PROJECT SUMMARY/ABSTRACT Hemorrhage is a common occurrence inside and outside of the clinical environment. Although advancements have been made to enable rapid hemostatic control, hemorrhage is still a significant contributor to morbidity and mortality. Current approaches to achieve hemostatic control focus on pharmacological and electrothermal means of intervention. These methods of addressing hemorrhage are effective; however, they are not broadly applicable and are associated with numerous adverse effects. The pharmacological methods rely on the use of biologic agents that present the risks of infection and immune dysregulation. Electrothermal means of addressing hemorrhage, such as electrocauterization often result in compromised tissue appearance and function. To address this need for improved hemostatic agents, we propose the use of microscale electrical fields to accelerate hemostasis, which has been demonstrated by our previous work. A fundamental question pertains to the mechanistic underpinnings of microscale-electrical-field hemostatic augmentation. The central hypothesis is that tunable (low voltage) electrical fields catalyze pro-hemostatic fibrin deposition and endothelial mechanics. This hypothesis will be investigated by the following proposed specific aims. Aim 1 will establish the mechanism underlying microscale-electrical-field hemostatic augmentation. The objective is to understand how microscale electrical fields target hemostasis in comparison to current hemostatic agents. Aim 2 will use novel in vitro models of blood vessels to characterize how blood vessel cells respond to electrical fields in the context of bleeding. The trainee will master a wide range of engineering, chemistry, and biological techniques, including nanofabrication, microsystem engineering using microfluidics, and advanced microscopy techniques. The laboratory in which the proposed work will be conducted is the ideal environment for this research trainee as it has demonstrated an abundance of resources and numerous opportunities for cross-training in fields ranging from life sciences to engineering all of which will foster the well-roundedness of the trainee. The proposed research will provide insight into a novel approach to accelerating hemostasis using microscale electrical fields. This research will provide a strong foundation for future medical microsystem- based strategies for evaluating disease and treatment options. The training plan proposed to accomplish these goals has been specifically designed to provide the PI with the environment, training, and mentorship necessary to succeed as a physician- scientist-engineer.