| Objective Both chitosan and calcium alginate are generally considered as the major components used in medical hemostatic materials.Howerver,either hemostatic product made of chitosan or calcium alginate has not a satisfactory hemostatic effect on great vessels.To our knowledge,the primary characteristics of calcium alginate are its capacities of rapid water absorption and gel formation,which can make up for the defects of chitosan in the hemostatic properties.Thus,the aim of this study is to investigate the hemostatic effects of the composite materials that are a combination of chitosan and calcium alginate according to different proportions,in order to provide an effective hemostatic dressing for clinical operation or emergency rescue.Methods The materials of chitosan,calcium alginate and the composite materials of chitosan/calcium alginate in the proportion of 7:3,5:5 and 3:7,were prepared using the freeze-drying method.The structure of compounds was determined using Fourier transform infrared spectroscopy(FT-IR),and the aperture size of composite materials was observed via SEM.The density,porosity and liquid absorbent capacity of composite materials were measured using the liquid displacement technique and the weight loss method.The optimal proportion of chitosan to calcium alginate was determinded via the in vitro coagulation tests.The composite non-woven fabric was made up of chitosan and calcium alginate according to the optimum proportion,and its aperture size,density,porosity and liquid absorbent capacity were determined.The femoral artery injury in the rabbit was established as a pharmacodynamics model to evaluate the hemostatic effects of the composite non-woven fabric,and subsequently a series of indicators including ESR,blood viscosity,platelet adhesion,the expression of P selectin and TAT concentration in the rabbits were determined.The formula of pilot process was determined after further adjustment and the samples of the composite hemostatic materials were produced.Moreover,the porcine femoral artery injury was established as a pharmacodynamics model to evaluate the hemostatic effects of the samples.The biological safety of the composite hemostatic materials was assessed via the in vitro cytotoxicity tests including the intradermal reaction test,delayed hypersensitivity test and acute systemic toxicity test.Results Compared with the material of chitosan or calcium alginate,the composite hemostatic materials showed an improved hydrophilic property.Based on the data in the coagulation tests,the optimal proportion of chitosan to calcium alginate was determined as 7:3.In the model of the rabbit femoral artery injury,the composite non-woven made of chitosan/calcium alginate(7:3)had a satisfactory hemostatic effect.The results showed that the hemostasis time was 7.32±0.89 min and the post-treatment blood loss was 17.15±1.88 g;the ESR was 28.33±2.89 and BVL was 9.90±0.84,and BVH was 4.18±0.40 and the concentration of TAT was 439.33±25.17 ng/ml in the samples of composite hemostatic materials.Compared with the control group,the above indicators as well as the expression of P selectin were all significantly increased in the treatment groups(P<0.01 or P<0.05).The hemostatic properties of the adjusted composite materials were futher improved(P<0.01).The data in the rabbit femoral artery injury model revealed that the hemostasis time was 2.57±0.33 min and the post-treatment blood loss was 11.37±1.81 g in the samples of composite materials.Futhermore,the findings in the model of porcine femoral artery injury showed that the hemostasis time was 3 min and the post-treatment blood loss was 23.7±2.0 g in the samples of composite materials,which suggested the designed composite materials had a good hemostatic effect on great vessels.Additionally,we found that there was no obvious cytotoxicity,skin irritation and acute systemic toxicity in the improved composite materials,which suggested that the hemostatic dressing had a good biological safety and can be applied in clinical trials.Conclusion In this study,the composite materials via a combination of chitosan and calcium alginate show a good capacity of adhesion and hydrophilicity and have a satisfactory hemostatic effect in the swine and rabbit models of lethal extremity arterial hemorrhage.The detailed mechanism underlying the hemostatic efficacy of the dressing may be associated with the promotion of red blood cell aggregation,the transformation from prothrombin to thrombin and the enhancement of platelet activation and adhesion. |
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