Synthetic hemostats for trauma treatment

用于创伤治疗的合成止血剂

• 批准号: 8822119
• 负责人: Suzie H. Pun
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8822119
• 关键词: 2-hydroxyethyl methacrylate; 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; Hemorrhage; Hemorrhagic Shock; Hemostatic Agents; Hemostatic function; Histopathology; Hospitals; Hour; In Vitro; Inflammation; Injectable; Injury; Intravenous; Kinetics; Knowledge; Life; Liquid substance; Mechanics; Medicine; 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; public health relevance; radiotracer; response; trauma care

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走约500万人的生命。出血占创伤相关死亡的30%-40%，是创伤后最初6小时内死亡的主要原因。该项目的总体目标是开发一种用于创伤医学的基于生物聚合物的治疗方法，以加强血液凝块和止血内伤口。这一点很重要，因为无法控制的出血是创伤受害者死亡的主要原因。我们的方法基于这样的知识，即血栓内纤维纤维网络结构是凝块强度的重要组成部分，增强纤维蛋白凝块结构是减少血栓破裂和出血的有效方法。我们将通过提供一种可溶的、与血液相容的聚合物来识别和加强血栓部位，从而改变血栓结构。这种新型聚合物是由多个纤维蛋白特异结合肽(FBP)功能化的，允许它与 纤维蛋白在聚合过程中改变凝块结构，从而加强凝块，使其更能抵抗分解。我们假设FBP修饰的生物聚合物可以增强纤维蛋白凝块的强度，减少酶促凝块的分解(纤溶)。在这项工作中，我们将优化潜在的聚合物止血剂的结构，并在体外和体内评估这些材料在没有相关毒性和心肺并发症的情况下稳定血栓和止血的能力。