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.

先天性心脏瓣膜畸形的儿童一生都面临着手术和困难。这些儿童中的许多人将接受人工心脏瓣膜替代品。目前的人工心脏瓣膜有许多问题，包括它们不能随着儿童的生长而生长。由活的生物组织制成的能够自我修复和生长的心脏瓣膜替代物将提供远为优越的上级治疗选择。这个教师早期职业发展（CAREER）项目的总体研究目标是使用新方法开发一种活的心脏瓣膜替代品，以克服目前的障碍。例如，一种新的折纸灵感设计有望实现一种更容易制造且持续时间更长的瓣膜。此外，瓣膜将以类似于心脏瓣膜自然形成的方式填充活细胞。这将允许细胞产生具有适当行为和功能的更自然的瓣膜。该CAREER项目还包括教育和推广活动，旨在通过招募来自不同团体的成员来扩大STEM参与研究，并通过在图书馆和中学提供教育社区推广和课堂活动来提高公众的科学素养和公众对科学技术的参与。活动包括在当地公共图书馆举办的面向公众的“科学新闻”系列研讨会，以及针对当地中学生的“折纸工程设计挑战赛”外联活动，迫切需要开发一种功能耐用且生理准确的组织工程心脏瓣膜，为先天性心脏病儿童提供更好的治疗选择。该项目的总体研究目标是开发一种具有细胞活性的生物瓣膜，以维持流体动力学功能。核心假设是，具有组织样特性的支架，巧妙地折叠成瓣膜构型，并接种发育适当的细胞，可以产生具有前所未有的功能和耐久性的生物瓣膜。目的1是合成一种多孔的弹性支架，模拟关键的组织特性。这将通过将氯化钠（NaCl）致孔剂掺入聚（癸二酸甘油酯）（PGS）中以产生具有组织样孔隙率和弹性的生物相容性支架来实现。目标2是开发具有流体动力学功能和耐久性的人工心脏瓣膜。这将使用一种新颖的折纸启发折叠方法来制造不包含传统失效点的功能性人工心脏瓣膜。目的3是产生具有适当生物活性的驻留瓣膜细胞类型。 这将通过使用患者来源的脐带血产生内皮祖细胞来实现，内皮祖细胞可以通过模拟胚胎发育产生天然样瓣膜细胞群。目的4是使组织工程心脏瓣膜成熟，以实现天然结构和持久功能。这将通过使用具有生物力学合理设计的组织工程心脏瓣膜和具有适当生物来源的驻留细胞来产生瓣膜neotissue.This奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。