Abstract：
Fibrin sealants are well-established components of the surgical toolbox, especially in procedures that harbor a high risk of perioperative bleeding. Their widespread use as hemostats, sealants or tissue-adhesives in various surgical settings has shown that the choice of the appropriate sealant system affects the clinical outcome. While many studies have compared the hemostatic efficiency of fibrin sealants to that of other natural or synthetic sealants, there is still limited data on how subtle differences in fibrin sealant formulations relate to their biological performance. Here, we performed an in-depth physicochemical and biological characterization of the two most commonly used fibrin sealants in the US and Europe: TISSEEL™ (\"FS\") and VISTASEAL™/VERASEAL™ (\"FS+Osm\"). Our chemical analyses demonstrated differences between the two sealants, with lower fibrinogen concentrations and supraphysiological osmolality in the FS+Osm formulation. Rheological testing revealed FS clots have greater clot stiffness, which strongly correlated with network density. Ultrastructural analysis by scanning electron microscopy revealed differences between FS and FS+Osm fibrin networks, the latter characterized by a largely amorphous hydrogel structure in contrast to the physiological fibrillar network of FS. Cytocompatibility experiments with human fibroblasts seeded on FS and FS+Osm fibrin networks, or cultured in presence of sealant extracts, revealed that FS+Osm induced apoptosis, which was not observed with FS. Although differential sealant osmolality and amounts of fibrinogen, as well as the presence of Factor XIII or additives such as antifibrinolytics, may explain the mechanical and structural differences observed between the two fibrin sealants, none of these substances are known to cause apoptosis at the respective concentrations in the sealant formulation. We thus conclude that hyper osmolality in the FS+Osm formulation is the primary trigger of apoptosis-a mechanism that should be evaluated in more detail, as it may affect the cellular wound healing response in situ.
摘要：
纤维蛋白密封剂是外科工具箱中公认的组成部分，尤其是在围手术期出血风险较高的手术中。它们广泛用作止血剂，在各种手术环境中的密封剂或组织粘合剂表明，选择合适的密封剂系统会影响临床结果。虽然许多研究已经比较了纤维蛋白封闭剂与其他天然或合成封闭剂的止血效率，关于纤维蛋白密封剂配方的细微差异与它们的生物学性能之间的关系，仍然存在有限的数据。这里,我们对美国和欧洲两种最常用的纤维蛋白封闭剂进行了深入的物理化学和生物学鉴定:TISSEEL™("FS")和VISTASEAL™/VERASEAL™("FS+Osm").我们的化学分析证明了两种密封剂之间的差异，在FS+Osm制剂中具有较低的纤维蛋白原浓度和超生理渗透压。流变学测试显示FS凝块具有更大的凝块刚度，与网络密度密切相关。通过扫描电子显微镜的超微结构分析显示FS和FS+Osm纤维蛋白网络之间的差异，后者的特征在于与FS的生理纤维状网络相反的大部分无定形的水凝胶结构。在FS和FS+Osm纤维蛋白网络上接种人成纤维细胞的细胞相容性实验，或在密封剂提取物存在下培养，揭示FS+Osm诱导细胞凋亡，这在FS中未观察到。虽然不同的密封剂渗透压和纤维蛋白原的量，以及因子XIII或添加剂如抗纤维蛋白溶解剂的存在，可以解释两种纤维蛋白密封剂之间观察到的机械和结构差异，已知这些物质中没有一种在密封剂制剂中的各自浓度下引起细胞凋亡。因此，我们得出结论，FS+Osm制剂中的高渗透压是细胞凋亡的主要触发因素-应该更详细地评估这种机制。因为它可能会影响细胞伤口原位愈合反应。
