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.
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.
|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|
|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; 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|
|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; White, Nathan J; Pun, Suzie H (2015) Synthetic Strategies for Engineering Intravenous Hemostats. Bioconjug Chem 26:1224-36|