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. (Photo by Jeff Fitlow)
Using sugar, silicone and a 3-D printer, a team of bioengineers at Rice University and surgeons at the University of Pennsylvania have created an implant with an intricate network of blood vessels that points toward a future of growing replacement tissues and organs for transplantation.
The research 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 new study was performed by a research team led by Jordan Miller, assistant professor of bioengineering at Rice, and Pavan Atluri, assistant professor of surgery at Penn. The study showed that blood flowed normally through test constructs that were surgically connected to native blood vessels. The report was published in the journal Tissue Engineering Part C: Methods.
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.
Bioengineering graduate student Samantha Paulsen and research technician Anderson Ta worked together to develop a proof-of-concept construct — 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.
It’s a technique pioneered by Miller in 2012 — and inspired by the intricate sugar glass cages crafted by pastry chefs to garnish desserts.
Using an open-source 3-D 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.
Collaborating surgeons at Penn in Atluri’s group connected the inlet and outlet 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 three hours.
Other authors on the study were Renganaden Sooppan, Jason Han, Patrick Dinh, Ann Gaffey, Chantel Venkataraman, Alen Trubelja, George Hung and Pavan Atluri, all from Penn.
A John S. Dunn Collaborative Research Award supported the research.
Rice University
bioengineering.rice.edu
