In-vitro and in-vivo mechanical stability and growth of a bio-hybrid heart valve

Current prostheses used to replace heart valves in children do not grow and have serious drawbacks such as thrombogenicity, calcification and degeneration. Thus, children require multiple resizing surgeries, life-long anti-coagulation treatment and have a reduced life expectancy. There is a critical need to develop a growth-accommodating valved device. Our long-term goal is to develop a growing biohybrid prosthesis using the concept of in-situ tissue regeneration with a growth-accommodating stable polymeric valve. The vessel component is made of two polymers: one biodegradable and one biostable. The biodegradable polymer in the vessel is replaced by a new tissue after implantation and the stable polymer maintains the continuity between the vessel and the valve. The valve has a specific design allowing to accommodate the growth of the vessel. The objectives of this proposal are to: (i) demonstrate the formation of a neo-tissue and its integration with the biostable polymer in the engineered hybrid vessel, (ii) demonstrate the potential of growth for the hybrid vessel, and iii) prove the robust mechanics of the stable valve¿living vessel joint region. Our hypothesis is that the breakdown of the biodegradable component of the vessel results in the integration of cells that can secrete extracellular matrix and interact with the remainder stable porous structure, while allowing the neo-vessel to grow. Our hypothesis is based on strong preliminary results. We pursue three following specific aims: 1- Demonstrate the formation of a neo-tissue and its integration into the biostable component of an engineered hybrid vessel. We will perform static and dynamic cell seeding and testing and use a rat model of subcutaneous implantation. Samples will be assessed via histology, immunohistochemistry, electronic microscopy, and mechanical testing to assess cell infiltration, phenotype, extracellular matrix formation, tissue architecture and mechanical properties. 2- Demonstrate the potential of growth for the hybrid vessel. We will use a model of implantation in the aorta of rats and a computational model of vessel growth. 3- Assess the mechanical impact of the moving valve on the tissue-engineered hybrid vessel and ensure the stability of the cohesion between the stable valve and the living vessel. We will use a valve fatigue tester and a COMSOL computational model with fluid-structure interaction. (AHA Program: Transformational Project Award)