Three-dimensional culture of small-diameter vascular grafts.

In this review we analyze a representative sample of efforts to engineer three dimensional small-diameter (<6 mm) vascular grafts, concentrating on biomaterial substrates, cellular choices, and biomechanical stimulation. Natural or synthetic scaffolds for vascular engineering need to mimic the natural extracellular matrix microenvironment, maintain physiological mechanical properties, be biocompatible and cell adhesive, and control cellular structure and function. Additionally, multicellular culture with stem cells that are highly proliferative and differentiable should be used to better recapitulate native vasculature. Fluid flow and co-culture of perivascular and endothelial cells produce synergistic effects. Also, fluid flow prevents cell disengagement and facilitates appropriate cellular orientation, making bioreactors an auspicious addition to graft culturing techniques. Overall, stem cells, co-culture, and pulsatile flow are important for the rapid and successful development of a viable small-diameter tissue engineered vascular graft for in vivo use.