Introduction: Mitral valve prolapse is the most common cause of regurgitation referred for surgical repair or replacement in the western world, but currently available substitutes do not adequately comply with the performance and flow pattern requirements of the left ventricle.
Hypothesis: Our hypothesis is that by maintaining the structural integrity of valve leaflets and chordae we prevent the tissue engineered valve from prolapse in a hypertensive and inflammatory environment.
Methods: Porcine mitral valves were decellularized using a detergent-based method optimized to preserve the natural ECM and mechanical characteristics. Scaffold stabilization was achieved using the well-characterized polyphenol, Pentagalloyl-glucose (PGG). Mitral valve constructs, recellularized with pre-differentiated fibroblasts and endothelial cells, were placed in a mitral valve bioreactor for preconditioning and maturation for 4 weeks.
Results: Characterization of the mitral valve scaffold has shown a well-preserved matrix and mechanical properties. Scaffold stabilization with PGG has shown to encourage polarization of the pro-healing M2 macrophage significantly over the pro-inflammatory M1 macrophage in rat-subdermal studies. Recellularized constructs preconditioned in the bioreactor express VIC-like markers while endothelial cell markers remained on the construct’s surface.
Conclusions: The overarching goal of this research was to develop a stable mitral valve construct. After bioreactor preconditioning, the seeded constructs yielded a mitral valve construct similar to a native valve. It is expected that the progress made by this project will have a positive impact on those that suffer from mitral valve pathologies.