3 D Digital Print Outs To Restore Damaged Nerves

Today's post from the always-reliable, sciencedaily.com (see link below) looks at the potential use of 3-D printed, custom silicone guides implanted with biochemical cues to help nerve regeneration after injury. Now this isn't the replacing of damaged nerves caused by any number of factors that we know of as being neuropathy (maybe later) but it is a major breakthrough with enormous potential. It's also not printing out digital 'plastic 'nerves' that could function as real ones - it's the placing of the right 'stimuli' between damaged nerve ends to encourage them to rejoin naturally. Of course, at the moment, experiments have only taken place on rats and who knows how long it will be before damaged nerves are regenerated in this way in humans but everybody living with neuropathy will be excited at the prospect of having a sort of, 'nerve transplant' in the same way that other organs of the body are currently transplanted. Science fiction? Not any more!

3-D printed guide helps regrow complex nerves after injury 
Date:September 18, 2015 Source:University of Minnesota

Summary:

Scientists have developed a first-of-its-kind, 3-D printed guide that helps regrow both the sensory and motor functions of complex nerves after injury. The groundbreaking research has the potential to help more than 200,000 people annually who experience nerve injuries or disease.


This is a 3-D printed nerve regeneration pathway implanted in a rat helped to improve walking in 10 to 12 weeks after implantation.
Credit: University of Minnesota College of Science and Engineering

A national team of researchers has developed a first-of-its-kind, 3D-printed guide that helps regrow both the sensory and motor functions of complex nerves after injury. The groundbreaking research has the potential to help more than 200,000 people annually who experience nerve injuries or disease.

Collaborators on the project are from the University of Minnesota, Virginia Tech, University of Maryland, Princeton University, and Johns Hopkins University.

Nerve regeneration is a complex process. Because of this complexity, regrowth of nerves after injury or disease is very rare, according to the Mayo Clinic. Nerve damage is often permanent. Advanced 3D printing methods may now be the solution.

In a new study, published today in the journal Advanced Functional Materials, researchers used a combination of 3D imaging and 3D printing techniques to create a custom silicone guide implanted with biochemical cues to help nerve regeneration. The guide's effectiveness was tested in the lab using rats.

To achieve their results, researchers used a 3D scanner to reverse engineer the structure of a rat's sciatic nerve. They then used a specialized, custom-built 3D printer to print a guide for regeneration. Incorporated into the guide were 3D-printed chemical cues to promote both motor and sensory nerve regeneration. The guide was then implanted into the rat by surgically grafting it to the cut ends of the nerve. Within about 10 to 12 weeks, the rat's ability to walk again was improved.

"This represents an important proof of concept of the 3D printing of custom nerve guides for the regeneration of complex nerve injuries," said University of Minnesota mechanical engineering professor Michael McAlpine, the study's lead researcher. "Someday we hope that we could have a 3D scanner and printer right at the hospital to create custom nerve guides right on site to restore nerve function."

Scanning and printing takes about an hour, but the body needs several weeks to regrow the nerves. McAlpine said previous studies have shown regrowth of linear nerves, but this is the first time a study has shown the creation of a custom guide for regrowth of a complex nerve like the Y-shaped sciatic nerve that has both sensory and motor branches.

"The exciting next step would be to implant these guides in humans rather than rats," McAlpine said. In cases where a nerve is unavailable for scanning, McAlpine said there could someday be a "library" of scanned nerves from other people or cadavers that hospitals could use to create closely matched 3D-printed guides for patients.

In addition to McAlpine, major contributors to the research team include Blake N. Johnson, Virginia Tech; Xiaofeng Jia, University of Maryland and Johns Hopkins University; and Karen Z. Lancaster, Esteban Engel, and Lynn W. Enquist, Princeton University.

This research was funded by grants from the National Institutes of Health, the Defense Advanced Research Projects Agency, the Maryland Stem Cell Research Fund, and the Grand Challenges Program at Princeton University.

To read more about the study entitled "3D Printed Anatomical Nerve Regeneration Pathways," visit the Advanced Functional Materials website.

Story Source:

The above post is reprinted from materials provided by University of Minnesota. Note: Materials may be edited for content and length.

Journal Reference: 
 
Blake N. Johnson, Karen Z. Lancaster, Gehua Zhen, Junyun He, Maneesh K. Gupta, Yong Lin Kong, Esteban A. Engel, Kellin D. Krick, Alex Ju, Fanben Meng, Lynn W. Enquist, Xiaofeng Jia, Michael C. McAlpine. 3D Printed Anatomical Nerve Regeneration Pathways. Advanced Functional Materials, 2015; DOI: 10.1002/adfm.201501760

http://www.sciencedaily.com/releases/2015/09/150918105030.htm

Growing New Nerves

Today's interesting post comes from sciencedaily.com (see link below) and talks about the work being done in a US research lab to encourage brain cells to create healthy nerves by introducing polymer nanofibres. The 'new' nerves can even grow a myelin layer (the protective sheath around healthy nerves). As with all these things, when they're first reported by researchers, the work is only in very early stages but the potential for 'growing' new nerves to replace damaged ones, or 'repair' damaged nerves themselves, gives hope for treatments of neuropathy in the future. The article is a little 'technical' but still understandable and it may be worth keeping an eye out for any progress in this area.

Researchers Coax Cells to Grow and Myelinate Along Thin Fibers; Potential Use in Testing Treatments for Neurological Diseases
ScienceDaily (Nov. 7, 2012)

Every week in his clinic at the University of Michigan, neurologist Joseph Corey, M.D., Ph.D., treats patients whose nerves are dying or shrinking due to disease or injury.

He sees the pain, the loss of ability and the other effects that nerve-destroying conditions cause -- and wishes he could give patients more effective treatments than what's available, or regenerate their nerves. Then he heads to his research lab at the VA Ann Arbor Healthcare System, where his team is working toward that exact goal.

In new research published in several recent papers, Corey and his colleagues from the U-M Medical School, VAAAHS and the University of California, San Francisco report success in developing polymer nanofiber technologies for understanding how nerves form, why they don't reconnect after injury, and what can be done to prevent or slow damage.

Using polymer nanofibers thinner than human hairs as scaffolds, researchers coaxed a particular type of brain cell to wrap around fibers that mimic the shape and size of nerves found in the body.

They've even managed to encourage the process of myelination -- the formation of a protective coating that guards larger nerve fibers from damage. They began to see multiple concentric layers of the protective substance called myelin start to form, just as they do in the body. Together with the laboratory team of their collaborator Jonah Chan at UCSF, the authors reported the findings in Nature Methods.

The research involves oligodendrocytes, which are the supporting actors to neurons -- the "stars" of the central nervous system. Without oligodendrocytes, central nervous system neurons can't effectively transmit the electrical signals that control everything from muscle movement to brain function.

Oligodendrocytes are the type of cells typically affected by multiple sclerosis, and loss of myelin is a hallmark of that debilitating disease.

The researchers have also determined the optimum diameter for the nanofibers to support this process -- giving important new clues to answer the question of why some nerves are myelinated and some aren't.

While they haven't yet created fully functioning "nerves in a dish," the researchers believe their work offers a new way to study nerves and test treatment possibilities. Corey, an assistant professor of neurology and biomedical engineering at the U-M Medical School and researcher in the VA Geriatrics Research, Education and Clinical Center, explains that the thin fibers are crucial for the success of the work.

"If it's about the same length and diameter as a neuron, the nerve cells follow it and their shape and location conform to it," he says. "Essentially, these fibers are the same size as a neuron."

The researchers used polystyrene, a common plastic, to make fibers through a technique called electrospinnning. In a recent paper in Materials Science and Engineering C, they discovered new techniques to optimize how fibers made from poly-L-lactide, a biodegradable polymer, can be better aligned to resemble neurons and to guide regenerating nerve cells.

They're also working to determine the factors that make oligodendrocytes attach to the long narrow axons of neurons, and perhaps to start forming myelin sheaths too.

By attaching particular molecules to the nanofibers, Corey and his colleagues hope to learn more about what makes this process work -- and what makes it go awry, as in diseases caused by poor nerve development.

"What we need to do for multiple sclerosis is to encourage nerves to remyelinate," he says. "For nerve damage caused by trauma, on the other hand, we need to encourage regeneration."

In addition to Corey, the research has been led by Chan, the Rachleff Professor of Neurology at UCSF, VAAAHS lab team member and U-M graduate Samuel J. Tuck, U-M biomedical engineering graduate student Michelle Leach, UCSF's Stephanie Redmond, Seonook Lee, Synthia Mellon and S.Y. Christin Chong, and Zhang-Qi Feng of U-M Biomedical Engineering.

Peripheral nerves, which have neurons at the center surrounded by cells called Schwann cells, can also be studied using the nanofiber technique. The system could also be used to study how different types of cells interact during and after nerve formation.

Toward creating new nerves, Corey's lab has collaborated with R. Keith Duncan, PhD, Associate Professor of Otolaryngology. Published in Biomacromolecules, they found that stem cells are more likely to develop into neurons when they are grown on aligned nanofibers produced in Corey's lab. They eventually hope to use this approach to build new nerves from stem cells and direct their connections to undamaged parts of the brain and to muscle.

Eventually, Corey envisions, perhaps nerves could be grown along nanofibers in a lab setting and then transferred to patients' bodies, where the fiber would safely degrade.

The research was supported by a VA Merit funding grant, the US National Multiple Sclerosis Society, the Harry Weaver Neuroscience Scholar Award, the Paralyzed Veterans of America and the National Institute of Neurological Disorders and Stroke (NS062796-02).

http://www.sciencedaily.com/releases/2012/11/121107145920.htm

Damaged Small Nerves Lead To Damaged Longer Nerves

Today's post from painnewsnetwork.org (see link below) covers a story that appeared about three weeks ago on this blog but this time it's much more understandable for the casual neuropathy reader. It talks about the discovery that the early symptoms of neuropathy that are often diagnosed as small fibre neuropathy, are in fact a warning signal of much greater deterioration of the longer nerves in the future. Many of you reading this will be having a 'duh' moment of 'So tell us something we didn't already know!' However, medical science likes things neatly packaged and labelled and the idea that small fibre neuropathy could lead to damage of other nerve sorts and much wider symptoms was not easily accepted. It was always thought that the longer nerves degraded first but these recent studies show that in fact it is just as likely that the short nerves begin the process leading to longer nerve degeneration. It's an interesting article which if you have any of the tingling, burning symptoms we're so accustomed too, may apply to you too.

Neuropathy More Damaging Than Previously Thought
By Pat Anson, Editor April 11, 2016
 
A tingling, sometimes painful sensation in the hands and feet – the early stages of small fiber neuropathy -- may be more damaging to the peripheral nervous system than previously thought, according to new research published in JAMA Neurology.

A 3-year study by Johns Hopkins neurologists found that patients with small fiber neuropathy showed unexpected deterioration over the entire length of sensory nerve fibers, not just nerve fibers at the surface of the skin.

“I liken small fiber neuropathy to the canary in the coal mine,” says senior author Michael Polydefkis, MD, professor of neurology at the Johns Hopkins University School of Medicine and director of the Cutaneous Nerve Lab. “It signals the beginning of nerve deterioration that with time involves other types of nerve fibers and becomes more apparent and dramatically affects people’s quality of life. The results of this new study add urgency to the need for more screening of those with the condition and faster intervention.”

Nearly 26 million people in the United States have diabetes and about half have some form of neuropathy, according to the American Diabetes Association. Small fiber neuropathy can also be caused by lupus, HIV, Lyme disease, celiac disease or alcoholism.

Diabetic peripheral neuropathy causes nerves to send out abnormal signals. Patients feel pain or loss of feeling in their toes, feet, legs, hands and arms. It may also include a persistent burning, tingling or prickling sensation. The condition can eventually lead to injuries, chronic foot ulcers and even amputations.

Polydefkis and his colleagues found that small fiber nerve damage occurs even in patients with prediabetes, and the early symptoms of burning pain may be less benign than most clinicians think. Routine nerve tests, like nerve conduction, often fail to identify nerve damage because they mostly assess injury to large diameter nerve fibers.

In an effort to measure nerve damage more accurately, Johns Hopkins researchers took small samples of skin — the size of a large freckle — from 52 patients diagnosed with small fiber neuropathy and from 10 healthy controls. Skin samples were taken from the ankle, the lower thigh near the knee and the upper thigh. Three years later, samples from the same area in the same patients were taken for comparison.

Microscopic analysis of the skin samples showed that patients with small fiber neuropathy initially had fewer nerve fibers on the ankle compared to the upper thigh, demonstrating the most nerve damage was further down the leg. But after three years, researchers found that longer nerve fibers were also lost from the lower and upper thighs, something that was not expected.

“We are all taught in medical school that the longest nerves degrade first, and we show that this isn’t always the case,” says lead author Mohammad Khoshnoodi, MD, assistant professor of neurology at Johns Hopkins,

Patients with prediabetes or diabetes had at least 50 percent fewer small nerve fibers in their ankles initially than those participants with an unknown cause for their small fiber neuropathy, indicating these patients started the study with more damage to their small nerve fibers.

The patients with prediabetes continued to have worsening damage to their small nerve fibers over the course of the study, losing about 10 percent of their nerve fiber density each year at all sites tested along the leg. Patients with diabetes also lost similar rates of nerve fibers along the three sites of the leg.

“I expected that people with diabetes would do worse, but I didn’t really expect people with prediabetes to experience a similar rate of degradation of their small nerve fibers,” says Polydefkis.

Researchers caution that their study was small, and that other factors such as high blood sugar, smoking, high blood pressure and high cholesterol, may also have contributed to the decline in nerve fibers.

http://www.painnewsnetwork.org/stories/2016/4/11/neuropathy-more-damaging-than-previously-thought

Neuropathy A Close Look At How The Nerves In The Foot Work

Today's video (11 minutes) comes from Dr Michael Graham DPM and is a fascinating look at how the nerves in the foot work and what the problems, causes and results of nerve damage are. It may leave you bewildered because of the amount of medical and scientific terms you've never met before but because of the series of clear images, it's not too difficult to follow. What it does show is how complex the nerve system and surrounding muscles and blood vessels in the foot are and how important it is to look after your feet, irrespective of whether you have neuropathy or not. Using the pause button at each new image may help you take in the information at your own pace.
(There is no sound track)




Uploaded on 1 Mar 2011

Nerves on the bottom of the foot have to make it through 2 tunnels in order to make it to the spine. Faulty foot mechanics and severely affect these nerves. Watch this video to learn more about this very condition and to find out about what additional factors can taken to help

Ultrasound For Troubled Nerves

Another of the 'buzz' subjects doing the rounds of the neurological forums, is that discussed in today's post from sciencedaily.com (see link below). It is the use of ultrasonic waves to stimulate nerve pathways leading to the brain. The logical outcome of this is the restoration of feeling in neuropathic feet and hands but apparently there are other implications as well. If the right specific sensory pathways can be targeted, it's possible that pain signals can also be reduced or suppressed. It's a fascinating article and not difficult reading but yet again, we are looking at something which may emerge in the future and certainly won't be ready for general use within say a year.

Fingers On the Pulse: Neuroscientists Show Ultrasound Can Be Tweaked to Stimulate Different Sensations

Dec. 6, 2012

A century after the world's first ultrasonic detection device -- invented in response to the sinking of the Titanic -- Virginia Tech Carilion Research Institute scientists have provided the first neurophysiological evidence for something that researchers have long suspected: ultrasound applied to the periphery, such as the fingertips, can stimulate different sensory pathways leading to the brain.

And that's just the tip of the iceberg. The discovery carries implications for diagnosing and treating neuropathy, which affects millions of people around the world.

"Ideally, neurologists should be able to tailor treatments to the specific sensations their patients are feeling," said William "Jamie" Tyler, an assistant professor at the Virginia Tech Carilion Research Institute, who led the study published this week in PLOS ONE.

"Unfortunately, even with today's technologies, it's difficult to stimulate certain types of sensations without evoking others. Pulsed ultrasound allows us to selectively activate functional subsets of nerve fibers so we can study what happens when you stimulate, for example, only the peripheral fibers and central nervous system pathways that convey the sensation of fast, sharp pain or only those that convey the sensation of slow, dull, throbbing pain."

An estimated 20 million people in the United States alone suffer from neuropathy, a collection of nervous system disorders that may cause pain, numbness, and sensations of burning, itching, and tingling. One of the most common causes of neuropathy is Type 2 diabetes. Autoimmune disorders, such as lupus and Guillain-Barré syndrome; traumatic nerve injury; genetic abnormalities; movement disorders; and infectious diseases such as HIV/AIDS, Lyme disease, and leprosy can also trigger neuropathy.

"Neuropathy involves both motor nerves that control how muscles move and sensory nerves that receive sensations such as heat, pain, and touch," Tyler said. "So clinicians may use, for example, small resonator devices to vibrate the skin or lasers to heat the surface of the skin. But we wanted to develop a method that could activate superficial and deep mechanical receptors, thermal receptors, and even combinations of both. So we used pulsed ultrasound."

In the 1970s, a group of Soviet scientists made observations that ultrasound could stimulate distinct neural pathways, but their evidence was only anecdotal, with subjects merely describing sensations of heat, pain, or vibration. In the current study, the researchers used functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) to provide physiological proof of those early observations.

Study participants rested their index fingers on ultrasound transducers while having their brain activity monitored with fMRI and EEG. The scientists found that they could stimulate specific somatosensory pathways just by tweaking the ultrasound waveforms.

Tyler believes the finding has important implications for pain diagnosis.

"Current methods of diagnosing and characterizing pain can sometimes seem archaic," Tyler said. "To measure pain through mechanical stimulation, for example, physicians might touch the skin with nylon monofilaments known as von Frey hairs, or they'll stroke the skin with a paintbrush. For thermal sensory testing, patients may even plunge their hands into ice water until the pain becomes too great. We're hoping to provide physicians with more precise diagnostic tools."

Better diagnostics will lead to better therapeutics, said neuroscientist Michael Friedlander, executive director of the Virginia Tech Carilion Research Institute.

"By combining pulsed ultrasound with the technologies to record brain activity, Jamie Tyler and his colleagues are taking this to a whole new level of diagnostics," Friedlander said. "And the diagnostics will ultimately drive the therapeutics. This research is a great example of how new technologies can be adapted for real-world, patient-centered diagnoses and treatments."

Tyler noted the discovery could lead to other applications.

"Ultrasound transducers could be fashioned into flexible, flat insoles to provide sensory stimulation to people who have lost sensation in their feet, including the elderly, who are at such risk of falling," he said. "Surgical instruments could provide tactile feedback to surgeons in training. And I can imagine countless applications for consumer electronics. Users already rely on two-way somatosensory communication with their devices, and peripheral stimulation using ultrasound could add new dimensionalities to this communication."

Researchers will now investigage which ultrasound parameters stimulate which types of nerve fibers or receptors. Tyler also hopes to study people with Type 2 diabetes who have not yet developed neuropathy, with the ultimate goal of providing clues to treating or even preventing the pain associated with the condition.

This research may get a boost from a discovery that surprised Tyler during the PLOS ONE study.

"One thing we didn't expect is that some brain scans showed activation of pain pathways, yet the volunteers reported feeling no discomfort," Tyler said. "That's an intriguing finding. Though we don't yet know its full implications, being able to activate classic pain pathways without inducing perceptual pain can help us understand how the brain processes pain."

A team of Virginia Tech Carilion Research Institute scientists -- including Wynn Legon, Abby Rowlands, Alexander Opitz, and Tomokazu Sato -- joined Tyler in conducting the research. In addition to his position at the institute, Tyler is an assistant professor of biomedical engineering and science at the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences. He recently shared a McKnight Technological Innovations in Neuroscience Award for work in using ultrasound to develop noninvasive approaches to modulating the activity of select circuits in the brain.

Reference:

1. Wynn Legon, Abby Rowlands, Alexander Opitz, Tomokazu F. Sato, William J. Tyler. Pulsed Ultrasound Differentially Stimulates Somatosensory Circuits in Humans as Indicated by EEG and fMRI. PLoS ONE, 2012; 7 (12): e51177 DOI:

http://www.sciencedaily.com/releases/2012/12/121206131558.htm