Study On Bacterial Cellulose/Calcium Ion-contained Polyglutamic Acid Rapid Hemostatic Materials

Since the existing hemostasis methods and devices are difficult to effectively cope with the hemostasis of the penetrating injuries in limbs,polyglutamic acid-based porous hemostatic materials:bacterial cellulose/calcium ion-contained polyglutamic acid?BC/PGA-Ca?with excellent biocompatibility and hemostasis were obtained based on ⁶⁰Co-ray irradiation and freeze-drying technology.The relationship between preparation,structure and hemostatic properties of BC/PGA-Ca materials was studied.And its physicochemical,drug loading,biosafety and hemostatic properties were optimized.Moreover,its multiple rapid hemostasis mechanisms and hemostatic applicability in the case of high-speed jetting of blood were explored to meet the need for immediate,efficient,and safe emergency hemostasis.Firstly,polyglutamic acid calcium?PGA-Ca?with tunable Ca²⁺content was prepared by gamma-PGA and CaCl₂ reaction and its purity can meet the requirements of medical materials,then PGA-Ca was mixed with bacterial cellulose?BC?nanofibers in aqueous solutions.After ⁶⁰Co-ray cross-linking with different irradiation doses and freeze-drying,BC/PGA-Ca hemostatic materials were obtained.Then,the BC/PGA-Ca structure was characterized by inductively coupled plasma spectrometer?ICP?,infrared spectroscopy?FT-IR?and X-ray diffraction analysis?XRD?,and its gel fraction,swelling behavior and calcium release behavior were investigated.The results showed that BC/PGA-Ca forms multiple cross-linked structure.And the relationship between the gel fraction and the irradiation dose was related to the calcium content.When the calcium content was low,the gel fraction of the hydrogel increased with the irradiation dose,and the low irradiation dose had little effect on the gel fraction of the hydrogel.With the increase of irradiation dose,the gel fraction of hydrogels was significantly increased,and at the same irradiation dose,the gel fraction of BC/PGA-Ca increased with the calcium ion content decreasing.However,when the calcium content was high,the gel fraction of the hydrogel did not change significantly with the increase of irradiation dose.For the same calcium content of BC/PGA-Ca,the increase of irradiation dose decreased the swelling ratio.And the release rate of calcium ion increased with increasing the content of calcium.Then,in vitro biological evaluations including coagulation time?CT?,thrombelastography?TEG?,as well as cytotoxicity and hemolysis were used to obtain the optimal formulation and process conditions?50 kGy,BC/PGA-Ca?2:1??.And the porcine femoral artery injury hemostasis experimental evaluation was performed to prove the validity for blood jet hemostasis.Furthermore,its ability of loading thrombin drugs and hemostatic performance were performed.The results indicated that:?1?CT experiment data results showed BC/PGA-Ca hemostatic powders can effectively reduce the coagulation time,and CT is 39±8 s;?2?TEG experiment data results showed smaller R-value?Coagulation factor response time?and K-value?blood clot formation time?than the Celox hemostatic powders,with a larger alpha angle?hemagglutination rate?,approximate MA-value?maximum strength or hardness of blood clot and stability?;?3?in vitro cytotoxicity experiment showed that BC/PGA-Ca hemostatic powders had no cytotoxic effect on L929 cells.?4?The porcine femoral artery injury hemostasis experimental showed that BC/PGA-Ca hemostatic powder could complete hemostasis within 5 minutes.The hemostasis success rate and animal survival rate were both 100%,and hemostatic powder dosage and hemostasis time were superior to Celox hemostatic powders,while gauze group hemostatic success rate was 0.?5?The BC/PGA-Ca hemostat can be loaded with thrombin,but it did not significantly improve the hemostatic performance.To sum up,bacterial cellulose/calcium ion-contained polyglutamic acid?BC/PGA-Ca?hemostatic powders had good hemostatic activity and biocompatibility,and is expected to be used in the field of wound and hemostatic dressings.