| Backgrounds:Excessive bleeding is the main cause of death in wartime and in peacetime accidents,while infection is the common complication of trauma and the main cause of death in the later treatment.Therefore,it is necessary to design and explore a safe hemostatic material with fast hemostasis and effective antibacterial.At present,the fast hemostasis products commonly used in the battlefield are mainly divided into organic polymer materials and inorganic materials.The hemostasis ability of inorganic hemostasis materials is obviously better than that of organic polymer hemostasis materials.As the optimized product of inorganic materials,mesoporous silica nanoparticles?MSN?have the characteristics of porous structure,large specific surface area and high rate of volume,which make it have the good hemostasis ability.Calcium ions,as one of the 13 coagulation factors,play an important role in the process of coagulation,which are often used in the study of hemostasis.In addition,gallium ions not only have a good antibacterial ability,but also have a good hemostatic performance,showing a good application prospect in hemostasis,which will start to attract people's interest.But at this stage,there is few studies on the preparation of hemostatic materials with gallium ion,so it is worth our research and exploration on it.The single component hemostatic materials have limitation,which will not meet the actual needs.Therefore,it is hoped that mesoporous silicon can be loaded with calcium ions and gallium ions to prepare ternary composite materials to improve the hemostatic performance of mesoporous silicon and endow it with antibacterial ability,so that it can achieve the requirements of fast hemostatic and effective antibacterial.Objective:Based on the preparation of mesoporous silica nanoparticles with controllable particle size and pore diameter,the ternary composite hemostatic materials were prepared by mixing MSN with different concentrations of calcium nitrate and gallium nitrate solution.The best mixing method was selected through the evaluation of coagulation test in vitro.And then the antibacterial performance of the material was studied and compared through the antibacterial experiment.The biocompatibility of the material was studied through the blood compatibility experiment and the cytotoxic test.The hemostatic performance of the composite was further verified through the animal experiment,in order to prepare a kind of safe hemostatic materials with rapid hemostasis and antibacterial ability.Method:?1?The mesoporous silica nanoparticles with controllable pore size and particle size were synthesized by hard template method,and the best mesoporous silica substrate was selected.?2?MSN were mixed with 0.5mo L/L,1mo L/L and 1.5mo L/L calcium nitrate solution respectively to prepare calcium doped mesoporous silica nanoparticles?CA-MSN?.CBT,APTT,Pt and TEG were used to study its hemostatic properties and find the most suitable mixture way.The surface chemistry,morphology and porous structure were characterized by TEM,XRD and FTIR.?3?MSN doped with gallium?Ga-MSN?were prepared by mixing MSN with 0.5mo L/L,1mo L/L and1.5mo L/L gallium nitrate solution respectively.The hemostatic properties of Ga-MSN were investigated by CBT,APTT,Pt and TEG to achieve the best mixture method.The surface chemistry,morphology and porous structure were characterized by TEM,XRD and FTIR.?4?MSN doped with calcium and gallium?Ca/Ga-MSN?were prepared by mixing MSN with 1mo L/L calcium nitrate and 0.5mo L/L gallium nitrate solution,0.5mo L/L calcium nitrate and 0.25mo L/L gallium nitrate solution.And then CBT,APTT,PT and TEG were measured to study the hemostatic properties of the materials.The surface chemistry,morphology and porous structure were characterized by TEM,N2 gas adsorption–desorption method,XRD and FTIR.Through the antibacterial experiment,the antibacterial properties of the materials were compared.The biocompatibility of the materials was studied by blood compatibility test and cytotoxic test.Based on the comprehensive hemostatic performance,antibacterial performance and biocompatibility,the materials with good hemostatic performance and antibacterial ability were selected.The hemostatic materials were tested by animal experiments to further verify the hemostatic performance of the composite materials.Results:?1?The pore size?12nm?and particle size?50nm?controlled MSN which were successfully prepared by organic template method were selected as the basic material;?2?The results of coagulation test in vitro showed that Ca MSN obtained by mixing MSN with 1mo L/L calcium nitrate solution had the best coagulation effect;?3?The results of coagulation test in vitro showed that Ga0.5MSN prepared by mixing MSN with 0.5mo L/L gallium nitrate solution had the best coagulation effect;?4?The results of blood compatibility test showed that the introduction of calcium or gallium ion also had no effect on blood compatibility and all the materials had good biocompatibility.The TEM,FTIR and XRD showed that the introduction of ion did not cause significant impact on the pore diameter and particle size of mesoporous silica.After the introduction of calcium or gallium ion,there was a only-(1350-1380cm-1)appeared at 1350cm-1.The other absorption peaks also had no obvious changes,which meant these two ion did not influence the skeleton structure and crystal form of the mesoporous materials,and they all existed in the skeleton of the mesoporous silicon materials in the form of amorphous state;?5?It could be found that the mesoporous silica mixed with 1mo L/L calcium nitrate solution and 0.5mo L/L gallium nitrate solution to prepare the calcium/gallium doped mesoporous silica materials?Ga0.5Ca MSN?had the best hemostatic ability.The antibacterial experiment results showed that the introduction of gallium ion could endow the material hemostasis performance and Ga0.5Ca MSN had good antibacterial performance on Staphylococcus aureus and Escherichia coli.The blood compatibility experiment results showed that the introduction of calcium ion and gallium ion would not affect the blood compatibility,and all materials had good biocompatibility.Cytotoxicity test showed that MSN could promote cell proliferation,and after the introduction of two ions,Ga0.5Ca MSN promoted cell proliferation much more obviously.Considering the hemostatic performance,antibacterial performance and biocompatibility,Ga0.5Ca MSN was the most suitable hemostatic agent.The TEM,N2 gas adsorption–desorption method,FTIR and XRD showed that the introduction of two kinds of ions also did not influence the pore size and particle size of mesoporous silica and had no influence on the skeleton structure and crystal form of mesoporous materials.The animal experiments proved that Ga0.5Ca MSN truly had good hemostatic ability.Therefore,the Ga0.5Ca MSN which meets the requirements of fast hemostasis,effective antibacterial and safety prepared in this study will be an ideal fast hemostatic material in the field of war.Conclusion:?1?The MSN with 12 nm pore size and 50 nm particle size had stable structure,large yield and excellent hemostatic performance;?2?Introduction of calcium ion could enhance the hemostatic performance of MSN and promote cell proliferation,without affecting the skeleton of MSN.The prepared Ca MSN had the best hemostatic ability and good biological activity;?3?The introduction of a small amount of gallium ion could enhance the hemostatic performance of MSN,but too much gallium ion would reduce the hemostatic effect,probably because the introduction of gallium ion affected the pore volume of MSN.The introduction of gallium ion also promoted cell proliferation and endowed the material antibacterial properties.The introduction of gallium ion did not affect the skeleton of MSN.Ga0.5MSN had the best hemostatic ability and good biological activity.?5?Combined with the advantages of calcium ion,gallium ion and MSN,the ternary composite Ga0.5Ca MSN had the best hemostatic performance,and also had strong antibacterial ability against Staphylococcus aureus and Escherichia coli.At the same time,it had good biocompatibility and promoted cell proliferation.In the animal experiment,Ga0.5Ca MSN showed the best hemostasis effect,with the shortest hemostasis time and the least blood loss.Therefore,the Ga0.5Ca MSN with high-efficiency hemostatic performance,effective antibacterial,safe and harmless usage will be an ideal material for quick hemostasis on the battlefield. |
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