Bionanomatrix coating for brain aneurysm coils to enhance healing

 描述(申请人提供)：超过3%的人口患有未破裂的脑动脉瘤，在美国大约有1000万人。每年大约有30,000次破裂，造成毁灭性的后果。超过30%的破裂动脉瘤患者死亡，存活下来的7人中有4人有明显的残疾。现在，70%以上的治疗动脉瘤都使用了可拆卸的微弹簧圈。复发或再通的风险仍然令人惊讶地高达约20%-30%。各种改良术在临床上应用，但仅有有限的证据表明它们能改善裸露的弹簧圈。提高弹簧圈临床疗效的一个重要因素是增强内皮化，导致持久的闭塞。我们已经开发出一种纳米基质涂层，它模仿天然内皮的特征属性。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个月内持续释放一氧化氮(NO)，从而招募和保留内皮细胞和内皮祖细胞。它还 结合内皮细胞黏附配体，促进内皮细胞的保留和迁移。Biononomatrix是一种生物相容的多肽基材料，通过简单的水蒸发涂覆在线圈上。这种包衣方法将炎症反应的风险降至最低。在这个第一阶段的SBIR中，我们建议评估和优化治疗脑动脉瘤的铂金弹簧圈涂层。这将包括优化这种特定设备的涂层方法，评估涂层的物理特性，以及评估对内皮细胞和平滑肌细胞生长的影响。与梅奥诊所的Kadirvel博士的团队合作，这种涂层将在已建立的兔动脉瘤模型中进行评估，并与裸露的铂金弹簧圈进行比较。开发纳米基质涂层，以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集成开发环境提交迈进。

 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.