Preparation?Biocompatibility And Hemostatic Properties Of Polyethylene Glycol Based Hydrogel

BackgroundHemostatic agents have been widely used in trauma surgery and have a very important role,which can improve hemostasis efficiency,reduce postoperative complications,improve clinical treatment and recovery.However,there are currently no ideal hemostatic agents in the clinic,and the main challenges arehow to achieve it:(1)Tostop bleeding quickly and effectively;(2)Hemostatic material is safe and easy to operate;(3)Hemostasis in patients with anticoagulation.In order to overcome the above problems,we are urgent and necessary to develop new hemostatic materials.After consulting the literature,we find that the polyethylene glycol hydrogel has a porous structure,which is close to the soft tissue structure and has good tissue biocompatibility,which can beoptimized through structure and performance.Taking technical means to synthesize polyethylene glycol(PEG)gelsand to give excellent hemostatic properties,is of great significance to meet the needs of clinical Hemostasis.ObjectiveTo develope a four-arm polyethylene glycol(Tetra-PEG)hydrogel based on aminolysis reaction,which has the characteristics of fast gel formation,good adhesion,strong mechanical strength,good biocompatibility andperformance of hemostasis.Methods1.Making use ofthe aminolysis reaction,we let four-arm polyethylene glycol amino group(Tetra-PEG-NH2)and four-arm poly(ethylene glycol)succinimidylglutarate(Tetra-PEG-SG)to synthesizeSG gel,which is study for structural and biomechanical characterization..2.The biocompatibility of SG gel was analyzed by co-culture of cells,metabolism and implantation in SD rats.Cytotoxicity was assessed by the CCK-8 cytotoxicity assay and biocompatibility was assessed by subcutaneous and muscle implants.3.To evaluate the hemostatic effect and biosafety of the gel by establishing a injury bleeding model ofrabbit liver.Results1.The prepared gel has in-situ rapid gelation.When the solid content of the two monomers in the SG gel is 15wt%,gelation time is the shortest(6s).The adhesion strength(21.2±0.24KPa),compressive strength(1.02±0.01MPa)and fracture pressure(195±6mmHg)of SG gel were higher than those of fibrin glue for clinical application(P<0.01).SG gel has a porous structure and a high expansion ratio(maximum 1396%),2.The SG gel is non-cytotoxic,which slowly degraded in PBS solution and reached a mass of 75%after 21 days.The SG gel is slowly degraded in vivo and in vitro by hydrolysis of ester bonds,whose the degradation products are excreted through the kidneys.SG gel exhibits excellent biocompatibility in vivo with subcutaneous and intramuscular implantation of rats.3.SG gel has the same hemostatic properties as fibrin in the hepatic hemorrhage model of rabbit with non-heparinization,which not to cause postoperative adhesions and hematological changes.In the case of heparinization,SG gel can still stop the hemorrhage of rabbit liver injury within 1 minute,while fibrin glue takes 10 minutes to stop bleeding,and the amount of bleeding with SG gel is also less than that of fibrin glue(P<0.01).).ConclusionsA hydrogel with good adhesion,high mechanical strength and rapid gelation has been successfully prepared,wich has good cell biocompatibility and hemostatic properties and can be used for heparinized hemostasis.