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

描述(申请人提供)：由于心血管疾病(CVD)在全世界造成可怕的死亡人数，改善CVD的治疗具有深远的医学、社会和经济意义。这项拟议的研究将与著名的人工心脏先驱罗伯特·贾维克博士合作进行，旨在将用于治疗心血管疾病的室性辅助设备(VAD)的使用寿命从2年提高到10年。要实现这一挽救生命的目标，剩下的两个最重要的障碍是提高某些高应力部件的耐磨性，以及改善VAD内部血液接触表面的抗凝血性。超纳米晶金刚石(UNCD)是申请人成功开发的一种极其光滑、低成本的金刚石涂层，适用于许多要求低磨损、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涂层提供了极佳的衬底匹配。ADT的初步UNCD沉积工作已经得到Jarvik Heart的验证，证明如果播种和沉积步骤控制得当，UNCD甚至可以在3-D部件的内表面生长。从这一起点开始，这一拟议项目将致力于开发具有VAD质量的UNCD薄膜，以显著改进关于UNCD薄膜缺陷机制的知识基础，减少或消除薄膜中已知的磨损诱发缺陷，然后彻底表征和测试薄膜和组装的UNCD涂层的VAD。还建议对功能化的UNCD膜进行进一步的研究，在最初的研究中观察到这些膜与凝血纤维蛋白原的相互作用甚至比非功能化的UNCD更少。在减少缺陷和提高薄膜附着力和涂层质量的种子实验后，将选择最佳的候选沉积方法来涂覆和组装来自Jarvik Heart的VAD部件。这些涂层将在Jarvik Heart进行机械和血液模拟流体力学测试，以全面验证新的涂层技术。这项研究建立在ADT成功应用UNCD的基础上，以及为Jarvik心脏开展了令人鼓舞的UNCD初步开发工作。UNCD的低成本是UNCD在可植入设备中的潜力的另一个因素。在生产中，一套Jarvik VAD部件可以以设备成本的1%的价格涂上UNCD。这一努力在医疗和经济上取得成功的潜力非常有希望，Jarvik心脏公司将从自己的资源中为所有部件成本、组装和测试提供资金。如果成功，10年期VAD的潜在美国市场每年至少有4万台，美国VAD的总市场规模为每年50亿美元。由于全球销售额约为这一数字的四倍，以及其他可能受益于UNCD应用的植入式设备，UNCD涂层的全球可用植入性设备市场总额为每年1.2亿美元。 与公共健康相关：心血管疾病是当今美国的头号杀手；然而，它正在通过救命的心血管辅助设备(VAD)在短时间内得到成功治疗。如果成功，拟议的研究将证明，超非晶金刚石(UNCD)薄膜可以用作这些救命设备的高耐磨性和廉价的抗血栓涂层，将其有效使用寿命从1-2年延长到10年，并大大降低患者的发病率和心血管疾病的死亡率。由于UNCD的抗血栓形成特性，VAD植入后对强大的免疫抑制药物的需求也有望减少或消除。

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.