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

项目摘要/摘要 出血是临床环境内外的常见现象。尽管技术进步 已经做出了能够快速止血控制的措施，但出血仍然是发病率和 死亡率。目前实现止血控制的方法主要集中在药理和电热方法上。 干预的结果。这些解决出血的方法是有效的；然而，它们并不广泛适用 并与许多不良反应有关。药理方法依赖于生物学的使用。 存在感染风险和免疫失调风险的药物。电热寻址方式 出血，如电灼术，通常会导致组织外观和功能受损。至 为了满足这种对改进止血剂的需求，我们建议使用微尺度电场来 加速止血，我们以前的工作已经证明了这一点。一个基本问题与以下问题有关 微尺度电场止血增强的机理基础。中心假设是 这种可调(低电压)的电场可以催化止血的纤维蛋白沉积和内皮机械。 这一假设将通过以下提议的具体目标进行研究。目标1将建立该机制 基础微尺度电场止血强化。目标是了解微尺度是如何 与目前的止血剂相比，电场具有止血的作用。AIM 2将在体外使用新技术 血管模型，以表征血管细胞如何响应电场 在流血。学员将掌握广泛的工程、化学和生物技术，包括 纳米制造、使用微流控技术的微系统工程和先进的显微技术。这个 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 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，所有这些都将培养学员的全面发展。建议数 研究将提供一种利用微尺度电场加速止血的新方法。 这项研究将为未来基于医疗微系统的战略评估提供坚实的基础 疾病和治疗方案。为实现这些目标而提出的培训计划已经明确 旨在为PI提供作为一名医生取得成功所需的环境、培训和指导- 科学家兼工程师。

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.