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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：
10687381
负责人：
Valerie Tutwiler
金额：
$ 24.9万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
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 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10687381
关键词：
Acute Affect Biocompatible Materials Biological Assay 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 Fibrin Fibrinogen Finite Element Analysis Hemorrhage Hemostatic Agents Hemostatic function Humoral Immunities Image Immune Immune response Immunity Immunoassay Impairment In Vitro Infection Inflammation Inflammatory Inflammatory Response Injury Investigation Knowledge Lead Leukocytes Link Mechanics Modeling Multiple Organ Failure Optics Patients Persons Phenotype Physiological Plasma Plasma Proteins Play Polymers Process Property Radiolabeled Rattus Rheology Risk Role Sampling Scanning Electron Microscopy Structure Techniques Testing Thrombosis Trauma Trauma patient Traumatic injury base density design experimental study healing immunoregulation improved outcome in vivo inflammatory marker insight interdisciplinary approach macrophage mathematical model mortality mortality risk multi-scale modeling novel prevent reconstitution response systemic inflammatory response trauma induced coagulopathy wound wound healing

项目摘要

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.

fixing通过提供机械稳定性在止血、血栓形成和伤口愈合中起关键作用涉及由于（病理）生理条件而发生变形的血凝块。纤维蛋白原迅速创伤性损伤后从血液中耗尽，可能导致凝血功能障碍，或出血;这与死亡风险增加和适应不良的炎症反应有关。反应重要的是，创伤是年轻人死亡的主要原因。我们已经积累大量证据表明，纤维蛋白原、纤维蛋白和凝块结构是血栓性疾病的关键驱动因素。然而，很少有人知道如何改变纤维蛋白原和纤维蛋白凝块形成在创伤凝血障碍可能与创伤后止血、炎症和免疫有关。在具体目标1中，采取多学科方法系统地检查血凝块的形成，结构，力学，和纤维蛋白溶解的特性。在具体目标2中，我计划研究纤维蛋白和炎症细胞，巨噬细胞，在凝血病。尖端的实验、成像和将在体外和体内试验中使用机械试验技术，样品，以全面了解这一复杂的过程。具体目标3：在该检查期间获得的信息将用于设计免疫调节止血剂用于创伤患者的潜在生物材料。获得这里提出的基本知识将告知出血和止血的理解，纤维蛋白和炎症细胞之间的相互作用，以及纤维蛋白在生物材料中的应用。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neurovascular Relationships in AGEs-Based Models of Proliferative Diabetic Retinopathy.

DOI：
10.3390/bioengineering11010063
发表时间：
2024-01-08
期刊：
BIOENGINEERING-BASEL
影响因子：
4.6
作者：
Pena, Juan S.;Ramanujam, Ranjini K.;Risman, Rebecca A.;Tutwiler, Valerie;Berthiaume, Francois;Vazquez, Maribel
通讯作者：
Vazquez, Maribel

To deform or not to deform: the evolutionary basis of mammalian red blood cell deformability.

变形或不变形：哺乳动物红细胞变形能力的进化基础。