Tag Archives: Yi Wang

Brain surgery with no scalpel or incisions

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A December 3, 2021 news item on ScienceDaily announces some very exciting work from the University of Virginia UVA) and Stanford University,

University of Virginia School of Medicine researchers have developed a noninvasive way to remove faulty brain circuits that could allow doctors to treat debilitating neurological diseases without the need for conventional brain surgery.

The UVA team, together with colleagues at Stanford University, indicate that the approach, if successfully translated to the operating room, could revolutionize the treatment of some of the most challenging and complex neurological diseases, including epilepsy, movement disorders and more. The approach uses low-intensity focused ultrasound waves combined with microbubbles to briefly penetrate the brain’s natural defenses and allow the targeted delivery of a neurotoxin. This neurotoxin kills the culprit brain cells while sparing other healthy cells and preserving the surrounding brain architecture.

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A November 22, 2021 University of Virginia news release (also on EurekAlert but published on December 3, 2021), which originated the news item, offers technical details (Note: Links have been removed),

“This novel surgical strategy has the potential to supplant existing neurosurgical procedures used for the treatment of neurological disorders that don’t respond to medication,” said researcher Kevin S. Lee of UVA’s Departments of Neuroscience and Neurosurgery and the Center for Brain Immunology and Glia, or BIG. “This unique approach eliminates the diseased brain cells, spares adjacent healthy cells and achieves these outcomes without even having to cut into the scalp.”

The Power of PING

The new approach, called “PING,” has already demonstrated exciting potential in laboratory studies. For instance, one of the promising applications for PING could be for the surgical treatment of epilepsies that do not respond to medication. Approximately a third of patients with epilepsy do not respond to anti-seizure drugs, and surgery can reduce or eliminate seizures for some of them. Lee and his team, along with their collaborators at Stanford, have shown that PING can reduce or eliminate seizures in two research models of epilepsy. The findings raise the possibility of treating epilepsy in a carefully targeted and noninvasive manner without the need for traditional brain surgery. 

Another important potential advantage of PING is that it could encourage the surgical treatment of appropriate patients with epilepsy who are reluctant to undergo conventional invasive or ablative surgery.

In a scientific paper newly published in the Journal of Neurosurgery, Lee and his collaborators detail the ability of PING to focally eliminate neurons in a brain region, while sparing non-target cells in the same area. In contrast, currently available surgical approaches damage all cells in a treated brain region. 

A key advantage of the approach is its incredible precision. PING harnesses the power of magnetic-resonance imaging to let scientists peer inside the skull so that they can precisely guide sound waves to open the body’s natural blood-brain barrier exactly where needed. This barrier is designed to keep harmful cells and molecules out of the brain, but it also prevents the delivery of potentially beneficial treatments.

The UVA group’s new paper concludes that PING allows the delivery of a highly targeted neurotoxin, cleanly wiping out problematic neurons, a type of brain cell, without causing collateral damage. 

Another key advantage of the precision of this approach is that it can be used on irregularly shaped targets in areas that would be extremely difficult or impossible to reach through regular brain surgery. “If this strategy translates to the clinic,” the researchers write in their new paper, “the noninvasive nature and specificity of the procedure could positively influence both physician referrals for, and patient confidence in, surgery for medically intractable neurological disorders.”

“Our hope is that the PING strategy will become a key element in the next generation of very precise, noninvasive, neurosurgical approaches to treat major neurological disorders,” said Lee, who is part of the UVA Brain Institute.

About the Research

Lee’s groundbreaking research has been supported by the National Institutes of Health, the Chester Fund and the Charlottesville-based Focused Ultrasound Foundation. The work is part of an expansive effort at UVA Health to explore the potential of scalpel-free focused ultrasound to treat complex diseases throughout the body.

UVA’s pioneering research has already paved the way for the federal Food and Drug Administration to approve focused ultrasound for the treatment of essential tremor, a common movement disorder, and Parkinson’s disease symptoms. Research is underway on its potential applications for many more conditions, including breast cancer and glioblastoma, a deadly form of brain tumor. Learn more about UVA’s focused ultrasound research.

The research team included Yi Wang, Matthew J. Anzivino, Yanrong Zhang, Edward H. Bertram, James Woznak, Alexander L. Klibanov, Erik Dumont and Max Wintermark. 

An application to patent the PING procedure has been submitted by members of the research group. 

The research was funded by the National Institutes of Health, grants R01 NS102194 and R01 CA217953-01; the Chester Fund; and the Focused Ultrasound Foundation.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu.

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

Noninvasive disconnection of targeted neuronal circuitry sparing axons of passage and nonneuronal cells by Yi Wang, Matthew J. Anzivino, Yanrong Zhang, Edward H. Bertram, James Woznak, Alexander L. Klibanov, Erik Dumont, Max Wintermark, and Kevin S. Lee. Journal of Neurosurgery DOI: https://doi.org/10.3171/2021.7.JNS21123 Online Publication Date: 19 Nov 2021

This paper is behind a paywall.

Inspiration from the sea for titanium implants (mussels) and adhesive panels for flexible sensors (octopuses/octopi/octopodes)

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I have two sea-inspired news bits both of which concern adhesion.

Mussels and titanium implants

A July 8, 2016 news item on ScienceDaily features some mussel-inspired research from Japan into how to make better titanium implants,

Titanium is used medically in applications such as artificial joints and dental implants. While it is strong and is not harmful to tissues, the metal lacks some of the beneficial biological properties of natural tissues such as bones and natural teeth. Now, based on insights from mussels–which are able to attach themselves very tightly to even metallic surfaces due to special proteins found in their byssal threads–scientists from RIKEN have successfully attached a biologically active molecule to a titanium surface, paving the way for implants that can be more biologically beneficial.

A July 11, 2016 RIKEN press release (also on EurekAlert but dated July 8, 2016), which originated the news item, provides more information,

The work began from earlier discoveries that mussels can attach to smooth surfaces so effectively thanks to a protein, L-DOPA, which is known to be able to bind very strongly to smooth surfaces such as rocks, ceramics, or metals (…). Interestingly, the same protein functions in humans as a precursor to dopamine, and is used as a treatment for Parkinson’s disease.

According to Chen Zhang of the RIKEN Nano Medical Engineering Laboratory, the first author of the paper published in Angewandte Chemie, “We thought it would be interesting to try to use various techniques to attach a biologically active protein—in our case we chose insulin-like growth factor-1, a promoter of cell proliferation—to a titanium surface like those used in implants” (…).

Using a combination of recombinant DNA technology and treatment with tyrosinase, they were able to create a hybrid protein that contained active parts of both the growth factor and L-DOPA. Tests showed that the proteins were able to fold normally, and further experiments in cell cultures demonstrated that the IGF-1 was still functioning normally. Thanks to the incorporation of the L-DOPA, the team was able to confirm that the proteins bound strongly to the titanium surface, and remained attached even when the metal was washed with phosphate-buffered saline, a water-based solution. Zhang says, “This is similar to the powerful properties of mussel adhesive, which can remain fixed to metallic materials even underwater.”

According to Yoshihiro Ito, Team Leader of the Emergent Bioengineering Research Team of the RIKEN Center for Emergent Matter Science, “We are very excited by this finding, because the modification process is a universal one that could be used with other proteins. It could allow us to prepare new cell-growth enhancing materials, with potential applications in cell culture systems and regenerative medicine. And it is particularly interesting that this is an example of biomimetics, where nature can teach us new ways to do things. The mussel has given us insights that could be used to allow us to live healthier lives.”

The work was done by RIKEN researchers in collaboration with Professor Peibiao Zhang of the Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, and Professor Yi Wang of the School of Pharmaceutical Sciences, Jilin University. The work was partially supported by the Japan Society for the Promotion of Science KAKENHI (Grant Number 15H01810 and 22220009), CAS-JSPS joint fund (GJHZ1519), and RIKEN MOST joint project.

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

A Bioorthogonal Approach for the Preparation of a Titanium-Binding Insulin-like Growth-Factor-1 Derivative by using Tyrosinase by Chen Zhang, Hideyuki Miyatake, Yu Wang, Takehiko Inaba, Yi Wang, Peibiao Zhang, and Prof. Yoshihiro Ito. Angewandte Chemie International Edition DOI: 10.1002/anie.201603155 Version of Record online: 6 JUL 2016

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Octopuses/octopi/octopodes and adhesive panels

Before launching into the science part of this news bit, here’s some grammar (from the Octopus Wikipedia entry; Note: Links have been removed),

The standard pluralized form of “octopus” in the English language is “octopuses” /ˈɒktəpʊsɪz/,[10] although the Ancient Greek plural “octopodes” /ɒkˈtɒpədiːz/, has also been used historically.[9] The alternative plural “octopi” — which misguidedly assumes it is a Latin “-us”-word — is considered grammatically incorrect.[11][12][13][14] It is nevertheless used enough to make it notable, and was formally acknowledged by the descriptivist Merriam-Webster 11th Collegiate Dictionary and Webster’s New World College Dictionary. The Oxford English Dictionary (2008 Draft Revision)[15] lists “octopuses”, “octopi”, and “octopodes”, in that order, labelling “octopodes” as rare and noting that “octopi” derives from the apprehension that octōpus comes from Latin.[16] In contrast, New Oxford American Dictionary (3rd Edition 2010) lists “octopuses” as the only acceptable pluralization, with a usage note indicating “octopodes” as being still occasionally used but “octopi” as being incorrect.[17]

Now the news. A July 12, 2016 news item on Nanowerk highlights some research into adhesives and octopuses,

With increased study of bio-adhesives, a significant effort has been made in search for novel adhesives that will combine reversibility, repeated usage, stronger bonds and faster bonding time, non-toxic, and more importantly be effective in wet and other extreme conditions.

A team of Korean scientists-made up of scientists from Korea Institute of Science and Technology (KIST) and UNIST has recently found a way to make building flexible pressure sensors easier–by mimicking the suction cups on octopus’s tentacles.

A July 5, 2016 UNIST (Ulsan National Institute of Science and Technology) press release, which originated the news item, provides more information,

According to the research team, “Although flexible pressure sensors might give future prosthetics and robots a better sense of touch, building them requires a lot of laborious transferring of nano- and microribbons of inorganic semiconductor materials onto polymer sheets.”

In search of an easier way to process this transfer printing, Prof. Hyunhyub Ko (School of Energy and Chemical Engineering, UNIST) and his colleagues turned to the octopus suction cups for inspiration.

An octopus uses its tentacles to move to a new location and uses suction cups underneath each tentacle to grab onto something. Each suction cup contains a cavity whose pressure is controlled by surrounding muscles. These can be made thinner or thicker on demand, increasing or decreasing air pressure inside the cup, allowing for sucking and releasing as desired.

By mimicking muscle actuation to control cavity-pressure-induced adhesion of octopus suckers, Prof. Ko and his team engineered octopus-inspired smart adhesive pads. They used the rubbery material polydimethylsiloxane (PDMS) to create an array of microscale suckers, which included pores that are coated with a thermally responsive polymer to create sucker-like walls.

The team discovered that the best way to replicate organic nature of muscle contractions would be through applied heat. Indeed, at room temperature, the walls of each pit sit in an ‘open’ state, but when the mat is heated to 32°C, the walls contract, creating suction, therby allowing the entire mate to adhere to a material (mimicking the suction function of an octopus). The adhesive strength also spiked from .32 kilopascals to 94 kilopascals at high temperature.

The team reports that the mat worked as envisioned—they made some indium gallium arsenide transistors that sat on a flexible substrate and also used it to move some nanomaterials to a different type of flexible material.

Prof. Ko and his team expect that their smart adhesive pads can be used as the substrate for wearable health sensors, such as Band-Aids or sensors that stick to the skin at normal body temperatures but fall off when rinsed under cold water.

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

Octopus-Inspired Smart Adhesive Pads for Transfer Printing of Semiconducting Nanomembranes by Hochan Lee, Doo-Seung Um, Youngsu Lee, Seongdong Lim, Hyung-jun Kim,  and Hyunhyub Ko. Advanced Materials DOI: 10.1002/adma.201601407 Version of Record online: 20 JUN 2016

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Observing nanoparticle therapeutics interact with blood in real time

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Sadly, there are no images showing nanoparticle therapeutics interacting with blood or anything else for that matter to illustrate this story but perhaps the insights offered should suffice. From Sept. 15, 2015 news item on Nanowerk,

Researchers at the National University of Singapore (NUS) have developed a technique to observe, in real time, how individual blood components interact and modify advanced nanoparticle therapeutics. The method, developed by an interdisciplinary team consisting clinician-scientist Assistant Professor Chester Lee Drum of the Department of Medicine at the NUS Yong Loo Lin School of Medicine, Professor T. Venky Venkatesan, Director of NUS Nanoscience and Nanotechnology Institute, and Assistant Professor James Kah of the Department of Biomedical Engineering at the NUS Faculty of Engineering, helps guide the design of future nanoparticles to interact in concert with human blood components, thus avoiding unwanted side effects.

A Sept. 15, 2015 NUS press release, which originated the news item, describes the research in more specific detail,

With their small size and multiple functionalities, nanoparticles have attracted intense attention as both diagnostic and drug delivery systems. However, within minutes of being delivered into the bloodstream, nanoparticles are covered with a shell of serum proteins, also known as a protein ‘corona’.

“The binding of serum proteins can profoundly change the behaviour of nanoparticles, at times leading to rapid clearance by the body and a diminished clinical outcome,” said Asst Prof Kah.

Existing methods such as mass spectroscopy and diffusional radius estimation, although useful for studying important nanoparticle parameters, are unable to provide detailed, real-time binding kinetics.

Novel method to understand nano-bio interactions

The NUS team, together with external collaborator Professor Bo Liedberg from the Nanyang Technological University, showed highly reproducible kinetics for the binding between gold nanoparticles and the four most common serum proteins: human serum albumin, fibrinogen, apolipoprotein A-1, and polyclonal IgG.

“What was remarkable about this project was the initiative taken by Abhijeet Patra, my graduate student from NUS Graduate School for Integrative Sciences and Engineering, in conceptualising the problem, and bringing together the various teams in NUS and beyond to make this a successful programme,” said Prof Venkatesan. “The key development is the use of a new technique using surface plasmon resonance (SPR) technology to measure the protein corona formed when common proteins in the bloodstream bind to nanoparticles,” he added.

The researchers first immobilised the gold nanoparticles to the surface of a SPR sensor chip with a linker molecule. The chip was specially modified with an alginate polymer layer which both provided a negative charge and active sites for ligand immobilisation, and prevented non-specific binding. Using a 6 x 6 microfluidic channel array, they studied up to 36 nanoparticle-protein interactions in a single experiment, running test samples alongside experimental controls.

“Reproducibility and reliability have been a bottleneck in the studies of protein coronas,” said Mr Abhijeet Patra. “The quality and reliability of the data depends most importantly upon the design of good control experiments. Our multiplexed SPR setup was therefore key to ensuring the reliability of our data.”

Testing different concentrations of each of the four proteins, the team found that apolipoprotein A-1 had the highest binding affinity for the gold nanoparticle surface, with an association constant almost 100 times that of the lowest affinity protein, polyclonal IgG.

“Our results show that the rate of association, rather than dissociation, is the main determinant of binding with the tested blood components,” said Asst Prof Drum.

The multiplex SPR system was also used to study the effect of modification with polyethylene (PEG), a synthetic polymer commonly used in nanoparticle formulations to prevent protein accumulation. The researchers found that shorter PEG chains (2-10 kilodaltons) are about three to four times more effective than longer PEG chains (20-30 kilodaltons) at preventing corona formation.

“The modular nature of our protocol allows us to study any nanoparticle which can be chemically tethered to the sensing surface,” explained Asst Prof Drum. “Using our technique, we can quickly evaluate a series of nanoparticle-based drug formulations before conducting in vivo studies, thereby resulting in savings in time and money and a reduction of in vivo testing,” he added.

The researchers plan to use the technology to quantitatively study protein corona formation for a variety of nanoparticle formulations, and rationally design nanomedicines for applications in cardiovascular diseases and cancer.

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

Component-Specific Analysis of Plasma Protein Corona Formation on Gold Nanoparticles Using Multiplexed Surface Plasmon Resonance by Abhijeet Patra, Tao Ding, Gokce Engudar, Yi Wang, Michal Marcin Dykas, Bo Liedberg, James Chen Yong Kah, Thirumalai Venkatesan, and Chester Lee Drum. Small  DOI: 10.1002/smll.201501603 Article first published online: 10 SEP 2015

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.