SBIR Phase I: VTE mitigation device

This SBIR Phase I project will support the research and development of a new medical device designed to prevent deep vein thrombosis in hospitalized patients. Deep vein thrombosis occurs when blood clots form in the veins and is a common complication in hospital patients that is also a leading cause of preventable death in the United States. This project will develop a device that modifies blood flow patterns in the legs in a new manner designed to specifically activate genetic changes inside the vein that protect against blood clot formation. The goal of this project is to generate a new device that it is capable of creating the desired blood flow patterns in patients while maintaining a high level of device comfort, reliability, and ease of use for clinical staff and patients. In addition to preventing death and disability in the hospitalized population of the US, this project will move a new device towards commercial production, thereby supporting economic growth, job formation, and tax revenue. This SBIR Phase I project will leverage novel molecular and cellular discoveries regarding the pathogenesis of deep vein thrombosis (DVT) to create a more effective device to prevent DVT in immobilized individuals who are at high risk for the disease. DVTs form in the sinus behind venous valves, where blood flow is reduced during immobility, promoting blood clot formation. This site is typically protected against clot formation by a powerful genetic program in the endothelial cells that is unique to the valve sinus microenvironment. Loss of this genetic expression program results in a prothrombotic environment that supports clot formation and DVT. Research has further revealed that the valve sinus anti-thrombotic genetic program is activated by a specific pattern of venous blood flow at that site that is driven by muscular activity. During prolonged periods of immobility, common during hospitalization, loss of this flow profile extinguishes the protective endothelial phenotype and supports DVT formation. Ultrasound analysis reveals that current mechanical therapy devices marketed to prevent DVT do not generate the hemodynamics at the valve that are produced by muscular activity due to their methods of action. This project will develop a device that generates a protective hemodynamic pattern in the valve sinus of immobile patients by actuating blood flow that accurately reproduce muscular activity. To accomplish this goal the device design alters the primary physical manipulation strategy of other existing devices away from calf and thigh compression and instead induces rapid calf expansion to replicate the effect of muscular activity on venous blood flow. Vascular ultrasound studies demonstrate that this actuation method successfully recapitulates the venous hemodynamics of the active limb required to support expression of the protective genetic pathway in the valve sinus. This SBIR Phase I project will optimize the device design to create this actuation while also improving patient comfort, mitigating common risks, and facilitating ease of use by clinical staff. This project will address key risks in advancing a medical device into clinical testing and use, thereby enabling the device to bridge to a phase of commercial manufacturing and use. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.