SBIR Phase II: Sprayable Reversible Hemostat for Treatment of Non-Compressible Hemorrhage

该小型企业创新研究(SBIR)第二阶段项目旨在开发一种可喷雾泡沫止血器，用于治疗不可压缩出血，这是与出血相关的创伤的主要死亡原因(约90%)。泡沫材料是以生物聚合物壳聚糖为基础的；使用新型疏水接枝对这种聚合物进行改性，可以使材料更快地凝结血液，并比未改性的版本更牢固地附着在组织上。此外，一种基于环糊精的互补技术能够根据需要逆转改性壳聚糖的止血作用。这种生物聚合物被包装在装有液化推进剂的手持式铝罐中，并通过机械致动器排出，形成一种能够膨胀成不规则形状的空腔的泡沫。该项目的预期结果是开发出一个工作原型，其中包含关于疏水接枝密度和疏水长度的优化的改性壳聚糖。泡沫配方将在体外通过动态和稳定的剪切流变学研究，在血液存在的情况下进行测试，并在体内使用猪的不可压缩出血模型进行测试。将进行生物兼容性测试和组织组织学研究，以确定优化配方的安全性。该项目的更广泛影响/商业潜力属于战场和创伤医学领域。泡沫是战场上和紧急医疗服务中急性伤口治疗的未来。严重的出血，特别是内出血，不容易用空间封闭的产品，如绷带来治疗。此外，在急性伤口上正确地放置绷带需要大量的技能和经验。然而，可喷雾泡沫是非常友好的用户，并允许充分的自我应用或由一个不熟练的‘伙伴’对各种出血类型的潜在应用。因此，我们设想我们的壳聚糖泡沫是士兵背包、急诊室和家庭急救箱的必需品。这一愿景是一个可行的经济前景，因为这种材料成本低，重量轻，即使在极端的环境条件下也非常耐用。此外，互补的环糊精系统提供的可逆性为创伤外科医生提供了一种简化工具。止血材料的去除和损伤部位的准确识别是手术室中必要的任务，这一独特的技术特征使这一任务变得容易得多。

This Small Business Innovation Research (SBIR) Phase II project aims to develop a sprayable foam hemostat for treatment of non-compressible hemorrhage, which is the leading cause of death (~90%) for bleeding-related trauma. The foam material is based on the biopolymer chitosan; a modification to this polymer with novel hydrophobic grafts allows the material to clot blood much more rapidly and adhere to tissue more strongly than the unmodified version. Also, a complementary cyclodextrin-based technology is able to reverse the hemostatic action of the modified chitosan on demand. The biopolymer is packaged into aluminum hand-held canisters with liquefied propellant and expelled via mechanical actuator creating a foam which is able to expand into irregularly shaped cavities. The desired outcome of the project is to develop a working prototype of the canister containing an optimized modified chitosan with respect to hydrophobic grafting density and hydrophobe length. Foam formulations will be tested for clotting and reversibility in vitro via dynamic and steady shear rheology studies in the presence of blood and in vivo using non-compressible bleeding models in pigs. Biocompatibility testing and tissue histology studies will be performed to determine the safety profile of the optimized formulations.The broader impact/commercial potential of this project falls in the arena of battlefield and trauma medicine. Foams are the future of acute wound treatment on the battlefield and in emergency medical services. Severe bleeding, especially internal bleeding, is not easily treated with a spatially contained product, such as a bandage. Furthermore, correct bandage placement on an acute wound requires a great deal of skill and experience. However, a sprayable foam is very user friendly and allows potential for adequate self-application or application by an unskilled 'buddy' for a wide range of hemorrhage types. Thus, we envision our chitosan foam as a necessary supply in the soldier's backpack, the emergency room and the home first aid kit. This vision is a viable economic prospect because the material is low cost, lightweight and highly durable even in extreme ambient conditions. Additionally, the reversibility provided by the complementary cyclodextrin system provides a streamlining tool for the trauma surgeon. Removal of hemostatic material and precise indentification of the injury site are necessary tasks in the operating room which are made much easier by this unique technological feature.