Use of Collagenase-Resistant Pigs to Generate Calcification-Resistant Bioprosthetic Aortic Valves

Technology #2010-061

Calcific aortic valve stenosis is a growing problem in developed countries, and valve replacement surgery is the second most common thoracic surgery performed worldwide (>100,000 procedures performed in the US in 2008). Bioprosthetic valves are the most commonly used devices to replace the stenotic valve, but only have a projected lifespan of 10-12 years. Cells infiltrating the bioprosthetic valve express MMP’s, which allow for cell migration and tissue remodeling. However, fragments generated by collagen cleavage are likely to create a pro-inflammatory environment and promote the re-differentiation of infiltrating cells to an osteoblast-like phenotype. This ultimately promotes valve calcification and failure. By modifying the collagen gene in the pig, we aim provide a highly regionalized and tissue-specific way to slow the rate of cell ingrowth and calcification of bioprosthetic valves and slow the rate of bioprosthetic valve degeneration and calcification.