Ideal Embolic for Portal Vein Embolization

门静脉栓塞的理想栓塞剂

• 批准号: 10081195
• 负责人: QUYNH P PHAM
• 金额: $ 36.72万
• 依托单位: ARSENAL MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-24 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10081195
• 关键词: Adhesions; Animal Model; Area; Biocompatible Materials; Blood flow; Caliber; Catheters; Clinical; Clinical Research; Cyanoacrylates; Data; Development; Disease; Distal; Environment; Evolution; Excision; FDA approved; Family suidae; Feedback; Fluoroscopy; Formulation; Future; Glues; Hepatectomy; Hepatic Insufficiency; Hypertrophy; Injections; Kinetics; Lead; Liquid substance; Literature; Liver; Medical; Microspheres; Modeling; Operative Surgical Procedures; Outcome; Paste substance; Patients; Penetration; Phase; Physicians; Portal vein structure; Postoperative Period; Preparation; Procedures; Property; Radiology Specialty; Research; Review Literature; Risk; Small Business Innovation Research Grant; Standardization; Structure; Technology; Testing; Therapeutic Embolization; Thinness; Time; United States; Viscosity; Visualization; Work; base; biomaterial compatibility; design; experience; innovation; insight; medical schools; neurovascular; novel; pre-clinical; preclinical safety; prevent; professor; success

PROJECT SUMMARY Significance: Portal vein embolization (PVE) is a procedure that is performed to induce hypertrophy of the non- diseased future liver remnant (FLR) to a sufficient volume to enable surgical resection of the diseased portion of the liver. One of the most important factors governing FLR hypertrophy is the embolic agent used. A review of the literature indicates that embolization with cyanoacrylate glue (“glue”) induces the greatest amount of FLR hypertrophy. Despite this evidence, physicians in the United States prefer PVE using microspheres, which are technically easier to administer than glue; additionally glue is only FDA-approved for neurovascular indications. Development of an embolic agent FDA indicated for PVE that induces the same (or better) amount of FLR hypertrophy as glue but without the associated risks and challenges would represent a significant advance in standardizing PVE and have potential applicability in other embolization applications. Approach: In this Phase I SBIR, Arsenal Medical, will evaluate its shear-thinning biomaterial technology as a distal penetrating embolic (DPE) therapy for PVE. In order to be effective, complete and distal embolization of the portal vein and its branches is desired in order to minimize the formation of porto-portal collaterals, which diverts portal flow away from the FLR and reduces hypertrophy. Therefore, in Aim 1, we will use a PVE swine model to identify a formulation with shear-thinning properties that adequately responds to the dynamic blood flow environment such that maximal distal penetration and occlusion are achieved. Subsequently, in Aim 2, we will evaluate the kinetics of FLR hypertrophy (and determine any differences with distal penetration and/or porto-portal collateralization) following embolization with our material compared to glue. Success will be demonstration of FLR hypertrophy similar to or better than the glue. The proposed studies would be the first to characterize the impact of distal penetration of different embolic agents on porto-portal collateralization and subsequent FLR hypertrophy kinetics, filling an important void in the literature. Innovation: Our DPE biomaterial has unique shear-thinning properties, making it adaptive and responsive to blood flow, becoming a low viscosity fluid under high shear that penetrates and fills the portal vein and distal branches. As flow decreases due to the embolization procedure, the shear decreases, and the viscosity of the material increases. In doing so, an entire cast of the vasculature is generated that provides complete occlusion, eliminates re- canalization, and minimizes collateralization. Unlike glue, the solidification mechanism of the DPE is independent of its microenvironment, thereby allowing a longer working time and making distal penetration unsusceptible to injection rate. Further, the material is not adhesive, so there is no risk of adhesion to the catheter, and is formulated to be radiopaque, enabling visualization under fluoroscopy. Leading interventionalists have attested to the procedural simplicity of using the DPE with respect to preparation, delivery, and control during embolization.

项目摘要 显着性：门静脉栓塞（PVE）是一种程序，用于诱导非 - 解散的未来肝残留（FLR）足够容纳足够的体积，以便对解剖部分的手术切除 肝。控制FLR肥大的最重要因素之一是使用的栓塞剂。评论 文献表明用氰基丙烯酸酯胶（“胶”）栓塞可诱导最大量的FLR 肥大。尽管有这些证据，但美国的医生更喜欢使用微球的PVE 从技术上讲，比胶水更容易管理；另外，胶水仅是FDA批准的，用于神经血管指示。 针对影响相同（或更高）FLR的PVE的栓塞剂FDA的开发 肥大为胶水，但没有相关的风险和挑战将代表重大进展 标准化PVE并在其他栓塞应用中具有潜在的应用。 方法：在这一阶段，阿森纳医学的SBIR将评估其剪切的生物材料技术 PVE的穿透性栓塞（DPE）疗法。为了有效，完整和远端栓子 门户网站 需要静脉及其分支 从FLR流出并减少肥大。因此，在AIM 1中，我们将使用PVE猪模型来识别 具有剪切稀释特性的形成，适当响应动态血流环境 达到了最大的远端穿透和阻塞。随后，在AIM 2中，我们将评估 FLR肥大（并确定远端穿透性和/或港口 - 门户抵押品的任何差异） 与胶水相比，与我们的材料栓塞后。成功将证明FLR肥大 类似于或更好。拟议的研究将是第一个表征识别影响的研究 不同栓塞物在港口 - 门户的抵押和随后的FLR肥大动力学上渗透， 填补文献中的重要空隙。 创新：我们的DPE生物材料具有独特的剪切特性，使其适应性且对血液有反应 流动，成为高剪切液下的低粘度流体，可以穿透并填充门静脉和远端分支。作为 由于栓塞程序，剪切降低，材料的粘度减小，流量减小。 这样，产生了整个脉管系统的整个铸件，可以完全闭塞，消除了重新脉络 口量，并最大程度地减少抵押品。与胶水不同，DPE的凝固机制与 它的微环境，从而允许更长的工作时间，并使远端穿透无法忍受 注射率。此外，材料不是粘合剂，因此没有粘合剂的风险，并配制 为了放射线，在荧光镜下可视化。领先的介入主义者已经证明了 在栓塞过程中使用DPE在制备，分娩和控制方面的程序简单性。