Treatment of arterial aneurysms using an injectable biomaterial

使用可注射生物材料治疗动脉瘤

• 批准号: 10171610
• 负责人: Ali Khademhosseini
• 金额: $ 60.75万
• 依托单位: MAYO CLINIC ARIZONA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10171610
• 关键词: 3-Dimensional; Adhesions; Adhesiveness; Adhesives; Aneurysm; Angiography; Animals; Arteries; Autopsy; Berry Aneurysm; Biocompatible Materials; Biomedical Engineering; Blood Coagulation Disorders; Catheters; Cessation of life; Clinical; Coagulation Process; Common iliac artery structure; Country; Coupled; Dangerousness; Data; Distant; Engineering; Ensure; Equipment and supply inventories; Etiology; Failure; Family suidae; Fatality rate; Formulation; Geometry; Hemostatic Agents; Histology; Hospitals; Human; Iatrogenesis; Iliac Vein; Image; Immune response; In Vitro; Incidence; Injectable; Intervention; Length; Medical; Medical Staff; Medical center; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Patients; Performance; Prevalence; Procedures; Property; Publications; Radiation Dose Unit; Radiation exposure; Reporting; Risk; Rodent; Rupture; Ruptured Aneurysm; Rural; Safety; Series; Shapes; Site; Structure; Technology; Testing; Therapeutic Embolization; Thinness; Time; Tissue Engineering; Translational Research; Treatment Cost; Treatment Failure; Work; base; biomaterial compatibility; bioprinting; cost; experience; implantation; in vivo; minimally invasive; mortality; prevent; skills; subcutaneous; success; surveillance imaging; tool; translational medicine

Abstract Arterial aneurysm rupture has a very high fatality rate. They can be fusiform or saccular in shape and can occur anywhere in the body. Saccular aneurysms (SAs) carry a greater risk of morbidity and mortality because they are more prone to rupture. These aneurysms can be idiopathic, iatrogenic, traumatic, or atherosclerotic in etiology. Regardless of the cause, SAs are highly-lethal and warrant close imaging surveillance and treatment to prevent a fatal rupture. The current standard of medical practice is primarily to treat SAs with minimally- invasive endovascular interventions such as coil embolization. Despite substantial advancements in coil- embolization technology, serious issues remain with current treatments, including difficulty in administration, the possibility of treatment failure, and extreme cost. Coil embolization requires a unique set of highly- specialized skills to navigate them within sub-millimeter micro-catheters to distant sites and require precise deployment within fragile aneurysm sacs. As a result, such cases are very lengthy and expose patients and medical staff to high radiation doses. While technical success of coil embolization may be high when performed by experienced operators, clinical success reaches only 80%, with failures often resulting from recanalization of the aneurysm and persistent flow through the coils in patients with coagulation disorders. In fact, death is 10 times more likely to occur in patients with coagulopathy, even with endovascular coiling. Furthermore, cost of treatment is excessive; coils can cost many thousands of dollars each and a typical case may require 4-8 coils per aneurysm and in some cases many dozens. We hypothesize that by using cutting- edge tissue engineering tools, it may be possible to produce a universal embolization biomaterial that is stable, durable, hemostatic, adhesive, inexpensive, does not rely on coagulation for clinical success, and requires less specialized skills to embolize SAs. This creative, bioengineering approach may reduce procedure time, decrease radiation exposure, and reduce world-wide morbidity and mortality by removing the need for a costly inventory enabling rural and 3rd world country hospitals to access such technology. We aim to develop a minimally invasive biomaterial-based platform to fill aneurysm sacs using groundbreaking shear-thinning biomaterials (STBs) based on our rich preliminary data. We will develop STBs for endovascular delivery through catheters (Aim 1) and refine STB biocompatibility, adhesiveness, and performance in in vitro aneurysm models (Aim 2). Finally, we will test the engineered STBs in porcine aneurysm models (Aim 3) that mimic the structure of aneurysms in humans.

抽象的 动脉瘤破裂的死亡率非常高。它们的形状可以是梭形或囊状，并且可以 发生在身体的任何部位。囊状动脉瘤 (SA) 具有更高的发病率和死亡率风险，因为 它们更容易破裂。这些动脉瘤可以是特发性的、医源性的、外伤性的或动脉粥样硬化性的 病因学。无论原因如何，SA 都具有高度致命性，需要进行密切的影像学监测和治疗 以防止致命的破裂。目前的医疗实践标准主要是用最低限度的治疗SAs 侵入性血管内介入治疗，例如弹簧圈栓塞。尽管线圈方面取得了实质性进展 栓塞技术，目前的治疗仍然存在严重问题，包括管理困难， 治疗失败的可能性和极高的费用。弹簧圈栓塞术需要一套独特的高度 需要专业技能才能在亚毫米微导管内将它们导航到遥远的部位，并且需要精确的 部署在脆弱的动脉瘤囊内。因此，此类案件的时间非常长，并且暴露了患者和 医务人员受到高辐射剂量。虽然弹簧圈栓塞的技术成功率可能很高，但 由经验丰富的操作者进行，临床成功率仅达80%，失败的原因往往是 患有凝血障碍的患者的动脉瘤再通和线圈的持续血流。在 事实上，即使采用血管内弹簧圈栓塞，凝血功能障碍患者的死亡可能性也要高出 10 倍。 此外，治疗费用过高；每个线圈的成本可能高达数千美元，而一个典型的案例 每个动脉瘤可能需要 4-8 个线圈，在某些情况下需要数十个。我们假设通过使用切割- 边缘组织工程工具，有可能生产出稳定的通用栓塞生物材料， 耐用、止血、粘合、价格低廉、临床成功不依赖凝血，并且需要较少 栓塞 SA 的专业技能。这种创造性的生物工程方法可以减少手术时间， 减少辐射暴露，并通过消除昂贵的治疗需求来降低世界范围内的发病率和死亡率 库存使农村和第三世界国家医院能够获得此类技术。我们的目标是开发一个 基于微创生物材料的平台，利用突破性的剪切稀化来填充动脉瘤囊 基于我们丰富的初步数据的生物材料（STB）。我们将开发用于血管内输送的 STB 通过导管（目标 1）并改善 STB 的生物相容性、粘附性和体外动脉瘤的性能 模型（目标 2）。最后，我们将在猪动脉瘤模型中测试工程化的 STB（目标 3），该模型模仿了 人类动脉瘤的结构。

项目成果

Roadmap on multifunctional materials for drug delivery.

• DOI: 10.1088/2515-7639/ad05e8
• 发表时间: 2024-01-01
• 期刊: JPhys materials

Assessing the aneurysm occlusion efficacy of a shear-thinning biomaterial in a 3D-printed model.

• DOI: 10.1016/j.jmbbm.2022.105156
• 发表时间: 2022-06
• 期刊: JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
• 影响因子: 3.9
• 作者: Schroeder, Grant;Edalati, Masoud;Tom, Gregory;Kuntjoro, Nicole;Gutin, Mark;Gurian, Melvin;Cuniberto, Edoardo;Hirth, Elisabeth;Martiri, Alessia;Sposato, Maria Teresa;Aminzadeh, Selda;Eichenbaum, James;Alizadeh, Parvin;Baidya, Avijit;Haghniaz, Reihaneh;Nasiri, Rohollah;Kaneko, Naoki;Mansouri, Abraham;Khademhosseini, Ali;Sheikhi, Amir
• 通讯作者: Sheikhi, Amir