A Kinder, Gentler Implant

For a neuroprosthetic device to deliver lasting treatment to an injured nervous system, it has to integrate seamlessly with the surrounding tissue and avoid rejection by the immune system. Researchers led by Grégoire Courtine and Stéphanie Lacour at the Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland, have designed an inert silicone-based neural implant they claim mimics the elasticity of the dura mater that cradles and protects the brain and spinal cord. Called the electronic dura mater, or e-dura, this device stretches and bends as much as its namesake, meaning it moves along with the neural tissue, rather than scraping and sliding against it. Various embedded components allow the e-dura to transmit electric signals and deliver chemical compounds. E-dura helped paralyzed rats walk again. Eventually, it could be developed as a long-lasting neural implant in humans, say the authors. Potential applications include treating spinal cord injuries, monitoring responses to local application of drugs, or even improving brain-computer interfaces. 

“The biggest barriers to using neural interface technology in the clinic are longevity and biocompatibility,” said Tracy Cui, University of Pittsburgh, who was not involved in the study. “The authors did a fantastic job designing a flexible device that would be tolerated by the delicate neural tissue.”

Courtine’s group previously found that a mix of electrical and chemical stimulation restored hind limb movements in rats with damaged spinal cords (see Oct 2009 news on Courtine et al., 2009). To translate this therapeutic strategy to people, they need to develop a system that minimizes damage and lasts a long time. Though neural implants used in research are somewhat flexible, they are still rigid compared to the soft tissue of the central nervous system. The friction generated between the device and nerve cells when an animal bends and twists its spinal cord, for instance, causes inflammation and damage (see Moshayedi et al., 2014). First authors Ivan Minev and Pavel Musienko set out to create a more biocompatible implant.

Soft gold wires, electrodes (black dots), and chemical delivery channels (blue) extend from a connector (right) through the silicon ribbon of the e-dura. © EPFL 2015.

They came up with the e-dura. In a ribbon-like silicone portion that contacts the spinal cord, cushy electrodes coated with a platinum-silicone composite receive electrical signals from, and deliver them to, neurons in the cord. Alongside this electrical hardware, supple silicone channels allow for delivery of chemicals directly to the tissue. To implant the e-dura, the researchers make a small incision in the dura mater and gently push the ribbon underneath and along the spinal cord’s soft tissue. They then mount a trapezoid-shaped connector piece to the nearby vertebra with a screw, and run attached wires under the animal’s skin to a plug on its head. Through this port, they can send chemical signals and transmit or measure electric ones.

Inserted into the spinal cord in rats, the e-dura recorded various types of electrical activity. It picked up both descending motor commands and sensory feedback after sciatic nerve stimulation. When the authors placed the device on the motor cortex, they detected distinct neural activation patterns associated with standing and walking in freely moving rats. The e-dura effectively delivered treatments, as well. In paralyzed rats, it transmitted a blend of electrical and chemical signals to an area of the spinal cord cut off from the brain, allowing them to walk again while supported above a treadmill. Lacour pointed out that such involuntary, reflexive walking movements are brought about by the motion of the treadmill, similar to training used to improve locomotion in people with spinal cord injuries (see Hicks and Ginis, 2008). Courtine’s group is working out how to restore voluntary walking after spinal injury (see Jun 2012 news).

To approximate how long the e-dura could last in the human body, the researchers mechanically stretched the implants a million times to see when the electrical and chemical signals would begin to fail. They estimated that the device could last up to 10 years, though Cui noted that it might deteriorate faster in the harsher in vivo environment.

The researchers also compared how the immune system responded to the e-dura and to standard implants. A stiffer polyimide film compressed spinal cord tissue, activated surrounding microglia and astrocytes, and caused gait impairments after six weeks. However, the e-dura left tissue intact, caused little neuroinflammation, and had no effect on locomotion. John Cirrito of Washington University in St. Louis noted that it would be useful to see added data about inflammation just after implantation, as microglia and astrocytes can fire up early on even if they calm down later. Cui wondered whether the device would escape eventual encapsulation by scar tissue, a typical problem for neuroprosthetics.

Lacour emphasized that the e-dura is not ready for clinical applications. It would have to work wirelessly and autonomously in people. The group is continuing to develop this technology with the ultimate goal of treating human spinal cord injuries. It also could help improve electrocorticography, Lacour said. This method of measuring electrical signals at the brain’s surface is used to identify epileptic regions and to read neural commands that could help control prosthetic devices.—Gwyneth Dickey Zakai

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References

News Citations

  1. Research Brief: Mojo for Motor Neurons
  2. New Treatment Restores Movement to Paralyzed Rats

Paper Citations

  1. Courtine G, Gerasimenko Y, van den Brand R, Yew A, Musienko P, Zhong H, Song B, Ao Y, Ichiyama RM, Lavrov I, Roy RR, Sofroniew MV, Edgerton VR. Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nat Neurosci. 2009 Oct;12(10):1333-42. PubMed.
  2. Moshayedi P, Ng G, Kwok JC, Yeo GS, Bryant CE, Fawcett JW, Franze K, Guck J. The relationship between glial cell mechanosensitivity and foreign body reactions in the central nervous system. Biomaterials. 2014 Apr;35(13):3919-25. Epub 2014 Feb 11 PubMed.
  3. Hicks AL, Ginis KA. Treadmill training after spinal cord injury: it's not just about the walking. J Rehabil Res Dev. 2008;45(2):241-8. PubMed.

Further Reading

Papers

  1. Fattahi P, Yang G, Kim G, Abidian MR. A review of organic and inorganic biomaterials for neural interfaces. Adv Mater. 2014 Mar 26;26(12):1846-85. PubMed.
  2. Konrad P, Shanks T. Implantable brain computer interface: challenges to neurotechnology translation. Neurobiol Dis. 2010 Jun;38(3):369-75. Epub 2009 Dec 24 PubMed.
  3. Kozai TD. Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies. ACS Chem Neurosci. 2014 Dec 29; PubMed.
  4. Mulliken GH, Bichot NP, Ghadooshahy A, Sharma J, Kornblith S, Philcock M, Desimone R. Custom-fit radiolucent cranial implants for neurophysiological recording and stimulation. J Neurosci Methods. 2014 Dec 24; PubMed.
  5. Alam M, Chen X, Zhang Z, Li Y, He J. A brain-machine-muscle interface for restoring hindlimb locomotion after complete spinal transection in rats. PLoS One. 2014;9(8):e103764. Epub 2014 Aug 1 PubMed.

Primary Papers

  1. Minev IR, Musienko P, Hirsch A, Barraud Q, Wenger N, Moraud EM, Gandar J, Capogrosso M, Milekovic T, Asboth L, Torres RF, Vachicouras N, Liu Q, Pavlova N, Duis S, Larmagnac A, Vörös J, Micera S, Suo Z, Courtine G, Lacour SP. Biomaterials. Electronic dura mater for long-term multimodal neural interfaces. Science. 2015 Jan 9;347(6218):159-63. PubMed.

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