NIH Phase II-UNCD as Bio-Inert Interface for Anti-Thrombogenicity Applications in

NIH II-UNCD 作为生物惰性界面，用于抗血栓形成应用

• 批准号: 8524646
• 负责人: Hongjun Zeng
• 金额: $ 54.61万
• 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 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8524646
• 关键词: 3-Dimensional; Address; Adhesions; Anticoagulants; Anticoagulation; Artificial Heart; Artificial Implants; Biocompatible; Biological; Biological Sciences; Blood; Blood Tests; Cardiovascular system; Chemistry; Collaborations; Complex; Data; Dependence; Development; Devices; Diamond; Drops; Economics; Endothelial Cells; Engineering; Environment; Evaluation; Failure; Fathers; Feedback; Fibrinogen; Film; Funding; Generic Drugs; Goals; Heart; Heart Valves; Hemolysis; Hemorrhage; Human; Immune; Implant; Individual; Inflammatory Response; Lead; Left; Maintenance; Marketing; Mechanics; Methods; Natural graphite; Oklahoma; Patients; Performance; Phase; Plasma; Platelet Activation; Production; Published Comment; Quality Control; Research; Resistance; Sampling; Scheme; Sheep; Small Business Innovation Research Grant; Staging; Stress; Surface; Techniques; Technology; Technology Transfer; Testing; Thrombosis; Thrombus; United States National Institutes of Health; Universities; Validation; Whole Blood; Work; absorption; adverse outcome; base; biomaterial compatibility; calcification; chemical stability; commercialization; cost; data sharing; density; design; dosage; economic implication; expectation; experience; hemodynamics; implantable device; implantation; improved; novel; performance tests; pregnant; public health relevance; pyrolytic carbon; research study; response; silicon carbide; success; ventricular assist device

DESCRIPTION (provided by applicant): Artificial cardiovascular devices (ACDs) including ventricular assist devices (VADs) and mechanical heart valves (MHVs) have been implanted into millions of patients, to save or improve their lives. The increasing success of ACD implants has been accompanied with the unfortunate fact that these patients have to take powerful anticoagulant drugs and maintain a critical dosage level in the blood to avoid thrombosis or hemorrhage. Long-term anticoagulant maintenance is individually, socially and economically expensive considering the complications to individual patients and the huge world-wide case load. In addition, most pregnant and immune compromised patients cannot normally take anticoagulants. Advanced Diamond Technologies (ADT) proposes to eliminate thrombus without the help of anticoagulants, by introducing a biocompatible interface material, Ultrananocrystalline diamond (UNCD(r)), for all the immune-triggering surfaces of ACDs. UNCD is an extremely smooth, hard, and low-cost polycrystalline diamond developed by the applicant. In the Phase I project, as a world first, UNCD was successfully integrated on a Jarvik 2000(r) heart VAD and implanted into a sheep which survived for 3 weeks with no adverse consequences from the diamond coating. The minimal thrombus build-up in the VAD implanted in the sheep suggests UNCD will be a near-ideal anti-thrombogenic material. With the partner collaboration and experience gained from the Phase I work, UNCD coated ACDs will be developed to near commercial stage through this Phase II project. Based on the sophisticated UNCD coating technology, the goal will be expanded from short term VAD implants to the long term ACD, mainly mechanical heart valve (MHV) in close collaboration with Jarvik Heart and Meril Life Science. The Phase II goals will address the issues of concern identified in Phase I, e.g., improving adhesion to an extremely robust level targeting long-term implantation. A major coating challenge in terms of the principle material for MHVs, pyrolytic carbon (PyC), will be addressed too. As a key step to bridge our technique to a product, ADT will work with Oklahoma State University to study the biocompatibility, hemodynamics and durability of the UNCD coated ACDs. If the project is successful, the potential US market for UNCD VADs and MHVs is at least 40,000 and 250,000 units respectively per year, over $400 million in total for UNCD coating worldwide. More importantly, the human, societal, and economic implications of the successful application of this novel antithrombogenic material would be staggering. As Dr. Gott, one of the fathers of the MHV commented in his review, "Eventually, with the right valve design and the right valve material, it is conceivable that we may someday have a mechanical valve that does not require lifelong anticoagulation therapy." We are making effort with an expectation that UNCD will be this "right material."

描述（由申请人提供）：包括心室辅助装置（VAD）和机械心脏瓣膜（MHV）在内的人工心血管装置（ACD）已被植入数百万患者体内，以挽救或改善他们的生活。 ACD 植入物的日益成功伴随着一个不幸的事实，即这些患者必须服用强效抗凝药物并维持血液中的临界剂量水平以避免血栓形成或出血。考虑到个体患者的并发症和全球范围内的巨大病例量，长期抗凝维持对个人、社会和经济来说都是昂贵的。此外，大多数怀孕和免疫功能低下的患者通常不能服用抗凝剂。 Advanced Diamond Technologies (ADT) 提出，通过为 ACD 的所有免疫触发表面引入生物相容性界面材料超纳米晶金刚石 (UNCD(r))，无需抗凝剂即可消除血栓。 UNCD是申请人开发的一种极其光滑、坚硬、成本低廉的聚晶金刚石。在第一阶段项目中，作为世界首例，UNCD 成功集成到 Jarvik 2000(r) 心脏 VAD 上，并植入绵羊体内，绵羊存活了 3 周，没有出现金刚石涂层带来的不良后果。植入绵羊体内的 VAD 中形成的血栓极少，表明 UNCD 将是一种近乎理想的抗血栓形成材料。凭借合作伙伴的合作以及从第一阶段工作中获得的经验，UNCD涂层ACD将通过第二阶段项目开发到接近商业化阶段。基于先进的 UNCD 涂层技术，与 Jarvik Heart 和 Meril Life Science 密切合作，目标将从短期 VAD 植入物扩展到长期 ACD，主要是机械心脏瓣膜 (MHV)。第二阶段的目标将解决第一阶段确定的问题，例如，将粘附力提高到极其牢固的水平，以实现长期植入。 MHV 的主要材料热解碳 (PyC) 方面的主要涂层挑战也将得到解决。作为将我们的技术与产品联系起来的关键一步，ADT 将与俄克拉荷马州立大学合作，研究 UNCD 涂层 ACD 的生物相容性、血流动力学和耐久性。如果该项目成功，UNCD VAD 和 MHV 的美国潜在市场每年至少分别为 40,000 辆和 250,000 辆，全球 UNCD 涂层总额超过 4 亿美元。更重要的是，这种新型抗血栓材料的成功应用对人类、社会和经济的影响将是惊人的。正如 MHV 之父之一戈特博士在他的评论中评论的那样，“最终，通过正确的瓣膜设计和正确的瓣膜材料，可以想象，有一天我们可能会拥有不需要终生抗凝治疗的机械瓣膜。 ”我们正在努力，期望《联合国防治荒漠化公约》将成为这种“正确的材料”。