‘Biohybrid’ device can restore paralyzed limbs’ function – ScienceDaily

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

In a study of rats, researchers from the University of Cambridge used the device to improve communication between the brain and paralyzed limbs. The device combines flexible electronics with human stem cells – the body’s “programmable” master cells – to better integrate nerve and limb function.

Previous attempts to use nerve implants to restore limb function often failed, as scar tissue tends to form around the electrodes over time, impeding communication between the device and the nerve. By sandwiching a layer of reprogrammed muscle cells from stem cells between the electrodes and living tissue, the researchers found that the device fused with the host’s body and the formation of scar tissue was prevented. Cells survived on the electrode for 28 days of the experiment, the first time this has been monitored over such a long period.

The researchers say that by combining two advanced nerve regeneration therapies — cell therapy and bioelectronics — into a single device, they can overcome the shortcomings of both approaches, improving function 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 the function of a limb or limb. The results are reported in the journal Science advances.

The great challenge when trying to reverse injuries that lead to the loss of a limb or the loss of function of a limb is the inability of neurons to regenerate and rebuild malfunctioning neural circuits.

said Dr Damiano Barone of the Department of Clinical Neurosciences at Cambridge, who co-led the research. “The challenge in integrating prostheses, or restoring function of the arms or legs, is extracting information from the nerve and delivering it to the limb until that function is restored.”

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

For better accuracy, any implant to restore function will need to extract more information from the electrodes. To improve sensitivity, the researchers wanted to design something that could operate at the scale of a single nerve fiber, or axon.

“The axon itself has minimal effort,” Baron said. “But once it’s connected to a muscle cell with a much higher voltage, it becomes easier to extract the signal from the muscle cell. This is 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. Then a layer of stem cells, reprogrammed into muscle cells, was placed on the electrode. This is the first time this type of stem cell, called induced pluripotent stem cells, has been used in an organism in this way.

“These cells give us an enormous degree of control,” Baron said. “We can tell them how to behave and check on them throughout the experiment. By placing the cells between the electronic devices and the living body, the body doesn’t see the electrodes, it just sees the cells, so scar tissue doesn’t form.”

The Cambridge biohybrid device was implanted in the paralyzed forearm of mice. Stem cells, which had been converted into muscle cells prior to transplantation, integrated with nerves in the rat’s forearm. While the mice did not regain movement of their forearms, the device was able to pick up signals from the brain that control movement. If connected to the rest of the nerve or prosthesis, the device can help restore movement.

The cell layer also improves device function, by improving resolution and allowing long-term monitoring within the organism. The cells survived the 28-day experiment: the first time that cells had been shown to survive in an extended experiment of this type.

The researchers say their approach has multiple advantages over other attempts to restore function in amputees. In addition to its easy integration and long-term stability, the device is small enough that its implantation requires only keyhole surgery. Other neurocommunicative techniques to restore function in amputees require complex, patient-specific interpretations of cortical activity to correlate them with muscle movements, while the device developed by Cambridge is a highly scalable solution because it uses “off-the-shelf” cells.

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

“This interface could revolutionize 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 for neuronal implants, which we hope will open up new therapies for patients in need,” said co-first author Dr.

“This was a high-stakes endeavor, and I’m very glad it worked,” said Professor George Maliaras of Cambridge’s Department of Engineering, who co-led the research. “It’s one of those things where you don’t know if it’s going to take two years or 10 before it works, and it ends up happening very efficiently.”

The researchers are now working on improving the hardware and improving its scalability. The team has filed a patent application on the technology with support from Cambridge Enterprise, the university’s technology transfer arm.

The technology is based on Opti-oxTM-enabled muscle cells. opti-ox is a precise cellular reprogramming technology that enables faithful execution of genetic programs in cells allowing their continuous manufacture on a large scale. The Opti-ox-enabled myogenic iPSC cell lines used in the experiment were provided by the Kotter Laboratory of the University of Cambridge. opti-ox reprogramming technology is proprietary to synthetic biology company bit.bio.

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

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