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Systematic multidisciplinary approach to study traumatic bleeding as a complex structural and biomechanical problem

系统性多学科方法将创伤性出血作为复杂的结构和生物力学问题进行研究

基本信息

批准号：
9806262
负责人：
Valerie Tutwiler
金额：
$ 9.17万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9806262
关键词：
Acute Affect Area Biochemical Biocompatible Materials Biological Assay Biomaterials Research Biomechanics Blood Blood Coagulation Disorders Blood coagulation Cause of Death Cells Cellular Immunity Cessation of life Coagulation Process Coculture Techniques Complex Coupled Development Early-life trauma Engineering Environment Failure Fibrin Fibrinogen Finite Element Analysis Fostering Foundations Growth Hemorrhage Hemostatic Agents Hemostatic function Human Human Biology Image Immune Immune response Immunity Immunoassay Impairment In Vitro Infection Inflammation Inflammatory Inflammatory Response Injury Investigation Knowledge Laboratories Lead Leadership Leukocytes Link Lytic Measures Mechanics Mentors Mission Modeling National Heart, Lung, and Blood Institute Optics Patients Phase Phenotype Physiological Plasma Plasma Proteins Play Polymers Positioning Attribute Process Property Radiolabeled Rattus Research Research Personnel Rheology Risk Role Sampling Scanning Electron Microscopy Structure Techniques Testing Thrombosis Trauma Trauma patient Traumatic injury Wound Healing base career design experimental study healing immunoregulation improved outcome in vivo inflammatory marker insight interdisciplinary approach macrophage mathematical model mortality mortality risk multi-scale modeling novel post-doctoral training prevent reconstitution response skills

项目摘要

Project Summary Fibrin plays a critical role in hemostasis, thrombosis and wound healing by providing mechanical stability to blood clots that undergo deformation due to (patho)-physiologic conditions. Fibrinogen is rapidly depleted from the blood following traumatic injury which can lead to the development of coagulopathy, or bleeding; this has been correlated with an increased risk of death and a maladaptive inflammatory response. Importantly, trauma is the leading cause of death among young people. We have amassed considerable evidence that fibrinogen, fibrin, and clot structure are key drivers of thrombotic disorders. However, little is known regarding how changes in fibrinogen and fibrin clot formation during trauma coagulopathy may link hemostasis, inflammation, and immunity after trauma. In Specific Aim 1 I propose to take a multidisciplinary approach to systematically examine blood clot formation, structure, mechanics, and fibrinolytic properties in the trauma setting. In Specific Aim 2 I plan to examine the interplay between fibrin and the inflammatory cells, macrophages, in coagulopathy. Cutting edge experimental, imaging, and mechanical testing techniques will be used in vitro and in vivo assays with both reconstituted and patient samples to develop a holistic understanding of this complex process. In Specific Aim 3, the information gained during this examination will be used to inform the design of immuno- modulatory hemostatic biomaterials for potential use in trauma patients. Gaining the fundamental knowledge proposed here will inform the understanding of bleeding and hemostasis, the interplay between fibrin and inflammatory cells, and the use of fibrin in biomaterials. During the mentored phases I will gain the background and experimental skills needed to accomplish the proposed research under the guidance of the mentoring team and collaborators and give me the foundation to take a multidisciplinary approach to this important and understudied area of research. Importantly, my mentoring team has a strong track record in training post-doctoral fellows for a transition into a career as an independent investigator and will foster the growth of not only my research skills but also my leadership, mentoring, and professional development acumen. Combining the new skills learned during the K99 mentored phase with my prior expertise in hemostasis, thrombosis, and clot contraction will uniquely position me to take a multidisciplinary approach to studying blood biomaterial interactions and allow me to launch an independent and distinct laboratory that can impact a variety of fields.

项目总结