̽��ֱ�� of Cambridge - Damiano Barone

‘Wraparound’ implants represent new approach to treating spinal cord injuries

sc604 — Wed, 08 May 2024 18:01:25 +0000

A team of engineers, neuroscientists and surgeons from the ̽��ֱ�� of Cambridge developed the devices and used them to record the nerve signals going back and forth between the brain and the spinal cord. Unlike current approaches, the Cambridge devices can record 360-degree information, giving a complete picture of spinal cord activity.

Tests in live animal and human cadaver models showed the devices could also stimulate limb movement and bypass complete spinal cord injuries where communication between the brain and spinal cord had been completely interrupted.

Most current approaches to treating spinal injuries involve both piercing the spinal cord with electrodes and placing implants in the brain, which are both high-risk surgeries. ̽��ֱ��Cambridge-developed devices could lead to treatments for spinal injuries without the need for brain surgery, which would be far safer for patients.

While such treatments are still at least several years away, the researchers say the devices could be useful in the near-term for monitoring spinal cord activity during surgery. Better understanding of the spinal cord, which is difficult to study, could lead to improved treatments for a range of conditions, including chronic pain, inflammation and hypertension. ̽��ֱ��results are reported in the journal Science Advances.

“ ̽��ֱ��spinal cord is like a highway, carrying information in the form of nerve impulses to and from the brain,” said Professor George Malliaras from the Department of Engineering, who co-led the research. “Damage to the spinal cord causes that traffic to be interrupted, resulting in profound disability, including irreversible loss of sensory and motor functions.”

̽��ֱ��ability to monitor signals going to and from the spinal cord could dramatically aid in the development of treatments for spinal injuries, and could also be useful in the nearer term for better monitoring of the spinal cord during surgery.

“Most technologies for monitoring or stimulating the spinal cord only interact with motor neurons along the back, or dorsal, part of the spinal cord,” said Dr Damiano Barone from the Department of Clinical Neurosciences, who co-led the research. “These approaches can only reach between 20 and 30 percent of the spine, so you’re getting an incomplete picture.”

By taking their inspiration from microelectronics, the researchers developed a way to gain information from the whole spine, by wrapping very thin, high-resolution implants around the spinal cord’s circumference. This is the first time that safe 360-degree recording of the spinal cord has been possible – earlier approaches for 360-degree monitoring use electrodes that pierce the spine, which can cause spinal injury.

̽��ֱ��Cambridge-developed biocompatible devices – just a few millionths of a metre thick – are made using advanced photolithography and thin film deposition techniques, and require minimal power to function.

̽��ֱ��devices intercept the signals travelling on the axons, or nerve fibres, of the spinal cord, allowing the signals to be recorded. ̽��ֱ��thinness of the devices means they can record the signals without causing any damage to the nerves, since they do not penetrate the spinal cord itself.

“It was a difficult process, because we haven’t made spinal implants in this way before, and it wasn’t clear that we could safely and successfully place them around the spine,” said Malliaras. “But because of recent advances in both engineering and neurosurgery, the planets have aligned and we’ve made major progress in this important area.”

̽��ֱ��devices were implanted using an adaptation to routine surgical procedure so they could be slid under the spinal cord without damaging it. In tests using rat models, the researchers successfully used the devices to stimulate limb movement. ̽��ֱ��devices showed very low latency – that is, their reaction time was close to human reflexive movement. Further tests in human cadaver models showed that the devices can be successfully placed in humans.

̽��ֱ��researchers say their approach could change how spinal injuries are treated in future. Current attempts to treat spinal injuries involve both brain and spinal implants, but the Cambridge researchers say the brain implants may not be necessary.

“If someone has a spinal injury, their brain is fine, but it’s the connection that’s been interrupted,” said Barone. “As a surgeon, you want to go where the problem is, so adding brain surgery on top of spinal surgery just increases the risk to the patient. We can collect all the information we need from the spinal cord in a far less invasive way, so this would be a much safer approach for treating spinal injuries.”

While a treatment for spinal injuries is still years away, in the nearer term, the devices could be useful for researchers and surgeons to learn more about this vital, but understudied, part of human anatomy in a non-invasive way. ̽��ֱ��Cambridge researchers are currently planning to use the devices to monitor nerve activity in the spinal cord during surgery.

“It’s been almost impossible to study the whole of the spinal cord directly in a human, because it’s so delicate and complex,” said Barone. “Monitoring during surgery will help us to understand the spinal cord better without damaging it, which in turn will help us develop better therapies for conditions like chronic pain, hypertension or inflammation. This approach shows enormous potential for helping patients.”

̽��ֱ��research was supported in part by the Royal College of Surgeons, the Academy of Medical Sciences, Health Education England, the National Institute for Health Research, MRC Confidence in Concept, and the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI).

Reference:
Ben J Woodington, Jiang Lei et al. ‘Flexible Circumferential Bioelectronics to Enable 360-degree Recording and Stimulation of the Spinal Cord.’ Science Advances (2024). DOI: 10.1126/sciadv.adl1230

A tiny, flexible electronic device that wraps around the spinal cord could represent a new approach to the treatment of spinal injuries, which can cause profound disability and paralysis.

Because of recent advances in both engineering and neurosurgery, the planets have aligned and we’ve made major progress in this important area

George Malliaras

SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY

Illustration of spinal cord

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Robotic nerve ‘cuffs’ could help treat a range of neurological conditions

sc604 — Fri, 26 Apr 2024 08:55:34 +0000

̽��ֱ��researchers, from the ̽��ֱ�� of Cambridge, combined flexible electronics and soft robotics techniques to develop the devices, which could be used for the diagnosis and treatment of a range of disorders, including epilepsy and chronic pain, or the control of prosthetic limbs.

Current tools for interfacing with the peripheral nerves – the 43 pairs of motor and sensory nerves that connect the brain and the spinal cord – are outdated, bulky and carry a high risk of nerve injury. However, the robotic nerve ‘cuffs’ developed by the Cambridge team are sensitive enough to grasp or wrap around delicate nerve fibres without causing any damage.

Tests of the nerve cuffs in rats showed that the devices only require tiny voltages to change shape in a controlled way, forming a self-closing loop around nerves without the need for surgical sutures or glues.

̽��ֱ��researchers say the combination of soft electrical actuators with neurotechnology could be an answer to minimally invasive monitoring and treatment for a range of neurological conditions. ̽��ֱ��results are reported in the journal Nature Materials.

Electric nerve implants can be used to either stimulate or block signals in target nerves. For example, they might help relieve pain by blocking pain signals, or they could be used to restore movement in paralysed limbs by sending electrical signals to the nerves. Nerve monitoring is also standard surgical procedure when operating in areas of the body containing a high concentration of nerve fibres, such as anywhere near the spinal cord.

These implants allow direct access to nerve fibres, but they come with certain risks. “Nerve implants come with a high risk of nerve injury,” said Professor George Malliaras from Cambridge’s Department of Engineering, who led the research. “Nerves are small and highly delicate, so anytime you put something large, like an electrode, in contact with them, it represents a danger to the nerves.”

“Nerve cuffs that wrap around nerves are the least invasive implants currently available, but despite this they are still too bulky, stiff and difficult to implant, requiring significant handling and potential trauma to the nerve,” said co-author Dr Damiano Barone from Cambridge’s Department of Clinical Neurosciences.

̽��ֱ��researchers designed a new type of nerve cuff made from conducting polymers, normally used in soft robotics. ̽��ֱ��ultra-thin cuffs are engineered in two separate layers. Applying tiny amounts of electricity – just a few hundred millivolts – causes the devices to swell or shrink.

̽��ֱ��cuffs are small enough that they could be rolled up into a needle and injected near the target nerve. When activated electrically, the cuffs will change their shape to wrap around the nerve, allowing nerve activity to be monitored or altered.

“To ensure the safe use of these devices inside the body, we have managed to reduce the voltage required for actuation to very low values,” said Dr Chaoqun Dong, the paper’s first author. “What's even more significant is that these cuffs can change shape in both directions and be reprogrammed. This means surgeons can adjust how tightly the device fits around a nerve until they get the best results for recording and stimulating the nerve.”

Tests in rats showed that the cuffs could be successfully placed without surgery, and formed a self-closing loop around the target nerve. ̽��ֱ��researchers are planning further testing of the devices in animal models, and are hoping to begin testing in humans within the next few years.

“Using this approach, we can reach nerves that are difficult to reach through open surgery, such as the nerves that control, pain, vision or hearing, but without the need to implant anything inside the brain,” said Barone. “ ̽��ֱ��ability to place these cuffs so they wrap around the nerves makes this a much easier procedure for surgeons, and it’s less risky for patients.”

“ ̽��ֱ��ability to make an implant that can change shape through electrical activation opens up a range of future possibilities for highly targeted treatments,” said Malliaras. “In future, we might be able to have implants that can move through the body, or even into the brain – it makes you dream how we could use technology to benefit patients in future.”

̽��ֱ��research was supported in part by the Swiss National Science Foundation, the Cambridge Trust, and the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI).

Reference:
Chaoqun Dong et al. ‘Electrochemically actuated microelectrodes for minimally invasive peripheral nerve interfaces.’ Nature Materials (2024). DOI: 10.1038/s41563-024-01886-0

Researchers have developed tiny, flexible devices that can wrap around individual nerve fibres without damaging them.

̽��ֱ��ability to make an implant that can change shape through electrical activation opens up a range of future possibilities for highly targeted treatments

George Malliaras

XH4D via iStock / Getty Images Plus

Illustration of the human nervous system

Yes

‘Biohybrid’ device could restore function in paralysed limbs

sc604 — Wed, 22 Mar 2023 17:55:29 +0000

Researchers have developed a new type of neural implant that could restore limb function to amputees and others who have lost the use of their arms or legs.

Drug incorporated into silicone coating reduces ‘foreign body reaction’ to implants

cjb250 — Mon, 14 Mar 2022 20:00:59 +0000

Implantable electronic medical devices are already widely used for a number of applications, but they also offer the prospect of transforming the treatment of intractable conditions, such as the use of neural electrical stimulators for spinal injury patients.

There is one major problem, however: our body recognises, attacks and surrounds these implants with a dense, ‘protective’ capsule of scar tissue that prevents electrical stimulation reaching the nervous system.

This so-called ‘foreign body reaction’ is driven by an inflammatory response against the implant. First, immune cells known as macrophages attack and try to destroy the device. Then a more long-term response kicks in, again coordinated by the macrophages, which leads to the build-up of a collagen-rich capsule to separate it from the surrounding tissue. This response then persists until the implant is removed from the body.

̽��ֱ��mechanisms by which foreign body reaction occurs are poorly understood, meaning that there are no effective methods to prevent it without interfering with the tissue repair mechanisms, for example after nerve damage.

First author Dr Damiano Barone from the Department of Clinical Neurosciences at the ̽��ֱ�� of Cambridge said: “Foreign body reaction is currently an unavoidable complication of implantation and is one of the leading causes of implant failure. At the moment, the only way we have of preventing it is to use broad-spectrum anti-inflammatory drugs such as dexamethasone. But these are problematic – they may stop the scarring, but they also stop the repair.”

In a study published today in the Proceedings of the National Academy of Sciences (PNAS), scientists implanted an electrical device into mice to compensate for sciatic nerve damage and compared the response within the surrounding tissue to that in mice who did not receive an implant. As well as using normal mice, the researchers used mice whose genes controlling the inflammatory response had been ‘knocked out’, preventing a response.

This allowed the team to see how the body’s inflammatory response generated the foreign body reaction, and which genes were involved. In turn, this showed that a particular molecule known as NLRP3 plays a key role.

̽��ֱ��researchers then added a small molecule known as MCC950 to the device coating and tested its effect in the mice. MCC950 has previously been shown to inhibit the activity of NLRP3. They found that this prevented the foreign body reaction without affecting tissue regeneration. This contrasted with dexamethasone treatment, which prevents the foreign body reaction but also blocks nerve regeneration.

NLRP3 inhibitors are being developed for a number of clinical applications including inflammatory disease, cancer, sepsis, Alzheimer’s disease and Parkinson’s disease. They are already being tested in clinical trials for certain conditions.

Joint senior author Professor Clare Bryant from the Department of Medicine at the ̽��ֱ�� of Cambridge said: “There’s a lot of excitement around this new class of anti-inflammatory drugs. Once they’ve been through clinical trials and have been shown to be safe to use, we should be in a good position to integrate them into the next generation of implantable devices.

“Combining these drugs with different materials and softer coatings for devices could transform the lives of individuals who need long-term implants to overcome serious disability or illness. In particular, this could make a huge difference to neuroprosthetics – prosthetics that connect to the nervous system – where the technology exists, but scarring has not yet made their widespread use viable.”

̽��ֱ��research was supported by the Medical Research Council and Wellcome.

Reference
Barone, DG et al. Prevention of the foreign body response to implantable medical devices by inflammasome inhibition. PNAS; 14 March 2022; DOI: 10.1073/pnas.2115857119

Long-term use of implantable electronic medical devices – such as pacemakers and cochlear implants – is hampered by the body’s reaction to foreign bodies. Now, in a study in mice, a team led by scientists at the ̽��ֱ�� of Cambridge has shown that this reaction can be dramatically reduced by incorporating an anti-inflammatory drug into the silicone coating around the implant.

Combining these drugs with different materials and softer coatings for devices could transform the lives of individuals who need long-term implants to overcome serious disability or illness

Clare Bryant

Charles O'Rear (Getty Images)

X-Ray Showing Pacemaker

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Inflatable, shape-changing spinal implants could help treat severe pain

sc604 — Fri, 25 Jun 2021 17:14:34 +0000

A team of engineers and clinicians has developed an ultra-thin, inflatable device that can be used to treat the most severe forms of pain without the need for invasive surgery.