A New Paradigm to Treat Bleeding by Augmenting Hemostasis via Microscale Electrical Fields

项目总结/摘要 出血是临床环境内外的常见事件。虽然进步 尽管已经使得能够快速止血控制，但出血仍然是发病率的重要因素， mortality.目前实现止血控制的方法主要集中在药理学和生物学手段上 干预。这些处理出血的方法是有效的;然而，它们并不广泛适用 并且与许多不利影响相关。药理学方法依赖于使用生物制剂， 存在感染和免疫失调风险的药物。电热寻址方式 出血，例如电烙术，经常导致组织外观和功能受损。到 为了解决这种对改进止血剂的需求，我们提出使用微尺度电场， 加速止血，这已经被我们以前的工作所证明。一个基本问题涉及到 微尺度电场止血增强的机械基础。核心假设是 可调（低电压）电场催化促止血纤维蛋白沉积和内皮力学。 将通过以下提出的具体目标对这一假设进行研究。目标1将建立机制 潜在的微尺度电场止血增强。我们的目标是了解微尺度 与目前的止血剂相比，电场靶向止血。Aim 2将在体外使用新型 血管的模型，以表征血管细胞如何响应电场的背景下， 流血了受训者将掌握广泛的工程、化学和生物技术，包括 纳米纤维、使用微流体的微系统工程和先进的显微镜技术。的 将进行拟议工作的实验室是该研究实习生的理想环境，因为它 已经展示了丰富的资源和众多的交叉培训机会， 从生命科学到工程学，所有这些都将促进受训者的全面发展。拟议 研究将提供一种新的方法来加速止血使用微尺度电场的洞察力。 这项研究将为未来基于医学微系统的评估策略提供强有力的基础 疾病和治疗选择。为实现这些目标而提出的培训计划具体包括： 旨在为PI提供成功成为医生所需的环境、培训和指导- 科学工程师

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.