How it works Fibrin sealant is a tissue sealing agent that contains a variety of substances that act via the final steps of the physiological coagulation cascade. The major components in fibrin sealant are thrombin and fibrinogen, and a critical interaction in the tissue-sealing process is the conversion by thrombin of fibrinogen into fibrin monomers. Factor XIIIa catalyzes the formation of covalent cross-links between the fibrin monomers and the tissue. The resulting fibrin network acts as a scaffold for collagen-producing fibroblasts and secures the graft transplant. In addition, the fibrin network increases phagocytosis, promotes angiogenesis and binds angiogenic factors and growth factors. As a result of this binding ability, the fibrin sealant itself includes natural growth factors such as epidermal growth factor, transforming growth factor-beta and vascular endothelial growth factor, all of which aid wound healing.
Mr. Mittermayr and colleagues at the Ludwig Boltzmann Institute collaborated with scientists at Baxter AG in Vienna to carry out a study evaluating the efficacy of each of two preparations of fibrin sealant applied as a spray compared to sutures for attachment of autologous skin grafts in a pig model. In evaluating fibrin sealant, their study objectives were threefold: to build on an earlier study investigating the influence of fibrin sealant setting time on final graft outcome, to compare the effect of thick (0.15 ml/cm2 ) versus thin (0.05 ml/cm2 ) application of fibrin sealant on final graft outcome, and to assess the effect on final graft outcome of diluting a concentrated thrombin preparation (500 IU/ml) to produce a slow-clotting fibrin sealant (containing 5 IU thrombin/ml).An air-driven dermatome was used to harvest skin at a thickness of approximately 0.4 mm from the back of each pig. Four full-thickness defects of 8x4 cm were created at the sites of harvesting, alongside the vertebral column of each animal at a distance of 4 cm from the column. Autologous skin grafts were then sealed or sutured to the full-thickness wound site. Primary endpoints were graft take rate, amount of wound healing at Day 21, hematoma formation within the first 21 days and graft dislocation.
In an earlier study evaluating the influence of setting time on final graft outcome, a fibrin sealant preparation containing 500 IU thrombin/ml had been compared to a preparation containing 4 IU thrombin/ml. "A concentration of 500 IU thrombin/ml results in a very fast clotting of the applied fibrin sealant and is excellent for hemostasis," Mr. Mittermayr says. "However, in grafting split-thickness skin you need a little more time for correct application and positioning of the graft, so this concentration would not be the best. A fibrin sealant with a lower concentration of thrombin, such as 4 IU/ml, would have a slower clotting time and this would facilitate the grafting procedure."