Traumatic injury is the leading cause of death for both men and women between the ages of 5 and 44 worldwide, and blood loss is the primary cause of death at acute time points. Immediate intervention is essential to minimize mortality and yet there is a derth of technologies to address internal bleeding. We have developed functionalized nanoparticles based on poly(lactic-co-gycolic acid) (PLGA), poly(ethylene glycol) (PEG), and the arginine-glycine-aspartic acid (RGD) peptide which binds the glycoprotein IIb/IIIa receptor. The receptor is only exposed on activated platelets. Our particles leverage the specificity of biology and are designed to help form stable clots faster to halt bleeding after intravenous administration. We have tested these hemostatic nanoparticles in a range of injury models including the femoral artery model and liver injury models. We have also tested these particles in a blast injury model of polytrauma and a model of brain injury with hemorrhaging. In all cases, we saw a reduction in bleeding, and in the case of lethal injury models, we saw significant improvements in survival. In both the blast injury models we see that the administration of the hemostatic nanoparticles reduces bleeding and this, in turn, leads to better behavioral outcomes. This suggests that reducing bleeding may be a critical component of providing neuroprotection after injury. The functionalized nanoparticles or hemostatic nanoparticles reduce bleeding in a number of models of trauma. Following administration, the particles participate in clot formation and can be found at the injury site post injury. The chemistry of the formulation including the length of the PEG arms and peptide play significant roles in the efficacy and clearance of the particles and provide means to tailor the particle behavior. This treatment has the potential to greatly impact survival outcomes related to internal hemorrhage and may lead to better functional outcomes more broadly.
ACKNOWLEDGEMENTS
We would like to acknowledge the NIH Directorâ??s New Innovator Award DP20D007338.
Biography: Erin Lavik is a professor of Chemical, Biochemical, and Environmental Engineering at the University of Maryland, Baltimore County (UMBC). Dr. Lavikâ??s research focuses on engineering polymers to protect and repair the nervous system and treat trauma more broadly. The lab does this through a set of approaches including developing intravenously administered nanoparticles to stop internal bleeding, developing drug delivery systems for traumatic brain injury as well as diseases of the eye, and by developing novel materials that can not only direct stem cells but report on their health and function. Dr. Lavik received her bachelorâ??s, masterâ??s, and doctoral degrees from MIT in Materials Science and Engineering. She has won a number of awards including the TR100 award in 2003 and the NIH Directorâ??s New Innovator Award in 2010. She became at Fellow of the American Institute of Medical and Biological Engineers in 2014. She is also an Associate Editor at Bioconjugate Chemistry. Beyond her research, Dr. Lavik has developed classes including Applied Tissue Engineering where the students make and test artificial arteries and learn about the issues involved in translating the technologies from the bench to patients.
