| Uncontrollable hemorrhage is an important cause of various unexpected accidents and traumatic deaths in wartime or peacetime.It is reported that 31 percent of all sudden traumatic deaths are caused by uncontrolled hemorrhage,and more than 50 percent of battlefield deaths are caused by uncontrolled bleeding.Therefore,actively control the bleeding on the battlefield,and gain valuable treatment time for the evacuation of the wounded,is an important means to effectively reduce the death rate of our army’s war wounds.Local hemostatic dressings and portable hemostatic devices are the most important means of first aid hemostasis in the field of war and pre-hospital.The research on new hemostatic materials and portable hemostatic devices has always been a research hotspot in the field of war trauma treatment.Chitosan（CS）is a kind of natural hemostatic material with good biocompatibility.Its main hemostatic mechanism is that it has a large number of free amino cations.It is easy to interact with the negative charge on red blood cells to adsorb and aggregate red blood cells so as to promote the formation of local blood clots.However,the red blood cell aggregates formed by pure chitosan materials are unstable and have insufficient hemostatic strength,which is easy to cause secondary bleeding for high-pressure arterial bleeding.Graphene oxide（GO）is a new type of inorganic hemostatic material that has attracted much attention in recent years.Its main hemostatic mechanism is that it can significantly aggregate and activate platelets to promote blood coagulation,which has the advantage of speed and stability.However,graphene oxide alone has high cytotoxicity and low biocompatibility,which limits its further application in the field of hemostasis.Therefore,the two materials with different hemostatic properties were compounded by using the easy modification of the chemical structure of chitosan and graphene oxide,respectively.A composite hemostatic material with better hemostatic performance and safety has been obtained,which provides new ideas for the development of new local hemostatic dressings.The joint part of the limb refers to the special anatomical part of the trunk and limbs,such as groin and armpit.In modern war,the research of individual soldier’s personal protective equipment for trunk,head and limbs has developed rapidly.There is a significant increase in the incidence of bleeding injuries from these vulnerable joint sites.According to statistics,in recent years,the incidence of injury and bleeding at the junction of limbs has reached 5 times that of previous wars.Therefore,the importance of field treatment research for massive bleeding in deep tissue of the limb joint site has become increasingly prominent.Due to special anatomy,the joint parts of the groin,armpit and other limbs cannot be pressed by conventional tourniquet and other devices to stop bleeding.At the same time,several major arteries such as femoral artery and subclavian artery are distributed locally.Once bleeding occurs,the bleeding degree is often serious,which requires very high activity of hemostatic materials.Especially in wartime bullet wounds,the surface wounds are often very narrow,the bleeding site in the body is deep,and hemostatic materials are difficult to be introduced into the deep bleeding site.Therefore,actively developing a portable hemostatic device for limb joints with good import function and excellent hemostatic activity is the key research content to be solved in the field of hemostasis in the treatment of war wounds in our army.In summary,this study first prepared a new composite hemostatic dressing with strong hemostatic activity and good safety by cross-linking chitosan and graphene oxide.On the basis of previous research in the laboratory,we developed a new type of push hemostatic device,which is suitable for massive hemorrhage in deep tissue of limbs,such as groin and armpit.At the same time,we successfully constructed two kinds of standardized models of massive hemorrhage at the limb joint site of swine.Use the model complete the unified hemostatic evaluation of many new hemostatic materials and devices,including chitosan-graphene oxide composite hemostatic materials and injection hemostatic devices.It provides a new type of hemostatic materials and devices for the treatment of massive hemorrhage in our army.It also provides the standardized animal model evaluation technology for the treatment of massive hemorrhage of war wound.1.Chitosan cross-linked graphene oxide composite hemostatic material researchIn this chapter,selecte glutaraldehyde as the crosslinking agent to optimize the preparation process of CS and GO crosslinking to prepare a novel chitosan-graphene oxide composite hemostatic material（CSGO）.We have completed the study on the structure and physicochemical properties of chitosan cross-linked graphene oxide composite hemostatic sponge.We also conducted a systematic review study on its hemostatic mechanism,hemostatic activity and safety.The results showed that when chitosan and graphene oxide aqueous solution were crosslinked at 5:2,the clotting time in vitro was the shortest and the hemostatic activity was the strongest.Fourier transform infrared spectroscopy and X-ray diffraction results showed that CS and GO were successfully crosslinked to produce composite hemostatic material.The results of scanning electron microscopy showed that the chitosan crosslinked GO composite hemostatic sponge had an obvious porous three-dimensional structure,and the porosity was 75.0%.The results of liquid absorption test show that chitosan crosslinked graphene oxide composite hemostatic sponge has strong water absorption,and the maximum absorption rate of physiological saline is about 60.0 times.The study on the mechanism of blood coagulation in vitro showed that chitosan cross-linked graphene oxide compound hemostatic sponge could significantly reduce the clotting time in vitro and enhance the strength of blood clots.Cryoelectron microscopy showed that the surface of CS crosslinked GO composite hemostatic sponge could adhere to erythrocytes,platelets and other cell components,thus promoting local coagulation.In addition,APTT and PT results showed that CS crosslinked GO composite hemostatic sponge could activate both internal and external coagulation pathways and promote coagulation.The tail amputation test and complete femoral artery and vein transection hemostatic test in rats showed that chitosan oxide graphene compound hemostatic sponge had good hemostatic performance on small blood vessels and microvascular bleeding.In the model test of complete femoral arteriovenous severing of massive hemorrhage in swine,the pressing hemostatic time of CS and GO composite hemostatic sponge was significantly less than that of the control material Celox Gauze.It is suggested that CS and GO compound hemostatic sponge has strong hemostatic activity and is also effective in the treatment of high pressure massive hemorrhage caused by large artery injury.HE staining of local blood vessels and histopathologic tissues after hemostasis showed no obvious inflammation or pathological reaction.There was no abnormality in cytotoxicity test,acute toxicity test and hemolysis test in vitro,which suggested that the biological safety was good.2.Study on a New Type of pushable compressed Cellulose hemostatic deviceOur research group independently developed a new type of pushable compressed cellulose hemostatic device with the function of deep introduction.The device is mainly composed of an external introduction part and an internal load of compressed cellulose hemostatic particles.The external import part mainly plays the role of storage and import.The compressed cellulose hemostatic particles loaded inside can effectively fill the wound cavity by rapidly absorbing water in the blood,expand in volume,and effectively compress the local damaged blood vessels to exert rapid and strong hemostatic activity.The test results of liquid absorption and expansion showed that compressed cellulose hemostatic particles could absorb liquid quickly and expand in normal saline system.The liquid absorption rate can reach 6.2±0.1 times in 3 seconds,the maximum absorption rate is 7.3±0.2 times,and the maximum volume expansion rate is 9.0±0.3 times.In the analysis of in vitro clotting time and thrombus elastograph,it can be concluded that compressed cellulose hemostatic particles can significantly shorten the clotting time.The hemostatic test results of the model of deep massive hemorrhage in the groin area of swine showed that compressed cellulose hemostatic particles can significantly shorten the hemostatic time and the number of products（p<0.05）,comparing with foreign product CELOX-A?.It is suggested that it is better than foreign control materials in hemostatic activity and service applicability.No abnormality was found in blood routine,PT,APTT and histopathological test of injured site before and after hemostasis.In vitro cytotoxicity test,hemolysis time,acute toxicity and other biological safety results are good.In summary,the push-injection compressed cellulose hemostatic device is expected to provide a key treatment technology for deep tissue bleeding injuries in special limb joints.It can provide support for candidate varieties for the treatment of war wounds in our army. |
PDF Full Text Request