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）：人工心血管器械（ACD），包括心室辅助器械（VAD）和机械心脏瓣膜（MHV）已植入数百万患者体内，以挽救或改善其生命。ACD植入物的日益成功伴随着不幸的事实，即这些患者必须服用强效抗凝药物并在血液中保持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巨大的全球病例负荷，长期抗凝维持在个体、社会和经济上都是昂贵的。此外，大多数孕妇和免疫功能低下的患者通常不能服用抗凝剂。Advanced Diamond Technologies（ADT）提出在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）），从而在不使用抗凝剂的情况下消除血栓。UNCD是由申请人开发的极其光滑、坚硬且低成本的多晶金刚石。在第一阶段项目中，作为世界上第一个，UNCD成功地整合在Jarvik 2000（r）心脏VAD上，并植入绵羊体内，存活了3周，没有金刚石涂层的不良后果。植入绵羊体内的VAD中的最小血栓积聚表明UNCD将是一种接近理想的抗血栓形成材料。借助合作伙伴的协作和从第一阶段工作中获得的经验，将通过第二阶段项目将UNCD涂层ACD开发到接近商业阶段。基于先进的UNCD涂层技术，目标将从短期VAD植入物扩展到长期ACD，主要是与Jarvik Heart和Meril Life Science密切合作的机械心脏瓣膜（MHV）。第二阶段的目标将处理第一阶段确定的关切问题，例如，将粘附性提高到针对长期植入的极其稳健的水平。一个主要的涂层挑战方面的主要材料的MHV，热解碳（PyC），也将得到解决。作为将我们的技术与产品相结合的关键步骤，ADT将与俄克拉荷马州州立大学合作，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的潜在美国市场每年至少分别为40，000和250，000台，全球UNCD涂层总额超过4亿美元。更重要的是，这种新型抗血栓形成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Gott博士在他的综述中评论的那样，“最终，通过正确的瓣膜设计和正确的瓣膜材料，可以想象，我们可能有一天会有一个不需要终身抗凝治疗的机械瓣膜。“我们正在努力，期望裁谈会将成为这一“正确的材料”。"