Development and characterization of improved tissue engineered valve-equivalents using chemical and mechanical signaling

Tissue engineered valves hold considerable promise as replacement valves that avoid many of the problems present in current replacement valve technology. Furthermore, these valves, as a living construct, would be able to grow and remodel in vivo. We have developed a bileaflet biopolymer-scaffold based valve equivalent that possesses the correct geometry and underlying collagen fibril alignment. These valve-equivalents, however, have significantly worse mechanical properties as compared to healthy, native valves (in terms of ultimate tensile stress and tangent modulus). Furthermore, valve equivalents with initial collagen scaffolds show very little compositional remodeling leaving a predominantly collagen valve with little of the elastin and proteoglycan content present in native valves. We present work here aimed at improving the compositional and mechanical properties of valve-equivalents (VEs) by using a combination of chemical signaling by using a fibrin (as opposed to collagen) scaffold incubated with TGF-β and insulin and mechanical signaling achieved by VE incubation in a bioreactor.