OsciFlex LLC SBIR Phase II Award, January 2021

Principal Investigator: Welsh, John D Project SummaryDeep venous thrombosis (DVT) and secondary pulmonary embolism (PE) affect 0.1-0.2% of the population and cause approximately 100,000 deaths annually in the US. Immobility and lack of muscular activity is the primary risk factor for DVT, an effect attributed to reduced venous flow. Autopsy studies have identified the venous valve sinus in the leg as the site of origin for DVT, but a molecular and cellular mechanism for this observation has not been identified. Present therapies for DVT include systemic anticoagulation pneumatic compression devices designed to augment venous flow. Our recent studies reveal that oscillatory shear forces generated in the venous valve sinus by muscular activity are required to stimulate a powerful anti-thrombotic endothelial phenotype that prevents venous thrombosis. Consistent with this mechanism, analysis of venous valves harvested at autopsy from individuals who died of DVT and fatal PE reveals reversal of the anti-thrombotic phenotype in the peri-valvular endothelium.These studies are the first to identify a hemodynamic, cellular and molecular mechanism for DVT that explains its tight association with immobility and its site of origin at the venous valve sinus. They suggests that a mechanical device that restored peri-valvular oscillatory flow in high-risk patients would effectively prevent DVT by maintaining the natural anti-thrombotic mechanism. Analysis of existing pneumatic devices reveals that they fail to drive oscillatory flow at the venous valve required to prevent DVT. Thus, we designed the OsciFlex device that uses a unique actuation technique to create robust oscillatory flow in the peri-valvular pocket. The goal of this proposal is to extend our initial studies to develop a finalized device design that is ready for prolonged human use, regulatory approval, and clinical testing. We will work with clinicians, engineers, and human factors experts to improve the device design and function and be ready to conduct a decisive clinical trial at the end of the project.Primary Investigator: Welsh, John D Project Narrative Deep venous thrombosis (DVT) affects millions of Americans and causes approximately 100,000 deaths annually. Mechanical compression therapy is the only option to treat DVT in patients at risk for bleeding, but controlled trials show little or no benefit using existing devices. The OsciFlex system has been developed on the basis of new scientific insight into DVT pathogenesis that links immobility to loss of peri-valvular hemodynamic forces that genetically protect against clot formation. The present proposal will optimize the OsciFlex system in preparation for rigorous clinical efficacy testing and commercial sale, thus creating a safe and effective new means of treating DVT based on a clearly defined pathogenic mechanism.