Tissue-engineered valves with commissural alignment

We present a novel approach to producing bioartificial valves using the tissue-equivalent method of entrapping cells within a biopolymer gel and using a mold design that presents appropriate mechanical constraints to the cell induced gel compaction so as to yield both the fibril alignment and the geometry of a native valve. Producing a bioartificial valve that has the same fibril alignment as the native valve is believed to be important in realizing mechanical properties similar to the native valve. Bileaflet valves were fabricated from bovine collagen and neonatal human dermal fibroblasts as proof of principle. The resultant valves possessed both commissure-to-commissure alignment of collagen fibers in the leaflets and circumferential alignment in the root. The leaflet alignment was reflected in anisotropic tensile properties. Histology of the leaflets, however, revealed an aligned collagen matrix with very little of the other ECM components present in the native valve. Consequently, valves were fabricated from fibrin instead of collagen, since fibrin has been shown to stimulate matrix production by entrapped tissue cells.