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A New Pathway to Pain Relief

 
An injectable neural stimulation electrode shows promise in treating a variety of conditions.
 

“If we can get the Injectrode into outpatient procedures, performed by pain physicians instead of neurosurgeons, then it would vastly expand the use of electrical stimulation.” 

– Andrew Shoffstall
Assistant Professor of Biomedical Engineering
Case Western Reserve University
Investigator, APT and FES Centers
Cleveland VA Medical Center

 

The lifetime prevalence of back pain in the United States is approximately 80%, according to the Cleveland Clinic. Low back pain is also one of the leading causes of disability and one of the most common ailments treated with opioids. A team of researchers from across the country, including Andrew Shoffstall at Case Western Reserve University, has created a novel injectable metal electrode that could provide an alternative to traditional drug therapy or surgically-implanted devices for back pain – and a host of other medical issues.

The Injectrode™ is a liquid composite mixture consisting of tiny metal particles mixed with a silicone base similar to surgical glue. When injected, the silicone cures inside the body and molds to the shape of the specific target.

Last fall, collaborators on the Injectrode project received a $2.2 million grant from the National Institutes of Health (NIH) as part of its HEAL Initiative (Helping to End Addiction Long-termSM), which is focused on improving prevention and treatment for opioid misuse and addiction and enhancing pain management. The team of researchers will test the Injectrode at the dorsal root ganglion, stimulating the target to alleviate pain.


Andrew Shoffstall works with PhD candidate, Kevin Yang on the insertion site for the injectrode using a model of the sacrum.

“The spinal cord is a great potential test bed for this technology,” says Shoffstall, assistant professor of biomedical engineering at Case Western Reserve University. One of his primary partners on the project is Manfred Franke, who earned his PhD in biomedical engineering at the university in 2014. Together with Kip Ludwig, associate professor at the University of Wisconsin, Franke and Shoffstall co-founded Neuronoff Inc. in 2017 to develop medical devices such as the Injectrode. The company now has its R&D arm at the BioEnterprise building at the intersection of Case Western Reserve University and the Cleveland Clinic.

We hope the NIH grant will prove out, with data, how clinicians can use the Injectrode most effectively to stimulate the dorsal root ganglion or nearby structures to suppress pain and do the entire placement procedure in a much faster, easier way than [neuromodulation] is currently done,” says Franke.

Partnering as PhD Students

In 2009, Shoffstall and Franke first met as graduate students at Case Western Reserve University who shared a curiosity about neuromodulation. Shoffstall worked in the labs of Associate Professor Erin Lavik, now the Associate Dean for Research and Faculty Development at the University of Maryland, Baltimore County. “Her work fused the two areas I have an interest in – biomaterials and neural engineering,” says Shoffstall. As a doctoral candidate, his work focused on creating synthetic platelets that could be injected into the bloodstream at sites of injury to stop bleeding after a spinal cord injury or traumatic brain injury.

Franke chose Case Western Reserve University for grad school because of its strong history and reputation as a leader in biomedical engineering. “Case Western is the cradle of neuromodulation,” he says. “Going back to the 1960s with work by Thomas Mortimer [professor emeritus] and others, the university has been on the leading edge of developing neuromodulation treatments for a variety of medical conditions.”

During his time at the university, Franke learned to push the boundaries of neuromodulation alongside innovators such as Dustin Tyler, Kent H. Smith Professor II of Biomedical Engineering, and Kenneth Gustafson, associate professor. “You can do so much with neuromodulation, but very few people truly appreciate and understand it because they don’t think beyond the possible,” says Franke. 

Franke certainly tests the limits of what’s possible: He began filing patents related to neuromodulation technology (currently at 45 granted and counting) in 2012 and earned the Doctoral Excellence Award in Biomedical Engineering in 2014. After surgical training to implant traditional electrodes while at the Case Neural Engineering Center and a stint with a neuromodulation company between 2013 and 2016, Franke conceived of the Injectrode in late 2016 to simplify the process of reaching nerves electrically. Teaming with Shoffstall, whose lab at Case Western Reserve University focuses on the interface of biomaterials with the nervous system, was a natural fit.

Refining the Materials and Delivery Methods 

The Injectrode researchers are developing and studying both the biomaterial – what they informally call the “goop” – as well as surgical targeting techniques to guide the liquid to the right spot. 


The Injectrode™ is a liquid composite mixture consisting of tiny metal particles mixed with a silicone base similar to surgical glue. When injected, the silicone cures inside the body and molds to the shape of the specific target.

“The composite goop has the consistency of Play-Doh™ and gets extruded out of the syringe when it’s injected,” says Shoffstall. Once injected, it cures to form a highly-conforming, compliant neural electrode in vivo. 

The team has tested material mixtures with various amounts of metal particles (such as silver and gold) and different commonly used surgical glues and sealants approved by the Federal Drug Administration to ascertain the percolation threshold. “We dope the material with a high enough field of particles to achieve percolation,” says Shoffstall. “The metal flakes or spheres bridge electrical signals from one side of the composite to another.” 

At that point, you have a fully-implanted passive conductor – the Injectrode – inside the body extending from the target nerve to approximately one to three millimeters from the surface of the skin. “In some cases, we have been able to pair the Injectrode with a transcutaneous electric nerve stimulation (TENS) unit, which is a standard, inexpensive device, to provide neuromodulation for that nerve,” says Franke.

Neuronoff – a word play on the idea of turning neural systems “on” and “off” – is focused on clinical translation of the minimum viable product. “With the Injectrode, we take all the know-how from 50-plus years of work on electrical stimulation done at Case and bring it to a minimally-invasive level that can be easily commercialized,” says Franke.  

Neuronoff’s role in the NIH HEAL grant is to supply Injectrode devices and electrodes to the researchers, while Shoffstall’s lab conducts material analysis and biocompatibility testing. Other collaborators include Doug Weber from the University of Pittsburgh and Scott Lempka, who earned his PhD from Case Western Reserve University and is now at the University of Michigan, who are conducting in vivo biologic studies and simulations for injection and stimulation parameter optimization.

Creating the ‘Last-Mile’ Interface

The Injectrode has many potential benefits. It is less invasive than other implanted neural stimulation devices, and it is more targeted than drug therapies. “Even though medications are less invasive than cutting someone open for surgery, those drugs circulate through your entire bloodstream and touch every cell and organ in your body,” says Shoffstall.

The Injectrode can also conform to a variety of targets to form different neural interfaces. For instance, it can stimulate complex neural structures – such as networks of intersecting nerves – that can be difficult to target with traditional cuff electrodes. “There are areas you can’t interface with today, such as thin fibers in your gut area or near organs, but you can glue some goop to those nerves,” says Franke. “That allows researchers and clinicians to think about new ways of treating conditions because the Injectrode provides this last-mile interface.”

While the NIH HEAL grant focuses on treating low back pain, the Injectrode has potential for multiple indications, including post-amputation neuropathic pain, migraine, overactive bladder, epileptic seizures and sciatic pain. “We want to demonstrate that the Injectrode works in one thing first – chronic back pain,” says Shoffstall. “But as we build out the tools, get more comfortable with the biomaterials and get more data, then we can start testing the Injectrode in a variety of places.” 

That, in turn, would open up opportunities to move neuromodulation beyond usage by a small group of highly-trained neurosurgeons. “They are the specialized of the specialized,” says Shoffstall. “If we can get the Injectrode into outpatient procedures, performed by pain physicians instead of neurosurgeons, then it would vastly expand the use of electrical stimulation.”