Samantha Paulsen, a bioengineering graduate student in Jordan Miller’s lab at Rice University, holds a plate on which several of 3-D-printed silicone constructs have been mounted. The constructs, which are each about the size of a small candy gummy bear, have been injected with red dye to better show the network of small vessels inside. Credit: Jeff Fitlow/Rice University
It may provide a method to overcome one of the biggest challenges in regenerative medicine: How to deliver oxygen and nutrients to all cells in an artificial organ or tissue implant that takes days or weeks to grow in the lab prior to surgery. The study showed blood flowed normally through test constructs that were surgically connected to native blood vessels.
Miller said one of the hurdles of engineering large artificial tissues, such as livers or kidneys, is keeping the cells inside them alive. Tissue engineers have typically relied on the body’s own ability to grow blood vessels – for example, by implanting engineered tissue scaffolds inside the body and waiting for blood vessels from nearby tissues to spread to the engineered constructs. Miller said that process can take weeks, and cells deep inside the constructs often starve or die from lack of oxygen before they’re reached by the slow-approaching blood vessels.
“We wondered if there were a way to implant a 3D printed construct where we could connect host arteries directly to the construct and get perfusion immediately,” said Miller said. They made a a small silicone gel about the size of a small candy gummy bear – using 3-D printing. But rather than printing a whole construct directly, the researchers fabricated sacrificial templates for the vessels that would be inside the construct.
Using an open-source 3D printer that lays down individual filaments of sugar glass one layer at a time, the researchers printed a lattice of would-be blood vessels. Once the sugar hardened, they placed it in a mold and poured in silicone gel. After the gel cured, Miller’s team dissolved the sugar, leaving behind a network of small channels in the silicone. “They don’t yet look like the blood vessels found in organs, but they have some of the key features relevant for a transplant surgeon,” Miller said. “We created a construct that has one inlet and one outlet, which are about 1 mm in diameter, and these main vessels branch into multiple smaller vessels, which are about 600 to 800 microns.”
Collaborating surgeons at Penn in Atluri’s group connected the inlet and of the engineered gel to a major artery in a small animal model. Using Doppler imaging technology, the team observed and measured blood flow through the construct and found that it withstood physiologic pressures and remained open and unobstructed for up to 3 hours. “In the future we aim to utilize a biodegradable material that also contains live cells next to these perfusable vessels for direct transplantation and monitoring long term.” http://news.rice.edu/2015/11/02/researchers-create-transplantation-model-for-3-d-printed-constructs/
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