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

基本信息

批准号：
8735985
负责人：
Hongjun Zeng
金额：
$ 38.79万
依托单位：
ADVANCED DIAMOND TECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-15 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8735985
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

项目摘要

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）：人工心血管设备（ACD），包括心室辅助设备（VAD）和机械心脏瓣膜（MHV），已植入数百万患者中，以挽救或改善其生活。不幸的是，这些患者必须服用强大的抗凝药并维持血液中的临界剂量水平以避免血栓形成或出血，因此ACD植入物的成功越来越多。考虑到各个患者的并发症以及全球范围内的巨大病例负荷，长期的抗凝剂维护在社会和经济上都是在社会，经济上昂贵的。此外，大多数怀孕和免疫受损的患者通常不能服用抗凝剂。高级钻石技术（ADT）提议通过引入所有免疫触发ACD的免疫触发表面的生物相容性界面材料，Ultranocrystalline Diamond（UNCD（R）），以无需抗凝剂的帮助即可消除血栓。 UNCD是由申请人开发的一种极其光滑，硬且低成本的多晶钻石。在第一阶段项目中，作为世界第一个项目，UNCD成功地集成在Jarvik 2000（R）心脏VAD上，并植入绵羊中，该绵羊幸存了3周，没有钻石涂层的不利影响。在绵羊中植入的VAD中的最小血栓堆积表明UNCD将是一种近乎理想的抗触及材料。通过合作伙伴的合作和从I阶段工作中获得的经验，UNCD涂层的ACD将通过此II阶段项目开发到近乎商业阶段。根据复杂的UNCD涂料技术，该目标将从短期VAD植入物扩展到长期ACD，主要是机械心脏阀（MHV），并与Jarvik Heart和Meril Life Science密切合作。第二阶段目标将解决第一阶段中确定的问题的问题，例如，将粘附到针对长期植入的极其强大的水平上。也将解决关于MHVS（Pyc）的主要材料（PYC）的主要涂料挑战。作为将我们的技术桥接到产品的关键步骤，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，血液动力学和耐用性。如果该项目成功，那么UNCD VADS和MHVS的潜在美国市场每年至少为40,000和250,000台，全球UNCD涂料的总计超过4亿美元。更重要的是，这种新颖的抗强化材料成功应用的人类，社会和经济影响将是惊人的。正如MHV的父亲之一戈特（Gott）在他的评论中评论说：“最终，有了正确的阀门设计和正确的阀门材料，可以想象，有一天我们可能有一个机械阀不需要终身抗凝治疗。”我们正在努力，期望UNCD将是这种“正确的材料”。