Blood vessels keep us alive. They are the highways that transport oxygen-rich blood and nutrients to all corners of our body while simultaneously removing toxic waste products. When they become diseased or dysfunctional, life-threatening situations arise, like heart attacks, strokes and aneurysms. In fact, blood vessel failures are a major reason why cardiovascular disease is the leading cause of death globally.
For years, scientists have been trying to perfect blood vessel tissue engineering, but they are complex and it has proved challenging. Current methods are slow, require specialized equipment, and above all, are low throughput—meaning researchers have not found a way to provide the necessary supply of engineered vessels.
Now, in a new study, researchers from the University of Melbourne have moved closer to engineering blood vessels from natural tissue with the development of a fast, inexpensive and scalable method that combines multiple materials and fabrication technologies.
From complex to simple(ish)
One of the main reasons scientists have had difficulty creating engineered blood vessels is because the native ones are complex, multi-layered tissues. The structure of the tissues is what boosts the vessels performance. Thus, the first step for researchers wanting to create engineered versions was to replicate the complex geometry of native blood vessels.
“First, we needed to create the shape, a kind of framework on which to grow the blood vessel layers,” explained the study authors, Daniel Heath, Andrea O’Connor and Hazam Alkazemi, all from the University of Melbourne.
To do so, they employed electrospinning, a technique that uses an electrical voltage to draw a polymer stream into thin fibers. They used electrospinning to turn a layer of polymer fibers onto a mandrel, which provided the tubular shape for the blood vessel graft. However, the electrospinning left the fibers randomly orientated when the researchers needed them to be aligned along the length of the tube to promote axial alignment of the endothelial cells.
To align the fibers, Heath and team developed a freezing technique where ice crystals grew along the axis, which pushed the fibres into alignment.
“We then grew endothelial cells on the tube to create the inner layer of the vessel—the endothelium,” said Heath. “The cells spontaneously align with the fibers, generating a continuous, aligned endothelial cell layer like we see in native blood vessels.”
Next, the researchers cast a soft hydrogel layer around the electrospun fibes to prevent leakage from the graft and to act as a scaffold. They tested hydrogels of varying stiffness, and found that the softer gels allowed the smooth muscle cells to rapidly and spontaneously align in a 3D ring structure, mimicking what is found in native blood vessels.
Although the study advances scientists’ ability to engineer human blood vessels, the team says more work needs to be done before they can progress to the clinic, including verifying that the electrospun layer degrades at an appropriate rate.
“In the future we hope these engineered blood vessels will be used to treat cardiovascular disease— especially in those vulnerable patients who lack appropriate donor vessels,” said Heath.