Reactive Ion Plasma Treatment of Cardiovascular Biomaterials to Understand the Effect of Nanotopography on Endothelialization

项目摘要 该项目建议通过将表面地形与内皮化脱钩来研究表面地形在内皮化中的作用 使用反应离子等离子体(RIP)的外周血管移植(PVG)生物材料的表面化学，包括 前景看好的材料：聚乙烯醇(PVA)。超过一半的由合成材料制成的PVG在两年内失效 多年的植入和治疗以减少导致移植物失败的因素在 下肢PVG结局。因为PVG的两种主要失效模式是血栓形成(血液 血栓)和内膜增生(移植物内的组织堆积)，理想的PVG生物材料应该具有抵抗力。 敬两个人。这种材料的主要属性是：1)它具有与原生材料相当的顺应性 血管系统，2)非血栓形成，3)促进内皮化。裂解PVA是一种很有前途的 我们前面展示的PVG材料1)很容易制造，符合的范围从 静脉到动脉的血管系统，2)比目前临床标准PVG材料更少的血栓形成，以及3) 允许内皮祖细胞(EPC)在体外至少48小时在表面增殖。取得的进展 可内皮化PVG的制造一直受到阻碍，因为这些方法主要涉及 小分子在PVG材料上的结合，这有与成本、稳定性、 尽管受到了极大的关注，但重复性、可伸缩性和可扩展性尚未转化为临床。 我们的项目专注于使用PVA的RIP处理，这是一种常见且可扩展的制造工艺，以 去偶联在内皮化过程中很重要的两种表面性质：表面化学 和地形，以了解促进内皮化的基本因素并实现 我们的长期目标是制造改进的PVG。我们已经证明，RIP-治疗引入了 以表面氮和纳米结构的形式进行细胞黏附所必需的反应性表面化学 对于PVA和不同的RIP处理有不同程度的影响。而大多数活性表面化学 RIP引入后230天仍明显，表面变得光滑，不再有EPC 储存后粘着或扩散。我们将首先描述表面化学和地形的变化。 在储存期间，以便在地形松弛时了解材料表面的性质(目标1)。我们 然后将分离表面化学和地形对内皮细胞(EC)和EPC的影响 依附、增殖和迁移(目标2)以及EC和EPC功能，无论是否暴露于 流体流动(目标3)。这种理解将使我们能够确定表面化学和地形的影响。 关于内皮化的重要过程和设计一种快速内皮化的PVG 专利时间比目前的临床材料长。我们的研究将提供对这些因素的更详细的了解 管理合成生物材料的内皮化，提供一个了解EC生物学的平台，以及 提高PVGs的转移率，可应用于其他生物材料，提高其生物集成度。

Project Summary This project proposes to investigate the role of surface topography in endothelialization by decoupling it from surface chemistry using reactive ion plasma (RIP) of peripheral vascular graft (PVG) biomaterials, including a promising material: polyvinyl alcohol (PVA). Over half of PVGs made from synthetic materials fail within two years of implantation and therapies to reduce the factors contributing to graft failure have shown no benefit in lower extremity PVG outcomes. Because the two predominant failure modes of PVGs are thrombosis (blood clotting) and intimal hyperplasia (tissue build-up inside the graft), an ideal PVG biomaterial should be resistant to both. The primary attributes of such a material are that it 1) have comparable compliance to the native vasculature, 2) be non-thrombogenic, and 3) encourage endothelialization. RIP-treated PVA is a promising PVG material which we have shown previously 1) is easily manufactured with compliance ranging from that of venous to arterial vasculature, 2) is less thrombogenic than the current clinical standard PVG material, and 3) allows endothelial progenitor cells (EPCs) to proliferate on the surface for at least 48 hours in vitro. Progress in manufacturing endothelializable PVGs has been hampered because the approaches predominantly involve conjugation of small molecules onto the PVG material, which have limitations associated with cost, stability, reproducibility, and scalability and despite significant attention have yet to be translated into the clinic. Our project is focused on using RIP treatment, a common and scalable manufacturing process, of PVA to decouple the two surface properties known to be important in the endothelialization process: surface chemistry and topography, in order to understand the fundamental factors that promote endothelialization and to achieve our long-term goal of manufacturing an improved PVG. We have shown that RIP-treatment introduces reactive surface chemistry necessary for cell adhesion in the form of surface nitrogen, as well as nanotexture to PVA and to varying degrees for different RIP treatments. While most of the reactive surface chemistry introduced by RIP is still apparent after 230 days in storage, the surface becomes smooth and EPCs no longer adhere or proliferate after storage. We will first characterize the changes in surface chemistry and topography during storage in order to understand the nature of the material surface as the topography relaxes (Aim 1). We will then decouple the effects of surface chemistry and topography on endothelial cell (EC) and EPC attachment, proliferation, and migration (Aim 2) as well as EC and EPC function with and without exposure to fluid flow (Aim 3). This understanding will allow us to determine the effect of surface chemistry and topography on the important processes of endothelialization and engineer a rapidly endothelializable PVG which remains patent longer than current clinical materials. Our studies will afford a more detailed understanding of the factors which govern endothelialization of synthetic biomaterials, provide a platform to understand EC biology, and improve translation of PVGs which can be applied to other biomaterials to improve their biointegration.