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）遍及世界的可怕损失，CVD治疗的改善具有深远的医疗，社会和经济意义。拟议的研究将与著名的人造心脏先驱Robert Jarvik博士合作进行，旨在改善用于治疗CVD的心室辅助设备（VADS）的运营寿命，从2年到10年。实现这一挽救生命的目标的两个最重要的障碍是改善某些高应力部位的耐磨性，并改善了VAD的内部血液接触表面的抗紧张性。 Ultranocrystalline Diamond（UNCD）是申请人成功开发了一种非常光滑，低成本的钻石涂层，用于许多不同的应用，需要低磨损，低摩擦和化学惰性。 Jarvik 2000 VAD中使用的底物材料，碳化硅和钛，为UNCD涂层提供了极好的底物匹配。 ADT的最初UNCD沉积工作并由Jarvik Heart进行了验证，已经证明，如果播种和沉积步骤受到良好的控制UNCD，即使在3-D部分的内表面也可以生长。从这个起点开始，该提出的项目介绍了VAD质量的UNCD膜的发展，以显着提高UNCD膜缺陷机制的知识库，并减少或消除膜中已知的磨损诱导不完美的缺陷，然后彻底表征和测试膜和组装的UNC涂层的VAD。提出了针对最初研究期间观察到的功能化UNCD膜的其他研究，以证明与非官能化的UNCD相比，与血液粘纤维蛋白原的相互作用更少。在减少缺陷和播种实验以改善膜的粘附和涂料质量之后，最佳候选沉积方法将被选中，以从Jarvik心脏涂层和组装VAD零件。这些将通过Jarvik心脏的机械和止血流体水动力测试进行彻底测试，以全面验证新的涂料技术。这项研究基于ADT展示了UNCD应用成功的基础，并为Jarvik Heart提供了令人鼓舞的UNCD开发工作。 UNCD的低成本是植入设备中UNCD潜力的另一个因素。在生产中，一组JARVIK VAD零件可以与UNCD涂覆，<1％的设备成本。通过这项努力获得医疗和经济成功的潜力非常有前途，即贾维克的心为自己的资源提供了所有零件成本，组装和测试的资金。如果成功的话，美国10年终身VAD的潜在市场每年至少为40,000个单位，而美国VAD的总市场每年> 50亿美元。随着全球销售的大约四倍，其他可植入的设备可能会受益于UNCD的应用，UNCD涂料的全球可植入设备市场每年可用> 1.2亿美元。 公共卫生相关性：心血管疾病是当今美国排名第一的杀手；但是，通过救生心室辅助设备（VADS），它在短时间内成功处理。如果成功的话，拟议的研究将证明，对于这些救生设备，可以将Ultranocrystalline Diamond（UNCD）薄膜用作高度耐磨和廉价的抗直血性涂料，以将其有效的运营寿命从1-2年延长至10年，并大大降低心血管疾病的患者发病率和死亡率。由于UNCD的抗直通异常特性，还希望减少或消除VAD植入后强大免疫抑制剂药物的需求。