Thursday, October 11, 2018

Pulses of Electrical Stimulation from Implantable, Biodegradable Device Help Heal Injured Nerves

Researchers at Northwestern University and Washington University School of Medicine in St. Louis have developed the first example of a bioresorbable electronic medicine: an implantable, biodegradable wireless device that speeds nerve regeneration and improves the healing of a damaged nerve.

The collaborators -- materials scientists and engineers at Northwestern and neurosurgeons at Washington University -- developed a device that delivers regular pulses of electricity to damaged peripheral nerves in rats after a surgical repair process, accelerating the regrowth of nerves in their legs and enhancing the ultimate recovery of muscle strength and control. The size of a dime and the thickness of a sheet of paper, the wireless device operates for about two weeks before naturally absorbing into the body.

Peripheral nerve injuries leave people with tingling, numbness and weakness in their arms, hands and legs. Researchers at Washington University School of Medicine in St. Louis and Northwestern have developed an implantable, bioabsorbable device that speeds recovery in rats by stimulating injured nerves with electricity. The device degrades in a few weeks when exposed to saltwater, which mimics bodily fluids, as shown above (top left, device before immersion; top right, 10 days after immersion; bottom left, 15 days; bottom right, 25 days).

Credit: Matthew Macewan/Mike Worful

Car accidents, sports injuries, even too much typing and texting can injure the peripheral nerves, leaving people with numbness, tingling and weakness in their hands, arms or legs. Recovery can take months, and doctors have little to offer to speed it along.

Now, researchers at Washington University School of Medicine in St. Louis and Northwestern University have developed an implantable, biodegradable device that delivers regular pulses of electricity to damaged peripheral nerves in rats, helping the animals regrow nerves in their legs and recover their nerve function and muscle strength more quickly. The size of a quarter, the device lasts about two weeks before being completely absorbed into the body.

The findings are published Oct. 8 in Nature Medicine.

For most people with peripheral nerve injuries, doctors suggest painkillers such as aspirin and physical therapy. Severe cases may require surgery, and standard practice is to administer some electrical stimulation to the injured nerves during the surgery to aid recovery.

“We know that electrical stimulation during surgery helps, but once the surgery is over, the window for intervening is closed,” said co-senior author Wilson “Zack” Ray, MD, an associate professor of neurosurgery, of biomedical engineering and of orthopedic surgery at Washington University. “With this device, we’ve shown that electrical stimulation given on a scheduled basis can further enhance nerve recovery.”

Unlike neurons in the brain and spinal cord, the peripheral nerves that run through the arms, legs and torso can regenerate after injury. Electrical stimulation triggers the release of growth-promoting proteins, boosting nerve cells’ natural abilities and helping them regrow faster and more completely.

But until now, doctors have lacked a means to continuously provide that added boost.

Co-senior author John Rogers, PhD, of Northwestern, and colleagues designed and developed a device that wraps around an injured nerve and delivers electrical pulses for days before the device harmlessly degrades in the body. The device is powered wirelessly by a transmitter outside the body that acts much like a cell phone charging mat.

An bioresorbable electronic device degrades upon exposure to saltwater. Researchers can fine-tune the device’s chemical components to dissolve in seconds, as in the video above, or in weeks, as in the devices used to enhance nerve regeneration in rats. 
Credit: J. Rogers/Northwestern

“These platforms represent the first examples of a ‘bioresorbable electronic medicine’ – engineered systems that provide active, therapeutic function in a programmable, dosed format and then naturally disappear into the body, without a trace,” Rogers said. “In the case reported here, we built bioresorbable electronic devices that support unique function relevant to recovery from damage to a peripheral nerve, via electrical stimulation at select time points during the healing process.”

The researchers studied rats with injured sciatic nerves. This nerve sends signals up and down the legs and controls the hamstrings and muscles of the lower legs and feet. They used the device to provide one hour per day of electrical stimulation to the rats for one, three or six days, or no electrical stimulation at all, and then monitored their recovery for the next 10 weeks. Any electrical stimulation was better than none at all at helping the rats recover muscle mass and muscle strength. In addition, the more days of electrical stimulation the rats received, the more quickly and thoroughly they recovered nerve signaling and muscle strength.

“Before we did this study, we weren’t sure that longer stimulation would make a difference, and now that we know it does we can start trying to find the ideal time frame to maximize recovery,” Ray said. “Had we delivered electrical stimulation for 12 days instead of six, would there have been more therapeutic benefit? Maybe. We’re looking into that now.”

By varying the composition and thickness of the materials in the device, Rogers and colleagues can control the precise number of days it lasts before disintegrating. They are working now on creating new versions that can provide electrical pulses for weeks before degrading.

“There really are no therapeutic options for some of these nerve injury patients,” Ray said. “This isn’t a therapeutic option yet either, as it hasn’t been tested in people. But I’m excited about it because it’s a new approach to treating peripheral nerve injury, and it might offer a solution where really there is none today in the clinical realm.” 



The scientists envision that such transient engineered technologies one day could complement or replace pharmaceutical treatments for a variety of medical conditions in humans. This type of technology, which the researchers refer to as a “bioresorbable electronic medicine,” provides therapy and treatment over a clinically relevant period of time and directly at the site where it’s needed, thereby reducing side effects or risks associated with conventional, permanent implants.

“These engineered systems provide active, therapeutic function in a programmable, dosed format and then naturally disappear into the body, without a trace,” said Northwestern’s John A. Rogers, a pioneer in bio-integrated technologies and a co-senior author of the study. “This approach to therapy allows one to think about options that go beyond drugs and chemistry.”

Rogers is the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery in the McCormick School of Engineering and Northwestern University Feinberg School of Medicine.

Koo J, MacEwan MR, Kang SK, Won SM, Stephen M, Gamble P, Xie Z, Yan Y, Chen YY, Shin J, Birenbaum N, Chung S, Kim SB, Khalifeh J, Harburg DV, Bean K, Paskett M, Kim J, Zohny ZS, Lee SM, Zhang R, Luo K, Ji B, Banks A, Lee HM, Huang Y, Ray WZ, Rogers JA. Wireless bioresorbable electronic system enables sustained non-pharmacological neuroregenerative therapy. Nature Medicine. Oct. 8, 2018. DOI: 10.1038/s41591-018-0196-2

This study was supported by the National Research Foundation of Korea, grant numbers NRF-2018R1C1B5043901 and 2011-0028612; the National Natural Science Foundation of China, grant number 11402134; National Science Foundation, grant numbers 1400169, 1534120, and 1635443; the Defense Advanced Research Projects Agency; and the Center for Bio-Integrated Electronics at Northwestern University.





Contacts and sources:
Tamara Bhandari
Washington University School of Medicine

Megan Fellman
Northwestern University


Citation: Wireless bioresorbable electronic system enables sustained nonpharmacological neuroregenerative therapy
Jahyun Koo, Matthew R. MacEwan, Seung-Kyun Kang, Sang Min Won, Manu Stephen, Paul Gamble, Zhaoqian Xie, Ying Yan, Yu-Yu Chen, Jiho Shin, Nathan Birenbaum, Sangjin Chung, Sung Bong Kim, Jawad Khalifeh, Daniel V. Harburg, Kelsey Bean, Michael Paskett, Jeonghyun Kim, Zohny S. Zohny, Seung Min Lee, Ruoyao Zhang, Kaijing Luo, Bowen Ji, Anthony Banks, Hyuck Mo Lee, Younggang Huang, Wilson Z. Ray, John A. Rogers.. Nature Medicine, 2018; DOI: 10.1038/s41591-018-0196-2

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