Controlling Fibrin Network Morphology, Polymerization, and Degradation Dynamics in Fibrin Gels for Promoting Tissue Repair.

Abstract

Fibrin is an integral part of the clotting cascade and is formed by polymerization of the soluble plasma protein fibrinogen. Following stimulation of the coagulation cascade, thrombin activates fibrinogen, which binds to adjacent fibrin(ogen) molecules resulting in the formation of an insoluble fibrin matrix. This fibrin network is the primary protein component in clots and subsequently provides a scaffold for infiltrating cells during tissue repair. Due to its role in hemostasis and tissue repair, fibrin has been used extensively as a tissue sealant. Clinically used fibrin tissue sealants require supraphysiological concentrations of fibrinogen and thrombin to achieve fast polymerization kinetics, which results in extremely dense fibrin networks that are inhibitory to cell infiltration. Therefore, there is much interest in developing fibrin-modifying strategies to achieve rapid polymerization dynamics while maintaining a network structure that promotes cell infiltration. The properties of fibrin-based materials can be finely controlled through techniques that modulate fibrin polymerization dynamics or through the inclusion of fibrin-modifying biomaterials. Here, we describe methods for characterizing fibrin network morphology, polymerization, and degradation (fibrinolysis) dynamics in fibrin constructs for achieving fast polymerization dynamics while promoting cell infiltration.