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

反应离子等离子体处理心血管生物材料以了解纳米形貌对内皮化的影响

• 批准号: 10172365
• 负责人: Patrick Jurney
• 金额: $ 14.05万
• 依托单位: SAN JOSE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10172365
• 关键词: Adhesions; Adopted; Affinity; Amputation; Atomic Force Microscopy; Attention; Autologous; Biocompatible Materials; Blood Vessels; Blood coagulation; Bypass; Cardiac; Cardiovascular system; Cell Adhesion; Cell Proliferation; Cell physiology; Cell-Matrix Junction; Cells; Cellular biology; Chemicals; Chemistry; Chronic Disease; Clinic; Clinical; Cytoskeleton; Deposition; Endothelial Cells; Endothelium; Engineering; Exposure to; Failure; Goals; Harvest; Hour; Human; Hydrophobicity; Hyperplasia; Image; In Vitro; Inflammation; Intervention; Ions; Legal patent; Lower Extremity; Measurement; Measures; Medical Care Costs; Medicine; Mission; Modification; Nanotopography; Nature; Nitrogen; Outcome; Pathology; Patients; Performance; Peripheral; Peripheral Vascular Diseases; Phenotype; Plasma; Platelet aggregation; Polystyrenes; Polytetrafluoroethylene; Polyvinyl Alcohol; Process; Proliferating; Property; Proteins; Pulsatile Flow; Relaxation; Reproducibility; Research; Resistance; Risk; Roentgen Rays; Role; Smooth Muscle Myocytes; Spectrum Analysis; Structure; Surface; Surface Properties; Technology; Testing; Thrombosis; Time; Tissues; Translating; Translations; United States National Institutes of Health; Vascular Graft; Venous; Water; aged; atheroprotective; base; cell motility; clinical material; cost; endothelial stem cell; fluid flow; graft failure; implantation; improved; manufacturing process; migration; mortality; nanoscale; physical model; shear stress; small molecule; stem cell function; thrombogenesis

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.

项目概要 该项目拟通过将表面形貌与内皮化脱钩来研究其在内皮化中的作用。 使用外周血管移植物 (PVG) 生物材料的反应离子等离子体 (RIP) 进行表面化学处理，包括 有前途的材料：聚乙烯醇（PVA）。超过一半由合成材料制成的 PVG 在两年内失效 多年的植入和治疗以减少导致移植失败的因素，但没有显示出任何益处。 下肢 PVG 结果。因为 PVG 的两种主要失效模式是血栓形成（血液 凝血）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 对两者。这种材料的主要属性是：1) 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。 RIP 处理的 PVA 是一种很有前途的 我们之前展示的 PVG 材料 1) 易于制造，符合以下范围的要求 静脉到动脉脉管系统，2) 比当前临床标准 PVG 材料更不易形成血栓，并且 3) 允许内皮祖细胞 (EPC) 在体外在表面增殖至少 48 小时。进展情况 可内皮化 PVG 的制造受到阻碍，因为这些方法主要涉及 将小分子缀合到 PVG 材料上，这在成本、稳定性、 尽管其可重复性和可扩展性尚未得到广泛关注，但尚未转化为临床。 我们的项目重点是使用 RIP 处理（一种通用且可扩展的制造工艺）对 PVA 进行处理 解耦已知在内皮化过程中重要的两种表面特性：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 处理会引入 细胞粘附所需的反应性表面化学，以表面氮的形式以及纳米纹理 PVA 和不同程度的不同 RIP 处理。虽然大多数反应性表面化学 存放230天后，RIP引入的现象仍然明显，表面变得光滑，EPC不再 储存后粘附或增殖。我们将首先表征表面化学和形貌的变化 存储过程中，以了解材料表面随着形貌松弛的性质（目标 1）。我们 然后将消除表面化学和形貌对内皮细胞 (EC) 和 EPC 的影响 接触和不接触条件下的附着、增殖和迁移（目标 2）以及 EC 和 EPC 功能 流体流动（目标 3）。这种理解将使我们能够确定表面化学和形貌的影响 内皮化的重要过程并设计快速内皮化的 PVG 专利时间比当前的临床材料更长。我们的研究将提供对这些因素的更详细的了解 控制合成生物材料的内皮化，提供了解 EC 生物学的平台，以及 改善 PVG 的翻译，可应用于其他生物材料以改善其生物整合。