Mar 3, 2017 | By Benedict

Researchers at the University of California San Diego have used 3D bioprinting to develop a functional blood vessel network. The researchers say their work could advance the creation of artificial organs and regenerative therapies.

Most experts in the biomedical community agree that 3D bioprinting holds huge promise for someday creating artificial humans organs, reducing the need for human donors and potentially saving millions and millions of lives. If this potential future is to become a reality, however, one of the biggest obstacles researchers face is the creation of functioning vasculatures, the parts of organs that allow blood to flow.

“Almost all tissues and organs need blood vessels to survive and work properly; this is a big bottleneck in making organ transplants, which are in high demand but in short supply,” said Nanoengineering professor Shaochen Chen, who leads the Nanobiomaterials, Bioprinting, and Tissue Engineering Lab at UC San Diego. “3D bioprinting organs can help bridge this gap, and our lab has taken a big step toward that goal.”

The big step Chen speaks of is this: his lab has managed to 3D print a vasculature network that can safely integrate with the body's own network to circulate blood. In a study that has been published in Biomaterials, Chen and his team show how they have developed a new bioprinting technology using homemade 3D printers that can quickly make 3D microstructures that mimic biological tissues. In the past, this 3D bioprinting method has been used to create liver tissue and these unusual 3D printed micro-fish that can deliver drugs within the human bloodstream.

In the language of orthodox 3D printing, Chen’s 3D bioprinting method is most similar to Stereolithography or DLP 3D printing, since it uses light to cure a light-sensitive substance in particular 3D shapes. Rather than use resins, however, the homemade bioprinter uses a solution containing both live cells and light-sensitive polymers that solidify upon exposure to UV light. 2D images of a 3D model are exposed by millions of microscopic mirrors which project these images as UV light, curing the mixture one layer at a time to create the biological 3D structure.

“We can directly print detailed microvasculature structures in extremely high resolution,” said Wei Zhu, a postdoctoral scholar in Chen's lab and a lead researcher on the study. “Other 3D printing technologies produce the equivalent of 'pixelated' structures in comparison and usually require sacrificial materials and additional steps to create the vessels.”

Incredibly, Chen and his team say that this UV 3D bioprinting process takes just seconds. By contrast, other 3D bioprinting techniques—many of which involve something more akin to layer-by-layer extrusion and deposition—can take hours to print a single structure. And there are other advantages to Chen’s method, too: the light-sensitive polymers used in the biological solution are cheap to obtain, despite being fully biocompatible.

Using their refined 3D bioprinting technique, the University of California San Diego researchers were able to 3D print a structure containing endothelial cells—cells that form the inner lining of blood vessels—based on a 3D model of a real human blood vessel network. Despite measuring just 4 mm x 5 mm x 600 μm, the researchers were able to use this imitation blood vessel network in live subjects.

After culturing a number of these 3D printed structures for one day, the researchers then grafted them onto the skin wounds of live mice. Two weeks later, these artificial vasculatures had grown into and merged with the blood vessel networks of the mice, with blood flowing throughout the animal as normal.

The study shows a great deal of promise, though there is much more work to be done before Chen and his team can think about using their 3D bioprinting method for human use. For example, real vasculatures are not just used to transport blood, but also nutrients, oxygen, and waste. “We still have a lot of work to do to improve these materials,” Chen said.

The next step for the researchers will be to build tissues using human induced pluripotent stem cells, which can conveniently be found in human skin, eliminating the need to dig any deeper. These tissues, the researcher say, could be used to help patients who have received transplants, which can be rejected by the immune system of the host’s body.

The main objective for the University of California San Diego researchers is to reach the clinical trials stage, though it could be “at least several years” before they get there.



Posted in 3D Printing Application



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