Flow Responsive Embolic Agent for the Complete Devascularization of Meningiomas

用于脑膜瘤完全断流的血流响应栓塞剂

• 批准号: 10256541
• 负责人: QUYNH P PHAM
• 金额: $ 79.14万
• 依托单位: ARSENAL MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10256541
• 关键词: Acute; Adoption; Animals; Area; Benign; Biocompatible Materials; Biological; Biological Assay; Blood flow; Brain; Brain Neoplasms; Chemicals; Clinic; Clinical; Collaborations; Communities; Complement; Cyanoacrylates; Data; Data Set; Development; Device Designs; Distal; Effectiveness; Ethylene Oxide; Evaluation; Evolution; Excision; Exhibits; External Carotid Artery Branch; Family suidae; Feasibility Studies; Formulation; Foundations; Glues; Goals; Grant; Hemorrhage; Human; Implant; In Situ; Injections; Kidney; Label; Lead; Learning; Life; Liquid substance; Manuals; Mediation; Medical; Methods; Neurosurgeon; New Agents; Operative Surgical Procedures; Pain; Paste substance; Pathway interactions; Patient Care; Patients; Penetration; Performance; Phase; Physicians; Polyvinyl Alcohol; Precipitation; Prevention; Procedures; Property; Radiology Specialty; Reflux; Reporting; Research; Risk; Safety; Silicones; Small Business Innovation Research Grant; Solvents; Sterilization; Structure; Syringes; System; Technology; Testing; Therapeutic Embolization; Thinness; Time; Toxicology; Trauma; United States; Universities; Vascular blood supply; Viscosity; Work; animal data; base; biomaterial compatibility; brain tumor resection; cohort; commercialization; cost effective; cytotoxicity; design; experience; first-in-human; hemocompatibility; human data; human study; in vivo; innovation; meningioma; neurosurgery; neurovascular; novel; off-label use; particle; pre-clinical research; preclinical study; prevent; professor; programs; research clinical testing; response; risk mitigation; secondary endpoint; standard of care; success; systemic toxicity; tumor; usability

PROJECT SUMMARY Significance: Pre-operative embolization (POE) of meningiomas is an established neuroendovascular procedure performed to reduce the extensive amount of blood loss that occurs during tumor resection. The current practice is significantly hampered because of efficacy and safety deficiencies of current embolic agents used off-label for this indication (none of which are designed specifically for POE). Polyvinyl alcohol particles are the most used embolic agent, but efficacy data raise concerns of their clinical benefit. Trufill and Onyx are liquid-based embolic alternatives but are fraught with limitations of their own. For example, Onyx contains toxic solvent that causes patient pain and discomfort while the technical risks associated with Trufill have negated its wide-spread adoption in the United States. Thus, there is a need for an easy-to-use, on-label embolic agent designed specifically for POE of meningiomas that provides safe and complete devascularization. Such an embolic would result in faster and safer surgical resection, representing a significant evolution in the treatment of meningioma patients. Approach: In this Direct to Phase II SBIR, Arsenal Medical will advance its shear-thinning biomaterial technology, a flow responsive embolic (FRE) agent, as a therapy for the POE of meningiomas. For POE to be effective, complete devascularization of the meningioma is desired, which is achieved by total occlusion of all distal vessels that supply the tumor. Our Phase I results have demonstrated that the FRE exhibits superior distal penetration compared to commercial liquid embolics, is biocompatible, and can be manually injected through a neurovascular microcatheter. The goal of this proposal is to advance the proof-of-concept formulation towards a product configuration that is ready for clinical testing via an early feasibility study (EFS), enabling an efficient path to commercialization. In Aim 1, we will finalize the delivery system and affirm the product’s usability with clinicians. Aim 2 will consist of selection of a commercially viable sterilization method, followed by confirmation of product shelf-life. Biocompatibility of the FRE will be confirmed via a pre-clinical study to determine the neurovascular response and safety (Aim 3) and ISO10993 biocompatibility testing through biological and chemical characterization assays (Aim 4). The proposed work provides a foundational data set that will be complemented with post-Phase II activities to advance towards commercialization. Innovation: The FRE biomaterial has adaptive properties enabling it to become a low viscosity fluid under high shear that penetrates and fills the distal vessels supplying the meningioma. As embolization progresses, flow and shear will continually decrease; in response, the FRE progressively increases in viscosity becoming a viscous paste for controlled injection. The result is complete casting and occlusion of the entire vasculature. Compared to other liquid embolics, the FRE is less susceptible to incomplete occlusion because its solidification mechanism occurs independent of its microenvironment. Onyx, for example, solidifies via a precipitation effect, forming a hard outer shell that can block vessel branch pathways preventing them from deep vessel embolization.

项目摘要 意义：脑膜瘤的术前栓塞（POE）是一种已建立的神经内血管手术 进行的旨在减少肿瘤切除期间发生的大量失血量。当前的做法 由于当前使用标签外的栓塞剂的高效和安全性缺陷而受到明显阻碍 这种迹象（这些都不是专门为POE设计的）。聚乙烯醇颗粒是最常用的 栓塞剂，但有效的数据引起了对其临床益处的关注。 Trufill和Onyx是液体栓塞 替代方案，但充满了自己的局限性。例如，Onyx包含引起的有毒溶剂 患者疼痛和不适，而与Trufill相关的技术风险已否定了其广泛采用 在美国。那就是需要专门为POE设计的易于使用的，标签的栓塞剂 提供安全，完整的血管形成的脑膜瘤。这样的栓塞会导致更快，并且 更安全的手术切除，代表脑膜瘤患者治疗的显着演变。 方法：在直接直接进入II阶段SBIR中，阿森纳医疗将推进其剪切稀释的生物材料技术， 流动敏感的栓塞（FRE）剂，作为脑膜瘤POE的一种疗法。 POE有效，完整 需要脑膜瘤的血管形成，这是通过全部闭塞所有远端视频来实现的 肿瘤。我们的阶段I结果表明，与 商业液体栓塞，具有生物相容性，可以通过神经血管手动注射 微量导线。该提议的目的是将概念验证公式推向产品 可以通过早期可行性研究（EFS）准备进行临床测试的配置，从而有效地通往 商业化。在AIM 1中，我们将最终确定交付系统，并向临床医生确认产品的可用性。 AIM 2将包括选择商业可行的灭菌方法，然后确认产品 保质期。 FRE的生物相容性将通过临床前研究确认，以确定神经血管 响应和安全性（AIM 3）和ISO10993生物相容性测试通过生物学和化学 表征分析（目标4）。拟议的工作提供了将完成的基础数据集 随着《阶段II后的活动》的发展，以迈向商业化。 创新：FRE生物材料具有自适应特性，使其成为高粘度流体的高粘度流体 穿透并填充提供脑膜瘤的远端血管的剪切。随着栓塞的进展，流动和 剪切将不断减小；作为回应，粘度逐渐增加成为粘性 用于受控注射。结果是整个脉管系统的完整铸造和阻塞。与其他相比 液体栓塞，FRE不太容易受到不完全闭塞的影响，因为其固化机制发生 独立于其微环境。例如，Onyx通过降水效应巩固，形成硬外部 可以阻止容器分支途径的壳，从而阻止其深船栓塞。