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

NIH SBIR 第一阶段：UNCD 作为抗血栓形成应用的生物惰性界面

• 批准号: 8125069
• 负责人: Hongjun Zeng
• 金额: $ 14.98万
• 依托单位: ADVANCED DIAMOND TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-15 至 2012-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8125069
• 关键词: 3-Dimensional; Address; Adhesions; Adsorption; Adverse effects; Anticoagulants; Artificial Heart; Artificial Organs; Biocompatible; Blood; Blood Clot; Blood Coagulation Factor; Blood coagulation; Body part; Carbon; Cardiovascular Diseases; Cardiovascular system; Cereals; Cessation of life; Chemicals; Chemistry; Coagulation Process; Collaborations; Complex; Defect; Deposition; Development; Devices; Diamond; Economics; Ethylene Glycols; Evaluation; Fibrinogen; Film; Foundations; Friction; Funding; Growth; Hardness; Heart; Heart Transplantation; Heparin; Human; Immune system; Immunosuppressive Agents; Infection; Injury; Investigation; Life; Liquid substance; Marketing; Mechanics; Medical; Medical Device; Medical Economics; Methodology; Methods; Morbidity - disease rate; Myocardial Infarction; Patients; Pharmaceutical Preparations; Phase; Production; Property; Proteins; Quality Control; Research; Resistance; Resources; Sales; Serious Adverse Event; Shapes; Simulate; Site; Small Business Innovation Research Grant; Stress; Surface; System; Technology; Testing; Thrombus; Time; Titania; Titanium; United States National Institutes of Health; Work; cost; cost effective; design; ethylene glycol; implantable device; implantation; improved; knowledge base; mortality; prevent; research study; silicon carbide; success; surface coating; ventricular assist device

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.

描述（由申请人提供）：由于心血管疾病 (CVD) 在全世界范围内造成的可怕损失，改善 CVD 治疗具有深远的医学、社会和经济重要性。拟议的研究将与著名的人造心脏先驱 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 年延长至 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。超纳米晶金刚石（UNCD）是一种极其光滑、低成本的金刚石涂层，由申请人成功开发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 中使用的基材材料是碳化硅和钛，为 UNCD 涂层提供了出色的基材匹配。由 ADT 进行并由 Jarvik Heart 验证的初步 UNCD 沉积工作表明，如果播种和沉积步骤得到良好控制，UNCD 甚至可以在 3D 零件的内表面上生长。从这个起点开始，该拟议项目致力于开发 VAD 质量的 UNCD 薄膜，以显着改善有关 UNCD 薄膜缺陷机制的知识库，减少或消除薄膜中已知的磨损诱导缺陷，然后彻底表征并测试薄膜和组装的UNCD涂层VAD。建议对功能化 UNCD 薄膜进行进一步的研究，这些薄膜在最初的研究中观察到，与非功能化 UNCD 薄膜相比，与凝血纤维蛋白原的相互作用甚至更少。经过减少缺陷和播种实验以提高薄膜附着力和涂层质量后，将选出最佳候选沉积方法用于 Jarvik Heart 的 VAD 零件的涂层和组装。这些将在贾维克心脏中心通过机械和血液模拟流体动力学测试进行彻底测试，以全面验证新的涂层技术。这项研究建立在 ADT 所展示的 UNCD 应用成功以及 Jarvik Heart 令人鼓舞的初步 UNCD 开发工作的基础上。 UNCD 的低成本是UNCD 在植入式设备中具有潜力的另一个因素。在生产过程中，一组 Jarvik VAD 部件可以涂上 UNCD，成本不到设备成本的 1%。这项工作在医疗和经济方面取得成功的潜力是非常有希望的，贾维克心脏公司正在用自己的资源资助所有零件成本、组装和测试。如果成功，10 年寿命 VAD 的美国潜在市场每年至少为 40,000 台，而美国 VAD 的可用市场总额每年超过 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 的应用中受益的植入式设备，UNCD 涂层的全球可植入设备市场总额每年超过 1.2 亿美元。 公共卫生相关性：心血管疾病是当今美国的第一大杀手；然而，使用救生心室辅助装置 (VAD) 可以在短时间内成功治疗该病。如果成功，拟议的研究将证明超纳米晶金刚石 (UNCD) 薄膜可用作这些救生设备的高耐磨且廉价的抗血栓涂层，将其有效使用寿命从 1-2 年延长至 10 年，并大大延长降低心血管疾病患者的发病率和死亡率。由于UNCD的抗血栓形成特性，VAD植入后对强效免疫抑制剂的需求也有望减少或消除。