SBIR-STTR Award

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.

Thesaurus Terms:
1,2-Ethanediol;2-Hydroxyethanol;3-D;3-Dimensional;Address;Adhesions;Adsorption;Adverse Effects;Anticoagulant Agents;Anticoagulant Drugs;Anticoagulants;Artificial Heart;Artificial Organs;Biocompatible;Blood;Blood Clot;Blood Clotting;Blood Coagulation Factor;Blood Coagulation Factor I;Blood Coagulation Factor One;Blood Factor One;Blood Coagulation;Body Part;C Element;Carbon;Cardiac Infarction;Cardiovascular;Cardiovascular Body System;Cardiovascular Diseases;Cardiovascular System;Cardiovascular System (All Sites);Cereals;Cessation Of Life;Chemicals;Chemistry;Clotting;Coagulation;Coagulation Factor I;Coagulation Factor One;Coagulation Factors;Coagulation Process;Collaborations;Complex;Death;Defect;Deposit;Deposition;Development;Devices;Diamond;Dihydroxyethanes;Drugs;Economics;Ethanediols;Ethylene Glycols;Evaluation;Factor I;Factor One;Fibrinogen;Film;Foundations;Friction;Funding;Generalized Growth;Grafting, Heart;Grain;Growth;Hardness;Heart;Heart Transplantation;Heart, Artificial;Heparin;Heparinic Acid;Human;Human, General;Immune System;Immunosuppressants;Immunosuppressive Agents;Infection;Injury;Investigation;Life;Liquid Substance;Man (Taxonomy);Man, Modern;Marketing;Mechanics;Medical;Medical Device;Medical Economics;Medication;Method Loinc Axis 6;Methodology;Methods;Monoethylene Glycol;Morbidity;Morbidity - Disease Rate;Mortality;Mortality Vital Statistics;Myocardial Infarct;Myocardial Infarction;Nih;National Institutes Of Health;National Institutes Of Health (U.S.);Organ System, Cardiovascular;Patients;Pharmaceutic Preparations;Pharmaceutical Preparations;Phase;Production;Property;Property, Loinc Axis 2;Proteins;Quality Control;Research;Research Resources;Resistance;Resources;Reticuloendothelial System, Blood;Sae;Sbir;Sbirs (R43/44);Sales;Science Of Chemistry;Serious Adverse Event;Shapes;Simulate;Site;Small Business Innovation Research;Small Business Innovation Research Grant;Stress;Surface;System;System, Loinc Axis 4;Technology;Testing;Thrombus;Ti Element;Time;Tissue Growth;Titania;Titanium;Transplantation, Cardiac;Treatment Side Effects;United States National Institutes Of Health;Vascular, Heart;Work;Biomedical Implant;Blood Thinner;Body System, Allergic/Immunologic;Cardiac Graft;Cardiac Infarct;Cardiac Prosthesis;Cardiovascular Disorder;Circulatory System;Clotting Factor;Coronary Attack;Coronary Infarct;Coronary Infarction;Cost;Cost Effective;Design;Designing;Drug /Agent;Drug/Agent;Ethylene Glycol;Experiment;Experimental Research;Experimental Study;Fluid;Gene Product;Heart Attack;Heart Infarct;Heart Infarction;Heart Prosthesis;Heart Transplant;Immunosuppressive;Implant Device;Implantable Device;Implantation;Improved;Indwelling Device;Knowledge Base;Liquid;Mechanical Heart;Ontogeny;Organ System, Allergic/Immunologic;Prevent;Preventing;Research Study;Resistant;Side Effect;Silicon Carbide;Success;Surface Coating;Therapy Adverse Effect;Thrombopoiesis Inhibitor;Treatment Adverse Effect;Ventricular Assist Device

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."

Public Health Relevance Statement:


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.

NIH Spending Category:
Assistive Technology; Bioengineering; Cardiovascular; Heart Disease; Hematology

Project Terms:
3-Dimensional; absorption; Address; Adhesions; adverse outcome; Anticoagulants; Anticoagulation; Artificial Heart; Artificial Implants; base; Biocompatible; Biological; Biological Sciences; biomaterial compatibility; Blood; Blood Tests; calcification; Cardiovascular system; chemical stability; Chemistry; Collaborations; commercialization; Complex; cost; Data; density; Dependence; design; Development; Devices; Diamond; dosage; Drops; economic implication; Economics; Endothelial Cells; Engineering; Environment; Evaluation; expectation; experience; Failure (biologic function); Fathers; Feedback; Fibrinogen; Film; Funding; Generic Drugs; Goals; Heart; Heart Valves; hemodynamics; Hemolysis; Hemorrhage; Human; Immune; Implant; implantable device; implantation; improved; Individual; Inflammatory Response; Lead; Left; Maintenance; Marketing; Mechanics; Methods; Natural graphite; novel; Oklahoma; Patients; Performance; performance tests; Phase; Plasma; Platelet Activation; pregnant; Production; public health relevance; Published Comment; pyrolytic carbon; Quality Control; Research; research study; Resistance; response; Sampling; Scheme; sharing data; Sheep; silicon carbide; Small Business Innovation Research Grant; Staging; Stress; success; Surface; Techniques; Technology; Technology Transfer; Testing; Thrombosis; Thrombus; United States National Institutes of Health; Universities; Validation; ventricular assist device; Whole Blood; Work