Flow Responsive Embolic Agent for the Complete Devascularization of Meningiomas

项目总结 意义：脑膜瘤的术前栓塞(POE)是一种公认的神经血管内治疗方法 手术是为了减少肿瘤切除过程中的大量失血。当前的做法 由于当前在标签外使用的栓塞剂的有效性和安全性不足，显著阻碍了 这一指示(它们都不是专门为PoE设计的)。聚乙烯醇颗粒是最常用的 栓塞剂，但疗效数据引起了人们对其临床益处的担忧。TruFill和Onyx是液体栓塞剂 其他选择，但都充满了自己的局限性。例如，玛瑙含有有毒的溶剂，会导致 患者的痛苦和不适，而与TruFill相关的技术风险否定了它的广泛采用 在美国。因此，需要一种专为PoE设计的易于使用的、标签上的栓塞剂 提供安全和完全断流血管的脑膜瘤。这种栓塞会导致更快和更快的 更安全的手术切除，代表着脑膜瘤患者治疗的重大进步。 方法：在这一直接到第二阶段的SBIR中，阿森纳医疗公司将推进其剪切稀释生物材料技术， 一种血流反应性栓塞剂(FRE)，用于治疗脑膜瘤的POE。要使PoE有效、完整 脑膜瘤的血管离断术是理想的，这是通过完全闭塞所有供应脑膜瘤的远端血管来实现的。 肿瘤。我们的第一阶段结果表明，FRE的远端穿透性优于 商用液体栓塞剂，具有生物相容性，可以通过神经血管手动注射 微导管。此建议的目标是将概念验证公式推向产品 通过早期可行性研究(EFS)为临床测试做好准备的配置，实现了一条有效的途径 商业化。在目标1中，我们将最终确定给药系统，并与临床医生确认该产品的可用性。 目标2包括选择一种商业上可行的灭菌方法，然后确认产品 保质期。FRE的生物相容性将通过临床前研究来确定神经血管 响应和安全性(目标3)和通过生物和化学进行的ISO10993生物兼容性测试 特征分析(目标4)。拟议的工作提供了一个将得到补充的基础数据集 与第二阶段后的活动一起向商业化迈进。 创新：FRE生物材料具有自适应特性，使其能够在高粘度下成为低粘度流体 穿透并填充供应脑膜瘤的远端血管的剪切力。随着栓塞术的进展，血流和 剪切力将不断降低；相应地，FRE的粘度逐渐增加，成为粘性糊状物 用于受控注射。其结果是整个血管系统完全铸型和闭塞。与其他 液体栓塞剂，FRE不太容易发生不完全闭塞，因为它的固化机制 与其微环境无关。例如，玛瑙通过沉淀作用固化，形成坚硬的外壳。 可以阻塞血管分支路径的外壳，防止它们被深血管栓塞。

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.