CAREER: Restoring Function in Chronic Venous Insufficiency: Unraveling the Structural-Mechanics of Venous Valve Tissues

1553430 Huang慢性静脉功能不全（CVI）是一种使人衰弱的血管疾病，估计在女性中的患病率是男性的两倍;风险随着怀孕、年龄和涉及站立的职业而增加。CVI被美国社会保障管理局认为是一种致残性疾病;然而，日益增加的患病率并没有得到康复研究的相应增加。该CAREER项目将首次提供静脉瓣叶、窦和相关静脉组织的详细成分、结构和双轴力学表征。因此，这项研究将填补静脉瓣膜基础科学的关键空白，并作为创新的跳板，为CVI的治疗方法提供信息。这个职业生涯项目将吸引各种各样的群体：高中生，本科生和研究生，博士后，代表性不足的群体，视力障碍者和当地社区。为当地社区举办的研讨会和讲习班将提高人们对CVI、静脉高压和静脉瓣膜功能不全的认识。无障碍的虚拟瓣膜图谱（VALV）网络工具将为知识共享提供一个全球知识库，包括视力受损者瓣膜组织宏观和微观解剖结构的触觉图形。VALV的浮雕触觉图形将有助于提供额外的无障碍教育材料，使视障人士能够通过触觉进行主动学习。本CAREER项目侧重于静脉瓣膜组织的结构-机械方面。PI的目的是首次确定静脉瓣叶、窦和邻近静脉组织的双轴、非线性和粘弹力学性能，以及静脉瓣细胞外基质（ECM）成分、胶原纤维取向和生物化学定量。ECM形态。实验结构力学的结果将被纳入粘弹性和基于结构的本构模型。总的来说，这些结果将为理解静脉瓣膜生理学、病理学以及推进姑息和恢复性治疗（包括药物、手术和康复干预）提供急需的全面基础，以对抗CVI。

1553430HuangChronic venous insufficiency (CVI) is a debilitating vascular disease with a prevalence estimated to be twice as high in women; risk increases with pregnancy, age, and occupations involving standing. CVI is considered a disabling condition by the US Social Security Administration; however, increasing prevalence has not been met with commensurate increases in rehabilitation research. For the first time, this CAREER project will provide a detailed compositional, structural and biaxial mechanical characterization of venous valve leaflet, sinus and associated vein tissues. Thus, this research will fill a critical gap in the basic science of venous valves, as well as serve as a springboard for innovation, informing approaches to the treatment of CVI. This CAREER project will engage a diverse range of groups: high school, undergraduate, and graduate students, postdocs, underrepresented groups, visually impaired persons, and the local community. Seminars and workshops for the local community will raise awareness of CVI, venous hypertension, and venous valve incompetence. The barrier-free Virtual Atlas of the Valves (VALV) web tool will provide a global repository for knowledge sharing, including tactile graphics of valvular tissue macro- and micro-anatomy for the visually impaired. The embossed tactile graphics from VALV will aid in providing additional accessible educational materials, enabling active learning by the visually impaired through their senses of touch. This CAREER project focuses on the structural-mechanical aspects of the venous valve tissues. The PI aims to determine, for the first time, the biaxial, nonlinear, and viscoelastic mechanical properties of venous valve leaflet, sinus and adjacent vein tissues, as well as biochemical quantification of venous valve extracellular matrix (ECM) constituents, collagen fiber orientation, and ECM morphology. Experimental structural-mechanical results will be incorporated into viscoelastic and structural-based constitutive models. Collectively, results will provide a much-needed comprehensive basis for understanding venous valve physiology, pathology, and for the advancement of both palliative and restorative therapies, including pharmacological, surgical, and rehabilitation interventions to combat CVI.