Engineering and Evaluating Fibrin-Targeted Biomaterials for Hemostasis

Abstract

Traumatic injury incurs a heavy burden on both civilian and military populations throughout the world, and a large proportion of these deaths are due to hemorrhage, or uncontrolled bleeding. Current interventions are not ideal as topical agents are not capable of treating non-compressible injury and biological coagulation products have short shelf-lives and stringent storage conditions. A synthetic, injectable hemostat can overcome the downsides of current interventions. This led to the development of PolySTAT, a polymer-peptide conjugate which crosslinks fibrin at the wound site. This thesis aims to optimize PolySTAT and determine its safety in large animals, with the ultimate goal of moving PolySTAT towards clinical translation. Optimization includes a structure-function study focused on varying the peptide content of the material and exploration of alternative synthesis strategies. Large animal data demonstrates safety of PolySTAT infusions in swine, which have notoriously strong adverse effects to infusion treatments.