title: PolySTAT-modified chitosan gauzes for improved hemostasis in external hemorrhage.
abstract: Positively-charged chitosan gauzes stop bleeding from wounds by electrostatically interacting with negatively-charged cell membranes of erythrocytes to cause erythrocyte agglutination and by sealing wounds through tissue adhesion. In the following work, nonwoven chitosan gauze was impregnated with PolySTAT, a synthetic polymer that enhances coagulation by cross-linking fibrin, to generate PolySTAT/chitosan gauzes with improved hemostatic efficacy. When comparing nonwoven chitosan and PolySTAT/chitosan to a commercially-available chitosan-containing gauze (Celox® Rapid), no appreciable differences were observed in fiber size, morphology, and pore size. However, PolySTAT/chitosan demonstrated more rapid blood absorption compared to Celox® Rapid. In a rat model of femoral artery injury, PolySTAT/chitosan gauzes reduced blood loss and improved survival rate compared to non-hemostatic controls and Celox® Rapid. While Celox® Rapid had stronger adherence to tissues compared to PolySTAT/chitosan gauzes, blood loss was greater due to hematoma formation under the Celox® dressing. Animals treated with PolySTAT/chitosan gauzes required less saline infusion to restore and maintain blood pressure above the target blood pressure (60mmHg) while other treatment groups required more saline due to continued bleeding from the wound. These results suggest that PolySTAT/chitosan gauzes are able to improve blood clotting and withstand increasing arterial pressure with the addition of a fibrin cross-linking hemostatic mechanism.
  
  
  CONCLUSIONS
  Blood loss remains one of the leading causes of death after traumatic injury in civilian populations and on the battlefield. Advanced biomaterials that interact with blood components and/or accelerate the clotting process to form a hemostatic plug are necessary to staunch bleeding after injury. Chitosan-based gauzes, which stop bleeding by causing red blood cell aggregation, are currently used on the battlefield and have shown variable performance under high pressure arterial blood flow in animal studies, suggesting that red blood cell aggregates require further mechanical stabilization for more reliable performance. In this work, we investigate the binding and cross-linking of fibrin, a major component in blood clots, on chitosan gauze fiber surfaces to structurally reinforce red blood cell aggregates.
authors.affiliation: Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: Leslie W
authors.initials: LW
authors.lastname: Chan
authors.affiliation: Technical Textile & Materials Group, Korea Institute of Industrial Technology (KITECH), Ansan 15588, Republic of Korea.
authors.forename: Chae Hwa
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Medicine, Division of Emergency Medicine, University of Washington, Seattle, WA 98104, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: Suzie H
authors.initials: SH
authors.lastname: Pun
authors.affiliation: Department of Medicine, Division of Emergency Medicine, University of Washington, Seattle, WA 98104, USA. Electronic address: whiten4@uw.edu.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: White
authors.affiliation: Technical Textile & Materials Group, Korea Institute of Industrial Technology (KITECH), Ansan 15588, Republic of Korea. Electronic address: thkim75@kitech.re.kr.
authors.forename: Tae Hee
authors.initials: TH
authors.lastname: Kim
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D001458:Bandages; D001704:Biopolymers / Q000737:chemistry; D001777:Blood Coagulation; D002448:Cell Adhesion; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004195:Disease Models, Animal; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005263:Femoral Artery / Q000293:injuries; D005337:Fibrin; D006470:Hemorrhage / Q000628:therapy*; D006487:Hemostasis; D006490:Hemostatics / Q000627:therapeutic use; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D051381:Rats
chemical_list: D001704:Biopolymers; C540163:Celox; D003432:Cross-Linking Reagents; D006490:Hemostatics; D011108:Polymers; C000611925:polySTAT; D005337:Fibrin; D048271:Chitosan
keywords: Chitosan gauze; Fibrin; Hemostasis; PolySTAT; Polymer; Trauma