Tag Archives: bioelectronic medicines

EGNITE, a derivative of graphene, improves performance of neuroprostheses

A July 10,2024 news item on ScienceDaily announces work on a new material for use in neuroprostheses could help people who are paralyzed or have amputated limbs, Note: This research involves use of animal models,

Neuroprostheses allow the nervous system of a patient who has suffered an injury to connect with mechanical devices that replace paralyzed or amputated limbs. A study coordinated by the UAB Institut de Neurociències, in collaboration with the l’Institut Català de Nanociència i Nanotecnologia (ICN2), demonstrates in animal models how EGNITE, a derivative of graphene, allows the creation of smaller electrodes, which can interact more selectively with the nerves they stimulate, thus improving the efficacy of the prostheses. The study also demonstrated that EGNITE is biocompatible, showing that its implantation is safe.

A July 10,2024 Universitat Autonoma de Barcelona press release (also on EurekAlert) provides more detail,

After an amputation or a severe nerve injury, patients lose to a greater or lesser extent the ability to move and feel a lost limb, which limits their autonomy in activities of daily living. Currently, the only strategy that allows to recover the lost functions consists of neuroprostheses: electrodes capable of stimulating the nerves, to induce specific sensations, and of recording motor signals that, once decoded, can be sent to a bionic prosthesis.

In the design of neuroprostheses, it is important that the electrodes are small enough that they are selective and interact electrically only with a reduced number of axons in the nerve. Therefore, although they have commonly been constructed from metals such as gold, platinum or iridium oxide, it is necessary to find other materials that have enhanced conductive capacity and allow the creation of even smaller electrode contacts. This is where graphene and its derivatives come into play; their excellent electrical properties have allowed the development of a new generation of microelectrodes.

A research coordinated by the UAB Institut de Neurociències (INc-UAB) has studied the capacity of a new material derived from graphene, EGNITE, to stimulate and record from the peripheral nerve. Furthermore, its biocompatibility has been validated, which is key for preserving the function of the interface over time. The research was carried out in the Neuroplasticity and Regeneration group of the INc-UAB, led by professor Xavier Navarro of the UAB Department of Cell Biology, Physiology and Immunology, in collaboration with Jose Garrido’s research group at the Institut Català de Nanociència i Nanotecnologia (ICN2), which was in charge of developing the EGNITE together with the neural interfaces.

These electrodes, implanted in rat sciatic nerve, were shown to be capable of producing selective muscle activation for up to a maximum of 60 days. “The reduction in the electrical current necessary to produce this muscle activation is notable in comparison to other larger metal microelectrodes”, explains Bruno Rodríguez-Meana, postdoctoral researcher at the INc-UAB and first author of the article. Furthermore, the electrodes with EGNITE demonstrated to be biocompatible, since none of the functional tests showed significant alterations produced by the implanted interfaces nor was exacerbated inflammation observed.

“The next steps will consist of the optimization of the EGNITE-based technology and its application in pre-clinical studies for vagus nerve or spinal cord stimulation systems. In parallel, progress is being made towards its clinical translation in bioelectronic medicine approaches”, explains Professor Navarro.

Together, these results indicate the potential of the material derived from graphene to be part of neuroprostheses that allow patients to recover lost functions, thus improving their capacity and quality of life.

Here’s a link to and a citation for the paper,

Engineered Graphene Material Improves the Performance of Intraneural Peripheral Nerve Electrodes by Bruno Rodríguez-Meana, Jaume del Valle, Damià Viana, Steven T. Walston, Nicola Ria, Eduard Masvidal-Codina, Jose A. Garrido, Xavier Navarro. Advanced Science Volume 11, Issue 29 August 7, 2024 2308689 DOI: https://doi.org/10.1002/advs.202308689 First published: 11 June 2024

This paper is open access.

Biohybrid device (a new type of neural implant) could restore limb function

A March 23, 2023 news item on ScienceDaily announces a neural implant that addresses failures due to scarring issues,

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.

In a study carried out in rats, researchers from the University of Cambridge used the device to improve the connection between the brain and paralysed limbs. The device combines flexible electronics and human stem cells — the body’s ‘reprogrammable’ master cells — to better integrate with the nerve and drive limb function.

Previous attempts at using neural implants to restore limb function have mostly failed, as scar tissue tends to form around the electrodes over time, impeding the connection between the device and the nerve. By sandwiching a layer of muscle cells reprogrammed from stem cells between the electrodes and the living tissue, the researchers found that the device integrated with the host’s body and the formation of scar tissue was prevented. The cells survived on the electrode for the duration of the 28-day experiment, the first time this has been monitored over such a long period.

A March 22, 2023 University of Cambridge press release (also on EurekAlert but published March 23, 2023) by Sarah Collins, delves further into the topic,

The researchers say that by combining two advanced therapies for nerve regeneration – cell therapy and bioelectronics – into a single device, they can overcome the shortcomings of both approaches, improving functionality and sensitivity.

While extensive research and testing will be needed before it can be used in humans, the device is a promising development for amputees or those who have lost function of a limb or limbs. The results are reported in the journal Science Advances.

A huge challenge when attempting to reverse injuries that result in the loss of a limb or the loss of function of a limb is the inability of neurons to regenerate and rebuild disrupted neural circuits.

“If someone has an arm or a leg amputated, for example, all the signals in the nervous system are still there, even though the physical limb is gone,” said Dr Damiano Barone from Cambridge’s Department of Clinical Neurosciences, who co-led the research. “The challenge with integrating artificial limbs, or restoring function to arms or legs, is extracting the information from the nerve and getting it to the limb so that function is restored.”

One way of addressing this problem is implanting a nerve in the large muscles of the shoulder and attaching electrodes to it. The problem with this approach is scar tissue forms around the electrode, plus it is only possible to extract surface-level information from the electrode.

To get better resolution, any implant for restoring function would need to extract much more information from the electrodes. And to improve sensitivity, the researchers wanted to design something that could work on the scale of a single nerve fibre, or axon.

“An axon itself has a tiny voltage,” said Barone. “But once it connects with a muscle cell, which has a much higher voltage, the signal from the muscle cell is easier to extract. That’s where you can increase the sensitivity of the implant.”

The researchers designed a biocompatible flexible electronic device that is thin enough to be attached to the end of a nerve. A layer of stem cells, reprogrammed into muscle cells, was then placed on the electrode. This is the first time that this type of stem cell, called an induced pluripotent stem cell, has been used in a living organism in this way.

“These cells give us an enormous degree of control,” said Barone. “We can tell them how to behave and check on them throughout the experiment. By putting cells in between the electronics and the living body, the body doesn’t see the electrodes, it just sees the cells, so scar tissue isn’t generated.”

The Cambridge biohybrid device was implanted into the paralysed forearm of the rats. The stem cells, which had been transformed into muscle cells prior to implantation, integrated with the nerves in the rat’s forearm. While the rats did not have movement restored to their forearms, the device was able to pick up the signals from the brain that control movement. If connected to the rest of the nerve or a prosthetic limb, the device could help restore movement.

The cell layer also improved the function of the device, by improving resolution and allowing long-term monitoring inside a living organism. The cells survived through the 28-day experiment: the first time that cells have been shown to survive an extended experiment of this kind.

The researchers say that their approach has multiple advantages over other attempts to restore function in amputees. In addition to its easier integration and long-term stability, the device is small enough that its implantation would only require keyhole surgery. Other neural interfacing technologies for the restoration of function in amputees require complex patient-specific interpretations of cortical activity to be associated with muscle movements, while the Cambridge-developed device is a highly scalable solution since it uses ‘off the shelf’ cells.

In addition to its potential for the restoration of function in people who have lost the use of a limb or limbs, the researchers say their device could also be used to control prosthetic limbs by interacting with specific axons responsible for motor control.

“This interface could revolutionise the way we interact with technology,” said co-first author Amy Rochford, from the Department of Engineering. “By combining living human cells with bioelectronic materials, we’ve created a system that can communicate with the brain in a more natural and intuitive way, opening up new possibilities for prosthetics, brain-machine interfaces, and even enhancing cognitive abilities.”

“This technology represents an exciting new approach to neural implants, which we hope will unlock new treatments for patients in need,” said co-first author Dr Alejandro Carnicer-Lombarte, also from the Department of Engineering.

“This was a high-risk endeavour, and I’m so pleased that it worked,” said Professor George Malliaras from Cambridge’s Department of Engineering, who co-led the research. “It’s one of those things that you don’t know whether it will take two years or ten before it works, and it ended up happening very efficiently.”

The researchers are now working to further optimise the devices and improve their scalability. The team have filed a patent application on the technology with the support of Cambridge Enterprise, the University’s technology transfer arm.

The technology relies on opti-oxTM enabled muscle cells. opti-ox is a precision cellular reprogramming technology that enables faithful execution of genetic programmes in cells allowing them to be manufactured consistently at scale. The opti-ox enabled muscle iPSC cell lines used in the experiment were supplied by the Kotter lab [Mark Kotter] from the University of Cambridge. The opti-ox reprogramming technology is owned by synthetic biology company bit.bio.

The research was supported in part by the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI), Wellcome, and the European Union’s Horizon 2020 Research and Innovation Programme.

Caption: In a study carried out in rats, researchers from the University of Cambridge used a biohybrid device to improve the connection between the brain and paralysed limbs. The device combines flexible electronics and human stem cells – the body’s ‘reprogrammable’ master cells – to better integrate with the nerve and drive limb function. Credit: University of Cambirdge

Here’s a link to and a citation for the paper,

Functional neurological restoration of amputated peripheral nerve using biohybrid regenerative bioelectronics by Amy E. Rochford, Alejandro Carnicer-Lombarte, Malak Kawan, Amy Jin, Sam Hilton, Vincenzo F. Curto, Alexandra L. Rutz, Thomas Moreau, Mark R. N. Kotter, George G. Malliaras, and Damiano G. Barone. Science Advances 22 Mar 2023 Vol 9, Issue 12 DOI: 10.1126/sciadv.add8162

This paper is open access.

The synthetic biology company mentioned in the press release, bit.bio is here

The memristor as the ‘missing link’ in bioelectronic medicine?

The last time I featured memrisors and a neuronal network it was in an April 22, 2016 posting about Russian research in that field. This latest work comes from the UK’s University of Southampton. From a Sept. 27, 2016 news item on phys.org,

New research, led by the University of Southampton, has demonstrated that a nanoscale device, called a memristor, could be the ‘missing link’ in the development of implants that use electrical signals from the brain to help treat medical conditions.

Monitoring neuronal cell activity is fundamental to neuroscience and the development of neuroprosthetics – biomedically engineered devices that are driven by neural activity. However, a persistent problem is the device being able to process the neural data in real-time, which imposes restrictive requirements on bandwidth, energy and computation capacity.

In a new study, published in Nature Communications, the researchers showed that memristors could provide real-time processing of neuronal signals (spiking events) leading to efficient data compression and the potential to develop more precise and affordable neuroprosthetics and bioelectronic medicines.

A Sept. 27, 2016 University of Southampton press release, which originated the news item, expands on the theme,

Memristors are electrical components that limit or regulate the flow of electrical current in a circuit and can remember the amount of charge that was flowing through it and retain the data, even when the power is turned off.

Lead author Isha Gupta, Postgraduate Research Student at the University of Southampton, said: “Our work can significantly contribute towards further enhancing the understanding of neuroscience, developing neuroprosthetics and bio-electronic medicines by building tools essential for interpreting the big data in a more effective way.”

The research team developed a nanoscale Memristive Integrating Sensor (MIS) into which they fed a series of voltage-time samples, which replicated neuronal electrical activity.

Acting like synapses in the brain, the metal-oxide MIS was able to encode and compress (up to 200 times) neuronal spiking activity recorded by multi-electrode arrays. Besides addressing the bandwidth constraints, this approach was also very power efficient – the power needed per recording channel was up to 100 times less when compared to current best practice.

Co-author Dr Themis Prodromakis, Reader in Nanoelectronics and EPSRC Fellow in Electronics and Computer Science at the University of Southampton said: “We are thrilled that we succeeded in demonstrating that these emerging nanoscale devices, despite being rather simple in architecture, possess ultra-rich dynamics that can be harnessed beyond the obvious memory applications to address the fundamental constraints in bandwidth and power that currently prohibit scaling neural interfaces beyond 1,000 recording channels.”

The Prodromakis Group at the University of Southampton is acknowledged as world-leading in this field, collaborating among others with Leon Chua (a Diamond Jubilee Visiting Academic at the University of Southampton), who theoretically predicted the existence of memristors in 1971.

Here’s a link to and a citation for the paper,

Real-time encoding and compression of neuronal spikes by metal-oxide memristors by Isha Gupta, Alexantrou Serb, Ali Khiat, Ralf Zeitler, Stefano Vassanelli, & Themistoklis Prodromakis. Nature Communications 7, Article number: 12805 doi:10.1038/ncomms12805 Published  26 September 2016

This is an open access paper.

For anyone who’s interested in better understanding memristors, there’s an interview with Forrest H Bennett III in my April 7, 2010 posting and you can always check Wikipedia.