Bionanomatrix coating for brain aneurysm coils to enhance healing

用于脑动脉瘤线圈的生物纳米基质涂层可增强愈合

• 批准号: 9047644
• 负责人: Patrick Hwang
• 金额: $ 55.34万
• 依托单位: ENDOMIMETICS, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9047644
• 关键词: Adhesives; Agreement; Aneurysm; Animals; Binding Sites; Biocompatible; Blood; Brain Aneurysms; Cell Differentiation process; Cell-Matrix Junction; Cells; Cerebral Aneurysm; Cessation of life; Characteristics; Clinic; Clinical; Clinical Data; Collaborations; Data; Development; Devices; Elastases; Elements; Endothelial Cells; Endothelium; Environment; Evaluation; Fright; Growth; Healed; Human; In Vitro; Inflammation; Inflammatory Response; Intracranial Aneurysm; Legal patent; Letters; Ligands; Mediating; Methodology; Methods; Modeling; Modification; Nitric Oxide; Organic solvent product; Oryctolagus cuniculus; Outcome; Patients; Peptides; Phase; Platinum; Population; Positioning Attribute; Production; Property; Recruitment Activity; Recurrence; Research; Research Infrastructure; Resources; Risk; Rupture; Ruptured Aneurysm; Site; Small Business Innovation Research Grant; Smooth Muscle Myocytes; Stem cells; Technology; Therapeutic Embolization; Tissues; Umbilical vein; United States Food and Drug Administration; Water; Work; base; cell growth; clinical care; clinical efficacy; disability; evaporation; good laboratory practice; healing; improved; in vivo; industry partner; migration; mortality; novel; phase 1 study; physical property; pre-clinical; public health relevance; quality assurance; scale up; spelling; success; surface coating; tyrosyl-isoleucyl-glycyl-seryl-arginine

 DESCRIPTION (provided by applicant): More than 3% of the population has unruptured cerebral aneurysms, approximately 10 million people in the US. About 30,000 rupture per year, with devastating consequences. More than 30% of patients with ruptured aneurysms die, and 4 of 7 who survive have significant disabilities. Detachable microcoils are now used in more than 70% of treated aneurysms. The risk of recurrence, or recanalization, remains surprisingly high at approximately 20-30%. Various modifications are used clinically with limited evidence that they provide improvement over bare coils. An important factor to improve clinical efficacy of the coils is to enhance endothelization, leading to durable occlusion. We have developed a nanomatrix coating that mimics the characteristic properties of native endothelium. Thus, we hypothesize that the nanomatrix coating on the coil can enhance healing, thereby promoting durable closure of aneurysms. The coating provides sustained release of nitric oxide (NO) over 2 months, thus recruiting and retaining endothelial cells and endothelial progenitor cells. It also incorporates an endothelial cell adhesive ligand that promotes endothelial cell retention and migration. The bionanomatrix is a biocompatable peptide based material and is coated on the coils by simple water evaporation. This coating method minimizes the risk of inflammatory responses. In this Phase I SBIR, we propose to evaluate and optimize the coating for platinum coils for treatment of brain aneurysms. This will include optimizing the coating method for this specific device, evaluating physical characteristics of the coating, and assessing effects on endothelial and smooth muscle cell growth. In collaboration with Dr. Kadirvel's group at the Mayo Clinic, the efficacy of this coating will be evaluated in an established rabbit model of aneurysms, compared with bare platinum coils. Development of the nanomatrix coating that enhances occlusion of aneurysms and healing over the microcoils may have significant impact in the treatment of patients with brain aneurysms. With successful completion of Phase I, we plan to move forward in Phase II towards IDE submission.

 描述（由适用提供）：超过3％的人口未破裂的大脑动脉瘤，在美国约有1000万人。每年约30,000次破裂，造成毁灭性后果。超过30％的动脉瘤破裂患者死亡，其中有4名幸存者有严重的残疾。现在，可拆卸的微型机油用于70％以上处理的动脉瘤。复发的风险或重新定性的风险仍然令人惊讶地高，约为20-30％。在临床上使用各种修改，证据表明它们对裸线圈提供了改进。提高线圈临床效率的一个重要因素是增强内皮化，从而导致耐用的闭塞。我们已经开发了一种模拟天然内皮特性的纳米质涂层。这就是我们假设，线圈上的纳米瘤涂层可以增强愈合，从而促进动脉瘤的持久闭合。涂层在2个月内提供了一氧化氮（NO）的持续释放，从而募集和保留内皮细胞和内皮祖细胞。也是如此 结合了促进内皮细胞保留和迁移的内皮细胞粘附配体。 Bionanomatrix是一种基于生物相容性的肽材料，并通过简单的水蒸发涂在线圈上。这种涂层方法最大程度地减少了炎症反应的风险。在此阶段I SBIR中，我们建议评估和优化铂线圈的涂层，用于治疗脑动脉瘤。这将包括优化该特定设备的涂料方法，并评估。涂层的物理特征，并评估对内皮和平滑肌细胞生长的影响。与裸铂线圈相比，与梅奥诊所的Kadirvel博士小组合作，将在既定的兔动脉瘤模型中评估这种涂层的有效性。纳米机涂层的开发，增强动脉瘤和在微丝上愈合的闭塞可能会对脑动脉瘤患者的治疗产生重大影响。随着第一阶段的成功完成，我们计划在第二阶段向IDE提出前进。