Novel Functional Nanocomposite Engineering of Stents

我们提出了一个四方合作研究计划，该计划结合了四所顶尖大学的材料科学、工程、表面科学和细胞生物学方面的专业知识。我们希望继续我们在腹主动脉瘤（AAA）支架移植和冠状动脉支架开发方面非常成功的旗舰资助项目，其中不锈钢和形状记忆合金（SMA）涂有纳米复合材料（NC）聚合物。我们的初步工作已经证明了优异的血液和组织生物相容性，我们将这种特性归因于纤维蛋白原的优先吸附，然后是其构象失活。体外和体内的机械和血流动力学测试需要进一步的工作。我们打算完成部署和定位研究，以便进行动物研究，从而实现商业化。为了实现这些目标，我们将使用一种新颖的包装技术将支架折叠成一个小而均匀的直径，避免几何不相容性。这种折叠是通过使用基于折纸的技术在接枝表面上产生一组褶皱来实现的。我们将使用包覆NC的SMA或完全不透明的SMNC来制作接枝。涂层将使用电流体动力喷涂沉积（ESD）来实现。光谱椭偏（SE）和中子反射（NR）将用于确定这些材料在体外的耐用性以及它们如何实现生物相容性。该方案的成功交付将导致支架的发展，它比现有设备具有显著的优势，包括几何简单，更可靠的膨胀机制，更高的径向强度，塑造动脉结构的能力，以及与血液和组织更好的生物相容性。随着工程、材料、表面科学和生物小组的密切合作，结构设计和新的制造概念可以应用于新材料开发和支架制造，简化监管途径和市场接受度。该提案具有独特的综合结构和方法，因此成功的可能性很大。所有申请人都在自己的领域拥有国际声誉，在综合冒险项目中建立了记录，并在将概念和产品商业化方面有公认的记录，并且作为一个团队非常适合开展拟议的研究。

We propose a four-party collaborative research programme that combines the expertise of the materials science, engineering, and surface science and cell biology from four leading universities. We wish to continue our highly successful Flagship Grant programme in the development of Abdominal Aortic Aneurysm (AAA) stent graft and coronary stent whereby stainless steel and shape memory alloy (SMA) are coated with nanocomposite (NC) polymer. Our preliminary work has demonstrated excellent blood and tissue biocompatibility and we have attributed this property to the preferential adsorption of fibrinogen followed by its conformational deactivation. Further work is required for mechanical and haemodynamic testing in vitro and in vivo. We intend to complete the deployment and positioning studies to allow an animal study to take place, leading to commercialisation. To achieve these aims we will use a novel packaging technique to fold the stent into a small and uniform diameter avoiding geometric incompatibility. The folding is achieved by generating a set of folds onto the surface of a graft using origami-based techniques. We will make the graft from either SMA with NC coated or entirely from a radio-opaque SMNC. Coating will be achieved using electrohydrodynamic spray deposition (ESD). Spectroscopic ellipsometry (SE) and neutron reflection (NR) will be utilised to determine how durable these materials are in vitro and how they achieve biocompatibility. Successful delivery of the programme will lead to the development of a stent that has significant advantages over existing devices including geometric simplicity, a more reliable expansion mechanism, higher radial strength, the ability to shape the structure to the artery, and better biocompatibility with both blood and tissue. With engineering, materials, surface science and biological groups in close collaboration, structural design and novel manufacturing concepts can be applied to new materials development and stent fabrication, simplifying the regulatory pathway and acceptance to the marketplace. The proposal is highly likely to succeed as it has a unique integrated structure and approach. All the applicants have international reputations in their own fields, have established records in integrated adventurous projects and have recognised track records for commercialising concepts and products and as a team are well suited for carrying out the proposed research.