Researchers from the University of Pennsylvania and the Massachusetts Institute of Technology may just have cracked a riddle that has, until now, stumped the collective minds in the tissue engineering field. The research team, headed up by Penn postdoctoral fellow Jordan S. Miller, Professor Christopher Chen of U Penn’s Bioengineering Department, and MIT Professor Sangeeta Bhatia, has come up with a short and sweet solution to the problem of keeping cells alive in engineered organs. And the best part? They used 3D printing to do it.
You see, “3D printing” tissue is the easy part; it’s vasculature that’s the problem. Vasculature refers to the circulatory system by which oxygen and nutrients are delivered to cells and waste is removed. Flat layers of engineered tissue have ready access to oxygen and nutrients, but in the case of larger, three dimensional masses—such as organs—without that circulation, cells in the middle will die off.
3d-Printed vasculate network
The solution as developed by Miller’s team is relatively simple: they 3D printed a mold—or template—with rods running through, so that when the living cells are poured into it, the cells form around the rods. Once the cells have set, the gel is broken out of the mold, and water is passed through, dissolving the rods and leaving channels that act as vasculature. In order for this to work, the mold would have to be constructed of a material that was structurally rigid, water soluble and extrude-able through a 3D printer. The researchers concluded that the best material would be sugar. The mold itself is composed of sucrose and glucose, with a little dextran thrown in for structural strength. As Miller explained, “We tested many different sugar formulations until we were able to optimize all of these characteristics together. Since there’s no single type of gel that’s going to be optimal for every kind of engineered tissue, we also wanted to develop a sugar formula that would be broadly compatible with any cell type or water-based gel.”
Results have been positive, so far: blood vessel cells injected throughout the channels sprouted new capillaries which would go on to extend the network, and a gel made up of liver cells showed improved functionality and survivability in cells around the vascular channels. The liver cell experiments show promise, but the work is still in its infancy. The clinical results are a long way’s off from a fully functional liver, but it’s certainly a step in the right direction. Plus, this work can double as a springboard for yet more research into engineered organs and their function. As Bhatia attested:
“The therapeutic window for human-liver therapy is estimated at one to 10 billion functional liver cells. With this work, we’ve brought engineered liver tissues orders of magnitude closer to that goal, but at tens of millions of liver cells per gel we’ve still got a ways to go… More work will be needed to learn how to directly connect these types of vascular networks to natural blood vessels while at the same time investigating fundamental interactions between the liver cells and the patterned vasculature.”
Perhaps the most intriguing angle to this story is the fact that, rather than having used a powerful, high-end 3D printer, the Penn team did it all on a RepRap. According to Miller, “We launched this project from innovations rooted in RepRap and MakerBot technology and their supporting worldwide communities. A RepRap 3D printer is a tiny fraction of the cost of commercial 3D printers, and, more important, its open-source nature means you can freely modify it.”
Miller plans to hold a workshop this summer to teach the construction and use of 3D printers, as well as moving forward with innovating new designs. He concluded by saying, “We want to redesign the printer from scratch and focus it entirely on cell biology, tissue engineering and regenerative medicine applications.”
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