Human U937 monocyte behavior and protein expression on various formulations of three-dimensional fibrin clots

Fibrin sealant products such as Tisseel (Baxter Healthcare Corporation) are used in hemostasis and tissue sealing. Tisseel consists of two components, a fibrinogen-containing component and thrombin, which when mixed together form a fibrin clot. There is an interest in delivering monocytes to the wound because they are known to play an important role in the wound-healing process. Therefore, we were interested in finding the best fibrin formulation for delivering monocytes by examining monocyte behavior on 3D-fibrin clots. Using standard adhesion and proliferation assays, we found that monocytes differentially adhere, proliferate, and cluster on and within the 3D-fibrin clots depending on the final fibrinogen and thrombin concentration. Moreover, using a Boyden chamber assay, we found that monocytes migrated through the 3D-fibrin clots in 1-2 days. Furthermore, the protein expression in monocytes seeded on 3D-fibrin clots for various time points varied depending on the fibrinogen and thrombin concentrations in the final 3D-fibrin clots. The above data suggest that various formulations of fibrin sealant Tisseel present a good surface for monocyte adhesion, proliferation and migration in vitro and potentially during the wound-healing process in vivo. Moreover, because the monocytes proliferated well and clustered in the 3D fibrin, Tisseel could be a good delivery vehicle for delivering monocytes into chronic wounds to overcome a healing deficiency.