A comparative high-resolution physicochemical analysis of commercially available fibrin sealants: Impact of sealant osmolality on biological performance

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.

Keywords: TISSEEL; VERASEAL; VISTASEAL; cytocompatibility; fibrin sealant; osmolality.