Three-Dimensional Rapid Prototyping of Vascular Substitutes for
Medical Applications
Connor Dodge, Tomonori Baba, Alex Bischoff, Tyler Hubbard, Sterling Rosqvist,
Jason Griggs, Sarah Livingston, Alonzo D. Cook, PhD.
Brigham Young University, Provo, Utah, USA
Autologous transplant of a patient’s living veins is the most common clinical
practice for atherosclerotic disease. However, the search for an ideal arterial
substitute has taken exciting new turns. The newest research focuses on
rebuilding arteries from a patient’s own cells in vitro, and then implanting the
blood vessels with no immunological effects and having every functional property
of a living artery. Our blood vessel research team has entered the tissue
engineering field in its most exciting effort: the scalable rendering of cell-seeded
vascular constructs with rapid prototyping machines or 3D printers. Gabor
Forgacs Ph.D. and other researchers have pioneered the organ printing field. To
date, these scientists have managed to build 3-dimensional scaffolds of organs
and vasculature while simultaneously seeding living cells using the same
machines.
We have built a 3D printer and are in search of the optimal material we can use to
print while also fostering cell adhesion. Cells must be able to perfuse and
differentiate while occupying the extracellular matrix. To promote cell adhesion
to the matrix, we are working with fibronectin, GAGs (glycosaminoglycans),
hyaluranic acid, and collagen. To be able to form functional arteries we also are
developing a strategy using lyophilization. Hopefully by lyophilizing the alginate
gel, we will be able to make a porous extracellular matrix and nutrients can be
supplied to all cells. We are using smooth muscle and endothelial cells in this
process because they have been shown to secrete and reform the extracellular
matrix of a vessel. To test functionality we will compare tensile strength with
Young’s modulus models, test for blood compatibility with thrombogenicity
measurements, ensure synchronization of smooth muscle contractions, and
eventually perform autologous animal tests to identify signs of immunogenic
rejection.
Our proposed method for the development of a living artery is to assemble a
three layered cylindrical shape, supported by agarose gel beads, with the outside
layer being a collagen-based film, the tunica media of smooth muscle cell
droplets, and a layer of endothelial cells to form the lumen (another agarose bead
will fill the lumen void). The hypothesis is that a subendothelial layer will form
between the cell layers.
Acknowledgements
Funding was provided by Brigham Young University