Buchta Christoph, Hedrich Hans Christian, Macher Maria, Höcker Paul, Redl Heinz
Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Biomaterials. 2005 Nov;26(31):6233-41. doi: 10.1016/j.biomaterials.2005.04.014.
Different principles for production of "autologous fibrin sealant" have been established, and commercial devices employing these methods are nowadays available and used in clinical routine. Users might anticipate for these autologous fibrin sealants features comparable to commercial homologous fibrin sealants, used in surgical routine for many years. However, only little is known about biochemical properties, formation, cross-linking and stability of fibrin sealant clots produced for autologous use with the aid of commercially available devices. We have investigated protein composition, formation and stability of clots obtained from autologuous fibrin sealants produced with commercially available devices (CryoSeal and Vivostat) and compared these parameters to those of the industrially produced homologous fibrin sealant Tissucol/Tisseel. The CryoSeal product is a mixture of many plasma proteins; the Vivostat product and Tissucol/Tisseel appear as comparatively pure plasma derivatives. The products differ in their protein composition and concentrations, including their concentration in fibrin. Significant fibrin alpha and gamma-chain cross-linking by FXIIIa occurs only in Tissucol/Tisseel clots. In test tubes CryoSeal and Vivostat (tranexamic acid-free formulation) fibrin clots liquefy within 1-2 days, but Vivostat (tranexamic acid containing formulation) clots were stable for 4 days and showed partial liquefaction after 5 days. Tissucol/Tisseel clots, containing the protease inhibitor aprotinin, appeared unchanged over the observation period of 5 days. In an in vitro model mimicking in vivo conditions (diffusion of protease inhibitors and proteolytic digestion) clot liquefaction occurs at day 1 for all autologous fibrin sealants clots, with an observable delay for the tranexamic acid containing Vivostat, and day 5 for Tissucol/Tisseel clots. Characterization of the CryoSeal and Vivostat fibrin sealants and Tissucol/Tisseel and their performance show a clear difference in biochemical properties.
现已确立了生产“自体纤维蛋白密封剂”的不同原则,采用这些方法的商用设备如今已可获得并应用于临床常规操作中。使用者可能期望这些自体纤维蛋白密封剂具有与多年来在外科常规操作中使用的商用同源纤维蛋白密封剂相当的特性。然而,对于借助商用设备生产的自体使用的纤维蛋白密封剂凝块的生化特性、形成、交联和稳定性,人们了解甚少。我们研究了用商用设备(CryoSeal和Vivostat)生产的自体纤维蛋白密封剂所形成凝块的蛋白质组成、形成过程和稳定性,并将这些参数与工业生产的同源纤维蛋白密封剂Tissucol/Tisseel的参数进行了比较。CryoSeal产品是多种血浆蛋白的混合物;Vivostat产品和Tissucol/Tisseel看起来是相对纯的血浆衍生物。这些产品在蛋白质组成和浓度上存在差异,包括纤维蛋白中的浓度。只有在Tissucol/Tisseel凝块中才会发生由FXIIIa介导的显著的纤维蛋白α链和γ链交联。在试管中,CryoSeal和Vivostat(不含氨甲环酸的配方)纤维蛋白凝块在1 - 2天内液化,但Vivostat(含氨甲环酸的配方)凝块在4天内保持稳定,5天后出现部分液化。含有蛋白酶抑制剂抑肽酶的Tissucol/Tisseel凝块在5天的观察期内没有变化。在模拟体内条件(蛋白酶抑制剂的扩散和蛋白水解消化)的体外模型中,所有自体纤维蛋白密封剂凝块在第1天发生凝块液化,含氨甲环酸的Vivostat凝块有明显延迟,而Tissucol/Tisseel凝块在第5天发生液化。CryoSeal和Vivostat纤维蛋白密封剂以及Tissucol/Tisseel的特性及其性能在生化特性上存在明显差异。