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，例如出于道路交通事故或故意暴力行为，每年约有500万人生命。出血负责30-40％的创伤相关死亡，是受伤后最初6小时死亡的主要原因。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，以增强血液凝块并停止因内部伤口流血。这很重要，因为无法控制的出血是创伤受害者的主要死亡原因。我们的方法是基于一个知识，即血凝块中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良好方法。我们将通过提供可溶性和血液兼容的聚合物来改变凝块结构，该聚合物识别和增强凝块位点。这种新型聚合物用多个纤维蛋白特异性结合肽（FBP）功能化，从而使其与 聚合过程中的纤维蛋白以改变凝块结构，从而加强了凝块并使其更耐崩溃。我们假设FBP装饰的生物聚合物可以增强纤维蛋白血块强度并减少酶促分解（纤维蛋白溶解）。在这项工作中，我们将优化潜在聚合物止血的结构，并在体外和体内评估这些材料的稳定能力并停止出血而没有相关的毒性和心肺并发症。