A synthetic fibrin cross-linking polymer for modulating clot properties and inducing hemostasis

Abstract

Clotting factor replacement is the standard management of acute bleeding in congenital and acquired bleeding disorders. We present a synthetic approach to hemostasis using an engineered hemostatic polymer (PolySTAT) that circulates innocuously in the blood, identifies sites of vascular injury, and promotes clot formation to stop bleeding. PolySTAT induces hemostasis by crosslinking the fibrin matrix within clots, mimicking the function of the transglutaminase Factor XIII. Furthermore, synthetic PolySTAT binds specifically to fibrin monomers and is uniformly integrated into fibrin fibers during fibrin polymerization, resulting in a fortified, hybrid polymer network with enhanced resistance to enzymatic degradation. In vivo hemostatic activity was confirmed in a rat model of trauma and fluid resuscitation in which intravenous administration of PolySTAT improved survival by reducing blood loss and resuscitation fluid requirements. PolySTAT-induced fibrin crosslinking is a novel approach to hemostasis utilizing synthetic polymers for non-invasive modulation of clot architecture with potentially wide-ranging therapeutic applications.

Tissue-Factor Targeted Peptide Amphiphile Nanofibers as an Injectable Therapy To Control Hemorrhage

“…Their therapeutic is designed to stabilize clots by creating a synthetic polymer with a fibrin-binding peptide. 24 They used a rat model Figure 5. Binding of RTL TF-targeted nanofiber with increasing ligand densities to injured liver.…”

Manipulating fibrin structure of hematomas enhances large bone defects healing

“…This is corroborated by other studies that report reduced clot porosity associated with increased levels of inflammatory cytokines (Wang, et al, 2016;. Indeed, only a denser fibrin clot with thinner fibers can provide the total surface area necessary to achieve adequate haemostasis (Chan et al, 2015;Chan et al, 2016).…”

Invention Is not an Option

“…Using a recently developed controlled polymerization technique known as RAFT (reversible addition-fragmentation chain transfer) polymerization, they synthesized the first generation PolySTAT, a polymer that displays on average 16 fibrin-binding peptides on a water-soluble polymer backbone (6). PolySTAT integrates into forming clots (Figure 2), resulting in a hybrid clot comprising natural fibrin protein as well as synthetic PolySTAT.…”