(54a) Design and Development of Intravenously Administered Hemostats to Target Hidden Wounds

Hemorrhage accounts for a large fraction of preventable deaths in both civilian and military populations. Receiving rapid care in the hospital is critical for this condition, because the most reliable hemostasis can be accomplished in the hospital setting. However, large number of patients suffer from blood loss on their way to hospital. Therefore, the development of intravenous hemostatic materials that can be injected by the first responder has become crucial, yet it is challenging due to stringent requirements that the new hemostats need to meet. The goal of this work is to advance a set of hemostatic materials that are intravenously injectable to treat wounds where the location of bleeding cannot be identified. The first approach is to utilize surface functionalized nanoparticles. The synthesis of PEG-b-PLGA polymer was achieved and optimized to conjugate with various peptide ligands which are known to interact with wounds to obtain nanoparticles with diverse targets. These nanoparticles were subjected to in vitro platelet aggregation and coagulation assays to understand the efficacy of particle formulations in establishing hemostasis. Binary combinations of peptides showed improved aggregation when compared to five singly functionalized peptides in the same assays. A binding assay on wound-mimetic surfaces with Human Umbilical Vein Cells (HUVECs) was also developed and performed to assist in understanding the role of the particles in enhancing platelet aggregation and selective binding on different surfaces. The preliminary results from two assays indicate that the multi-functional particle ligands are essential to improve targeting abilities and demonstrate a promising future in the design of novel biomaterials toward efficient hemostatic agents.