A synthetic fibrin cross-linking polymer for modulating clot properties and inducing hemostasis.
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 cross-linking 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 cross-linking is a novel approach to hemostasis using synthetic polymers for noninvasive modulation of clot architecture with potentially wide-ranging therapeutic applications.
Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, 3720 15th Avenue Northeast, Box 355061, Seattle, WA 98195, USA.
Leslie W
LW
Chan
Division of Emergency Medicine, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Xu
X
Wang
Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, 3720 15th Avenue Northeast, Box 355061, Seattle, WA 98195, USA.
Hua
H
Wei
Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA.
Lilo D
LD
Pozzo
Division of Emergency Medicine, Department of Medicine, University of Washington, Seattle, WA 98195, USA. spun@uw.edu whiten4@uw.edu.
Nathan J
NJ
White
Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, 3720 15th Avenue Northeast, Box 355061, Seattle, WA 98195, USA. spun@uw.edu whiten4@uw.edu.
Suzie H
SH
Pun
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D005337:Fibrin / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D058105:Polymerization / Q000187:drug effects; D011108:Polymers / Q000138:chemical synthesis / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution / Q000187:drug effects
D003432:Cross-Linking Reagents; D011108:Polymers; D005337:Fibrin