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 动脉动脉瘤破裂的死亡率很高。它们可以是梭形的或形状的，可以 发生在体内的任何地方。囊性动脉瘤（SAS）具有更大的发病率和死亡风险，因为 它们更容易破裂。这些动脉瘤可以是特发性，医源性，创伤性或动脉粥样硬化的 病因。不管原因是什么，SAS都是高度致命的和保证的近距离成像监视和治疗 防止致命破裂。目前的医学实践标准主要是用最低限度地处理SAS 侵入性血管内干预措施，例如线圈栓塞。尽管线圈取得了很大进步 栓塞技术，当前治疗中仍然存在严重问题，包括管理困难， 治疗失败和极高成本的可能性。线圈栓塞需要一组唯一的高度 - 专门的技能可以在亚毫米微观仪器中导航到遥远的地点，并且需要精确 脆弱的动脉瘤囊中的部署。结果，此类情况非常长，暴露于患者， 医务人员达到高辐射剂量。虽然线圈栓塞的技术成功可能会很高 由经验丰富的运营商执行，临床成功仅达到80％，而失败通常是由 凝血疾病患者的动脉瘤并持续流过线圈的持续流动。在 事实，即使存在血管内卷曲的患者，死亡的可能性是凝血病患者的10倍。 此外，治疗费用过高；线圈可能要花费数千美元，这是一个典型的情况 每个动脉瘤可能需要4-8个线圈，在某些情况下可能需要数十个线圈。我们通过使用剪裁来假设 边缘组织工程工具，可能会产生稳定的通用栓塞生物材料， 耐用，止血，粘合剂，廉价，不依赖凝血来取得临床成功，需要更少 栓塞SAS的专业技能。这种创造性的生物工程方法可能会减少程序时间， 减少辐射暴露，并通过消除昂贵的需求来降低全球发病率和死亡率 库存使农村和第三次世界乡村医院能够进入此类技术。我们旨在发展 使用开创性的剪切粉末填充动脉瘤的基于生物材料的最小基于生物材料的平台 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交付的STB 通过导管（AIM 1）和完善体外动脉瘤的STB生物相容性，粘附性和性能 模型（AIM 2）。最后，我们将测试猪动脉瘤模型中的工程STB（AIM 3），以模仿 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