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

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, andlow-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 developedto 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 JarvikHeart 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 materialfor 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 issuccessful, 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 havea mechanical valve that does not require lifelong anticoagulation therapy. We are making effort with an expectation that UNCD will be this right material. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Artificial cardiovascular devices (ACDs) have been implanted into millions of patients, to save or improve their lives, but leaving almost the only issue of the dependence on using anticoagulants. If successful, the proposed research will lead to a durable, affordable and biocompatible UNCD(tm) interface to inhibit or eliminate thrombosis on implanted ACDs without using anticoagulants.