Biochemical and Physical Properties of a Solvent‐Detergent‐Treated Fibrin Glue

Abstract

A fibrin glue preparation has been obtained from pooled human plasma using a procedure which includes a solvent-detergent (SD) treatment to inactivate lipid-enveloped viruses. The SD treatment inactivated greater than or equal to 5.5 log10 of HIV in less than 45 min, and greater than or equal to 5 log10 and greater than or equal to 6.5 log10 of VSV and Sindbis virus, respectively, in less than 2 h. The product was found to contain high quantities of fibrinogen (116 +/- 2.49 g/l; n = 12), factor XIII (35 +/- 2.88 U/ml) and von Willebrand factor (23 +/- 1.9 U/ml ristocetin cofactor activity), and relatively low levels of fibronectin (5.9 +/- 0.51 g/l). Plasminogen, the precursor of plasmin, which may play a negative role by decreasing the resistance of the fibrin clot, was at only 0.03 g/l. Cellulose acetate electrophoresis showed 95% gamma-proteins and 5% alpha-2-beta proteins. Sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions detected three main protein bands with apparent molecular weights of 65, 56 and 47 kilodaltons, probably corresponding to the alpha, beta, and gamma fibrinogen subunits. Other characteristics of the product included (1) high clottability of fibrinogen (over 85%); (2) absence of low molecular weight fibrin degradation products; (3) rapid solubilization at room temperature (less than 10 min); (4) high tensile strength (202 +/- 27 g/cm2 after 2 h of application), and (5) high elasticity of the fibrin clot. In addition, scanning electron microscopy revealed a highly organized structure showing tridimensional arrangement of the fibrin fibers. SD treated fibrin glue should efficiently replace autologous fibrinogen or cryoprecipitate preparations for surgical application.

Migration of keratinocytes through tunnels of digested fibrin

“…Fibrin matrices were made from a freeze-dried surgical fibrinogen prepared from human plasma obtained from blood donors (Biocol-Human Thrombin, LFB, Les Ullis, France) as described (21). The protein composition of the product has been reported in detail (22). It contains clottable fibrinogen (95-130 mg ml Ϫ1 ), fibrinonectin (4-13 mg ml Ϫ1 ), factor XIIIa (10-25 units ml Ϫ1 ), and traces of other plasma proteins.…”

Blood-Derived, Tissue Engineering Biomaterials

“…Both fibrinogen and thrombin components undergo viral inactivation and reduction steps such as by solvent-detergent [9][10], pasteurization [ 11 ], dryheat or vapour-heat treatment [12][13] and nanofiltration [14]. Table 1 summarizes the typical composition of commercial FS.…”

“…The fibrinogen fraction undergoes further purification, viral reduction, concentration steps, aseptic filtration, aseptic filling, and freeze-drying [9]. The resulting concentrate has high protein content (typically more than 80g/l in fibrinogen) and may contain fibronectin, von Willebrand factor, and Factor XIII [3,9]. Thrombin is usually obtained by activation of a prepurified human prothrombin (factor II) fraction (similar to the prothrombin complex concentrate) followed by chromatographic purification, concentration, aseptic filtration, aseptic filling, and freeze-drying.…”

“…The fibrinogen concentrate is usually obtained by precipitation methods from crryyoprecipitate (obtained by thawing plasma at 1-3'U) or Cohn fraction I (obtained by 8-10% cold ethanol precipitation) [9]. The fibrinogen fraction undergoes further purification, viral reduction, concentration steps, aseptic filtration, aseptic filling, and freeze-drying [9]. The resulting concentrate has high protein content (typically more than 80g/l in fibrinogen) and may contain fibronectin, von Willebrand factor, and Factor XIII [3,9].…”

Vasal Reanastomosis Using Fibrin Glue Combined with Sutures: Which Combination of Sutures in a Delayed Protocol?

“…The fibrin glue we used (Biocol ® , currently produced by LFB, France) is a French licensed product made from pooled human plasma using a manufacturing procedure that includes a solvent-detergent treatment to inactivate plasma-borne lipid-enveloped viruses [3]. …”