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

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。

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.