Preparation Of Keratin/polyacrylamide Interpenetrating Porous Hydrogel And Study Of Hemostatic Properties

Nowadays,uncontrolled bleeding from trauma has become a major cause of death on the battlefield and the second leading cause of death in trauma patients in daily life.Traditional hemostatic materials include bandages and hemostatic dressings,etc.,which show a good hemostatic effect for wound bleeding on the body surface,but for deep bleeding sites such as penetrating wounds or incompressible parts,the hemostatic effect of conventional hemostatic materials is not ideal.Therefore,it is of great significance to develop new hemostatic products to meet the hemostasis needs of clinical or emergency.Physical compression is a commonly used hemostasis method.With the help of external force,the bleeding blood vessels can be occluded,thus achieving the purpose of temporary hemostasis.In clinical and emergency rescue,deep tissue hemorrhage treatment often uses a method of filling gauze,relying on the gauze on the surrounding tissue damage of physical pressure to stop the bleeding.In view of this,the self-expanding modification is performed based on the excellent hemostatic material,which can expand the volume by absorbing blood when contacting the damaged tissue,thereby achieving the effect of hemostasis of deep tissue damage.In this paper,we aimed at the hemostasis for deep tissue damage,and based on the excellent hemostatic performance of kerateine(KTN),KTN/polyacrylamide(PAM)porous interpenetrating network hydrogel(IPH)was prepared.The prepared KTN/PAM-IPH(KPI)could expand in volume at the bleeding site by rapidly absorbing water in the blood,increasing the concentration of blood coagulation factor and cells while accelerating hemostasis with its physical compression.At the same time,the porous structure of KPI and KTN were conducive to adsorbing blood cells,thereby promoting the formation of blood clots,and ultimately achieving the purpose of rapid hemostasis.The main research contents and experimental conclusions of this paper are as follows:(1)KPI was successfully prepared by free radical polymerization and foaming method.According to the swelling rate experiment,the swelling rate of hydrogel was affected by the pore-forming agent,foam stabilizer,crosslinking agent and monomer ratio.The optimized hydrogel reached equilibrium around 90 s,and the swelling ratio exceeded 30 g/g.From the results of scanning electron microscopy(SEM),the more KTN,the larger the pore size of the hydrogel,and the more uniform the pore formation.The rheological test results showed that the elasticity of the hydrogel increased with the increase of KTN,but when the ratio of KTN to PAM was higher than 3:10,the elasticity of hydrogel decreased significantly.Finally,Fourier transform infrared spectroscopy(FT-IR)and X-ray diffraction(XRD)analysis showed that PAM was successfully synthesized in the experiment,and KTN was inserted into the PAM network in the form of physical action.(2)The hemostatic properties of KPI was investigated by in vitro coagulation experiments and in vivo hemostasis experiments.In vitro coagulation results showed that KPI significantly accelerated the formation of blood clots compared to the gauze control group.And in vivo animal experiments found that the implantation of KPI in the rat liver perforation model could significantly reduce the bleeding time and reduce the amount of bleeding,and the hemostasis time of KPI group was about 360% faster than the control group.Besides,KPI expanded in volume in the perforation model of different diameters,and the expansion volume of KPI increased as the diameter of the wound increases.In addition,the hemostatic effect of KPI in large animal injury was investigated by the porcine femoral artery half-cut injury experiment.Compared with KTN powder and gauze,KPI can achieve hemostasis of porcine femoral artery injury within 3 min,and significantly reduce the amount of bleeding(868%).Finally,the blood cell adsorption test found that KPI had better blood cell adsorption capacity than the gauze,and the rat liver shear wave elastography(SWE)results showed that the hemostatic effect of KPI was due to the physical compression caused by its expansion.(3)KPI was implanted into the skin of rats to study its biocompatibility and biodegradability.The experimental results showed that KPI was gradually degraded in the body over time and degraded by about 80% in 28 days.In addition,the results of tissue hematoxylin-eosin(H&E)staining indicated that there was no obvious abnormality in the tissues around the implant material and major organs compared with the sham operation group,which demonstrated that KPI did not cause obvious pathological changes.Furthermore,the results of enzyme linked immunosorbent assay(ELISA)showed that there was no significant difference in the expression of the pro-inflammatory factors including interleukin-1?(IL-1?),interleukin-6(IL-6)and tumor necrosis factor-?(TNF-?)between the experimental group and the sham operation group,which indicated that KPI implantation did not cause obvious inflammatory reaction.Through the above experiments,the following conclusions can be drawn: with the excellent hemostatic properties of KTN and the swelling characteristics of PAM,KPI could rapidly expand by implantation in the deep tissue injury site to achieve rapid hemostasis.And KPI showed good histocompatibility and biodegradability in vivo.The preparation and performance study of KPI has important theoretical and practical value for the hemostasis treatment of penetrating wound in clinical and emergency situations.