SBIR Phase I: VTE mitigation device

这个SBIR第一期项目将支持研发一种新的医疗设备，旨在预防住院患者的深静脉血栓形成。当静脉中形成血栓时，就会发生深静脉血栓形成，这是住院患者的常见并发症，也是美国可预防的死亡的主要原因。该项目将开发一种设备，以一种新的方式修改腿部的血液流动模式，旨在专门激活静脉内防止血液凝块形成的基因变化。该项目的目标是生成一种新设备，它能够在患者体内创建所需的血流模式，同时为临床工作人员和患者保持高水平的设备舒适性、可靠性和易用性。除了预防美国住院人口的死亡和残疾外，该项目还将使一种新设备走向商业生产，从而支持经济增长、就业机会和税收。这个SBIR第一阶段项目将利用关于深静脉血栓形成(DVT)发病机制的新的分子和细胞发现，创建一种更有效的设备，以预防处于这种疾病高风险的固定个人的DVT。深静脉血栓形成于静脉瓣膜后的静脉窦内，在静止状态下，血液流量减少，从而促进血栓的形成。这一部位通常由瓣膜窦微环境特有的内皮细胞中强大的遗传程序保护，以防止血栓形成。这种基因表达程序的缺失会导致血栓前环境，从而支持血栓形成和DVT。研究进一步揭示，瓣膜窦抗血栓遗传程序是由肌肉活动驱动的该部位特定的静脉血流模式激活的。在住院期间常见的长时间不动期间，这种血流轮廓的丧失会使保护性内皮细胞表型消失，并支持深静脉血栓的形成。超声分析显示，目前市场上销售的用于预防DVT的机械治疗设备不会在瓣膜处产生血液动力学，而这种血流动力学是由肌肉活动产生的，因为它们的作用方法。该项目将开发一种设备，通过激活准确复制肌肉活动的血液流动，在静止患者的瓣膜窦中产生保护性血流动力学模式。为了实现这一目标，该装置的设计改变了其他现有装置的主要物理操作策略，不再压缩小腿和大腿，而是诱导小腿快速扩张，以复制肌肉活动对静脉血流的影响。血管超声研究表明，这种驱动方法成功地重现了活动肢体的静脉血流动力学，这是支持保护遗传途径在瓣膜窦中表达所必需的。这个SBIR第一阶段项目将优化设备设计，以创建这种驱动，同时还提高患者舒适度，降低常见风险，并促进临床人员的易用性。该项目将解决推动医疗设备进入临床测试和使用的关键风险，从而使该设备能够过渡到商业制造和使用阶段。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.