| Polymer-based hemostatic materials/devices are increasingly used in different clinical bleeding scenarios,yet the hemostatic mechanisms of these materials and the interaction between blood and its procoagulant surfaces remain to be revealed.Natural polysaccharides are biosafe,widely available and inexpensive,while cationic polymers have a variety of biomedical functions such as hemostasis and antibacterial properties,both of which have a wide range of applications in the field of biomedical materials.Hemostatic gels are common hemostatic materials and are more suitable for irregular and deep internal bleeding wounds than traditional hemostatic materials such as hemostatic bandages or hemostatic gauze.In this study,cationic modified polysaccharides were prepared by chemically grafting cationic substances onto natural polysaccharides,and temperature-sensitive gels were prepared by blending the preferred cationic polysaccharides with the temperaturesensitive substance F127.The hemostatic properties were investigated and the hemostatic/coagulation mechanism was investigated.In Chapter 2,aldehyde-PS was firstly prepared by oxidation of porous starch,and then degradable hemostatic granules(PLPS)with different EPL grafting rates were prepared by grafting poly(lysine)(EPL)onto aldehydePS.The results of in vitro and in vivo hemostasis experiments showed that PLPS2 with moderate EPL grafting had the best hemostatic properties.The blood-substance interactions of PLPS2 revealed that PLPS2 did not negatively affect the endogenous and exogenous coagulation pathways,that EPL significantly increased platelet adhesion and activation of PLPS2,and that it promoted erythrocyte adhesion.PLPS2 showed selective fibrinogen adsorption in disassembled,simulated plasma in competitive protein adsorption assays.Further,a temperature-sensitive gel F127-PLPS was prepared by simple blending of PLPS2,which has the best hemostatic properties,with F127.in vitro coagulation data showed that the gel F127-PLPS2 with moderate PLPS2 addition had the best procoagulant properties,which did not affect endogenous or exogenous coagulation pathways and had the highest platelet adhesion rate.Together with the tunable thermal response,F127-PLPS showed superior hemostatic properties in both the femoral artery injury hemostasis model and the renal artery embolism model.In Chapter 3,QSA was prepared by grafting long alkyl chain quaternary ammonium salts onto sodium alginate(SA),and its structure was characterized by NMR and elemental analysis.FQSA gels were prepared by blending QSA-3 with F127 at the preferred grafting rate,which maintained good hemocompatibility at high QSA-3 concentrations(QSA = 15 mg/m L).In vitro antimicrobial experiments showed that the gel could achieve excellent antimicrobial effect by contact sterilization,solving the problem of incompatibility between QSA antimicrobial properties and blood compatibility.In terms of hemostatic properties,the lower concentration of FQSA-1(QSA = 1 mg/m L)was found to have superior hemostatic properties in vitro,without affecting the endogenous and exogenous coagulation pathways and with a high platelet adhesion rate,and it also showed superior hemostatic properties in a rat femoral artery injury assay.In summary,in this thesis,cationic modified polysaccharides were prepared by grafting cationic substances onto natural polysaccharides.Through the study of their in vivo and ex vivo hemostatic properties,the blood-substance interactions were investigated and the rational design of the surface of the cationic polymer-based hemostatic material was revealed.At the same time,hemostatic gels were prepared by blending cationic polymers with the thermally responsive substance F127,and the hemostatic properties and mechanisms of the hemostatic gels were investigated in depth through in vivo and ex vivo tests.This study not only proposes a strategy for the preparation of effective hemostatic materials in a simple manner,but also provides ideas for the rational design of procoagulant surfaces. |
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