CAREER: Origami-inspired design for a tissue engineered heart valve

职业：受折纸启发的组织工程心脏瓣膜设计

• 批准号: 2337540
• 负责人: Brandon Tefft
• 金额: $ 57.28万
• 依托单位: Marquette University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-07-01 至 2029-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2337540&HistoricalAwards=false
• 关键词: CAREER; Origami; inspired; design; tissue

Children born with improperly formed heart valves face a lifetime of surgeries and hardship. Many of these children will receive artificial heart valve substitutes. Current artificial heart valves have many problems including that they cannot grow as the child grows. A heart valve substitute made from living biological tissue that can self-repair and grow would provide a far superior treatment option. The overall research goal of this Faculty Early Career Development (CAREER) project is to develop a living heart valve substitute using new approaches that will overcome current barriers. For example, a new origami-inspired design is expected to achieve a valve that is easier to make and that lasts longer. Additionally, the valve will be populated with living cells in a way that is similar to how heart valves naturally form. This will allow the cells to produce a more natural valve with appropriate behavior and functionality. This CAREER project also includes education and outreach activities designed to broaden STEM participation by recruiting members from diverse groups to work on the research and to increase public scientific literacy and public engagement with science and technology by offering educational community outreach and classroom activities in libraries and middle schools. Activities include a “Science in the News” seminar series open to the public and hosted at local public libraries and an “Origami-based Engineering Design Challenge” outreach activity targeted towards students in local middle schools.There is an urgent need to develop a tissue engineered heart valve that is both functionally durable and physiologically accurate to provide better treatment options for children born with congenital heart disease. The overall research objective of this project is to develop a biological valve with cellular activity that sustains hydrodynamic functionality. The central hypothesis is that a scaffold with tissue-like properties, cleverly folded into a valve configuration, and seeded with developmentally appropriate cells, can produce a biological valve with unprecedented functionality and durability. Objective 1 is to synthesize a porous and elastic scaffold that mimics critical tissue properties. This will be accomplished by incorporating a sodium chloride (NaCl) porogen into poly(glycerol sebacate) (PGS) to create a biocompatible scaffold with tissue-like porosity and elasticity. Objective 2 is to develop a prosthetic heart valve with hydrodynamic functionality and durability. This will be accomplished using a novel origami-inspired folding approach to fabricate a functional prosthetic heart valve that does not contain traditional failure points. Objective 3 is to generate resident valve cell types with appropriate biological activity. This will be accomplished by using patient-derived umbilical cord blood to generate endothelial progenitor cells which can give rise to native-like valve cell populations by mimicking embryonic development. Objective 4 is to mature a tissue engineered heart valve to achieve native structure and durable functionality. This will be accomplished by using a tissue engineered heart valve with a biomechanically sound design and resident cells with appropriate biological origins to generate valve neotissue.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.

出生于心脏瓣膜不当的孩子面临着一生的手术和困难。这些孩子中的许多人会接收人造心脏瓣膜替代品。当前的人造心脏瓣膜有许多问题，包括随着孩子的成长无法成长。可以自我修复和生长的活生物组织制成的心脏瓣膜替代品将提供优越的治疗选择。这个教师早期职业发展（职业）项目的总体研究目标是使用将克服当前障碍的新方法开发活着的心脏阀替代品。例如，有望实现新的折纸风格设计，可以实现更容易制造的阀门，并且持续更长的时间。此外，阀门将以与心脏瓣膜自然形成的方式相似的方式填充活细胞。这将使细胞产生具有适当行为和功能的更自然的阀门。该职业项目还包括旨在通过招募潜水员团体进行研究的成员来扩大STEM参与的教育和外展活动，并通过在图书馆和中学中提供教育社区的外展和课堂活动来提高公共科学素养和与科学和技术的公众参与。活动包括向公众开放的“新闻中的科学”半隔离系列，并在当地的公共图书馆举办，以及针对当地中学学生的“基于折纸的工程设计挑战”活动。迫切需要开发一个既耐用又精确的组织工程心脏瓣膜，以便为患有先天性心脏病的儿童提供更好的治疗选择。该项目的总体研究目标是开发具有维持流体动力功能的细胞活性的生物瓣膜。中心假设是具有类似组织的特性的脚手架，巧妙地折叠成阀构型，并用开发的细胞播种，可以产生具有前所未有的功能和耐用性的生物阀。目标1是合成模仿关键组织特性的多孔和弹性支架。这将通过将氯化钠（NaCl）孔子掺入聚（甘油酯）（PGS）中来创建具有组织样孔隙和弹性的生物相容性支架。目标2是开发具有水动力功能和耐用性的假肢心脏瓣膜。这将使用一种新型的折纸式折叠方法来实现，以制造不含传统故障点的功能性假肢心脏阀。目标3是生成具有适当生物学活性的驻留阀细胞类型。这将通过使用患者衍生的脐带血来产生内皮祖细胞来实现，这可以通过模仿胚胎发育来产生类似天然的瓣膜细胞群。目标4是成熟的组织工程心脏阀，以实现天然结构和耐用的功能。这将通过使用具有生物力学声音设计的组织工程心脏阀和具有适当生物学起源的居民细胞来实现。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子优点和更广泛的影响审查标准来通过评估来诚实地通过评估来诚实地支持。