Gene therapy approaches to alter the mechanical properties of tissue-engineered construct

One of the current issues in the development of a tissue engineered vascular graft is sufficient mechanical strength to erase concerns with burst failure. The goal of this project was to assess the mechanical integrity of tissue engineered constructs through modulation of enzymes involved in extracellular matrix crosslinking. Vascular smooth muscle cell-populated collagen gels were subjected to dynamic tensile strength testing in the presence of altered crosslink densities. The enzymes chosen were lysyl oxidase and tissue transglutaminase. It was found that cells naturally higher in lysyl oxidase activity imparted increased tensile strength and elastic modulus in these constructs. Smooth muscle cells transfected with lysyl oxidase were observed to increase mechanical integrity to a greater degree than the cells with naturally higher lysyl oxidase. A 3-fold enhancement in mechanical strength was observed when tissue transglutaminase was directly added into the gels.