Bionanomatrix coating for brain aneurysm coils to enhance healing

 描述（由申请人提供）：超过3%的人群患有未破裂的脑动脉瘤，在美国约有1000万人。每年约有30，000例破裂，造成毁灭性后果。超过30%的动脉瘤破裂患者死亡，7名幸存者中有4名患有严重残疾。可分离微弹簧圈目前用于超过70%的治疗动脉瘤。复发或再通的风险仍然惊人地高，约为20- 30%。临床上使用了各种改良，但证明其优于裸线圈的证据有限。提高弹簧圈临床疗效的一个重要因素是增强内皮化，从而实现持久闭塞。我们已经开发了一种纳米基质涂层，模仿天然内皮的特性。因此，我们假设弹簧圈上的纳米基质涂层可以促进愈合，从而促进动脉瘤的持久闭合。该涂层在2个月内提供一氧化氮（NO）的持续释放，从而募集和保留内皮细胞和内皮祖细胞。它还 结合了促进内皮细胞保留和迁移的内皮细胞粘附配体。生物纳米基质是一种生物相容的肽基材料，通过简单的水蒸发涂覆在线圈上。这种涂层方法最大限度地降低了炎症反应的风险。在本I期SBIR中，我们建议评价和优化用于治疗脑动脉瘤的铂弹簧圈的涂层。这将包括优化该特定器械的涂层方法，评价涂层的物理特性，以及评估对内皮细胞和平滑肌细胞生长的影响。与马约诊所的Kadirvel博士小组合作，将在已建立的兔动脉瘤模型中评价该涂层的有效性，并与裸铂弹簧圈进行比较。纳米基质涂层的开发可增强动脉瘤的闭塞和微弹簧圈的愈合，可能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提交申请。

 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.