In this Quantum Phase I project, a thrombogenicity predictive technology for blood contacting cardiovascular (CVS) devices will be developed. This innovative Device Thrombogenicity Emulator (DTE) will use stress loading waveforms extracted from detailed numerical flow modeling in devices that will be programmed into a computer-controlled Hemodynamic Shearing Device (HSD) capable of emulating device hemodynamics with great accuracy, and measure thrombogenicity using an innovative platelet activity state (PAS) assay. The DTE is also aimed at optimizing the thrombogenic performance of devices by facilitating the testing of virtual device design modifications before prototypes are built and tested in costly pre-clinical/clinical trials. The ultimate goal is to reduce device thrombogenicity to a level that will liberate device recipients from the need for difficult pharmacological anticoagulation therapy. During the Phase I of the proposed quantum project, a prototype DTE will be tested for predicting the thrombogenic potential of a sub-group of CVS devices: Prosthetic Heart Valves (PHV) and Ventricular Assist Device (VAD). Various PHV types and designs will be tested, as well as a pulsatile VAD model, according to the following Specific Aims: A state of the art comprehensive numerical methodology for modeling flow induced thrombogenicity in prosthetic devices will be utilized to study various Prosthetic Heart Valves and a pulsatile VAD. The models will include highly resolved device geometries for studying flow-induced thromboembolism. The `hot spot'regions that may lead to device thrombogenicity will be mapped and computed. A computer controlled HSD will be tested for its ability to replicate in vitro the dynamic stress loading conditions leading to device thromboembolism as extracted from the numerical simulations. The thrombogenic potential will be measured in it using an innovative and highly sensitive platelet activity state (PAS) assay of flow induced platelet hemostatic activity in devices. These measurements will be correlated to in-vitro PAS measurements performed with PHV mounted in a LVAD system. The DTE (HSD interfaced with the numerical simulations) will serve as the test-bed for optimizing devices for reducing their thrombogenicity to a level that will eliminate the need for anticoagulants. The technology offered will become an essential R&D tool for CVS devices manufacturers. Besides reducing R&D costs, it may prevent unfortunate situations where devices need to be recalled or clinical trials stopped, because of unacceptable thrombogenicity levels situations that could be catastrophic to patients and with devastating financial costs to society and device manufacturers alike. These savings will be passed on to patients and help in reducing healthcare costs. It is envisioned that it will also facilitate the use of these devices for long term therapy by reducing the need for difficult pharmacological management with anticoagulants, which is mandated for most existing devices.
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