Imagine what brain surgeons could do with a three-dimensional (3D)-printed model of the brain. Not a structural model printed in plastic and uniform throughout, but one that mirrors the heterogeneity of real human brain tissue — its mechanical, thermal, and electromagnetic properties.

“If somebody has a brain tumor, you could take an MRI of their brain and make a 3D model from it that includes the tumor, and then practice surgery on that model,” said Christopher O’ Bryan, PhD, MS, assistant professor of mechanical and aerospace engineering at the University of Missouri (UM) in Columbia, Missouri. “You could learn how sound, electromagnetic waves, or physical insults interact with the brain to better understand concussions and traumatic brain injury.”

O’Bryan and colleagues in UM’s College of Engineering recently published a study in the journal Materialia describing how the researchers designed a unique 3D printer ink made from a modified polymer — called a photo-crosslinkable poly(vinyl alcohol) methacrylate polymer — and then used it to print a scaled-down 3D model of the brain, about 15% of a real brain’s size. The scientists relied on a method called embedded 3D printing, crosslinking the polymer in a microgel bath, to achieve a model that mimicked the soft tissue and the structural complexities of a real human brain.

How They Did It

To provide a broader picture of why they conducted the study, O’Bryan described his lab’s goals. “The focus areas in our lab include the designing of soft materials, the testing of these materials, and then how to actually manufacture things out of these soft materials. And that’s especially challenging when you take into account that most soft materials are hydrogels and biopolymers which start out in a liquid phase ,” he said.

The researchers’ embedded 3D printing approach uses “sacrificial support baths,” jelly-like baths, which act as a supportive matrix during the printing phase. “What this allows us to do is to print materials as liquids and keep them as liquids until we’ve completely printed our structure, and then we crosslink the printed structure using heat or UV [ultraviolet] light to make it solid. Then we take it out of the gel bath, and it’s become a soft, deformable structure — meaning it can change shape when a force is applied,” O’Bryan said.

Scientists who use embedded 3D printing methods typically use polymers that go into the gel as a liquid and then require freezing and thawing in order to convert to a soft solid form. The drawback: it results in a very homogenous structure material-wise, said O’Bryan.

The polymer-based ink his lab developed, however, captures the material properties that are mechanically, thermally, and dielectric ally close to real brain tissues. “We’ve successfully altered the polymer, and now we don’t have to rely on the traditional freeze/thaw cycle required when using 3D embedded printing. We can use heat or UV light to crosslink our polymers to create these small-scale models. It’s a very materials-focused paper,” O’Bryan said.

Damon Coyle, a medical sculptor and innovation specialist at UM, who was not involved with the study, said, “I think it represents an important step forward in the manufacturing of soft tissue phantoms — devices used in my industry to teach interventional or diagnostic imaging systems in a repeatable environment.”

Coyle works in UM’s Russell D. and Mary B. Sheldon Clinical Simulation Center, where his work centers on creating lifelike training devices for medical professionals. He’s made hundreds of training organs and body parts, typically sculpted from materials such as silicone and rubber. “Traditionally, soft tissue models are poured into molds, which means they look right on the outside but are pretty uniform inside. Dr O’Bryan’s approach allows researchers to actually ‘build’ internal varied structure directly into soft tissue analogues,” Coyle said.

What Comes Next?

One problem the researchers want to explore is the shelf life of the materials they are using to print their models vs other commercially available alternatives.

“There’s always a trade-off,” O’Bryan said. For example, he explained that polymers made from agars and gelatins are “incredibly biocompatible” and are used to 3D print biomaterials because they mimic a lot of the material behavior of tissues and organs. “But they’re also incredibly susceptible to contamination, which leads to a shorter shelf life. So, then you can move to synthetic, oil-based materials, which won’t facilitate the growth of fungi, bacteria, or contaminants. But you lose a lot of the aqueous-based properties that you get from hydrogels and biopolymers,” O’Bryan said.

Because of these issues, a lot of researchers will focus on just getting one thing right in their models — either the mechanical performance, the thermal performance, or the dielectric properties. “What we’re trying to do is find a polymer system that lets us get close with all three and then apply it to the embedded 3D printing method to fabricate hydrogel structures from that polymer that closely match actual [brain] tissue,” O’Bryan said.

The researchers also plan to start capturing different structural behaviors by experimenting with combination s of materials for the bioink. “We want to print these polymers in a liquid phase and do multi-material different stiffnesses, and then crosslink it all at once using covalent crosslinking chemistry,” O’Bryan said.

Coyle said how the materials hold up outside the lab will be an important issue to address. “Hydrogels are inherently water-rich materials, which means durability, storage stability, and lifespan become real considerations outside of a controlled lab setting,” he said.

One Day…

One of the goals of the authors’ future research is to build test beds that allow the engineers to validate their computational models, O’Bryan said.

They also hope their findings may eventually give a boost to personalized medicine, where physicians could create a 3D printed model from a patient’s MRI or CT scan and use the model to practice surgery. And to better understand the brains of individuals with conditions like Alzheimer’s or traumatic brain injury.

Coyle said there are practical considerations to be made, as well. “From a clinical simulation center perspective, we also think about scalability and cost — how quickly something can be produced, how consistently it performs, and whether it’s affordable enough for repeated training use,” he said. “So while this work expands what’s technically possible, the real test will be how it performs when subjected to the demands of everyday medical education and device validation environments.”

This research was sponsored by the Army Research Laboratory. The authors declared having no competing financial interests or personal relationships that could have appeared to influence the work reported in the manuscript.