Coagulation is a biological process regulated through a series of cleavage events by protease clotting factors culminating in the formation of a blood clot. Clotting factor depletion or dysfunction, which commonly occurs after major blood loss in traumatic injury, can lead to coagulation impairment. Hemostasis, or the arrest of bleeding, must be rapidly achieved to maintain blood perfusion to prevent organ failure and eventual death. For a more scalable alternative to fresh frozen plasma/purified clotting factors (biologics currently used in factor replacement therapy), I developed a synthetic hemostatic polymer (polySTAT) that homes to sites of vascular injury following systemic administration by binding fibrillar clot proteins (i.e. fibrin) and increases mechanical strength of clots via fibrin crosslinking. These functions were made possible through multivalent display of fibrin-binding peptides on a synthetic polymer backbone. In femoral artery injury models, I showed that polySTAT could reduce hemorrhage volumes, maintain adequate blood perfusion to prevent blood acidosis, and improve survival rate. Press coverage of this work is available through KIRO 7 News, KNKX Seattle Radio Station, and The Verge.
L. W. Chan, X. Wang, H. Wei, L. D. Pozzo, N. J. White, S. H. Pun. A synthetic fibrin-crosslinking polymer for modulating clot properties and inducing hemostasis. Sci. Transl. Med. 7, 277ra29 (2015). *Front cover
L. W. Chan, C. H. Kim, X. Wang, S. H. Pun, N. J. White, T. H. Kim. PolySTAT-modified chitosan gauzes for improved hemostasis in external hemorrhage. Acta Biomaterialia 31, 178-85 (2015).
L. W. Chan, N. J. White, S. H. Pun, Synthetic strategies for engineering intravenous hemostats. Bioconjug. Chem. 26, 1224–1236 (2015).
L. W. Chan, N. J. White, S. H. Pun. A fibrin cross-linking polymer enhances clot formation similar to factor concentrates and tranexamic acid in an in vitro model of coagulopathy. ACS Biomater. Sci. Eng. 2, 403-408 (2016).