Development of an Innovative Material for Transcatheter Peripheral Embolization

项目摘要 出血和不受控制的出血是导致死亡的主要原因，当不致命时，可导致不良反应。 具有长期负面后果的健康结果，包括器官损伤或衰竭以及昏迷。 不受控制的出血可由多种疾病、创伤性损伤和健康状况引起，例如 房颤，在美国有超过260万人受到影响。大多数房颤患者需要 服用抗凝血剂（ACA）。内出血的标准治疗（SOC）是经导管栓塞 然而，为了闭塞出血的动脉或静脉，目前可用的方法存在主要缺点， 包括高成本、缺乏完全闭塞、依赖于患者凝血、难以正确给药 成像伪影以及材料迁移或碎裂的可能性。有一个重要的问题 需要与ACA相容的栓塞材料，易于使用，并且对 使用.为了满足这一需求，在这个快速通道提案中，Obsidio公司正在开发一种创新的栓塞剂， 一种被称为剪切稀化生物材料（STB）的材料，具有多功能和 有效栓塞材料。STB即用型，无需混合或准备，易于管理 通过标准的微导管，可以在短时间或长时间内输送，而不用担心堵塞 导管，在给药后不会产生图像伪影，并且由安全的材料组成， 生物相容性。此外，STB对患者和医院来说都是更具成本效益的选择，并且不需要 与其他方法相同的专业知识水平。本快速通道建议的目标是 开发临床级STB制剂用于外周出血控制，并启动设计 冷冻，通过体外和体内研究证明生物材料和器械的安全性， 并完成FDA要求的测试，包括生物相容性研究和GLP动物研究。 在快速通道的第一阶段，我们建议最终确定STB配方，验证临床- 分级STB，并在非GLP啮齿动物模型中评价其性能。在快速通道的第二阶段， 根据ISO-10993，在非GLP出血猪出血模型中确认STB性能 生物相容性研究，以确认生物材料的安全性，包括体外体内相关性研究， 确定STB的退化。最后，我们将在猪模型中进行GLP研究， 机顶盒的性能和安全性。成功完成这项工作，使Obsidio能够推进到510 k 清除STB用于外周出血。总的来说，这种新型生物材料的开发将提供 physcians是一种新型栓塞选择，具有上级性能和多功能性，最终将有助于挽救 每年都有成千上万的人死去

PROJECT SUMMARY Hemorrhage and uncontrolled bleeding are a leading cause of death, and when not fatal can result in adverse health outcomes with long term negative consequences including organ damage or failure, and coma. Uncontrolled bleeding can arise from a variety of diseases, traumatic injuries, and health conditions, such as atrial fibrillation, which afflicts over 2.6M people in the United States. Most atrial fibrillation patients are required to take anticoagulants (ACAs). The standard of care (SOC) for internal hemorrhage is transcatheter embolization to occlude the bleeding artery or vein, however, there are major drawbacks of currently available methods, including high cost, lack of complete occlusion, reliance on patient coagulation, difficultly of proper administration, imaging artifacts, and the chance of migration or fragmentation of the material. There is a significant unment need for embolization materials that are compatible with ACAs, are easy to use, and are effective and safe for use. To address this need, in this Fast-track proposal Obsidio, Inc is developing an innovative embolic material called shear-thinning biomatieral (STB) that has the qualities required for a versatile and effective embolic material. STB is ready to use and does not require mixing or preparation, is easy to administer via standard microcatheters, can be delivered over a short or extended time period without fear of clogging the catheter, does not produce an image artifact after administration, and is comprised of materials that are safe and biocompatible. Moreover, STB is a more cost-effective option for both patients and hospitals and does not require the same level of expertise to administer as other methods.The objective of this Fast-track proposal is to develop a clinical-grade formulation of STB for peripheral hemorrhage control and initate a design freeze, demonstrate safety of both the biomaterial and the device through ex vivo and in vivo studies, and complete the testing required by the FDA including biocompatibility studies and GLP animal studies. In Phase I of the Fast-track we propose to finalize STB formulation, validate the safety and efficacy of clinical- grade STB, and evaluate its performance in a non-GLP rodent model. In Phase II of the Fast-track we propose to validate STB performance in a non-GLP bleeding porcine model of hemorrhage, followed by ISO-10993 biocompatbility studies to confirm safety of the biomateirals, including an in vitro in vivo correlation studies to determine the degradation of STB. Finally, we will conduct GLP studies in a porcine model to characterize the performance and safety of STB. Successful completion of this work with enable Obsidio to advance to 510k clearance for STB used in peripheral hemorrhage. Overall, development of this novel biomaterial will provide physcians a novel embolization option with superior performance and versatility that will ultimately help to save hundreds of thousands of lives annually.