LLNL

Lawrence Livermore National Laboratory has developed a way to create living bioprinted aneurysms that allow researchers to perform medical procedures and then observe how the artery walls heal.

Bioprinting is a form of 3D printing that uses cells and other biological materials as “inks” to create biological structures.

Brain aneurysms, a ballooning in an artery wall, affect about one in every 50 Americans and can lead to stroke, brain damage and death if they burst. Existing treatment options are limited, and surgical outcomes can vary widely from person to person.

But a team led by LLNL engineers William Hynes and Monica Moya were able to replicate an aneurysm by 3D printing blood vessels with human cerebral cells. Hynes then performed an endovascular repair of the printed aneurysm by inserting a microcatheter and packing platinum coils inside the aneurysm sac.

The research team, which also includes scientists from Duke University and Texas A&M, was then able to introduce blood plasma into the aneurysm and observe the formation of a clot and cutting the aneurysm off from the artery. They were also able to observe the post-op healing of the cells lining the walls of the aneurysm.

LLNL said the bioprinting, combined with computer modeling, could be a significant step in developing patient-specific care for aneurysms. It also could speed up the time it takes for new surgical techniques and technologies to move from the laboratory to the clinic.

“While there are a lot of promising treatment options, some still have a long way to go,” said Moya, the project’s current principal investigator. “Animal models aren’t necessarily the best way to try out these options. Having this robust, human in-vitro testing platform could help facilitate new treatments. If we can replicate aneurysms as much as we need to, we might help accelerate some of these products into the clinic and essentially provide patients with better treatment options.”

Hynes, the original principal investigator who proposed the project, realized researchers needed a way to confirm what they were seeing with computer-modeling.

“We looked at the problem and thought that if we could pair computational modeling and experimental approaches, maybe we could come up with a more deterministic method of treating aneurysms or selecting treatments that could best serve the patient,” said Hynes, who led the project for its first year. “Now we can start to build the framework of a personalized model that a surgical practitioner could use to determine the best method for treating an aneurysm.”

To create the bioprinted aneurysm, Hynes and team started by printing the blood vessel with a “sacrificial” ink, surrounded by a protein-based hydrogel. The ink dissolved as it cooled, leaving the vasculature shape behind. Then they introduced human brain endothelial cells to coat the channels, forming the actual blood vessels and the aneurysm.

Hynes performed the coiling procedure with a microcatheter, believed to be the first surgical procedure ever performed on artificial living tissue.

Researchers said combining the 3D-printed process with computer modeling could allow surgeons to select the best coil types to pack an aneurysm and perform “test runs” before operating on the human patient.

“Essentially a clinician could literally look at somebody’s brain scan, run it through the modeling software, and the software could show the fluid dynamics prior to treatment,” Hynes said. “It should also be able to simulate that treatment and allow the practitioner to narrow down to a certain type of coil or packing volume to ensure the best possible outcome.”

In addition to patient-specific care and serving as a testbed for surgical training, researchers said the platform has potential for improving the understanding of basic biology and post-surgery healing.

While early results are promising, researchers cautioned they still have a long way to go. The team’s next step is to simulate how blood clots form in response to experimental shape-memory polymer coils designed to expand inside the aneurysm, compared to traditional bare coils.