CLOTTING FACTORS FROM FISH BLOOD FOR FIBRIN SEALANTS

该项目的目的是从鲑鱼血浆中制备一种安全、有效的外科纤维蛋白密封剂。水产养殖业饲养了数百万条大鲑鱼，这些鱼的血浆为高度保守的凝血因子提供了一种创新的替代来源。三文鱼原料的一个可能的健康优势是不受哺乳动物传染病的影响。具体目标有；(1)从框架鲑鱼的血浆中提取、纯化和体外评价凝血酶和纤维蛋白原；(2)评估跨物种（鲑鱼-人类）感染源可能存在的风险；(3)确定三文鱼材料的免疫原性；(4)在动物模型上对三文鱼材料进行体内测试。鲑鱼凝血酶和纤维蛋白原将被纯化，并在不同浓度和条件下进行体外测试。将对大量（约1000条）鲑鱼血浆进行鲑鱼病毒筛查，并对发现的任何病毒进行鉴定并测试其对人类细胞系的传染性。免疫原性将在大鼠和家兔中进行评估。将在大鼠、狗和猪模型中比较鲑鱼纤维蛋白密封胶和商业（人类来源的）密封胶的体内功效。拟议的商业应用：从鲑鱼血浆中提取的纤维蛋白密封剂可以提供免受哺乳动物感染性病原体感染的安全性，并且比哺乳动物材料具有一定的物理化学优势。除了军事用途外，美国的市场价值超过4亿美元。

The objective of this project is to create a safe, efficacious surgical fibrin sealant from salmon plasma. Millions of large salmon are reared by the aqua-culture industry, and the plasma from these fish offers an innovative and alternative source of highly conserved clotting factors. A likely health advantage of the salmon material is safety from mammalian infectious agents. Specific aims are; (1) to extract, purify, and evaluate in vitro, thrombin and fibrinogen from the plasma of framed salmon; (2) evaluate the possible risks of trans-species (salmon-human) infectious agents; (3) determine the immunogenic properties of the salmon material; and (4) test the salmon material in vivo in animal models. Salmon thrombin and fibrinogen will be purified, and tested in vitro at varying concentration and conditions. Lots (>1000 fish) of salmon plasma will be screened for salmon virus, and any virus found will e identified and tested for infectivity in human cell lines. Immunogenicity will be evaluated in both rats and rabbits. The in vivo efficacy of a salmon fibrin sealant and a commercial (human-derived" sealant will be compared in rat, dog, and swine models. PROPOSED COMMERCIAL APPLICATIONS: A fibrin sealant derived from salmon plasma could offer safety from mammalian infectious agents, and certain physical-chemical advantages over mammalian material. The U.S. market is over $400 million, in addition to military use.