Protein and Cell Adhesion on Novel PTFE Nanostructures

描述(由申请人提供)：我们建议，通过一种新的喷射吹塑工艺制备的纳米纤维/纳米结构聚四氟乙烯将显示出有用的生物医学性能，特别是在心血管应用方面，如血管移植物。 这项研究要回答的一个基本问题是，与蛋白质具有相同长度的纳米结构是否会带来常规表面修饰策略迄今无法获得的有益医学结果。为了回答这个问题，我们提出了以下工作假设：(1)由于聚四氟乙烯在喷射过程中形成的独特的纳米形貌/纳米形态，血小板不会黏附并被激活，依赖锚定的哺乳动物细胞(如内皮细胞)不会黏附在这些未经修饰的表面上。(2)纳米纤维/纳米结构聚四氟乙烯及其相关复合材料的表面可以被工程/化学功能化，以允许目标细胞类型(例如内皮细胞)的选择性黏附和发展适当的表型行为。 为了验证这些假设，拟议的研究分为三个具体目标，旨在开发独特的纳米结构聚四氟乙烯材料和复合材料，能够防止医疗器械的生物污垢。由于血管移植物设计中涉及到复杂的宿主-材料相互作用，因此我们将重点研究这些材料上的内皮细胞增殖，因为移植物管腔表面的完全内皮化是非常必要的。与体内血小板黏附、补体激活、血栓形成、栓子形成相关的问题将是未来提案的主题(使用从R21收集的数据作为初步数据)。这里提出的研究风险很高，几乎没有医学初步数据描述这些纳米材料在心血管应用中的性能。然而，这些纳米材料由于其纳米形态和设计的表面功能化而可能具有独特的生物材料特性，因此可能会获得很高的回报。 这项研究将导致医疗设备的改进，特别是用于心血管疾病的治疗。

DESCRIPTION (provided by applicant): We propose that nanofibrous/nanostructured PTFE prepared by a novel jet-blowing process will exhibit useful biomedical properties, especially for cardiovascular applications such as vascular grafts. A fundamental question to be answered in this study is whether nanoarchitecture at the same length scale as proteins will lead beneficial medical outcomes thus far inaccessible to conventional surface modification strategies. To answer this question we have formulated the following working hypotheses: (1) Because of the unique nanotopography/nanomorphology of polytetrafluoroethylene formed during the jet-blowing process, platelets will not adhere and become activated and anchorage-dependent mammalian cells such as endothelial cells will not adhere to these unmodified surfaces. (2) The surface of nanofibrous/nanostructured PTFE and related composites may be engineered/chemically functionalized to permit the selective adhesion of target cell types (e.g. endothelial cells) and development of appropriate phenotypic behavior. To test these hypotheses, the proposed research is divided into three specific aims directed toward the goal of developing unique nanostructured PTFE materials and composites capable of preventing the biofouling of medical devices. Because of the complex host-material interactions involved in vascular graft design, we will focus our efforts here on the study of endothelial cell proliferation on these materials since complete endothelialization of the lumen surface of a graft is highly desired. Issues related to in vivo platelet adhesion, complement activation, thrombogenesis, emboli formation will be the subject of future proposals (using the data gathered from this R21 as preliminary data). The research proposed here is of high risk, with little medical preliminary data describing the performance of these nanomaterials in cardiovascular applications. However, these nanomaterials may possess unique biomaterials properties resulting from their nanomorphology and designed surface functionalization and thus the reward may be high. This research will lead to improved medical devices, especially for treatment of cardiovascular disease.