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Future soft optical fibers could allow for exploring new treatments to block peripheral nerve pain

Engineers at MIT have developed experimental soft, implantable optical fibers that could deliver light to major nerves to explore causes and potential treatments for peripheral nerve disorders in animal models.

(Peripheral nerve pain—from sciatica, motor neuron disease, and general numbness and pain—can occur when nerves outside the brain and spinal cord are damaged, resulting in tingling, numbness, and pain in affected limbs. Peripheral neuropathy is estimated to affect more than 20 million people in the United States.) 

“Current devices used to study nerve disorders are made of stiff materials that constrain movement, so that we can’t really study spinal cord injury and recovery if pain is involved,” says Siyuan Rao, assistant professor of biomedical engineering at the University of Massachusetts.

Optogenetics

The study is based on optogenetics, an animal research technique (originally developed at MIT) that genetically modifies neurons in the brain to respond to light. Neuroscientists have applied optogenetics in animals to precisely trace the neural pathways underlying a range of brain disorders, information that has led to targeted therapies for these conditions. 

But peripheral nerves experience constant pushing and pulling from the surrounding muscles and tissues. Rigid silicon devices would constrain an animal’s natural movement and potentially cause tissue damage.  

Testing transparent hydrogel fiber

Their new design is a soft, stretchable, transparent fiber made from hydrogel—a rubbery, biocompatible mix of polymers and water (a more Jell-O-like solution). 

The team tested the optical fibers in mice whose nerves were genetically modified to respond to blue light (to excite neural activity) or yellow light (to inhibit sciatic pain). 

“Now, people have a tool to study the diseases related to the peripheral nervous system, in very dynamic, natural, and unconstrained conditions,” said Xinyue Liu, an assistant professor at Michigan State University (MSU).

“We hope to help dissect mechanisms underlying pain in the peripheral nervous system. With time, our technology may help identify novel mechanistic therapies for chronic pain and other debilitating conditions such as nerve degeneration or injury.”

This research was supported, in part, by the National Institutes of Health, the National Science Foundation, the U.S. Army Research Office, the McGovern Institute for Brain Research, the Hock E. Tan and K. Lisa Yang Center for Autism Research, the K. Lisa Yang Brain-Body Center, and the Brain and Behavior Research Foundation.

Details of the team’s new fibers are reported today (Oct. 19, 2023), in a study appearing in Nature Methods. 

Citation: Liu, X., Rao, S., Chen, W., Felix, K., Ni, J., Sahasrabudhe, A., Lin, S., Wang, Q., Liu, Y., He, Z., Xu, J., Huang, S., Hong, E., Yau, T., Anikeeva, P., & Zhao, X. (2023). Fatigue-resistant hydrogel optical fibers enable peripheral nerve optogenetics during locomotion. Nature Methods, 1-8. c9 https://doi.org/10.1038/s41592-023-02020-9

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Wearable device could read or write data by just bending your finger

Researchers have invented an experimental wearable device using a material that generates power to create and store data by bending a finger—a possible, promising step towards health monitoring and other uses.

Multifunctional devices normally require several materials in layers, requiring nanomaterials with high precision, the researchers note.

The team, led by RMIT University and the University of Melbourne in collaboration with other Australian and international institutions, created the proof-of-concept device using a safe oxide of a low-temperature metal called bismuth.

Senior lead researcher Ali Zavabeti said the invention could be developed to create medical wearables that monitor vital signs and store personal data.

“The innovation was used in our experiments to write, erase and re-write images in nanoscale, so it could feasibly be developed to one day encode bank notes, original art or authentication services,” said Zavabeti, an engineer from RMIT and the University of Melbourne.

The team’s research is published in the journal Advanced Functional Materials.

“We tested natural motion behavior with the device attached to a finger joint, with an average output peak of about 1 volt,” Zavabeti said.

Memory functions

Lead author and PhD student Xiangyang Guo from RMIT said the team can print layers of bismuth oxide in just a few seconds.

“We fundamentally investigated this instant-printing technique for the first time, using low-melting point liquid metals,” said Guo.

The device was able to perform the memory functions of “read,” “write” and “erase” for various images. The device, which was not worn by a user during these memory experiments, wrote and stored the logo and symbol in a space that could fit 20 times within the width of a human hair.  

Other possible uses include sensing and energy harvesting, he said. “The material can act as a semiconductor, meaning it can be used for computation. It is a nanogenerator, meaning it’s energy efficient, with a green-energy supply from environmental vibrations and mechanical movements.”

Guo also said bismuth oxide was likely to cause less irritation to skin, compared with silicon, and it was durable, so it was stretchable and can be integrated into wearable technologies.

The researchers plan to adapt their approach to other low-temperature liquid and solid metals and alloys that could be developed for personalized wearables.

The Australian Research Council and the National Computational Infrastructure funded the research. The team included researchers from the University of Toronto, Western Sydney University, University of Sydney, University of New South Wales and Australian National University.

The researchers’ peer-reviewed article, “Multi-Functional Atomically Thin Oxides from Bismuth Liquid Metal,” was published in the journal Advanced Functional Materials.

Citation: Guo, X., Nguyen, C. K., Syed, N., Ravindran, A., Islam, M. A., Filleter, T., Cao, K., Wang, Y., Mazumder, A., Xu, C., Walia, S., Ghasemian, M. B., Kalantar-Zadeh, K., Scholten, S. C., Robertson, I. O., Healey, A. J., Tetienne, P., Lu, T., Liu, Y., . . . Zavabeti, A. Multi-Functional Atomically Thin Oxides from Bismuth Liquid Metal. Advanced Functional Materials, 2307348. https://onlinelibrary.wiley.com/doi/full/10.1002/adfm.202307348 (open access)

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When you walk, you intuitively avoid puddles or pavement cracks—now robots are about to catch up with you

There’s a biological component that allows humans and other mammals to navigate complex environments: Our human “central pattern generators” (CPG) are neural networks that produce rhythmic patterns of control signals for limbs, using simple environmental cues.

University of Pittsburg engineers have received a $1,606,454 award from the National Science Foundation to lead a two-year project to engineer these patterns and signals in neural networks in robots.

Fully functional robots with biomimetic sensorimotor control

Neuromorphic engineering—computing inspired by the human brain—will be key to achieving efficient, adaptive sensorimotor control in these robots, says Rajkumar Kubendran, principal investigator and assistant professor of electrical and computer engineering at Pitt.

“We aim to demonstrate a fully functional quadropod or hexapod robot that can learn to move, using principles informed by neuroscience, leading to biomimetic sensorimotor control for energy-efficient locomotion, and using learning algorithms running on bio-realistic neural networks,” Kubendran said. 

Critical uses include disaster response

“Agile robots that can explore unknown and treacherous terrains have the potential to enable autonomous navigation for commercial transport, enhance disaster response during floods and earthquakes or to remote and unsafe areas like malfunctioning nuclear plants or space exploration,” he said. 

The project, set to begin in 2024, is part of a larger $45 million initiative by the NSF to invest in the future of semiconductors. 

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New material could reconnect severed nerves or stimulate them remotely

Rice University neuroengineer Jacob Robinson and his team have designed a new magnetic-to-electric conversion material that is 120 times faster than similar materials. It can stimulate neurons remotely or bridge the gap in a broken sciatic nerve (tested using a rat model).

In a study published in the journal Nature Materials, the researchers showed that the new material could allow for neurostimulation treatments (such as transcranial magnetic stimulation) with less-invasive procedures. Instead of implanting a neurostimulation device, tiny amounts of the material could simply be injected at the desired site.

Stimulating 120-times-faster neural activity

The researchers started with a magnetoelectric material made up of a piezoelectric (generating electrical current from shape changes) layer of lead zirconium titanate sandwiched between two layers of metallic glass alloys. This material could be rapidly magnetized and demagnetized.

research illustration
Schematic of neural response for linear magnetic-to-electric conversion (top two conversions) versus nonlinear (bottom). (credit: Josh Chen/Rice University)

The researchers stacked layered platinum, hafnium oxide and zinc oxide on top of the original magnetoelectric film. This made it 120 times faster at stimulating neural activity, compared to previous magnetic materials and with a layer thiner than 200 nanometers (so in the future it could be injectable).

Proof of concept in neuroprosthetics

The researchers used the material with rats to stimulate peripheral nerves, restore function in a severed nerve, and prove fast electric signal speeds.

According to the researchers, the new metamaterial overcomes many challenges in neurotechnology, and this framework for advanced material design can be applied toward other applications, like sensing and memory in electronics.

The research was supported by the National Science Foundation (2023849) and the National Institutes of Health (U18EB029353).

Citation: Chen, J. C., Bhave, G., Alrashdan, F., Dhuliyawalla, A., Hogan, K. J., Mikos, A. G., & Robinson, J. T. (2023). Self-rectifying magnetoelectric metamaterials for remote neural stimulation and motor function restoration. Nature Materials, 1-8. https://doi.org/10.1038/s41563-023-01680-4

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New AI tool predicts viral outbreaks, using generative model

A radical new AI tool called EVEscape predicts viral mutations and new variants, using evolutionary biological information.

In tests, it successfully predicted the most concerning new SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) variants that occurred during the COVID-19 pandemic, according to its developers at Harvard Medical School and the University of Oxford. EVEscape can also help inform the development of vaccines and therapies for SARS-CoV-2 and other rapidly mutating viruses.

Model predicts changes about likely variants every two weeks

EVEscape has a generative model of evolutionary sequences that predicts changes that can occur to a virus, along with detailed biological and structural information about the virus. Together, they allow EVEscape to make predictions about the variants most likely to occur as the virus evolves.

In a study published Oct. 11 in Nature, the researchers show that if it had been deployed at the start of the COVID-19 pandemic, EVEscape would have predicted the most frequent mutations and identified the most concerning variants for SARS-CoV-2. The tool also made accurate predictions about other viruses, including HIV and influenza.

“We want to know if we can anticipate the variation in viruses and forecast new variants—because if we can, that’s going to be extremely important for designing vaccines and therapies,” said senior author Debora Marks, associate professor of systems biology in the Blavatnik Institute at Harvard Medical School.

From EVE to EVEscape

The researchers first developed EVE, short for evolutionary model of variant effect, in a different context: gene mutations that cause human diseases. In a previous study, EVE allowed researchers to discern disease-causing from benign mutations in genes linked to various conditions, including cancers and heart rhythm disorders.

Designing mutation-proof vaccines and therapies 

The team is now applying EVEscape to SARS-CoV-2 in real time, using all of the information available to make predictions about how it might evolve next. 

The researchers publish a biweekly ranking of new SARS-CoV-2 variants on their website and share this information with entities such as the World Health Organization. The complete code for EVEscape is also freely available online.

They are also testing EVEscape on understudied viruses such as Lassa and Nipah, two pathogens of pandemic potential for which relatively little information exists.al.

Funding for the research was provided by the National Institutes of Health (GM141007-01A1), the Coalition for Epidemic Preparedness Innovations, the Chan Zuckerberg Initiative, GSK, the UK Engineering and Physical Sciences Research Council, and the Alan Turing Institute.

Citation: Thadani, N. N., Gurev, S., Notin, P., Youssef, N., Rollins, N. J., Ritter, D., Sander, C., Gal, Y., & Marks, D. S. (11-Oct-2023). Learning from prepandemic data to forecast viral escape. Nature, 1-8. https://doi.org/10.1038/s41586-023-06617-0 (open-access)

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Wound-healing research produces full-thickness human bioprinted skin

Researchers at the Wake Forest Institute for Regenerative Medicine (WFIRM) have developed bioprinted skin that accelerates wound healing, supports healthy extracellular matrix remodeling, and may lead to complete wound recovery, according to a research paper in Science Translational Medicine.

This study involved bioprinting all six major primary human cell types present in skin. When transplanted onto mice and pigs in pre-clinical settings, the bioprinted skin formed blood vessels, skin patterns, and normal tissue formation. The study demonstrated improved wound closure, reduced skin contraction, and more collagen production to reduce scarring.

Important for burn victims, wounded warriors, and those with skin disorders

Skin regeneration has long been studied with hopes of providing complete healing for burn victims, wounded warriors, and those with skin disorders. Available grafts are often temporary, or if permanent, have only some of the elements of normal skin, which often have a scarred appearance. The creation of full-thickness skin has not been possible to date.

Anthony Atala, M.D., director of WFIRM and Adam Jorgensen, M.D., Ph.D., post-doctorate researcher at WFIRM, co-led the study.

Citation: Jorgensen, A. M., Gorkun, A., Mahajan, N., Willson, K., Clouse, C., Jeong, C. G., Varkey, M., Wu, M., Walker, S. J., Molnar, J. A., Murphttps://doi.org/adf7547hy, S. V., Lee, S. J., Yoo, J. J., Soker, S., & Atala, A. (2023). Multicellular bioprinted skin facilitates human-like skin architecture in vivo. Science Translational Medicine. https://doi.org/adf7547. https://www.science.org/doi/10.1126/scitranslmed.adf7547

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Researchers find evidence of largest-ever solar storm in ancient 14,300-year-old tree rings

Evidence of a largest-ever solar storm —a huge spike in radiocarbon levels—has been found by a team of scientists in ancient 14,300-year-old tree rings in the French Alps.

A similar solar storm today would be catastrophic for modern technological society, potentially wiping out telecommunications and satellite systems, causing massive electricity grid blackouts lasting months and costing us billions of pounds, the scientists say.

Miyake Events

Extreme solar storms could have huge impacts on Earth,” said Tim Heaton, Professor of Applied Statistics in the School of Mathematics at the University of Leeds. Nine such extreme solar storms—known as Miyake Events—have now been identified as having occurred over the last 15,000 years. 

The collaborative research is published today (Oct. 9) in the Royal Society’s Philosophical Transactions A: Mathematical, Physical and Engineering Sciences.

The largest, directly-observed solar storm occurred in 1859, known as the Carringon Event. It caused massive disruption on Earth, destroying telegraph machines and creating a night-time aurora so bright that birds began to sing, believing the Sun had begun to rise. 

Citation: Bard E, Miramont C, Capano M, Guibal F, Marschal C, Rostek F, Tuna T, Fagault Y, Heaton TJ (9-Oct-2023). A radiocarbon spike at 14,300 cal yr BP in subfossil trees provides the impulse response function of the global carbon cycle during the Late Glacial. Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences. DOI 10.1098/rsta.2022.0206 (pending publication)

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First map of neural connections of a mouse brain at the synapse level

The brain is incredibly complex, with nearly 100 billion neurons that communicate across trillions of junctions called synapses.

To understand how it all works, Harvard neuroscientist Jeff Lichtman has spent several decades generating maps of this complexity, pioneering a field known as “connectomics.”

Jeff Lichtman on connectomics

To further explore connectomics, Lichtman and partners, including Princeton University, MIT, Cambridge University and Johns Hopkins, have just received $30 million from the National Institutes of Health (NIH) and an additional $3 million from Harvard and Princeton.

Starting with mouse hippocampus

For this initial funding, the researchers will image just a 10-cubic-millimeter region in the hippocampus. “This region is of clinical interest because it is an essential part of the circuit underlying spatial navigation and memory, and of the earliest impairments and degeneration related to Alzheimer’s disease,” Lichtman said.

“The mouse brain is much smaller than a human’s. But when looking at individual neurons, synaptic vesicles and glial cells, you can’t tell the difference, At the level of cells and synapses, all mammalian brains are basically the same.”

The 33 million funding is “a grant for a proof-of-concept prequel to doing a whole mouse brain and the funds support the entire team,” Lichtman explained in an interview.

Wiring diagram to use machine learning

To explore the brain, the researchers will apply biological imaging techniques that Lichtman and colleagues have invented over several decades. For the NIH project, they will use two 91-beam scanning electron microscopes at Harvard and Princeton to capture images of thin sections of the mouse hippocampal formation.

Next, to explore further, the surface of each studied section will be etched away with an ion beam a few nanometers at a time. This imaging process will be repeated until the entire volume is viewed.

A team at Google Research will then computationally extract the resulting wiring diagram, using machine learning.

The team expects to generate about 10,000 terabytes of data for this initial 10-square-millimeter mouse brain section (50 times that amount of data would be generated, in future research, for a whole mouse brain).

The researchers also plan to develop a rapid-imaging strategy for connectomics, working with other awardees.

Related papers

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Artificial-life nanostructures: medicine of the future?

Two researchers have proposed that we use a type of “artificial life” called “hybrid peptide-DNA nanostructures” (based on viral vaccines and artificial life forms) to develop new methods of diagnosing and treating diseases.

Associate professor Chenguang Lou from the Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark and Professor Hanbin Mao from Kent State University have just written a research review of such nanostructures, published today in the open-access journal Cell Reports Physical Science.

Lou’s vision is to create viral vaccines (modified and weakened versions of a virus) and artificial life forms to diagnose and treat diseases.

“In nature, most organisms have natural enemies, but some do not,” Lou says. “For example, some disease-causing viruses have no natural enemy. It would be a logical step to create an artificial life form that could become an enemy to them.”

Artificial cellular organisms

Lou also envisions that such artificial life forms can act as vaccines against viral infection—using nanorobots or nanomachines loaded with medication or diagnostic elements, and sent and delivered to a patient’s body.

“An artificial viral vaccine may be about 10 years away,” says Lou. “An artificial cell, on the other hand, is on the horizon, because it consists of many elements that need to be controlled before we can start building with them. But with the knowledge we have, there is, in principle, no hindrance to produce artificial cellular organisms in the future.”

Building blocks: DNA and peptides

“DNA and peptides are some of the most important biomolecules in nature, making DNA technology and peptide technology the two most powerful molecular tools in the nanotechnological toolkit today,” according to Lou. “DNA technology provides precise control over programming, from the atomic level to the macro level; but it can only provide limited chemical functions since it only has four bases: A, C, G, and T.

“Peptide technology, on the other hand, can provide sufficient chemical functions on a large scale, as there are 20 amino acids to work with. Nature uses both DNA and peptides to build various protein factories found in cells, allowing them to evolve into organisms.”

Mao and Lou have recently succeeded in linking three-stranded DNA structures with three-stranded peptide structures, creating an artificial hybrid molecule that combines the strengths of both (see “Chirality transmission in macromolecular domains” by Lou et al., 2022).

Other Approaches

Other researchers are also working on connecting DNA and peptides, because this connection forms a strong foundation for the development of more advanced biological entities and life forms. These include:

Oxford University: A nanomachine made of DNA and peptides that can drill through a cell membrane, creating an artificial membrane channel through which small molecules can pass (Spruijt et al., Nat. Nanotechnol. 2018, 13, 739-745).

Arizona State University: Nicholas Stephanopoulos and colleagues have enabled DNA and peptides to self-assemble into 2D and 3D structures. (Buchberger et al., J. Am. Chem. Soc. 2020, 142, 1406-1416)

Northwest University: researchers have shown that microfibers can form in conjunction with DNA and peptides self-assembling. DNA and peptides operate at the nano level, so when considering the size differences, microfibers are huge. (Freeman et al., Science, 2018, 362, 808-813)

Ben-Gurion University of the Negev: scientists have used hybrid molecules to create an onion-like spherical struture containing cancer medication, which holds promise to be used in the body to target cancerous tumors. ()

“In my view, the overall value of all these efforts is that they can be used to improve society’s ability to diagnose and treat sick people. Looking forward, I will not be surprised that one day we can arbitrarily create hybrid nanomachines, viral vaccines and even artificial life forms from these building blocks to help the society to combat those difficult-to-cure diseases. It would be a revolution in healthcare,” says Lou.

Citation: Mathias Bogetoft Danielsen, Hanbin Mao, Chenguang Lou. (Oct. 5, 2023) Peptide-DNA conjugates as building blocks for de novo design of hybrid nanostructures. Cell Reports Physical Science (Open Access) DOI: https://doi.org/10.1016/j.xcrp.2023.101620 (open access)

Citation: Pandey, S., Mandal, S., Danielsen, M. B., Brown, A., Hu, C., Christensen, N. J., Kulakova, A. V., Song, S., Brown, T., Jensen, K. J., Wengel, J., Lou, C., & Mao, H. (2022). Chirality transmission in macromolecular domains. Nature Communications, 13(1), 1-11. https://doi.org/10.1038/s41467-021-27708-4 (open-access)

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Microdosing psilocybin mushrooms as a therapeutic tool

New research supports the use of psilocybin—the active compound in mushrooms with psychedelic properties—as a therapeutic tool. It examines the effects of microdosing (small daily doses) of psilocybin on rats, avoiding bias in humans from suggestion and other factors.

Understanding the effects and side effects of lower doses

Psilocybin is being widely investigated for its potential to assist in the treatment of various psychiatric disorders, primarily depression and addiction, through therapy supplemented with a high dose of psilocybin.

Now, research by Associate Professor Mikael Palner and PhD student Kat Kiilerich at the University of Southern Denmark has focused on repeated microdoses of psilocybin, which are significantly lower than the doses typically used in therapeutic settings.

Published in the journal Nature Molecular Psychiatry, the paper focuses on a study of how rats tolerated the repeated low doses of psilocybin (well) and didn’t exhibit signs of reduced pleasure, anxiety, or altered locomotor activity.

New research method

“The increased anxiety and stress in society currently have placed a strong focus on microdosing, leading to a surge in the trade of mushrooms,” said Palner. “Countries such as the Netherlands, Australia, the USA, and Canada have either legalized or are in the process of legalizing psilocybin for therapeutic treatment.”

The researchers say they have established a valid new method that can be used for further research into the effects of repeated low doses of psilocybin. The study also supports the numerous anecdotal reports of the benefits of microdosing as a therapeutic intervention, and suggests new approaches to treating various mental disorders.

Enhanced Understanding

Mikael Palne, an associate professor affiliated with the Research Unit for Clinical Physiology and Nuclear Medicine at SDU and OUH, conducts research on the biological understanding of mental illness and treatment with psychedelic substances.

Palner developed an interest in researching psychedelic substances and psilocybin when he lived in Silicon Valley, California, eleven years ago, where he witnessed the surge of self-improvement practices that garnered significant media attention and prompted more people to experiment with microdosing.

“This motivated me to launch the project I’ve been devoted to for the past six years,” he says.

Psilocybin’s ubiquitous uses

Palner notes that Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is a naturally occurring psychoactive compound found in over 200 different species of mushrooms. It has been used in religious and ceremonial contexts by various cultures for centuries, particularly among Native American tribes.

In the body, psilocybin is converted into psilocin, which is responsible for its psychoactive effects. Psilocin affects serotonin receptors in the brain that can alter mood, perception, and cognition.

Citation: Kiilerich, K.F., Lorenz, J., Scharff, M.B. et al. Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-02280-z

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