NIH SBIR Phase I: UNCD as Bio-Inert Interface for Anti-Thrombogenicity Applicati

描述（由申请人提供）：由于心血管疾病（CVD）在世界范围内的可怕死亡人数，改善心血管疾病的治疗具有深远的医学，社会和经济意义。拟议的研究将与著名的人工心脏先驱Robert Jarvik博士合作进行，旨在将用于治疗CVD的心室辅助装置（vad）的使用寿命从2年延长到10年。实现这一救生目标的两个最重要的障碍是提高某些高应力部件的耐磨性和提高VAD内部血液接触表面的抗血栓形成性。超微晶金刚石（UNCD）是一种非常光滑、低成本的金刚石涂层，由申请人成功开发，适用于许多需要低磨损、低摩擦和化学惰性的不同应用。Jarvik 2000 VAD中使用的衬底材料，碳化硅和钛，为UNCD涂层提供了极好的衬底匹配。ADT的初始UNCD沉积工作和Jarvik Heart的验证表明，如果播种和沉积步骤得到很好的控制，UNCD甚至可以在3d部件的内表面生长。从这个起点开始，本项目将致力于开发vad质量的UNCD薄膜，以显著提高关于UNCD薄膜缺陷机制的知识库，并减少或消除薄膜中已知的磨损缺陷，然后彻底表征和测试薄膜和组装的UNCD涂层vad。在最初的研究中观察到功能化UNCD膜，并提出进一步的研究，以证明与凝血纤维蛋白原的相互作用比非功能化UNCD更少。通过减少缺陷和播种实验，提高薄膜附着力和涂层质量，选出最佳候选沉积方法，用于Jarvik Heart VAD零件的涂层和装配。这些涂层将在Jarvik Heart进行机械和血液模拟流体动力学测试，以全面验证新涂层技术。这项研究建立在ADT示范的UNCD应用成功和Jarvik Heart令人鼓舞的UNCD初步开发工作的基础上。UNCD的低成本是将UNCD应用于植入式装置的另一个潜在因素。在生产中，一套Jarvik VAD部件可以用UNCD涂层，成本低于设备成本的1%。这一努力在医疗和经济上取得成功的潜力是非常有希望的，Jarvik Heart公司正在从自己的资源中资助所有的零件成本、组装和测试。如果成功，10年寿命的VAD的潜在美国市场每年至少有40,000台，美国VAD的总可用市场每年为50亿美元。由于全球销售额约为这一数字的四倍，以及其他可从UNCD应用中受益的植入式设备，UNCD涂层的全球可植入式设备市场总额为每年1.2亿美元。

DESCRIPTION (provided by applicant): Due to the gruesome toll of cardiovascular disease (CVD) through-out the world, improvements in treatment for CVD are of profound medical, societal and economic importance. The proposed research will be conducted in collaboration with renowned artificial heart pioneer, Dr. Robert Jarvik, and is designed to improve the operating lifetime of Ventricular Assist Devices (VADs) used to treat CVD, from 2 years to 10 years. The two most important remaining hurdles to accomplish this life-saving objective are improvements in the wear resistance of certain high stress parts and improvements in anti-thrombogenicity of the interior blood-contacting surfaces of the VAD. Ultrananocrystalline diamond (UNCD), an extremely smooth, low cost diamond coating was successfully developed by the applicant for many diverse applications requiring low wear, low friction and chemical inertness. The substrate materials utilized in the Jarvik 2000 VAD, silicon carbide and titanium, provide an excellent substrate match for UNCD coating. Initial UNCD deposition work by ADT and verified by Jarvik Heart, has demonstrated that if the seeding and deposition steps are well controlled UNCD, can be grown even on the inside surfaces of 3-D parts. Beginning from this starting point, this proposed project addresses the development of VAD-quality UNCD films to significantly improve the knowledge base regarding the defect mechanisms of UNCD films, and to reduce or eliminate known wear-inducing imperfections in the film and to then thoroughly characterize and test the films and assembled UNCD-coated VADs. Additional research is proposed on functionalized UNCD films that were observed during the initial research to demonstrate even less interaction with the blood-clotting fibrinogen than non-functionalized UNCD. After the defect reduction and seeding experiments to improve film adhesion and coating quality, the best candidate deposition method will be down-selected for coating and assembly of VAD parts from Jarvik Heart. These will be thoroughly tested with mechanical and blood-simulating fluid hydrodynamic testing at Jarvik Heart for full verification of the new coating technology. This research builds upon a foundation of demonstrated UNCD application success at ADT and the encouraging initial UNCD development work for Jarvik Heart. The low cost of UNCD is another factor in the potential for UNCD in implantable devices. In production, a set of Jarvik VAD parts could be coated with UNCD for <1% of the device cost. The potential for medical and economic success with this effort is sufficiently promising that Jarvik Heart is funding all of the parts costs, assembly and testing from its own resources. If successful, the potential US market for a 10-year lifetime VAD is at least 40,000 units per year and the total available US market for VADs is >$5 billion annually. With world-wide sales of approximately four times this, and other implantable devices that could benefit from the application of UNCD, the total available world-wide implantable device market for UNCD coatings is >$120 million annually. PUBLIC HEALTH RELEVANCE: Cardiovascular disease is the #1 killer in the US today; however, it is being treated successfully for short periods of time with lifesaving Ventricular Assist Devices (VADs). If successful, the proposed research will demonstrate that ultrananocrystalline diamond (UNCD) thin films can be used as highly wear resistant and inexpensive anti-thrombotic coatings for these lifesaving devices to extend their effective operating lifetime from 1-2 years up to 10 years and greatly reduce patient morbidity and mortality from cardiovascular disease. A reduction or elimination of the need for powerful immunosuppressant drugs after VAD implantation is also expected because of the anti-thrombogenic properties of UNCD.