Traumatic injury is the leading cause of death for young people worldwide, and hemorrhage is the primary cause of death in the early hours following injury. We know that immediate intervention is key to promoting survival, but we have very limited means to stop bleeding in the field. Not surprisingly, then, a number of groups have focused on developing infusible agents to stop bleeding. While many agents have shown promise in small animal models, translating the work to large animal models has been exceptionally difficult in great part because of infusion-associated complement activation to nanomaterials in the large animal models. Unfortunately, the reaction is not limited to large animals and is seen in humans as well. At least 10% of the population experiences such a reaction to infusions of nanomaterials such as DOXIL. The reaction triggers a host of events including vasodilation. We have developed hemostatic nanoparticles that were effective in small animal models but triggered massive vasodilation and exsanguination in a porcine trauma model. By investigating components of the nanoparticles, we were able to tailor a second generation that did not trigger the infusion response at low and moderate doses. At these doses, the particles led to rapid and effective hemostasis. However, at high doses, the particle can still trigger vasodilation that counters the hemostatic effect. This work is encouraging in that it demonstrates that when the infusion-associated complement response is managed, the hemostatic nanoparticles are capable of rapidly stopping bleeding in a large animal model of trauma. It also lays the groundwork for further investigating the molecular features of nanomaterials that trigger complement activation as well as strategies for managing complement activation.

Engineering nanoparticles to stop bleeding: Challenges and opportunities

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.