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

这项小型企业创新研究（SBIR）一期项目旨在开发一种可喷涂的“可逆”泡沫止血剂，用于治疗不可压缩性出血。不可压缩性出血是导致出血相关创伤死亡的主要原因（约90%）。泡沫材料是基于生物聚合物壳聚糖；用新型疏水移植物对这种聚合物进行修饰，使这种材料比未经修饰的材料更快地凝结血液，并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铝制手持罐中，并通过机械致动器排出，形成一种能够膨胀成不规则形状空洞的泡沫。该项目的预期结果是开发一个含有优化改性壳聚糖的罐的工作原型，其中涉及疏水接枝密度和疏水长度。泡沫配方将通过血液存在下的动态和稳定剪切流变学研究在体外进行凝血和可逆性测试，并在体内使用大鼠不可压缩出血模型进行测试。该项目更广泛的影响/商业潜力是更好地控制战场上的非压缩性出血和创伤医学。泡沫是战场上急性伤口治疗和紧急医疗服务的未来。严重出血，特别是内出血，不容易用绷带等空间封闭的产品来治疗。此外，在急性伤口上正确放置绷带需要大量的技巧和经验。然而，可喷涂泡沫非常用户友好，允许充分的自我应用或由不熟练的“伙伴”应用于各种出血类型。因此，我们设想壳聚糖泡沫将成为士兵背包、急诊室和家庭急救箱中的必需品。这是一个可行的经济前景，因为这种材料成本低，重量轻，即使在极端环境条件下也非常耐用。此外，互补环糊精系统提供的可逆性为创伤外科医生提供了一个精简的工具。清除止血材料和精确识别损伤部位是手术室中必要的任务，这种独特的技术特点使其变得更加容易。

This Small Business Innovation Research (SBIR) Phase I project aims to develop a sprayable "reversible" 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 that 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 rats.The broader impact/commercial potential of this project is better control of non-compressable hemorrhage on the 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 identification of the injury site are necessary tasks in the operating room, which are made much easier by this unique technological feature.