D. J. Zhou1,2, R. Spretz1,3, G. Larsen3,4, W. H. Velander4, M. A. Carlson1,2 1University Of Nebraska Medical Center,Department Of Surgery,Omaha, NE, USA 2VA Nebraska-Western Iowa Healthcare System,Omaha, NE, USA 3LNK Chemsolutions, LLC,Lincoln, NE, USA 4University Of Nebraska-Lincoln,Department Of Chemical & Biomolecular Engineering,Lincoln, NE, USA
Introduction:
Bandage adhesion to bleeding tissue in the setting of traumatic coagulopathy can be improved with fibrin glue (FG). The objective of this study was first to establish an ex vivo assay of bandage adhesion to liver and then to test our hypothesis that use of FG containing recombinant Factor XIII (rFXIII) would improve the adhesion strength (AS) of bandage glued to liver compared to FG without rFXIII.
Methods:
Customized FG (0.2 mL; 9 mg/mL plasma-derived fibrinogen, pdFI, + 106 U/mL r-thrombin + 0.36 mg/mL rFXIII) or commercial FG (0.2 mL Tisseel; Baxter), an FG that contains ~75 mg/mL pdFI and only trace pdFXIII, was applied to a 1×2 cm interface between custom electrospun polycaprolactone (PCL) mesh and a fresh porcine liver strip, and the interface was compressed with a 170 g weight for 5 min at 37°C (default setup). A T-peel adhesion test was performed with an Instron 5943 tensiometer with a 10 N load cell. Force vs. displacement data were used to calculate AS (N/cm), defined as average force during the peel divided by the interface width. AS data were compared with ANOVA (α<0.05) and unpaired t-tests (p<0.05).
Results:
Using the default setup, AS of custom FG was ~2-fold greater by gluing the PCL mesh to the capsular surface of the liver vs. raw parenchyma (Fig. 1A), so use of the liver capsule was incorporated into the default setup. Neither capsular surface wetness (patted dry vs. pre-wet with PBS) nor prolonged compression time (5 vs. 10 min) affected AS (Fig. 1B). There appeared to be decreased AS with lower temperature during compression (25 vs. 37?C), but this was not significant (Fig. 1B). Decreasing FG volume by 50% (0.05 vs. 0.1 mL/cm2) resulted in a lower AS (Fig. 1B). Increasing FG volume beyond 0.1 mL/cm2 was ineffective secondary to glue spillage during compression. Removing rFXIII from the default setup decreased AS by ~50%, but doubling the [rFXIII] did not increase AS (Fig. 1C). AS of customized FG vs. commercial FG was not different (Fig. 1C).
Conclusion:
An ex vivo adhesion test of synthetic resorbable mesh applied to porcine liver with customized FG was optimized with respect to liver surface qualities, adhesion compression time and temperature, and FG quantity. AS was augmented by rFXIII in the FG. The customized FG produced AS similar to that of commercial FG, despite the former having only ~1/8 the pdFI. The AS equivalence between these two FGs likely was a result of the added rFXIII to the customized FG, suggesting that efficacy testing of rFXIII addition to biologic hemostatic devices may be warranted.
