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Researchers have produced some “electrifying” results in a new study examining how graphene foam can help to construct better lab-grown cartilage tissue for osteoarthritis treatment.
The study, published in ACS Applied Materials & Interfaces, used graphene foam as an electrically-conductive three-dimensional (3D) bioscaffold on which progenitor cells could be grown while receiving direct electrical stimulation. The researchers found that this stimulation increased the mechanical strength of the resultant graphene foam–cell constructs. The graphene foam bioscaffolds also enabled complete immersion of the construct in cell growth media, improving cell interconnectivity.
To learn more about this research, how these findings could shine a light on broader questions about cell signaling and what it could mean for osteoarthritis treatment, Technology Networks spoke with senior study author David Estrada, PhD, a professor of materials science and engineering at Boise State University.
Alexander Beadle (AB):
Science Writer & Editor
Technology Networks
Alexander Beadle is a science writer and editor for Technology Networks. He holds a masters degree in Materials Chemistry from the University of St Andrews, Scotland.
Can you tell us a little more about osteoarthritis and the different treatment options that are currently available/being investigated for patients?
Professor of Materials Science and Engineering
Boise State University
David Estrada is a professor of materials science and engineering at Boise State University, where he serves as the site director for the National Science Foundation's ATOMIC Center, as well as the associate director for the Center for Advanced Energy Studies. He holds a joint appointment with the Idaho National Laboratory in advanced manufacturing.
Estrada received his doctorate from the University of Illinois at Urbana-Champaign in electrical and computer engineering, where he studied electrical and thermal transport in emerging nanomaterials and semiconductor devices. He is a recipient of the National Science Foundation’s Graduate Research Fellowship, the National Science Foundation’s CAREER Award and the Presidential Early Career Award for Scientists and Engineers, nominated through the National Aeronautics and Space Administration for his work related to in-space manufacturing. His research focuses on two-dimensional materials and their intersections with advanced manufacturing techniques that have applications in energy, healthcare and the environment.
Osteoarthritis is a degenerative joint disease where the articular cartilage of joints and the underlying bone degrade over time, for example, in your knees and hips. It can lead to increased pain, loss of mobility and disability.
Common treatments range from weight loss, prosthetic support devices, pain management with medication, site injection of stem cells and most commonly for severe cases, total joint replacement surgery.
Science Writer & Editor
Technology Networks
Alexander Beadle is a science writer and editor for Technology Networks. He holds a masters degree in Materials Chemistry from the University of St Andrews, Scotland.
What are the major challenges relating to engineered cartilage materials?
Professor of Materials Science and Engineering
Boise State University
David Estrada is a professor of materials science and engineering at Boise State University, where he serves as the site director for the National Science Foundation's ATOMIC Center, as well as the associate director for the Center for Advanced Energy Studies. He holds a joint appointment with the Idaho National Laboratory in advanced manufacturing.
Estrada received his doctorate from the University of Illinois at Urbana-Champaign in electrical and computer engineering, where he studied electrical and thermal transport in emerging nanomaterials and semiconductor devices. He is a recipient of the National Science Foundation’s Graduate Research Fellowship, the National Science Foundation’s CAREER Award and the Presidential Early Career Award for Scientists and Engineers, nominated through the National Aeronautics and Space Administration for his work related to in-space manufacturing. His research focuses on two-dimensional materials and their intersections with advanced manufacturing techniques that have applications in energy, healthcare and the environment.
In my opinion, the biggest challenge related to engineered cartilage materials is developing patient-specific tissues that have the correct zonal architecture and can form osteochondral junctions, allowing the cartilage to be inserted into the human body and fully integrated with the surrounding tissue and joint.
Osteochondral junctions
The interface between bone and cartilage in a joint. This area is crucial for proper joint function, as it facilitates frictionless movement and the transfer of load-bearing forces.
Doing this in a minimally invasive manner would have a tremendous impact on the more than 75 million individuals that are expected to suffer from osteoarthritis by 2040.
Science Writer & Editor
Technology Networks
Alexander Beadle is a science writer and editor for Technology Networks. He holds a masters degree in Materials Chemistry from the University of St Andrews, Scotland.
What is graphene foam and why is it such a promising bioscaffold material?
Professor of Materials Science and Engineering
Boise State University
David Estrada is a professor of materials science and engineering at Boise State University, where he serves as the site director for the National Science Foundation's ATOMIC Center, as well as the associate director for the Center for Advanced Energy Studies. He holds a joint appointment with the Idaho National Laboratory in advanced manufacturing.
Estrada received his doctorate from the University of Illinois at Urbana-Champaign in electrical and computer engineering, where he studied electrical and thermal transport in emerging nanomaterials and semiconductor devices. He is a recipient of the National Science Foundation’s Graduate Research Fellowship, the National Science Foundation’s CAREER Award and the Presidential Early Career Award for Scientists and Engineers, nominated through the National Aeronautics and Space Administration for his work related to in-space manufacturing. His research focuses on two-dimensional materials and their intersections with advanced manufacturing techniques that have applications in energy, healthcare and the environment.
Graphene foam is a carbon-based foam that is graphitic in nature, with an occasional region of true atomically thin graphene. It became popular in 2011 after a paper appeared in Nature Materials by Zongping Chen and Hui-Meng Cheng, who reported on its synthesis through chemical vapor deposition on nickel foam substrates and demonstrated its applications in flexible and stretchable sensors.
As a bioscaffold, graphene foam has several attractive features, including its carbon composition, biocompatibility and its 3D porous structure, which allows for nutrient delivery and waste removal. Of most interest to my team are its excellent mechanical and electrical properties, which can be tuned through the synthesis process. When it is seeded with cells, you now have an embedded electrode to directly apply voltage and/or current to the cells, allowing for fundamental investigations into the role of electrical stimulus and cell signaling pathways.
Science Writer & Editor
Technology Networks
Alexander Beadle is a science writer and editor for Technology Networks. He holds a masters degree in Materials Chemistry from the University of St Andrews, Scotland.
In this new study, you investigated the effects of applying direct electrical stimulation to progenitor cells on a graphene foam scaffold. What did you observe?
Professor of Materials Science and Engineering
Boise State University
David Estrada is a professor of materials science and engineering at Boise State University, where he serves as the site director for the National Science Foundation's ATOMIC Center, as well as the associate director for the Center for Advanced Energy Studies. He holds a joint appointment with the Idaho National Laboratory in advanced manufacturing.
Estrada received his doctorate from the University of Illinois at Urbana-Champaign in electrical and computer engineering, where he studied electrical and thermal transport in emerging nanomaterials and semiconductor devices. He is a recipient of the National Science Foundation’s Graduate Research Fellowship, the National Science Foundation’s CAREER Award and the Presidential Early Career Award for Scientists and Engineers, nominated through the National Aeronautics and Space Administration for his work related to in-space manufacturing. His research focuses on two-dimensional materials and their intersections with advanced manufacturing techniques that have applications in energy, healthcare and the environment.
We observed several interesting things in this study, but, most importantly, we noticed that by creating custom bioreactors for electrical stimulus through graphene foam, we were able to overcome the hydrophobic nature of the foam – fully submerging the scaffold in the media during culture – which led to a 13-fold increase in cell-cell interconnectivity. This is extremely important for cell-cell communication during both the proliferation and differentiation processes.
For one week, we applied electrical signals to the cells for five minutes a day and then passively cultured the cells for another week. We then measured the dynamic mechanical properties of the cell-graphene foam constructs and noticed that cells stimulated at 40 mV and 60 mV had increased proliferation and collagen type II production, which manifested in increased mechanical strength and energy dissipation as compared to our controls.
We are now digging deep into genomics and proteomics data to get a better understanding of the fundamental cell signaling pathways that were affected by direct electrical stimulus.
Science Writer & Editor
Technology Networks
Alexander Beadle is a science writer and editor for Technology Networks. He holds a masters degree in Materials Chemistry from the University of St Andrews, Scotland.
Were there any notable challenges you came across in developing this technique, and if so, how did you overcome them?
Professor of Materials Science and Engineering
Boise State University
David Estrada is a professor of materials science and engineering at Boise State University, where he serves as the site director for the National Science Foundation's ATOMIC Center, as well as the associate director for the Center for Advanced Energy Studies. He holds a joint appointment with the Idaho National Laboratory in advanced manufacturing.
Estrada received his doctorate from the University of Illinois at Urbana-Champaign in electrical and computer engineering, where he studied electrical and thermal transport in emerging nanomaterials and semiconductor devices. He is a recipient of the National Science Foundation’s Graduate Research Fellowship, the National Science Foundation’s CAREER Award and the Presidential Early Career Award for Scientists and Engineers, nominated through the National Aeronautics and Space Administration for his work related to in-space manufacturing. His research focuses on two-dimensional materials and their intersections with advanced manufacturing techniques that have applications in energy, healthcare and the environment.
Global pandemics aside, there were many challenges that we faced. First and foremost was imaging the cells on the graphene foam using standard confocal fluorescence. Since graphene foam is opaque in the visible spectrum, getting light out of the scaffold from cells that were more than 50 μm deep into the foam proved problematic. This was overcome by using a new staining protocol that combined fluorophores with gold nanoparticles, allowing us to use X-ray imaging via micro-computed tomography to understand how cells were proliferating across – and within – the graphene foam branches. This resulted in a separate publication detailing that technique.
Secondly, was how to reliably apply the electrical signals in a manner that allowed for consistent delivery of the target voltages. We used 3D printing to design our own bioreactors that were compatible with our tissue culture protocols and enabled direct electrical connections to the graphene foam for electrical stimulus. After some modifications, our approach proved to be scalable and compatible with existing tissue cultureware and with electrical multiplexing forming the basis of a provisional patent for our e-stim chambers. Only after overcoming these challenges were we able to get to the fundamental study on the electrical stimulus and the impact on the mechanical performance of our cell-graphene foam constructs.
Science Writer & Editor
Technology Networks
Alexander Beadle is a science writer and editor for Technology Networks. He holds a masters degree in Materials Chemistry from the University of St Andrews, Scotland.
What do you believe to be the future impact of this research?
Professor of Materials Science and Engineering
Boise State University
David Estrada is a professor of materials science and engineering at Boise State University, where he serves as the site director for the National Science Foundation's ATOMIC Center, as well as the associate director for the Center for Advanced Energy Studies. He holds a joint appointment with the Idaho National Laboratory in advanced manufacturing.
Estrada received his doctorate from the University of Illinois at Urbana-Champaign in electrical and computer engineering, where he studied electrical and thermal transport in emerging nanomaterials and semiconductor devices. He is a recipient of the National Science Foundation’s Graduate Research Fellowship, the National Science Foundation’s CAREER Award and the Presidential Early Career Award for Scientists and Engineers, nominated through the National Aeronautics and Space Administration for his work related to in-space manufacturing. His research focuses on two-dimensional materials and their intersections with advanced manufacturing techniques that have applications in energy, healthcare and the environment.
If we can understand the fundamental impact of electrical stimulus on cell signaling pathways, this not only opens the door to creating patient-specific cartilage implants, but will also broaden our knowledge of how cells communicate electrically to determine their fate in tissue formation.
The human body is incredibly complex, and while recent foci on the human microbiome have led to new insights on gut health, immune system development and more, comparatively very little attention has been given to the human electrobiome. If we can understand the molecular mechanisms of charge transport at the cellular level, then I think we will be well-positioned to further connect these findings with the electrical systems of the human body, which impact everything from signal transmission, cellular development, vision and even consciousness itself.
