Engineers Use Bioprinted Blood Vessels to Model Deadly Brain Tumors

Glioblastoma is a brain cancer with a very low chance of survival. Most drugs cannot cross the blood-brain barrier, which means that unlike other cancers, there are not many treatments available for brain tumors.

But cutting-edge technology developed at the University of Cincinnati aims to change that. Researchers are using 3D bioprinting to create artificial blood vessels that can be used to test new, custom-made drugs and study why glioblastoma is so resistant.

“Our goal is to develop models that can be used to gain new insights into the mechanism that drives tumor regeneration and drug resistance, allowing us to test new therapies,” said Riccardo Barrile, assistant professor of biomedical engineering in UC’s College of Engineering and Applied Science.

The study was published in the journal Advanced health materials.

Organs on a chip

“Glioblastoma is the most aggressive form of primary brain tumor. It’s usually fatal,” Barrile said. “It’s a terrible disease.”

Doctors typically prescribe chemotherapy combined with surgical removal of tumors and radiation therapy. But glioblastoma is resistant and usually becomes resistant to the drugs over time, he said.

“It’s difficult to target these tumors,” he explained. “They are strategically infiltrated into healthy parts of the brain tissue.”

The first “organs on chips” were made less than 20 years ago. It’s a very promising area in drug development, but it’s still in its infancy, Barrile said.

With standard technology, it can take months to build organs on a chip. But Barrile and his students can use 3D bioprinting to create customized synthetic blood vessels much more quickly for each patient.

“The molds are generated using conventional manufacturing techniques. It can take weeks or even months to generate a prototype. Our 3D printing approach takes just a few hours,” he said.

And that opens up a world of research and treatment possibilities, he said.

Similarly, Barrile said, traditional organs-on-chips use silicone materials. But the drugs needed to treat glioblastoma are small molecule drugs, so small that they can easily be absorbed into the silicone form rather than into the tissue where they are needed.

“We do not use silicone materials but microfluidic hydrogels. This is an advantage because silicon devices reduce the effectiveness of the drug. The molecules simply disappear into the structure,” he said.

Organs-on-chips could one day eliminate the need for medical testing on animals, Barrile said.

Creating personalized therapies

Lead author Sirjana Pun, a UC biomedical engineering doctoral student, said organ-on-a-chip devices hold great potential for advancing the development of new therapies.

“Existing treatments for glioblastoma follow a one-size-fits-all approach, which has proven ineffective in significantly improving patient survival. Our system can be used to create personalized disease models, allowing new therapies to be tested that are tailored to each patient’s unique needs,” she said.

“I am grateful for the opportunity to do research at UC and work in a field that I am deeply passionate about,” Pun said.

They collaborated with Soma Sengupta of the UC College of Medicine, Daniel Pomeranz Krummel of the University of North Carolina and Giuseppe Sciumé of the University of Bordeaux in France. UC biomedical engineering students Dalee Demaree and Anusha Prakash also contributed to the project.

“I am excited to be part of this company as we work with other scientists from academia, industry and regulatory agencies to drive adoption of this technology with the long-term idea of ​​replacing animal models and providing alternative methods for drug testing,” Barrile said.