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

Marquette University, Milwaukee WI

Investigators

Abstract

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.