Collagen-Based Template for Treatment /Cerebral Aneurysm

本研究提案的总体目标是设计、设计和体内测试用于治疗脑动脉瘤的基于I型胶原的血管内模板。脑动脉瘤至少存在于0.5-1.0%的美国人口中，动脉瘤破裂仍然是发病率和死亡率的重要原因。即使在主要的转诊中心，也有相当数量的动脉瘤不适合手术修复。本提案中描述的器械专门设计用作血管模板，以支持和引导动脉瘤基部的血管再生，并抑制血液流入动脉瘤囊，导致动脉瘤血栓形成。使用本提案的主要研究者开发的初始原型进行了初步体外研究。结果表明，I型胶原可用于构建血液相容性管状模板，其产生动脉管腔尺寸的适度减小和流量的微小变化。在第一阶段，我们将检查胶原模板在兔模型中的体内可行性，而在第二阶段，我们将延长兔模型中的研究时间，以评估胶原模板的长期作用。神经外科和介入神经放射学社区迫切需要一种可行的宽颈动脉瘤治疗方法。如果开发出一个可接受的模板，估计每年从这样一个模板获得的收入毛额将至少超过1亿美元。此外，本提案中描述的工作可以扩展到广泛的临床应用，包括经皮血管成形术、动静脉瘘闭合以及胆道、肾脏和食管手术。如果广泛应用于临床，基于胶原蛋白的模板每年可以在全球产生超过10亿美元的收入。拟议商业应用：见上述摘要

The overall goal of this research proposal is to design, engineer, and test in vivo a type I collagen-based endovascular template for the therapy of cerebral aneurysms. Cerebral aneurysms are present in at least 0.5-1.0% of the United States population, and aneurysm rupture remains an important cause of morbidity and mortality. Even in major referral centers, a significant number of aneurysms are not amenable to surgical repair. The device described in this proposal is specifically designed to act as a vascular template to support and guide vascular regeneration at the base of the aneurysm and to inhibit blood flow into the aneurysm sac, resulting in thrombosis of the aneurysm. A preliminary in vitro study was performed using the initial prototype developed by the principle investigator of this proposal. The results demonstrated that type I collagen may be used to construct a hemocompatible tubular template that produces a modest reduction in arterial luminal dimension and little change in flow. During phase I, we will examine the in vivo feasibility of the collagen template in a rabbit model, while in phase II we will extend the period of study in the rabbit model to evaluate the long term effects of the collagen template. The neurosurgical and interventional neuroradiology community is in serious need of a viable therapy for wide-neck aneurysms. If an acceptable template is developed, it is estimated that the yearly gross revenues from such a template would exceed at least $100 million. Furthermore, the work described in this proposal could be expanded to apply to a wide range of clinical applications, including percutaneous angioplasty, closure of arteriovenous fistulae, and billary, renal and esophageal procedures. If widely applied clinically, a collagen-based template could generate well over $1 billion per year worldwide. PROPOSED COMMERCIAL APPLICATIONS: See above abstract