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.

项目概要 意义：门静脉栓塞术（PVE）是一种诱导非门静脉肥大的手术。 患病的未来肝脏残余物（FLR）达到足够的体积，以便能够通过手术切除肝脏的患病部分 控制 FLR 肥大的最重要因素之一是所使用的栓塞剂。 文献表明，氰基丙烯酸酯胶（“胶水”）栓塞可诱导最大量的 FLR 尽管有这些证据，美国的医生还是更喜欢使用微球进行 PVE，因为微球具有以下优点： 从技术上讲，胶水比胶水更容易使用；此外，胶水仅获得 FDA 批准用于神经血管适应症。 开发 FDA 指定用于 PVE 的栓塞剂，可诱导相同（或更好）量的 FLR 肥大作为粘合剂但没有相关的风险和挑战将代表着重大进步 标准化 PVE 并在其他栓塞应用中具有潜在的适用性。 方法：在第一阶段 SBIR 中，Arsenal Medical 将评估其剪切稀化生物材料技术作为远端 穿透性栓塞（DPE）治疗PVE以便有效、完整和远端栓塞门静脉。 静脉及其分支是必要的，以便最大限度地减少门静脉循环的形成，从而使门静脉分流 因此，在目标 1 中，我们将使用 PVE 猪模型来识别猪。 具有剪切稀化特性的配方，可充分响应动态血流环境，例如 随后，在目标 2 中，我们将评估其动力学。 FLR 肥大（并确定远端穿透和/或门静脉侧支的任何差异） 与胶水相比，使用我们的材料进行栓塞后将成功证明 FLR 肥大。 拟议的研究将是第一个描述远端影响的研究。 不同栓塞剂对门静脉侧支的渗透和随后的 FLR 肥大动力学， 填补了文献中的一个重要空白。 创新：我们的 DPE 生物材料具有独特的剪切稀化特性，使其对血液具有适应性和响应性 流动，在高剪切力下变成低粘度流体，渗透并填充门静脉和远端分支。 由于栓塞过程，流量减少，剪切力降低，并且材料的粘度增加。 这样做时，生成了整个脉管系统模型，提供完全闭塞，消除了重新 与胶水不同，DPE 的固化机制独立于管道化。 它的微环境，从而允许更长的工作时间并使远端渗透不易受到影响 此外，该材料不具有粘性，因此不存在粘连到导管的风险，并且是配制的。 不透射线，可在透视下实现可视化，领先的介入医生已经证明了这一点。 使用 DPE 在栓塞过程中的准备、输送和控制方面的程序简单。