Traumatic injuries, such as from road traffic accidents or intentional acts of violence, claim approximately 5 million lives annually. Hemorrhage is responsible for 30-40% of trauma- associated deaths and is the leading cause of the death in the initial 6 hours after injury The overall goal of this project is to develop a biopolymer-based treatment for use in trauma medicine to strengthen blood clots and stop bleeding from internal wounds. This is important because uncontrollable bleeding is a major cause of death for trauma victims. We base our approach on the knowledge that the structure of the fibrin fiber network within a blood clot is an essential component of clot strength and that enhancing fibrin clot structure is a proven method for reducing clot breakdown and bleeding. We will alter clot structure by delivering a soluble and blood-compatible polymer that recognizes and reinforces clot sites. This novel polymer is functionalized with multiple fibrin-specific binding peptides (FBP's) allowing it to interface with fibrin during polymerization to alter clot structure, thus reinforcing the clot and making it more resistant to breakdown. We hypothesize that FBP-decorated biopolymers can enhance fibrin clot strength and reduce enzymatic clot breakdown (fibrinolysis). In this work, we will optimize structures of potential polymeric hemostats and evaluate these materials both in vitro and in vivo for their ability to stabilize clots and stop bleeding without associated toxicity and cardiopulmonary complications.

Public Health Relevance

There is a great need for alternative methods in early trauma treatment to rapidly stop hemorrhage and reverse coagulopathy. The main goal of this application is to develop injectable, synthetic hemostats that recognize clot sites and stabilizes clots against enzymatic degradation. We expect that these materials will significantly impact trauma care and save lives.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB018637-01A1
Application #
8822119
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Hunziker, Rosemarie
Project Start
2014-09-30
Project End
2016-07-31
Budget Start
2014-09-30
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$193,125
Indirect Cost
$68,125
Name
University of Washington
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Lamm, Robert J; Lim, Esther B; Weigandt, Katie M et al. (2017) Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer. Biomaterials 132:96-104
Comedy, Yolanda L; Gilbert, Juan E; Pun, Suzie H (2017) INVENTION IS NOT AN OPTION. Technol Innov 18:267-274
Chan, Leslie W; Kim, Chae Hwa; Wang, Xu et al. (2016) PolySTAT-modified chitosan gauzes for improved hemostasis in external hemorrhage. Acta Biomater 31:178-185
Chan, Leslie W; White, Nathan J; Pun, Suzie H (2016) A Fibrin Cross-linking Polymer Enhances Clot Formation Similar to Factor Concentrates and Tranexamic Acid in anin vitroModel of Coagulopathy. ACS Biomater Sci Eng 2:403-408
Chan, Leslie W; White, Nathan J; Pun, Suzie H (2015) Synthetic Strategies for Engineering Intravenous Hemostats. Bioconjug Chem 26:1224-36
Wang, Christine E; Stayton, Patrick S; Pun, Suzie H et al. (2015) Polymer nanostructures synthesized by controlled living polymerization for tumor-targeted drug delivery. J Control Release 219:345-354
Chan, Leslie W; Wang, Xu; Wei, Hua et al. (2015) A synthetic fibrin cross-linking polymer for modulating clot properties and inducing hemostasis. Sci Transl Med 7:277ra29