Development of an Innovative Material for Transcatheter Peripheral Embolization

项目总结 出血和失控出血是导致死亡的主要原因，如果不是致命的，可能会导致不良反应。 具有长期负面后果的健康后果，包括器官损伤或衰竭以及昏迷。 失控出血可由各种疾病、创伤性损伤和健康状况引起，例如 房颤，在美国有超过260万人受到这种疾病的困扰。大多数房颤患者是必需的 服用抗凝剂(ACAs)。内出血的标准护理(SOC)是经导管栓塞术 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陷， 包括费用高，缺乏完全闭塞，依赖患者凝血，难以适当地给药， 成像人工制品，以及材料迁移或碎裂的机会。有一个意义重大的统一 需要与ACAs兼容、使用方便、有效且安全的栓塞剂 使用。为了满足这一需求，在这份快速通道提案中，Obsidio公司正在开发一种创新的栓塞剂 一种名为剪切稀化生物矿物(STB)的材料，它具有多功能和 有效的栓塞剂。STB即可使用，不需要混合或制备，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，而不必担心堵塞 导管，给药后不会产生图像伪影，并且由安全和 生物相容。此外，对于患者和医院来说，STB是一个更具成本效益的选择，不需要 与其他方法管理的专业知识水平相同。这项快速通道建议的目标是 开发临床级控制周围出血的STB配方并启动设计 冷冻，通过体外和体内研究证明生物材料和装置的安全性， 并完成FDA要求的测试，包括生物兼容性研究和GLP动物研究。 在快速通道的第一阶段，我们建议最终确定STB的配方，验证临床- 对STB进行分级，并在非GLP啮齿动物模型中评估其性能。在快速通道的第二阶段中，我们建议 在符合ISO-10993标准的非GLP出血猪模型中验证STB的性能 生物相容性研究，以确认生物制剂的安全性，包括体外和体内相关性研究 测定STB的降解率。最后，我们将在猪模型中进行GLP研究，以表征 机顶盒的性能和安全。使用Enable Obsidio to Advance to 510k成功完成此工作 清除用于外周出血的STB。总体而言，这种新型生物材料的开发将提供 一种具有卓越性能和通用性的新型栓塞剂，最终将有助于节省 每年有数十万人丧生。

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.