Collagen-based tissue engineering as applied to heart valves

Using the method of directed collagen gel shrinkage, we have been fabricating heart valves and mitral valve chordae [1,2,3]. The principle involves mixing solubilized coHagen with the appropriate cells. When the collagen-cell mixture is neutralized, soluble collagen reassembles into fibrils and a gel is created. When the gel is mechanically constrained, the collagen fibrils align in the direction of constraint. The generation of tensile force during contraction is crucial for the formation of highly aligned, compacted collagenous constructs. So far, inappropriate mechanical properties have been one of the main limitations of most collagen-based tissue equivalents. In this study, we focused on providing both biomechanical and biochemical stimuli to increase cellular proliferation, matrix synthesis, and hence improve the mechanical properties of the collagen constructs. We explored a number of holder materials and configurations, with an objective to maximize the lateral compaction of our constructs. We designed a bioreactor that can provide controlled static tension to our collagen constructs. We also developed a nutrition-fortified medium that includes trace elements (Zn2+, Cu2+, Fe2+ and Mn2+), various amino acids, and vitamins (A, B complex, and C). Our ultimate goal was to combine biomechanical and biochemical stimuli, and enhance the mechanical strength of our coHagen constructs.