Investigating PolySTAT's role in clot contraction and fibrin network mechanics.

Abstract

PolySTAT is a synthetic polymer-based hemostat that binds to and physically crosslinks fibrin, the primary structural component of blood clots. By modifying fibrin architecture and enhancing resistance to fibrinolysis, PolySTAT increased survival rates rat models of severe hemorrhage. Recently, we observed that clots treated with PolySTAT contracted at a higher rate than untreated controls. Clot contraction, driven by platelet activity, is known to contribute to clot stabilization and reduction of blood loss by promoting wound closure. This work explores PolySTAT's influence beyond its antifibrinolytic function, with emphasis on platelet-driven clot contraction. We demonstrate that PolySTAT enhances clot contraction in human blood by altering the fibrin network rather than directly modulating platelet activity. Using direct measurements of clot contraction forces in human whole blood, we observed that PolySTAT increased both the rate and magnitude of platelet-generated forces. To assess the mechanical consequences of these microstructural changes, rheological testing was performed across both linear and nonlinear viscoelastic regimes. The data indicate that PolySTAT increases the elastic modulus of clots, providing a stiffer substrate for platelet engagement, and strengthens the fibrin network against mechanical failure while enabling recovery after deformation. Based on these findings, we propose that clots formed in the presence of PolySTAT transmit platelet forces through the fibrin matrix with greater efficiency, which may accelerate clot contraction and contribute to improved hemostatic function.