微孔淀粉复合介孔硅酸钙材料止血性能的研究
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摘要
目的:探讨微孔淀粉复合介孔硅酸钙材料(PHS/m-CS)的止血性能与生物安全性。方法:采用溶胶-凝胶法合成介孔硅酸钙m-CS,生物酶解法制备微孔玉米淀粉PHS,并将两者复合制备PHS/m-CS止血材料。根据部分凝血活酶时间(APTT)和凝血酶原时间(PT)指标考察PHS/m-CS的体外止血性能;通过将PHS/m-CS与MC3T3-L1细胞体外共培养,研究PHS/m-CS的体外生物安全性;通过体内动物实验,探讨PHS/m-CS对肝脏与脾脏的止血效果。结果:m-CS呈短棒状,内部具有高度有序的介孔孔道;制备的PHS颗粒尺寸均匀,并且内部具有疏松多孔的结构。相比于单纯PHS,PHS/m-CS复合材料具有更高的吸水率与体外凝血功能。生物安全性测试表明材料对细胞无毒性。体内肝脏与脾脏止血实验表明,PHS/m-CS可缩短凝血时间。结论:PHS/m-CS复合止血材料具有良好的止血性能与生物安全性,对临床急诊止血材料具有指导意义。
Objective:To investigate the haemostatic property and biosafety of PHS/m-CS composites.Method:The mesoporous calcium silicate(m-CS)was synthesized via Sol-Gel method as well as microporous corn starch(PHS)was prepared by biological enzymolysis way.What's more,the PHS/m-CS composite was fabricated via mechanical blending method.The APTT and PT assay were used to analyze the in vitro thrombogenic property,and in vitro biosafety of PHS/m-CS was evaluated by co-cultivation with MC3T3-L1 cells.The in vivo hemostatic properties to liver and spleen were also investigated.Result:The high ordered mesopores could be detected inside of the as-prepared rod-like m-CS,and the PHS with homogeneous particle size had loose interconnected pores.AndPHS/m-CS had higher water absorption and better in vitro thrombogenic property comparing with bare PHS.The in vitro biosafety evaluation results revealed that PHS/m-CS had excellent cytocompatibility.Moreover,the in vivo homeostasis tests of liver and spleen showed that PHS/m-CS could shorten the clotting time.Conclusion:The whole study showed that the as prepared PHS/m-CS composite possessed excellent haemostatic performance and biosafety,which has potential for being adopted as clinical emergency haemostatic materials.
Objective:To investigate the haemostatic property and biosafety of PHS/m-CS composites.Method:The mesoporous calcium silicate(m-CS)was synthesized via Sol-Gel method as well as microporous corn starch(PHS)was prepared by biological enzymolysis way.What's more,the PHS/m-CS composite was fabricated via mechanical blending method.The APTT and PT assay were used to analyze the in vitro thrombogenic property,and in vitro biosafety of PHS/m-CS was evaluated by co-cultivation with MC3T3-L1 cells.The in vivo hemostatic properties to liver and spleen were also investigated.Result:The high ordered mesopores could be detected inside of the as-prepared rod-like m-CS,and the PHS with homogeneous particle size had loose interconnected pores.AndPHS/m-CS had higher water absorption and better in vitro thrombogenic property comparing with bare PHS.The in vitro biosafety evaluation results revealed that PHS/m-CS had excellent cytocompatibility.Moreover,the in vivo homeostasis tests of liver and spleen showed that PHS/m-CS could shorten the clotting time.Conclusion:The whole study showed that the as prepared PHS/m-CS composite possessed excellent haemostatic performance and biosafety,which has potential for being adopted as clinical emergency haemostatic materials.
引文
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[2]Kheirabadi B S,Acheson E M,Deguzman R,et al.The potential utility of fibrin sealant dressing in repair of vascular injuryin swine[J].J Trauma,2007,62(1):94-103.
[3]Turner A S,Parker D,Egbert B,et al.Evaluation of a novel hemostaticdevice in an ovine parenchymal organ bleeding model of normal andimpaired hemostasis[J].J Biomed Mater Res,2002,63(1):37-47.
[4]Li X,Liu C,Yuan Y,et al.Preparation and hemostatic properties ofmesoporous silica-based xerogels[J].J Inorg Mater,2008,23(2):327-331.
[5]Sugamori T,Iwase H,Maeda M,et al.Local hemostatic effects ofmicrocrystalline partially deacetylated chitin hydrochloride[J].J BiomedMater Res,2000,49(2):225-232.
[6]Dai C L,Yuan Y,Liu C,et al.Degradable,antibacterial silverexchanged mesoporous silica spheres for hemorrhage control[J].Biomaterials,2009,30(29):5364-5375.
[7]Emily B,Trang P,Denis B,et al.Direct synthesisof mesoporous silica presenting large and tunable pores using BABtriblock copolymers:influence of each copolymer block on theporous structure[J].Micropor Mesopor Mat,2007,112(1-3):612-620.
[8]Antisdel J L,West-Denning J L,Sindwani R,et al.Effect of microporous polysaccharide hemospheres(MPH)on bleeding after endoscopic sinus surgery:randomized controlled study[J].OtolaryngolHead Neck Surg,2009,141(3):353-357.
[9]Che L M,Li D,Wang L J,et al.Effect of high-pressure homogenization on the structure of cassava starch[J].Int J Food Prop,2007,10(4):911-922.
[10]Filler G.Value of therapeutic drug monitoring of MMFtherapy in pediatric transplantation[J].Pediatr Transplant,2006,10(6):707-711.
[11]Murat F J,Le C Q,Ereth M H,et al.Evaluation of microporouspolysaccharide hemospheres for parenchymal hemostasis duringlaparoscopic partial nephrectomy in the porcine model[J].JSLS,2006,10(3):302-306.
[12]Humphreys M R,Castle E P,Andrews P E,et al.Microporouspolysaccharide hemospheres for management of laparoscopic trocarinjury to the spleen[J].Am J Surg,2008,195(1):99-103.
[13]Alam H B,Burris D,DaCorta J A,et al.Hemorrhage control in the battlefield:role of newhemostatic agents[J].Mil Med,2005,170(1):63-69.
[14]Rhee P,Brown C,Martin M,et al.QuikClot use intrauma for hemorrhage control:case series of 103documented uses[J].J Trauma,2008,64(4):1093-1099.
[15]Kauvar D S,Lefering R,Wade C E.Impact of hemorrhage on trauma outcome:an overview of epidemiology,clinical presentations,and therapeutic considerations[J].J Trauma,2006,60(6Suppl):S3-11.
[16]Hebert M F,Lam A Y.Diltiazem increases tacrolimus con-centrations[J].Ann Pharmacother,1999,33(6):680-682.
[17]Wortham L.Hemorrhage control in the battlefield:role of newhemostatic agent[J].Mil Med,2005,170(12):1004-1007.