The Future is Here: “Terminator-style” Liquid Metal Treatment

t1000_1For ideal physical rehab, it might be necessary to go a little “cyborg”. That’s the reasoning a Chinese biomedical firm used to develop a new method of repairing damaged nerve endings. Borrowing a page from Terminator 2, their new treatment calls for the use of liquid metal to transmit nerve signals across the gap created in severed nerves. The work, they say, raises the prospect of new treatment methods for nerve damage and injuries.

Granted, it’s not quite on par with the liquid-metal-skinned cyborgs from the future, but it is a futuristic way of improving on current methods of nerve rehab that could prevent long-term disabilities. When peripheral nerves are severed, the loss of function leads to atrophy of the effected muscles, a dramatic change in quality of life and, in many cases, a shorter life expectancy. Despite decades of research, nobody has come up with an effective way to reconnect them yet.

nerveVarious techniques exist to sew the ends back together or to graft nerves into the gap that is created between severed ends. And the success of these techniques depends on the ability of the nerve ends to grow back and knit together. But given that nerves grow at the rate of one mm per day, it can take a significant amount of time (sometimes years) to reconnect. And during this time, the muscles can degrade beyond repair and lead to long-term disability.

As a result, neurosurgeons have long hoped for a way to keep muscles active while the nerves regrow. One possibility is to electrically connect the severed ends so that the signals from the brain can still get through; but up until now, an effective means of making this happen has remained elusive. For some time, biomedical engineers have been eyeing the liquid metal alloy gallium-indium-selenium for some time as a possible solution – a material that is liquid at body temperature and thought to be entirely benign.

Liquid metal nervesBut now, a biomedical research team led by Jing Liu of Tsinghua University in Beijing claims they’ve reconnected severed nerves using liquid metal for the first time. They claim that the metal’s electrical properties could help preserve the function of nerves while they regenerate. Using sciatic nerves connected to a calf muscle, which were taken from bullfrogs, they’ve managed to carry out a series of experiments that prove that the technique is viable.

Using these bullfrog nerves, they applied a pulse to one end and measured the signal that reached the calf muscle, which contracted with each pulse. They then cut the sciatic nerve and placed each of the severed ends in a capillary filled either with liquid metal or with Ringer’s solution – a solution of several salts designed to mimic the properties of body fluids. They then re-applied the pulses and measured how they propagated across the gap.

liquid metal nerves_1The results are interesting, and Jing’s team claim that the pulses that passed through the Ringer’s solution tended to degrade severely. By contrast, the pulses passed easily through the liquid metal. As they put it in their research report:

The measured electroneurographic signal from the transected bullfrog’s sciatic nerve reconnected by the liquid metal after the electrical stimulation was close to that from the intact sciatic nerve.

What’s more, since liquid metal clearly shows up in x-rays, it can be easily removed from the body when it is no longer needed using a microsyringe. All of this has allowed Jing and colleagues to speculate about the possibility of future treatments. Their goal is to make special conduits for reconnecting severed nerves that contain liquid metal to preserve electrical conduction and therefore muscle function, but also containing growth factor to promote nerve regeneration.

future_medicineNaturally, there are still many challenges and unresolved questions which must be resolved before this can become a viable treatment option. For example, how much of the muscle function can be preserved? Can the liquid metal somehow interfere with or prevent regeneration? And how safe is liquid metal inside the body – especially if it leaks? These are questions that Jing and others will hope to answer in the near future, starting with animal models and possibly later with humans..


The Future of Medicine: Non-Invasive Nerve Repair

neuronsRepairing severed nerves remains one of the most challenging aspects of modern medicine. In addition to being common, due to spinal injuries, pressure or stretching, the severing or damaging of nerves can lead to a loss of mobility as well as sensation. And up until recently, doctors hoping to repair the damage have been heavily reliant on long-term methods that can be expensive and invasive.

However, Professor George Bittner and his colleagues at the University of Texas at Austin Center for Neuroscience have developed a new and inexpensive procedure to quickly repair severed peripheral nerves. Taking advantage of a mechanism similar to that which permits many invertebrates to regenerate and repair damaged nerves, the new procedure involves applying healing compounds directly to the severed nerve ends.

nerveTrauma to peripheral nerves, which connect the central nervous system to the muscles and sensory organs, is quite common, and is usually the result of excessive pressure or stretching. In most cases, this means that the axon of a nerve – the central bundle of cylindrical sheaths that contains individual nerve cells – is separated from the nerve fiber, leaving the nerve intact but disconnected from the muscle.

Afterward, the nerve cell slowly begins to regrow, and can form a twisted ball of nerve fiber at the cut in the axon. Such nerve scars are called neuroma, and in current medical practice, they are repaired by using microsutures to reconnect the cut ends of the axon and provide a continuous axon to guide the regrowth of the nerve fiber. However, this procedure is extremely delicate, and recovery can take months or even years.

george_bittner1Bittner and his colleagues’ new method involve using a natural healing process to aid in repair and recovery. Already, his team discovered that when a plasma membrane in a cell is damaged, a calcium-mediated healing mechanism begins to draw vesicles (small sacks of lipid membranes) towards the site of the injury. These provide the raw material needed to repair the site.

However, when these vesicles are attracted to the site of a severed axon, both ends of the axon are sealed off by this repair mechanism, preventing regrowth of the nerve. To avoid this problem, the first step of the Texas group’s nerve repair procedure is to bathe the area of the severed nerve with a calcium-free saline solution, thus preventing and even reversing premature healing of the axon ends.

nerve_rootThe damaged axons remain open, and can more easily be reattached. This is then done by pulling the severed ends to within a micron of each other, whereupon a small amount of a solution containing polyethylene glycol (PEG) is injected. The PEG removes water from the axonal membranes, allowing the plasma membranes to merge together, thereby healing the axon.

At the same time, the nerve fibers are brought into close enough proximity that they receive chemical messengers from each other, making them believe they are still whole and preventing the death of the disconnected nerve fiber. The severed nerve fibers can then grow together in a short period of time and with relatively good fidelity to the original connectivity of the nerve fibers.

nerves_pinwheeltestThe final step of the procedure is to inject the area with a calcium-rich saline solution, which restarts the vesicle-based repair mechanism, thereby repairing any residual damage to the axonal membrane. At this point, the nerve is structurally repaired, and use of the affected area begins to return within a few hours instead of months.

To test the procedure, Bittner and his colleges experimented on a series of rats that had had their sciatic nerves severed, resulting in paralysis of the affected limb. In each case, once the rats awoke, they were able to move the limbs containing the severed nerves within moments. Normal function was partially restored within a few days,  nd 80-90% of the pre-injury function was restored within two to four weeks.

mouseThe chemicals used in Bittner’s procedure are common and well understood in interaction with the human body. Because of this, there is no clear obstacle to beginning human clinical trials of the procedure, and teams at Harvard Medical School and Vanderbilt Medical School and Hospitals are currently conducting studies aimed at gaining approval for such trials.

While the procedure developed by Bittner’s group will not apply to the central nervous system or spinal cord injuries, the procedure offers hope to people whose futures include accidents involving damaged nerves. In the past, such people would have to undergo surgery, followed by months or years of physiotherapy (often with inconclusive results).

Now they can look forward to a full recovery that could take as little as a few weeks and cost them comparatively very little. And we, as human beings, would be one step closer to eliminating the term “permanent injury” from our vocabulary!