SBIR Phase I: VTE mitigation device

SBIR 第一阶段：VTE 缓解装置

• 批准号: 1842867
• 负责人: John Welsh
• 金额: $ 22.5万
• 依托单位: OSCIFLEX LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1842867&HistoricalAwards=false
• 关键词: SBIR; Phase; 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.

该 SBIR 第一阶段项目将支持新型医疗设备的研发，该设备旨在预防住院患者的深静脉血栓形成。当静脉中形成血凝块时，就会发生深静脉血栓形成，是医院患者的常见并发症，也是美国可预防死亡的主要原因。该项目将开发一种设备，以一种新的方式改变腿部的血流模式，旨在专门激活静脉内的基因变化，防止血栓形成。该项目的目标是开发一种新设备，能够为患者创造所需的血流模式，同时为临床工作人员和患者保持高水平的设备舒适度、可靠性和易用性。除了防止美国住院人口死亡和残疾外，该项目还将推动新设备商业化生产，从而支持经济增长、就业机会形成和税收收入。该 SBIR 第一阶段项目将利用有关深静脉血栓形成 (DVT) 发病机制的新分子和细胞发现，创造一种更有效的设备来预防处于该疾病高风险的固定个体中的 DVT。深静脉血栓形成于静脉瓣后面的窦中，不动时血流量减少，促进血栓形成。该部位通常通过瓣膜窦微环境所特有的内皮细胞中强大的遗传程序来防止凝块形成。该基因表达程序的缺失会导致血栓形成环境，从而支持血栓形成和深静脉血栓形成。研究进一步表明，瓣膜窦抗血栓基因程序是由该部位由肌肉活动驱动的特定静脉血流模式激活的。在住院期间常见的长时间不动期间，这种血流分布的丧失会消除保护性内皮表型并支持 DVT 的形成。超声分析表明，目前销售的用于预防 DVT 的机械治疗设备由于其作用方法，不会在瓣膜处产生由肌肉活动产生的血流动力学。该项目将开发一种设备，通过驱动血流，在不动患者的瓣膜窦中产生保护性血流动力学模式，从而准确地再现肌肉活动。为了实现这一目标，该设备设计改变了其他现有设备的主要物理操作策略，远离小腿和大腿压缩，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概括了支持瓣膜窦中保护性遗传途径表达所需的活动肢体的静脉血流动力学。该 SBIR 第一阶段项目将优化设备设计以创建这种驱动，同时提高患者舒适度、减轻常见风险并促进临床工作人员的易用性。该项目将解决将医疗器械推进临床测试和使用的关键风险，从而使该器械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点和更广泛的影响审查标准进行评估，被认为值得支持。