Synthetic hemostats for trauma treatment

用于创伤治疗的合成止血剂

基本信息

批准号：
8934103
负责人：
Suzie H. Pun
金额：
$ 23.18万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-30 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8934103
关键词：
Affect Alteplase Anticoagulation Antidotes Antifibrinolytic Agents Binding Biochemical Biodistribution Biological Assay Biopolymers Blood Blood Circulation Blood Coagulation Disorders Blood Component Transfusion Blood coagulation Breathing Cardiopulmonary Cause of Death Cessation of life Coagulation Process Dose Early-life trauma Enzymes Evaluation Factor XIII Family suidae Fiber Fibrin Fibrinolysis Functional disorder Funding Future Goals Health Hemorrhage Hemorrhagic Shock Hemostatic Agents Hemostatic function Histopathology Hospitals Hour In Vitro Inflammation Injectable Injury Intravenous Kinetics Knowledge Life Liquid substance Mechanics Medicine Methacrylates Methods Modeling Nature Organ failure Patients Peptides Pharmaceutical Preparations Plasma Plasminogen Polymers Porosity Property Radiolabeled Rattus Resistance Resuscitation Rodent Safety Scanning Electron Microscopy Site Staging Structure Techniques Tertiary Protein Structure Testing Thrombelastography Time Toxic effect Traffic accidents Translating Trauma Violence Whole Blood Work base biomaterial compatibility clinical application crosslink cytokine cytotoxicity design fibrinmonomer improved in vivo innovation novel polymerization prevent radiotracer response trauma care

项目摘要

DESCRIPTION: Traumatic injuries, such as from road traffic accidents or intentional acts of violence, claim approximately 5 million lives annually. Hemorrhage is responsible for 30-40% of trauma- associated deaths and is the leading cause of the death in the initial 6 hours after injury The overall goal of this project is to develop a biopolymer-based treatment for use in trauma medicine to strengthen blood clots and stop bleeding from internal wounds. This is important because uncontrollable bleeding is a major cause of death for trauma victims. We base our approach on the knowledge that the structure of the fibrin fiber network within a blood clot is an essential component of clot strength and that enhancing fibrin clot structure is a proven method for reducing clot breakdown and bleeding. We will alter clot structure by delivering a soluble and blood-compatible polymer that recognizes and reinforces clot sites. This novel polymer is functionalized with multiple fibrin-specific binding peptides (FBP's) allowing it to interface with fibrin during polymerization to alter clot structure, thus reinforcing the clot and making it more resistant to breakdown. We hypothesize that FBP-decorated biopolymers can enhance fibrin clot strength and reduce enzymatic clot breakdown (fibrinolysis). In this work, we will optimize structures of potential polymeric hemostats and evaluate these materials both in vitro and in vivo for their ability to stabilize clots and stop bleeding without associated toxicity and cardiopulmonary complications.

描述：道路交通事故或故意暴力行为等造成的创伤每年夺去大约 500 万人的生命。出血导致 30-40% 的创伤相关死亡，并且是受伤后最初 6 小时内死亡的主要原因该项目的总体目标是开发一种基于生物聚合物的治疗方法，用于创伤医学，以强化血液凝结并止血内伤。这很重要，因为无法控制的出血是创伤受害者死亡的主要原因。我们的方法基于以下知识：血块内的纤维蛋白纤维网络结构是血块强度的重要组成部分，并且增强纤维蛋白血块结构是减少血块破裂和出血的行之有效的方法。我们将通过提供可溶性且与血液相容的聚合物来改变凝块结构，该聚合物可识别并加固凝块部位。这种新型聚合物通过多种纤维蛋白特异性结合肽 (FBP) 进行功能化，使其能够与纤维蛋白在聚合过程中改变凝块结构，从而增强凝块并使其更耐分解。我们假设 FBP 修饰的生物聚合物可以增强纤维蛋白凝块强度并减少酶促凝块分解（纤维蛋白溶解）。在这项工作中，我们将优化潜在聚合物止血剂的结构，并在体外和体内评估这些材料稳定血栓和止血的能力，而不会产生相关的毒性和心肺并发症。