Peptide Valency Plays an Important Role in the Activity of a Synthetic Fibrin-Crosslinking Polymer

Published

July 1, 2017

Author(s)

Robert J. Lamm, Esther B. Lim, Kathleen Weigandt, Lilo D. Pozzo, Nathan J. White, Suzie H. Pun

Abstract

Therapeutic polymers have the potential to improve the standard of care for hemorrhage, or uncontrolled bleeding, as synthetic hemostats. PolySTAT, a fibrin-crosslinking peptide-polymer conjugate, has the capacity to rescue fibrin clot formation and improve survival in a model of acute traumatic bleeding. PolySTAT consists of a synthetic polymer backbone to which targeting fibrin-binding peptides are linked. For translation of PolySTAT, the optimal valency of peptides must be determined. Grafting of fibrin-binding peptides to the poly(hydroxyethyl methacrylate)-based backbone was controlled to produce peptide valences ranging from 0 to 10 peptides per polymer. PolySTATs with valencies of 4 or greater resulted in increased clot firmness, kinetics, and decreased breakdown as measured by thromboelastometry. A valency of 4 increased clot firmness 57% and decreased clot breakdown 69% compared to PBS. This trend was characterized by neutron scattering, which probed the structure of clots formed in the presence of PolySTAT. Finally, PolySTAT with valencies of 4 (100% survival; p = 0.013) and 8 (80% survival; p = 0.063) improved survival compared to an albumin control in a femoral artery injury model (20% survival). This work demonstrates tunability of hemostatic polymers and the ability of in vitro assays to predict i}in vivo efficacy.

Citation

Biomaterials

Volume

132

Pub Type

Journals

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Citation

Lamm, R. , Lim, E. , Weigandt, K. , Pozzo, L. , White, N. and Pun, S. (2017), Peptide Valency Plays an Important Role in the Activity of a Synthetic Fibrin-Crosslinking Polymer, Biomaterials, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=922628 (Accessed October 5, 2024)