Synthetic Hemostats for Trauma Treatment

项目摘要 诸如道路交通事故或故意暴力行为造成的创伤， 年轻人，每年夺走大约500万人的生命，并占更多的潜在寿命损失年数。 比美国癌症或心脏病。出血是造成30-40%的创伤相关性 死亡，是受伤后最初6小时内死亡的主要原因。因此，有很大的需求 以及急救人员可用于管理出血的新技术的潜在临床影响 在创伤后的最初时间内。该提案旨在开发一种静脉内合成止血剂， 创伤护理的临床翻译该项目小组包括创伤医学、生物工程、 材料、软材料结构分析和动物病理学。我们假设一种合成的 一种生物聚合物能特异性识别并交联血纤维蛋白（血凝块的一种蛋白质成分）， 静脉注射后伤口部位。在我们的初步工作中，我们设计了一种可注射的，生物工程的 聚合物，并证明了其整合形成凝块的能力，并显着提高动物的存活率 创伤后静脉注射时的创伤模型。临床翻译的最终目标是 材料，本项目提出三个目标：（i）确定最佳聚合物结构和合成路线，（ii） 评价该材料的药代动力学、安全性和储存稳定性，以及（iii）确定 多种临床前动物创伤性出血模型。在完成这些目标后， 与FDA进行IND前会议，并在向食品和药物管理局提交IND的几年内 管理局（FDA）。

PROJECT SUMMARY Traumatic injuries, such as from road traffic accidents or intentional acts of violence, preferentially affects the young, claims approximately 5 million lives annually, and accounts for more years of potential life lost in the United States than cancer or heart disease. 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. Thus, there is a significant need and potential clinical impact for new technologies that can be used by first responders to manage hemorrhage in the initial time frame after trauma. This proposal seeks to develop an intravenous synthetic hemostat for clinical translation for trauma care. The project team includes experts in trauma medicine, bioengineered materials, structural analysis of soft materials, and animal pathology. We hypothesize that a synthetic biopolymer that specifically recognizes and crosslinks fibrin, a protein component of clots, will stop bleeding at wound sites after intravenous injection. In our preliminary work, we have designed an injectable, bioengineered polymer and demonstrated its ability to integrate in forming clots and significantly improve survival in an animal model of trauma when injected intravenously after injury. With the ultimate goal of clinical translation for this material, this project proposes three aims: (i) define the optimal polymer structure and synthesis route, (ii) evaluate the pharmacokinetics, safety profile and storage stability of the material, and (iii) establish efficacy in multiple preclinical animal traumatic bleeding models. Upon completion of these aims, the team will be ready for a pre-IND meeting with the FDA and be within a few years of an IND submission to the Food and Drug Administration (FDA).