Synthetic hemostats for trauma treatment

用于创伤治疗的合成止血剂

• 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
• 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

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：创伤性伤害，如道路交通事故或故意暴力行为，每年夺去约500万人的生命。出血是造成30-40%的创伤相关死亡的原因，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用于创伤医学的基于生物聚合物的治疗，以加强血凝块并停止内部伤口的出血。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，即血凝块内的纤维蛋白纤维网络的结构是凝块强度的重要组成部分，并且增强纤维蛋白凝块结构是减少凝块分解和出血的经证实的方法。我们将通过提供一种可溶性和血液相容性的聚合物来改变凝块结构，这种聚合物可以识别和加强凝块部位。这种新型聚合物用多个纤维蛋白特异性结合肽（FBP）官能化，使其与 纤维蛋白在聚合过程中改变凝块结构，从而加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，减少酶促凝块分解（纤维蛋白溶解）。在这项工作中，我们将优化潜在的聚合物止血剂的结构，并在体外和体内评估这些材料稳定凝块和止血的能力，而不会产生相关的毒性和心肺并发症。