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A new open-source method for bioprinting represents a breakthrough for the field of regenerative medicine, and its success stems from a special ingredient: food dye.



This week’s cover of Science features a spectacular entangled network of blood vessel-like hydrogels, which is one of several constructs created by a team of bioengineers from Rice University, University of Washington, Duke University, Rowan University, and Nervous System (a design firm in Somerville, Massachusetts).



The group overcame key hurdles in bioengineering which has unlocked crucial design freedoms in the bioprinting world, evident in the other achievements reported today in Science. The method has been released as an open-source resource and enabled the development of a bioinspired alveolar model, a 3D functional bicuspid venous valve, and a carrier for liver tissue that was engrafted into a mouse model of chronic liver injury.



Overcoming one of the biggest regenerative medicine roadblocks

Food coloring shapes regenerative medicine

One giant leap for biomaterials tissue engineering

The vessels were strong enough to withstand the “breathing” motion of the alveolar models

The alveolar model delivered oxygen to red blood cells that passed through the vessels

3D bicuspid valves were incorporated that responded rapidly to changes in flow direction

Miller recalls one of the most exciting moments of the project:

“It was the first time that we started using the pneumatic system to ventilate the airway. It really did look like it was breathing… and it was so startling in the complexity of the architecture – we were seeing new things in the bloodstream immediately, as soon as we started doing that. It really transformed our view of what's possible inside of the soft materials that are more than 80% water.”





Video credit: Rice University

Looking ahead to replacement organs

To better mimic the biochemical conditions in vivo, the group showed that endothelial cells injected into the airway could line the vessels, and survive. Miller says that the group is looking to do similar types of experiments in blood vessel architectures.



“We have shown that human cells can survive the pre-hydrogel mixture, they can survive the polymerization process, and they survive inside the functional gel that we've made. One of the studies we put in the supplement was with mesenchymal stem cells. We were able to show that they're able to survive and grow and spread in 3D inside the gel. They were able to also differentiate towards a bone-like lineage of cells starting to prepare to mineralize that matrix. We really see the full potential of this technique is not just to model living tissue, but also to build it and understand its function in the body.”



As a test of the relevance of this approach to therapeutic implants, the team 3D printed hydrogel carriers, loaded them with hepatocyte aggregates, and implanted them into mice models of chronic liver injury. After 14 days of engraftment, there were positive signs; there were signs of surviving functional hepatocytes, and host blood was present in the explanted tissues.



Experiments performed by Rice University and University of Washington researchers explored whether hepatocytes would function normally if they were incorporated into a bioprinted implant and surgically implanted in mice for 14 days. (Image credit: Jordan Miller/Rice University).



Stevens shares her plans for the future: “Here, we tested just one liver cell function. But, liver cells have about 500 functions. In the future, we will test whether our bioprinted tissues can perform many more of these functions. We are also working to improve the resolution of our patterning, which is still about an order of magnitude larger than the size of most human cells.”



Science and art: a dream match

"We believe that science should be open-source"



Reference:



Grigoryan, B., Paulsen, S., Corbett, D., Sazer, D., Fortin, C., Zaita, A., Greenfield, P., Calafat, N., Gounley, J., Anderson, H., Johansson, F., Randles, A., Rosenkrantz, J., Louis-Rosenberg, J., Galie., P., Stevens, K., Miller, J. (2019). Multivascular networks and functional intravascular topologies within biocompatible hydrogels. Science doi: 10.1126/science.aav9750