Cell Compatibility of Fibrin Sealants: In Vitro Study with Cells Involved in Soft Tissue Repair

Abstract

Fibrin sealants can be used to support tissue regeneration or as vehicles for delivery of cells in tissue engineering. Differences in the composition of fibrin sealants, however, could determine the success of such applications. The results presented in this article show clear differences between Fibrin sealant A (FS A) clots and Fibrin sealant B (FS B) clots with respect to their compatibility with primary human cells involved in soft tissue repair. FS A clots, which are characterized by a physiological coarse fibrin structure, promoted attachment, spreading, and proliferation of keratinocytes, fibroblasts, and endothelial cells. In contrast, FS B clots displaying a fine to medium clot structure failed to support spreading of all three cell types. Adhesion of keratinocytes was decreased on FS B clots compared to FS A clots after 3 h incubation, whereas number of attached fibroblasts and endothelial cells was initially comparable between the two fibrin sealants. However, all three cell types proliferated on FS A clots but no sustained proliferation was detected on FS B clots. We further demonstrate that the observed differences between FS A and B clots are partly based upon 1 M sodium chloride extractable constituents, like thrombin, and partly on nonextractable constituents or the fibrin structure. In conclusion, our in vitro results demonstrate that FS A clots serve as a provisional matrix that encourages adhesion and growth of keratinocytes, fibroblasts, and endothelial cells. Therefore, FS A seems to be well suited for applications in tissue engineering.

Thrombin as important factor for cutaneous wound healing: Comparison of fibrin biomatrices in vitro and in a rat excisional wound healing model

“…NHEKs on FS E showed less adhesion and a deteriorated morphology. These results match with other published data . Because concentrations of thrombin differ strongly between these two matrices, we hypothesize thrombin could be the reason for deteriorated biocompatibility.…”

Thrombin based gelatin matrix and fibrin sealant mediated clot formation in the presence of clopidogrel

“…Although differences can be seen with FESEM based on the type of hemostat used, the fibrin morphology and incorporation of red blood cells between clots formed with clopidogrel donor blood and those of the controls were similar. The clots formed with fibrin sealant were similar to those seen previously [40,41] as well as those formed with the thrombin based gelatin matrix hemostat [42]. Therefore, not only does the use of thrombin attenuate the impact of clopidogrel by initiating platelet activation while retaining normal clot kinetics and strength, it also facilitates structurally similar clots when used in combination with gelatin matrix and fibrin sealant hemostats.…”

High thrombin concentrations in fibrin sealants induce apoptosis in human keratinocytes

“…8,9 The combined use of keratinocytes and a fibrin matrix for skin regeneration was first described in 1988. 14 Because the thrombin concentration of these two products is substantially different ($4 IU mL À1 in Artiss V R and $800-1200 IU mL À1 in Evicel V R ), we speculated that thrombin plays a key role in mediating cell compatibility. 11,12 Very recently, Sese, Cole, and Tawil.…”

“…Whereas Artiss V R promoted adhesion, spreading, and growth of the investigated cell types, Evicel V R failed to support such cellular functions. 14 Because the thrombin concentration of these two products is substantially different ($4 IU mL À1 in Artiss V R and $800-1200 IU mL À1 in Evicel V R ), we speculated that thrombin plays a key role in mediating cell compatibility. The collective, various effects of thrombin are vital for the wound healing process.…”