Synthesis And Properties Of Poly(DEX-GMA/AAc) Microgel Particle As A Hemostatic Agent

Extensive bleeding could be triggered by transportation accident,traumatic injury,surgery or combat,which are the common causes of shock and even life-threatening for patients.Therefore,immediate control of hemorrhage is imperative to raise the survival rate and reduce bleeding complications.Excessive blood loss and intracavitary bleeding or irregular shapes are constant challenges that clinicians face.Numerous hemostatic agents,such as Dry Fibrin Sealant Dressing,gelatin sponges,?-Cyanoacrylate Medical Adhesive,HemCon and QuikClot,have been developed in clinics,however,many of them have limitations for emergency medical treatment.In the present study,Poly(DEX-GMA/AAc)microgel particles with excellent water absorption behaviors,large specific surface area and strong adsorption capacity as hemostatic agents were explored.And we had studied it in the following three priority areas.In the first section,emulsion Polymerization method was chosen to prepare Poly(DEX-GMA/AAc)by Polymerizing DEX-GMA and acrylic acid(AAc).Poly(DEX-GMA/AAc)had been successfully synthesized,which was characterised by 1H Nuclear magnetic resonance(NMR)and infrared spectroscopy(IR).In the second section,the synthetic conditions of Poly(DEX-GMA/AAc)were screened out by single-factor experimental analysis and orthogonal layout method.In addition,drying method was studied because it could influence swelling ratio.Then the size of microgel particles was measured by dynamic light scattering(DLS).Scanning Electron Microscope(SEM)and Transmission Electron Microscope(TEM)were employed to study the morphology of the microgel particles.Finally,the dosages of crosslinking agent(MBA),initiator(APS)and monomer's mole ratio(n(AAc:DEX-GMA))were 0.8%,0.5% and 4:1,respectively.And the products were dried by vacuum drying to remove 70% water,and then lyophilization to remove 30% water.The results revealed that Poly(DEX-GMA/AAc)microgel particles had excellent swelling ratio of 68.95 g/g(w/w)and showed very short gelation time(less than 20 s).The resultant microgel particles with uniform three-dimensional network structure had size distribution ranged from 500 to 800 nm.In the last section,the effect of Poly(DEX-GMA/AAc)on blood clotting was examined using in vitro coagulation experiment and thromboelastography(TEG)analysis.Furthermore,cytotoxicity assay and degradation behavior were studied to guarantee safety and biodegradability of Poly(DEX-GMA/AAc)microgel particles.Their hemostatic effect was systematically demonstrated by decreasing blood loss and reducing hemostasis time dramatically in several hemorrhage models.Poly(DEX-GMA/AAc)microgel particles showed better clotting ability than commercial hemostatic agent Flashclot in vitro.In addition,Poly(DEX-GMA/AAc)would not cause exothermic burn when absorbing liquid,which was superior to Flashclot.No obvious toxicity was found in the cytotoxicity study and skin irritancy test.The blood loss and hemostasis time were dramatically reduced by Poly(DEX-GMA/AAc)microgel particles in hemorrhage models of ear vein,ear artery,liver and femoral artery in rabbits.These results indicated that the Poly(DEX-GMA/AAc)microgel particle was a potential hemostatic agent with almost no cytotoxicity and good biocompatibility.In vivo hemostatic experiments displayed that the Poly(DEX-GMA/AAc)was able to control acute hemorrhage.Furthermore,the microgel particles would not cause exothermic burn.Thus,Poly(DEX-GMA/AAc)microgel particles may be a good candidate for the external bleeding injuries of the wounded in critical situations.