The team’s fabricated gauze comprises two click-activated hydrogel layers and an inner-section which can be loaded with regenerative medicine. Once wrapped around the site of an injured nerve, the device releases the medication in a way that encourages the growth of glial cells in the Peripheral Nervous System (PNS).
In the future, the scientists believe that their novel 3D printed dressing design, could assist doctors while they carry out widely-used nerve repair operations such as neurorrhaphy.
New treatments for nerve traumas
It’s possible to injure a peripheral nerve in a variety of ways, ranging from sporting incidents to illnesses such as tumors, but they are almost always followed by a loss of sensory function in the affected area. Although the PNS has regenerative capabilities and is able to heal itself in certain situations, this is highly dependent on the size and scale of the injury.
In some cases, neurorrhaphy (a specialized surgery) has to be deployed to stitch the nerves together, but according to research from the US Air Force, only 50 percent of the treatments are successful. To make the procedure more effective, a number of scientists are currently working on ways of creating a more favorable environment, promoting cell growth, and eliciting a more active response.
In 2019 another team from Sichuan University incorporated PNS drugs into Nerve Guidance Scaffolds (NGS’) designed to be released near the site of an injured nerve. The problem with scaffold-based methods is that they’re often inaccurate, causing the medication to leak into surrounding tissues, and running the risk of side effects.
In addition to being leaky, NGS’ can be tricky to install, which is not ideal for use around delicate nerve endings, which need to be treated carefully to avoid further damage. 3D printing technology, meanwhile, has shown great potential for creating NGS’ that can be pre-loaded with drugs and released in situ at the site of the injury.
Building on this drug-infused additive manufacturing approach, the team set about fabricating their own biodegradable nerve-healing solution.
The scientists’ ‘clickable’ 3D printed bandages
To create their self-adhesive bandages, the researchers polymerized a set of clickable functionalized monomers into rectangles using a Digital Light Processing (DLP) 3D printer. For the second layer of each structure, a different ink was deployed which contained XMU-MP-1 nanoparticles, a drug used to encourage protein and cell growth in patients.
After rolling and self-adhering, the gauze became a wrap shape with layer thicknesses of 139 µm for the drug-loaded ‘grated’ side, and 110 µm on the polymer side. In order to verify the in vivo healing capabilities of their bandage, the team proceeded to carry out a series of biocompatibility tests.
Initial evaluations saw the additive wound dressing exposed to ‘Schwann’ cells, which are generally critical to keeping nerve fibers alive in the PNS. Results showed that the team’s 3D printed gauze hadn’t impacted negatively on cell viability, while drug release analyses revealed that within ten hours, the hydrogel had dissolved.
During the next phase of testing, the bandages were injected into the back of lab rats, and observed over the course of 15 weeks. The implants caused no visual inflammation and exhibited good biocompatibility, proving that the devices are capable of being used in vivo, without leading to irritation or body rejection.
This was followed by in-vivo surgery on the rats’ sciatic nerves, during which, the surface tension of the team’s 3D-printed hydrogel bandage enabled it to roll around and adhere to the affected area. Three months later, the researchers re-opened the wounds and found that the nerve was fully healed, and their device had been central to its recovery.
Having proved during testing that their additive dressing could deploy its drug payload without damaging nearby tissues, the team considered their approach to be a success. With further research and optimization, the scientists hope that their bandage can either be used within existing surgeries or develop novel biomaterials for nerve repair.
3D printing and repairing the nervous system
Using additive manufacturing to aid nerve cell repair isn’t a novel concept in itself, and a number of researchers have applied the technology in this way in recent years.
Scientists from the Canadian University of Saskatchewan, have developed 3D printed tissue scaffolds that could be used to treat damaged peripheral nerves. The bioprinted scaffolds proved to be more mechanically stable than previous hydrogels and showed greater cell viability too.
Similarly, researchers at Kyoto University in Japan, have devised an innovative method of 3D printing regenerative nerve tissues. By fabricating the cells inside a ‘needle array,’ the team was able to inject them directly into the site of the injury.
Elsewhere, scientists at the University of Wollongong, Australia, have successfully 3D printed nerve cells that are usually found in the brain. According to the researchers, their work could represent an important first step towards the creation of synthetic tissues for treating various mental illnesses.
The researchers’ findings are detailed in their paper titled “A 3D-Printed Self-Adhesive Bandage with Drug Release for Peripheral Nerve Repair.” The study was co-authored by Jiumeng Zhang, Yuwen Chen, Yulan Huang, Wenbi Wu, Xianming Deng, Haofan Liu, Rong Li, Jie Tao, Xiang Li, Xuesong Liu, and Maling Gou.
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Featured image shows the polymer-coated hydrogel enclosed within the team’s 3D printed bandages. Image via Advanced Science journal.