary ammonium salt antibacterial hydrogels（Gel MA/QCS）were prepared by loading macromolecular QCS into hydrogels based on the photocross-linking properties of Gel MA in the presence of photoinitiator LAP.The results of blood compatibility test show that the hemolysis rate of all hydrogels is below 2%,which will not cause damage to red blood cells,and has reliable blood safety.The survival rate of L929 mouse fibroblasts cultured with Gel MA/QCS₁ hydrogel extract was higher than 70%,the safety performance of hydrogel was proved.Compared with Gel MA hydrogel,the addition of QCS significantly improved the antibacterial activity of the hydrogel against S.aureus and E.coli.After 8 h of Gel MA/QCS₁ hydrogel with S.aureus and E.coli,the two bacterial solutions decreased by 93.25%and 45.08%,respectively.With the further increase of QCS concentration,in the same amount of time,the Gel MA/QCS₂ hydrogel could kill 99.5%and 53.34%of S.aureus and E.coli.In addition,The effect of QCS concentration on the porosity and swelling properties of hydrogels was investigated.The addition of QCS significantly improved the antibacterial performance,but it took a long time to achieve rapid sterilization.So N-halamine with broad-spectrum antibacterial and rapid bactericidal efficacy are selected as functional components in this part.Firstly,glycidyl methacrylate-chitosan（CS-GMA）was prepared and obtained by grafting chitosan（CS）with functional monomer glycidyl methacrylate（GMA）,that endowing chitosan with the properties of photocross-linking.Gel MA/CS-GMA hydrogel was prepared by cross-linking CS-GMA with Gel MA through 2959photoinitiator.Then those gel freeze drying,and through the adsorption N-halamine antibacterial agent 1-Chloro-2,2,5,5-tetramethyl-4-imidazolinone（MC）,with efficient antibacterial effect is preparation Gel MA/CS-GMA/MC.The results of blood compatibility test showed that Gel MA/CS-GMA/MC did not cause hemolysis on red blood cells.Biocompatibility test results showed that Gel MA/CS-GMA/MC had no significant effect on the survival rate of L929 fibroblasts.The bactericidal rate of S.aureus and E.coli reached 84.99%and 94.62%within 10 min,respectively,with excellent antibacterial performance.After 60 min of contact with the two kinds of bacteria,the inactivation of the two kinds of bacteria reached 99.99%.In addition,the chlorine content,swelling property,porosity,and hemostatic performance of Gel MA/CS-GMA/MC were comprehensively evaluated.