Biomaterials
healing. To get the tissue to repair itself, you need to figure out how to stimulate growth within that complex biological environment.
Researchers are investigating how biomaterials could be used to help here. Not only are these materials biocompatible, but they can be engineered to provide cues that could promote repair. Plus, their properties can be tailored depending on how the material is to be used – for instance, if it needs to be injected via a syringe – or what it needs to facilitate, such as passing electric signals across injured tissue to stimulate regrowth of nerve fibres (axons).
“What we’re trying to do is focus on how we can make the body regenerate itself,” says Aleksandra Serafin, postdoctoral fellow at the University of Limerick, who worked on developing a new biomaterial for spinal cord repair for her PhD research. “Can we promote axons to keep on regrowing, to have these connections established again? And getting around the glial scar and all the inflammation. It’s actually incredibly difficult.” Yet labs around the world are rising to the challenge. “There are so many materials that are being tried and tested,” Serafin says. “The field right now is booming.”
Conductive scaffolds
One approach is using electroconductive scaffolds to induce repair. The spinal cord is naturally conductive and passes on messages – i.e. electrical signals, between the body and the brain. If the tissue is injured, this ability is impaired or completely blocked. Here, scaffolds can be thought of as a kind of bridge: they’re materials that provide a framework for tissue growth. In this case, they facilitate transmission of signals over the ‘gap’ created by the injury, to help re-establish those damaged pathways. It’s a strategy that shows promise.
Electroconductive hydrogel scaffolds have been found to promote regeneration of axons both in the lab and animal models, for instance. In 2021 research published in the journal Neural Regeneration Research, describe how their scaffold fabricated with graphene oxide and chitosan, a sugar found naturally in the outer skeleton of shellfish, promoted growth of nerve cells, the formation of new blood vessels, neuron migration and neural tissue regeneration in rats. To increase the conductivity of their biomaterials, people often add components like carbon nanofibres or conductive polymers, Serafin explains. But during her PhD research, she found that a lot of these commonly used polymers didn’t degrade well within the body – which could potentially bring on toxicity. “Sometimes the carbon nanofibres can end up in the liver or kidneys, because the body doesn’t really know how to get rid of them,” she says.
The researchers then set out to create a new biomaterial that retained its conductive properties while being biodegradable. They started with the PEDOT:PSS, a commercially available polymer that’s used in tissue engineering. The PSS component is what makes the polymer soluble, but it also shows poor biocompatibility once implanted – meaning it could potentially bring on a toxic response in already- damaged tissue. Via a miniemulsion technique using a surfactant, the team was able to create novel PEDOT nanoparticles without the PSS component. These nanoparticles were then incorporated with gelatin and hyaluronic acid to create a scaffold. So far, the material has been tested in stem cells and rats that had undergone a complete spinal cord injury at the T3 level. Due to time constraints, the rats could only be observed for a month – but the researchers did see some progress.
“Can we promote axons to keep on regrowing, to have these connections established again?”
Aleksandra Serafi n, University of Limerick
The protein GFAP is used as a biomarker for the severity and extent of recovery following spinal cord injury. In rats treated with the material, there was diminished GFAP activity and less scarring present, Serafin shares. “The second thing we’ve seen is that we had more axons growing into the lesion site in our group rather than the control group… and the third thing was that there were less inflammatory responses happening in the scaffold group.” These results demonstrate early signs of regeneration, but we don’t yet know the extent to which the material could reverse an injury nor whether any motor function would be restored. The same might be said about the approach more broadly – some studies on electroconductive scaffolds have shown signs of tissue repair, but we can’t yet say what outcomes those effects could lead to. “All of it is quite in its infancy,” says Serafin. “There’s still a lot of unknowns in the field at the moment.”
Repair cues
Biomaterials can also be used to provide cues or information that would prompt cells to engage in repair activities. That’s what the lab of Tim O’Shea, assistant professor of biomedical engineering at Boston University, is currently investigating. “We’re really interested in astrocytes,” he explains. “For us, the astrocyte is the main cell that’s enabling the repair process to take place.” Astrocytes are the predominant type of glial cell – cells that maintain the viability of connections
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