LAB-GROWN CARTILAGE
Researchers have developed a new technique and platform that drive cells to cartilage formation and may lead to new treatments for osteoarthritis.
Written by Claudia Hoffacker
IF YOU OR SOMEONE YOU KNOW HAS OSTEOARTHRITIS, you know how painful and frustrating it can be—and how limited treatment options are. Researchers at Boise State University College of Engineering have conducted a series of tissue engineering studies that may lead to more advanced treatments leveraging lab-grown cartilage.
The researchers used a three-dimensional biocompatible form of carbon called graphene foam to develop a new technique and platform to communicate with cells and help drive them toward cartilage formation.
“The human body provides chemical, electrical, and mechanical signals to cells as they develop, but mimicking these signals in the lab to guide cell behavior toward functional tissue outcomes remains a major challenge,” said Mone’t Sawyer, who as a graduate student at Boise State was the lead author of the study, recently published in American Chemical Society’s Applied Materials and Interfaces. “The goal of this work was to gain a fundamental understanding of how electrical signals influence cell behavior by creating a system that allows for high-throughput studies that are both controlled and repeatable.”
Osteoarthritis is driven by the irreversible degradation of hyaline cartilage in the joints. It is the leading cause of pain and disability, currently affecting over 595 million people around the world. Global costs of the condition exceed $460 billion annually, including healthcare expenses, lost productivity, and disability-related expenses. For late-stage osteoarthritis, the standard clinical treatment is complete or partial joint replacement.
“There’s no cure for osteoarthritis,” Sawyer said. “So, that’s the motivation behind tissue engineering and the work that we do in our group.”
“At the most basic level, this work was designed to probe the fundamental interactions between pluripotent cells and electrical signals,” said David Estrada, professor at Boise State’s Micron School of Materials Science and Engineering. “We set out to show that electrical stimulus of cells can impact their fate through different signaling pathways, and found that we needed to create novel bioreactors and e-stim protocols to reliably apply such signals to cells in a controlled and repeatable manner.”
“It’s a really lengthy process between realizing that you can use this material and then using it for clinical applications. We’re hoping that our work is one of the big steps along the way to doing that.”
—Mone’t Sawyer, a doctoral student at Boise State University
Using custom designed and 3D printed bioreactors with electrical feedthroughs, researchers were able to deliver brief daily electrical impulses to cells being cultured on 3D graphene foam. They found that applying direct electrical stimulation to ATDC5 cells that are adhered to the 3D graphene foam bioscaffolds significantly strengthens their mechanical properties and improves cell growth. These are key metrics for achieving lab-grown cartilage.
The researchers used graphene foam because it has unique properties, such as mechanical strength and electrical conductivity. This makes it a strong candidate for providing a robust microenvironment for cell growth while also serving as an electrode to supply direct electrical signals.
However, graphene foam is also hydrophobic, which limits cell migration into its 3D structure. “To address that, we developed additively manufactured e-stim bioreactors that facilitate a direct electrode connection to graphene foam while keeping it fully submerged in media throughout the culture period,” Sawyer said.
The devices overcame the foam’s hydrophobic limitations, resulting in twice the cell volume and 13 times the cell connectivity, as measured by microcomputed tomography.
“To our knowledge, this is the first e-stim bioreactor that directly couples to a conductive bioscaffold,” she added. It’s also the only system that works with standard 24-well plates, which are found in almost every lab. So, no special infrastructure is needed.
Mone’t Sawyer explained that the goal of this work was to gain a fundamental understanding of how electrical signals influence cell behavior by creating a system that allows for high-throughput studies that are both controlled and repeatable. Photo: Boise State University
But the most unique aspect is the ability to monitor stimulation in real time, Sawyer said. “In 2D cultures, it’s possible to model what electric fields cells are exposed to. But in 3D systems, those models fall apart because the scaffold’s conductivity changes how the signal propagates,” she continued. “In our system, we don’t need to guess; we can measure exactly what the cells are experiencing on the graphene foam.”
The study showed that you can use electrical signals to modulate the viscoelastic properties of the graphene foam-cell constructs by influencing both proliferation and extracellular matrix production. “That’s a big deal when you’re engineering tissues for load-bearing joints like the knee,” Sawyer said.
The researchers used just one frequency and three amplitudes. Now that they’ve validated the system, they can tune the inputs to drive other outcomes, bringing them closer to replicating what the body does.
“Even though we focused on cartilage tissue engineering, this platform has implications far beyond that,” Sawyer said. “Cardiac, muscle, neural, and bone tissues are all electroactive, and the same limitations around tracking how cells respond to electrical input exist in those systems, too. Our devices open up high-throughput experimentation that can help bridge those gaps.”
This image illustrates the growth of ATDC5 cells on 3D graphene foam bioscaffolds for tissue engineering applications. Photo: Ella Maru Studios/Boise State University
While the study is a big breakthrough for cartilage tissue engineering, the discoveries did not come easily. Sawyer and her team have been working on this for over five years, and she plans to continue the work as a post-doctoral research fellow at Boise State. She hopes to “make it more translatable to humans” and continue moving closer to clinical applications.
“In our work, we won’t be using animal models or doing any human studies, but the goal would be for us to create a platform that other researchers could use to get closer to actually using these materials in the human body,” Sawyer said. “It’s a really lengthy process between realizing that you can use this material and then using it for clinical applications. We’re hoping that our work is one of the big steps along the way to doing that.”
Sawyer, who earned her bachelor’s degree in material science engineering and her doctorate in biomedical engineering, said she enjoys being able to combine the two disciplines in her work. “I really believe that the cure for a lot of things lies at the intersection of biology and engineering, where we can engineer better and smarter materials to work better and smarter for the body,” she said. “Being at the forefront of something like that is really exciting.”
Claudia Hoffacker is an independent writer in Minneapolis.
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