How 3-D-printed blood vessels may help organ transplantation
Monday, November 23, 2015
Transplant surgeons need more than simply a mass of cells — they need vessel inlets and outlets that they can connect directly to arteries and veins.
One of the largest hurdles scientists face when engineering livers, kidneys or other large artificial tissues is keeping the cells alive. Today, tissue engineers rely on the body's ability to grow blood vessels. They typically implant engineered tissue scaffolds inside the recipient's body and wait for blood vessels to spread from nearby tissues to the engineered constructs. This process can take weeks and, in the meantime, cells deep within the engineered tissue starve or suffocate before blood vessels ever reach them.
A new study, published in the journal Tissue Engineering Part C: Methods, showed that blood flowed normally through 3-D-printed test constructs surgically connected to native blood vessels. Bioengineers at Rice University and surgeons at the University of Pennsylvania wondered if they could implant a 3-D-printed construct that would allow them to connect host arteries directly to the construct and gain immediate perfusion.
This study was the first step toward that goal.
The team printed a 3-D implant with a complex network of blood vessels, potentially creating a method to overcome one of the largest challenges in regenerative medicine — delivering oxygen and nutrients to all the cells in an artificial organ or tissue implant.
They did it with only sugar, silicone, a 3-D printer and a technique inspired by the intricate sugar glass cages created by pastry chefs to help them garnish desserts. The researchers then tested the material and found it could withstand the physiologic pressures to remain open and unobstructed.
Bioengineering graduate student Samantha Paulsen and research technician Anderson Ta used 3-D printing to develop a proof-of-concept construct in the form of a small gummy bear-sized silicone gel. Instead of printing a whole construct, the team created sacrificial templates using a technique developed by Jordan Miller, research team leader and assistant professor of bioengineering at Rice.
Miller's French pastry-inspired technique involved using an open-source printer to lay down individual filaments of sugar glass to act as a lattice of would-be blood vessels. After the sugar hardened, the researchers placed it in a mold and poured in silicone gel. The team dissolved the sugar once the gel cured, leaving behind an intricate network of tiny channels in the silicone.
The researchers created a construct that had one inlet and one outlet, each measuring about a millimeter in diameter. The main vessels branch into several smaller vessels measuring 600 to 800 microns.
University of Pennsylvania surgeons connected the inlet and outlet of the construct to a major artery in a small animal model, then used Doppler imaging technology to observe and measure blood flow through the engineered gel. The research showed the printed construct could remain open and unobstructed for up to three hours.
This study is the first step in developing tissue engineering transplant models where the surgeon connects arteries directly to engineered tissue. Future technologies could use biodegradable material that contains live cells placed near perfusable vessels.
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