Category Archives: medicine

“Injectable tissue prosthesis coupled with closed-loop bioelectronic system” for damaged muscle/nerve regeneration and robot-assisted rehabilitation

A fascinating new use for hyaluronic acid (usually discussed in relation to cosmetic wrinkle-reduction) has been found according to a November 1, 2023 news item on ScienceDaily.

In a recent publication in the journal Nature, researchers from the Institute of Basic Science (IBS) in South Korea have made significant strides in biomaterial technology and rehabilitation medicine. They’ve developed a novel approach to healing muscle injury by employing “injectable tissue prosthesis” in the form of conductive hydrogels and combining it with a robot-assisted rehabilitation system.

Let’s imagine you are swimming in the ocean. A giant shark approaches and bites a huge chunk of meat out of your thigh, resulting in a complete loss of motor/sensor function in your leg.

If left untreated, such severe muscle damage would result in permanent loss of function and disability.

How on Earth will you be able to recover from this kind of injury?

Traditional rehabilitation methods for these kinds of muscle injuries have long sought an efficient closed-loop gait rehabilitation system that merges lightweight exoskeletons and wearable/implantable devices.

Such assistive prosthetic system is required to aid the patients through the process of recovering sensory and motor functions linked to nerve and muscle damage.

Unfortunately, the mechanical properties and rigid nature of existing electronic materials render them incompatible with soft tissues.

This leads to friction and potential inflammation, stalling patient rehabilitation.

To overcome these limitations, the IBS researchers turned to a material commonly used as a wrinkle-smoothing filler, called hyaluronic acid.

A November 2, 2023 Institute of Basic Science (IBS) press release (also on EurekAlert but published November 1, 2023), which originated the news item, explains how hyaluronic acid helps in tissue rehabilitation and regeneration,

Using this substance [hyaluronic acid], an injectable hydrogel was developed for “tissue prostheses”, which can temporarily fill the gap of the missing muscle/nerve tissues while it regenerates. The injectable nature of this material gives it a significant advantage over traditional bioelectronic devices, which are unsuitable for narrow, deep, or small areas, and necessitate invasive surgeries.

Thanks to its highly “tissue-like” properties, this hydrogel seamlessly interfaces with biological tissues and can be easily administered to hard-to-reach body areas without surgery. The reversible and irreversible crosslinks within the hydrogel adapt to high shear stress during injection, ensuring excellent mechanical stability. This hydrogel also incorporates gold nanoparticles, which gives it decent electrical properties. Its conductive nature allows for the effective transmission of electrophysiological signals between the two ends of injured tissues. In addition, the hydrogel is biodegrdable, meaning that the patients do not need to get surgery again.

With mechanical properties akin to natural tissues, exceptional tissue adhesion, and injectable characteristics, researchers believe this material offers a novel approach to rehabilitation.

Next, the researchers put this novel idea to the test in rodent models. To simulate volumetric muscle loss injury, a large chunk of muscle has been removed from the hind legs of these animals. By injecting the hydrogel and implanting the two kinds of stretchable tissue-interfacing devices for electrical sensing and stimulation, the researchers were able to improve the gait in the “injured” rodents. The hydrogel prosthetics were combined with robot assistance, guided by muscle electromyography signals. Together, the two helped enhance the animal’s gait without nerve stimulation. Furthermore, muscle tissue regeneration was effectively improved over the long term after the conductive hydrogel was used to fill muscle damage.

The injectable conductive hydrogel developed in this study excels in electrophysiological signal recording and stimulation performance, offering the potential to expand its applications. It presents a fresh approach to the field of bioelectronic devices and holds promise as a soft tissue prosthesis for rehabilitation support.

Emphasizing the significance of the research, Professor SHIN Mikyung notes, “We’ve created an injectable, mechanically tough, and electrically conductive soft tissue prosthesis ideal for addressing severe muscle damage requiring neuromusculoskeletal rehabilitation. The development of this injectable hydrogel, utilizing a novel cross-linking method, is a notable achievement. We believe it will be applicable not only in muscles and peripheral nerves but also in various organs like the brain and heart.”

Professor SON Donghee added, “In this study, the closed-loop gait rehabilitation system entailing tough injectable hydrogel and stretchable and self-healing sensors could significantly enhance the rehabilitation prospects for patients with neurological and musculoskeletal challenges. It could also play a vital role in precise diagnosis and treatment across various organs in the human body.”

The research team is currently pursuing further studies to develop new materials for nerve and muscle tissue regeneration that can be implanted in a minimally invasive manner. They are also exploring the potential for recovery in various tissue damages through the injection of the conductive hydrogel, eliminating the need for open surgery.

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

Injectable tissue prosthesis for instantaneous closed-loop rehabilitation by Subin Jin, Heewon Choi, Duhwan Seong, Chang-Lim You, Jong-Sun Kang, Seunghyok Rho, Won Bo Lee, Donghee Son & Mikyung Shin. Nature volume 623, pages 58–65 (2023) DOI: https://doi.org/10.1038/s41586-023-06628-x Published: 01 November 2023 Issue Date: 02 November 2023

This paper is behind a paywall.

Nanoparticle treatment for rheumatoid arthritis

An October 26, 2023 news item on phys.org announced a possible new treatment for rheumatoid arthritis (RA), Note: Links have been removed,

A team of scientists [Korea] has developed a new solution for the treatment of rheumatoid arthritis (RA). The work has been published in Nature Nanotechnology.

RA is a chronic disease that, unfortunately, has no cure. The disease triggers a mix of troublesome symptoms like inflamed joints, harmful cytokines, and immune system imbalances, which work together to create a relentless cycle of worsening symptoms. While targeting some of these factors can provide short-term relief, others remain unresolved, leading to a frustrating cycle of remission and flare-ups.

One of the major hurdles in RA treatment is the inability to restore the immune system to its healthy state. This leaves the body unable to control the continuous production of harmful substances like reactive oxygen species (ROS) and inflammatory cytokines, leading to persistent inflammation and discomfort.

In essence, the ideal treatment for RA should not only provide immediate relief from inflammation and symptoms but also address the root cause by restoring the immune system to its normal, balanced state.

New nanoparticle-based system as a solution

The new platform involves immobilizing ceria nanoparticles (Ce NPs) onto mesenchymal stem cell-derived nanovesicles (MSCNVs). Both of these components can hinder different pathogenic factors, allowing them to work both individually and cooperatively to achieve a comprehensive treatment.

Caption: Schematic illustration of comprehensive and combination RA therapy by Ce-MSCNV nanoparticles. Ce-MSCNVs scavenge the over-produced ROS in an RA knee joint, induce M1 to M2 macrophage polarization for immediate relief of inflammation and symptoms, modulate DCs into tDCs, and finally induce Tregs. Credit: Institute for Basic Science

An October 27, 2023 Institute for Basic Science (IBS) press release (also on EurekAlert but published October 26, 2023), which originated the news item, provides more details about the proposed treatment,

Ce NPs – can scavenge the overproduced ROS in RA-inflicted knee joints. They also induce polarization of M1 macrophages into M2, achieving immediate relief of inflammation and symptoms.

MSCNVs – deliver immunomodulatory cytokines, which turn dendritic cells (DC) into tolerogenic dendritic cells (tDCs). This consequently generates regulatory T cells for long-term immune tolerance.

In short, this approach aims to bridge both innate and adaptive immunity to achieve both short-term pain relief, as well as convert the tissue environment into an immune-tolerant state to prevent the recurrence of symptoms.

Researchers confirmed the efficacy of this approach using a collagen-induced arthritis mouse model. The Ce-MSCNV system was able to comprehensively treat and prevent RA by simultaneously relieving the immediate and restoring T cell immunity. Supporting data suggest that improvement in conditions can be achieved after only a single-dose treatment.

The mice treated with the Ce-MSCNV combination fared far better compared to the ones only treated using the Ce NP or MSCNV group. This clearly demonstrates the synergy between anti-inflammation and immunomodulation and underlines the importance of the combined therapy for effective RA treatment. In addition, Ce-MSCNV administration prior to booster injection markedly reduced the incidence and severity of symptoms, supporting the prophylactic potential of these nanoparticles.

First author KOO Sagang stated, “One of the hardest decisions in intractable disease therapy is determining how long the treatment should be carried on. For RA, it would not be appropriate to stop treatment just because the target marker is stabilized. A safer indicator should be that the innate and adaptive components of the collapsed immune system are normalized to protect the body.”

Koo believes that the strategy adopted by Ce-MSCNVs, where different treatment mechanisms work together, provides a unique advantage in this regard. Furthermore, she predicts that a similar approach would also be applicable to other intractable, inflammatory, and autoimmune diseases for this purpose. The components within the system may also be modified. For example, other catalysts for generating ROS or other cell-derived nanovesicles could be utilized depending on the types of diseases. Overall, this study proves the potential of a hybrid nanoparticle system for the comprehensive treatment of autoimmune disease and modulation of the immune system.

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

Ceria-vesicle nanohybrid therapeutic for modulation of innate and adaptive immunity in a collagen-induced arthritis model by Sagang Koo, Hee Su Sohn, Tae Hee Kim, Siyeon Yang, Se Youn Jang, Seongryeol Ye, Boomin Choi, Soo Hyeon Kim, Kyoung Sun Park, Hyun Mu Shin, Ok Kyu Park, Cheesue Kim, Mikyung Kang, Min Soh, Jin Yoo, Dokyoon Kim, Nohyun Lee, Byung-Soo Kim, Youngmee Jung & Taeghwan Hyeon. Nature Nanotechnology (2023) DOI: https://doi.org/10.1038/s41565-023-01523-y Published: 26 October 2023

This paper is behind a paywall.

Antimicrobial ‘safe-tea’ with silver nanoparticles and green tea

This work is not about drinking tea with silver nanoparticles in it or ingesting colloidal silver by any means, a dangerous practice as Nicole Karlis’s January 7, 2024 article for Salon highlights, Note: Links have been removed,

The HBO docuseries “Love Has Won: The Cult of Mother God” begins with a jarring image. The corpse of the cult leader, Amy Carlson, laying in a bed, wrapped in blankets and string lights. She is noticeably gaunt and her face is a very blue color. When Carlson died in 2021 at the age of 45, a coroner’s report deemed her cause of death to be “alcohol abuse, anorexia and chronic colloidal silver ingestion.”

Most medical experts advise against ingesting silver — especially in large amounts. That’s because too much of it can build up in a person’s body and lead to argyria, which is the condition that Carlson and Stan Jones both had that turned them a blue. While argyria alone isn’t a serious health condition, it doesn’t go away when a person stops ingesting silver. Plus, too much silver can be fatal. [emphasis mine]

A November 17, 2023 news item on phys.org announced research from the Polish Academy of Sciences into improving antimicrobial activity, Note: A link has been removed,

Researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) have demonstrated that green tea–silver nanoparticles as a powerful tool against pathogens such as bacteria and yeast. Their work is published in Nanoscale Advances.

An undated Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) press release (also published on EurekAlert and dated November 17, 2023), which originated the news item, describes this work, which is intended for medical applications, in more detail,

Once upon a time, people believed to be invincible against bacterial diseases, thanks to the antibiotics. Does this sound like a fairy tale? By all means! Nothing could be further from the truth. Despite widespread access to antibiotic therapy, many lives are lost due to pathogens invisible to the eye. The ability to develop drugs that can combat resistant strains of bacteria has not kept pace with the spread of resistance. So far, innovations to defeat antimicrobial-resistant strains of bacteria are in high demand. Recently, researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) demonstrated green tea-silver nanoparticles as a powerful tool against pathogens such as bacteria and yeast. Their goal was to develop an efficient method to combat bacteria that are otherwise unaffected by antimicrobial agents, such as antibiotics.

Following the discovery of antibiotics, there came a change in the curse of mankind by accelerating the development of medicine and extending human life expectancy. Their successful implementation led to the rapid development of pharmacy, providing more and more drugs against many pathogens. Nevertheless, the overuse of antibiotics has led to the emergence of resistance to these compounds, becoming one of the biggest health threats worldwide. As a result, antibiotic resistance has emerged faster than the advancement of antibiotics . The appearance of new drugs on the horizon to combat these pathogens is a short-lasting spark. Even if we seem to be on the losing end, there is still a chance to defeat an invisible enemy.

This hitch was researched by the team of scientists from the IPC PAS under the supervision of Prof. Jan Paczesny, who proposed new nanoformulations for use against widespread and challenging pathogens such as ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and other problematic yeast pathogens such as Candida auris or Cryptococcus neoformans. These microorganisms, treated with commercially available antibiotics, rapidly develop antibiotic resistance. Researchers chose ESKAPE as the target group since these pathogens lead to serious diseases, from sepsis to even cancer. How? This is where the story begins.

A few months ago, Paczesny’s team decided to try combining silver nanoparticles, which are known for their antimicrobial and antifungal properties, and tea extracts rich in polyphenols additionally possessing antioxidant properties. The concept was built to enhance broad-spectrum efficacy against pathogens using green hybrid silver nanoparticles (AgNPs), which are significantly more effective than all ingredients and even more effective than certain antibiotics. Why are these hybrid particles so special? In their work, three well-known tea varieties: black tea (B-Tea), green tea (G-Tea) and Pu-erh tea (R-Tea) were used as a capping agent, which acts as a stabilizer to protect the synthesized  particles from aggregation. In this way, the particles offer a high active surface area compared to other formulations. Additionally, such synthesis is eco-friendly for the use of natural ingredients during precipitation. The structures produced vary in shape and size from 34 to 65 nm, depending on the type of tea used during synthesis, and show different reactivity towards microorganisms.

Initially, silver nanoparticles produced in the presence of tea extracts (B-TeaNPs, G-TeaNPs and R-TeaNPs) were used to treat Gram-negative (E. coli) and Gram-positive (E. faecium) bacterial strains to test the effect on strains with different cell envelope morphologies. They looked at the interactions between the manufactured nanoparticles and the pathogens to determine efficacy, comparing the results with commercially available antibiotics. The ESKAPE pathogens were then tested according to a protocol for the most effective concentration and composition of the particles, revealing up to a 25% decrease in the number of bacterial cells in E. faecium and a 90% decrease in the case of E. cloacae. Interestingly, the green silver nanoparticles also showed antifungal activity, leading to an 80% decrease in the number of viable cells of C. auris and about a 90% decrease for C. neoformans.

The first author, Sada Raza claims “What is more, the size of nanoparticles is usually related to the cytotoxic effect of nanomaterials, with smaller particles being more cytotoxic. This should favor control AgNPs and R-TeaNPs over G-TeaNPs and B-TeaNPs in our experiments. This was not the case. In most experiments, C-AgNPs and R-TeaNPs showed the lowest antimicrobial efficacy. This is in line with other studies, which demonstrated that size is not a primary factor affecting the antimicrobial activity of AgNPs.

The antibacterial and antifungal properties of silver nanoparticles made with tea extracts are greater than those of silver nanoparticles alone due to their high content of phenolic compounds, isoflavonoids (especially catechins such as epigallocatechin (EGC) and epigallocatechin gallate (EGCG)). These combinations, using biologically active tea extracts and smaller amounts of silver nanoparticles, appear to be a potential way to combat a range of infections and even replace antibiotics in some applications.

“We established that silver nanoparticles synthesized with tea extracts have higher antibacterial properties than silver nanoparticles alone. Therefore, lower dosages of TeaNPs could be used (0.1 mg mL−1). We confirmed that in some cases, the synergistic effect of tea extracts and silver nanoparticles allowed for efficacy higher than that of antibiotics (ampicillin) when tested at the same concentrations (0.1 mg mL−1) and after a relatively short exposure time of three hours.” – remarks Mateusz Wdowiak, co-author of this work.

The researchers found that the antimicrobial hybrid nanoparticles resulted in a significant reduction in bacteria compared to antibiotics or compounds separately. Although not all bacteria were killed, this is a significant improvement that could aid the treatment of superbugs using much lower doses than other commercially available compounds. The amount of hybrid silver nanoparticles needed to overcome bacteria or fungal infections is extremely low, making them cost-effective, so the key to using them well is not only functionality, but also the low cost of application.

It is an approach that can also be adapted to combat other difficult-to-treat bacterial infections. The new nanoparticles developed by researchers at the IPC PAS could bring us one step closer to effectively killing deadly drug-resistant superbugs, providing an alternative to antibiotics against Gram-negative and Gram-positive bacteria. This study also shows how much more work there is to be done in this field. Compounds used separately were much less effective than the green hybrid.

In the future, the researchers’ main goal is to use nanoparticles in everyday life, starting with agricultural applications, replacing harmful compounds used in fields to overcome infestations in plants and bring us closer to organic farming. On a larger scale, the proposed material could also be used in biomedical applications, such as an additive for wound dressings to protect against Gram-negative and Gram-positive bacteria. They hope to use nanotechnology to develop more targeted treatments for drug-resistant superbugs.

Their work was published in Nanoscale Advances journal and was financed by the National Science Centre, Poland, within the SONATA BIS grant number 2017/26/E/ST4/00041 and Foundation for Polish Science from the European Regional Development Fund within the project POIR.04.04.00-00-14D6/18-00 ‘Hybrid sensor platforms for integrated photonic systems based on ceramic and polymer materials (HYPHa)’ (TEAM-NET program).

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

Enhancing the antimicrobial activity of silver nanoparticles against ESKAPE bacteria and emerging fungal pathogens by using tea extracts by Sada Raza, Mateusz Wdowiak, Mateusz Grotek, Witold Adamkiewicz, Kostiantyn Nikiforow, Pumza Mente, and Jan Paczesny. Nanoscale Adv., 2023,5, 5786-5798 DOI: https://doi.org/10.1039/D3NA00220A

This paper is licensed under a Creative Commons Attribution 3.0 Unported Licence. “You can use material from this article in other publications without requesting further permissions from the RSC [Royal Society of Chemistry], provided that the correct acknowledgement is given.” Or, consider it an open access paper.

Finally, this is not a recommendation not is it an endorsement for the ingestion of colloidal silver.

Simon Fraser University’s (SFU; Vancouver, Canada) Café Scientifique Winter/Spring 2024 events + a 2023 Nobel-themed lecture

There are three upcoming Simon Fraser University (SFU) Café Scientifique events (Zoom) and one upcoming Nobel=themed lecture (in person) according to a January 15, 2024 notice (received via email), Note: All the events are free,

Hello SFU Cafe Scientifique friends!

We are back with a brand new line up for our Cafe Scientifique discussion series.  Zoom invites will be sent closer to the event dates [emphasis mine].  We hope you can join us.

All event information and registration links on this page: https://www.sfu.ca/science/community.html

Café Scientifique: Why Do Babies Get Sick? A Systems Biology Approach to Developing Diagnostics and Therapeutics for Neonatal Sepsis. 

Tuesday, January 30, 5:00-6:30pm over Zoom 

Around the world five newborn babies die each second from life-threatening infections. Unfortunately there is no fast or easy way to tell which microbes are involved. Molecular Biology and Biochemistry assistant professor Amy Lee will share how we can use genomics and machine learning approaches to tackle this challenge.
Register here. https://events.sfu.ca/event/38235-cafe-scientifique-january-why-do-babies-get-sick?

Cafe Scientifique: From data to dollars: A journey through financial modelling
Tuesday, February 27, 5:00-6:30 pm over Zoom 

Financial modelling involves using mathematical and statistical techniques to understand future financial scenarios, helping individuals and businesses make informed decisions about their investments. Join Dr. Jean-François Bégin as he explores how these models can empower us to navigate the complexities of financial markets.

Register here: https://www.eventbrite.ca/e/763521010897

Cafe Scientifique: Overtraining and the Everyday Athlete
Tuesday, April 30, 5:00-6:30 pm over Zoom 

What happens when we train too hard, don’t take enough time to recover, or underfuel while exercising, and how that applies to both elite athletes and just your “everyday athlete.” Join Dr. Alexandra Coates from our Biomedical Physiology and Kinesiology Department in this interesting discussion.

Register here: https://www.eventbrite.ca/e/763521010897

Missed our last Café Scientifique talk [Decoding how life senses and responds to carbon dioxide gas] with Dustin King? [SFU Molecular Biology and Biochemistry Assistant Professor Dustin King’s Indigenous background is central to his work and relationship with the biochemical research he conducts. He brings Indigenous ways of knowing and a two-eye seeing approach to critical questions about humanity’s impact upon the natural world …] Watch it on YouTube: https://www.youtube.com/watch?v=xCHTSbF3RVs&list=PLTMt9gbqLurAMfSHQqVAHu7YbyOFq81Ix&index=10

The ‘2023 Nobel Prize Lectures’ being presented by SFU do not feature the 2023 winners but rather, SFU experts in the relevant field, from the January 15, 2024 SFU Café Scientifique notice (received via email),

BACK IN-PERSON AT THE SCIENCE WORLD THEATRE!

Location: Science World Theatre 1455 Quebec Street Vancouver, BC V6A 3Z7

NOBEL PRIZE LECTURES  

Wednesday, March 6, 2024 

6:30-7:30 pm Refreshments, 7:30-9:30 pm Lectures 

Celebrate the 2023 Nobel awardees in Chemistry, Physics, Physiology or Medicine!

SFU experts will explain Nobel laureates’ award-winning research and its significance to our everyday lives. 

Featured presenters are

*Mark Brockman from Molecular Biology and Biochemistry for the Nobel Prize in Medicine and Physiology;

*Byron Gates from Chemistry for the Nobel Prize in Chemistry; and

*Shawn Sederberg from the School of Engineering Science for the Nobel Prize in Physics.

Register here: https://www.eventbrite.ca/e/nobel-prize-lectures-tickets-773387301237

For anyone who has trouble remembering who and why the winners were awarded a 2023 Nobel Prize, here’s a nobleprize.org webpage devoted to the 2023 winners.

Reversing lower limb paralysis

This regenerative treatment is at a very early stage, which means the Swiss researchers have tried it on mice as you can see in the following video (runtime: 2 mins. 15 secs.). Towards the end of the video, researcher Grégoire Courtine cautions there are many hurdles before this could be used in humans, if ever,

A September 22, 2023 Ecole Polytechnique Fédérale de Lausanne (EPFL) press release (also on EurekAlert but published September 21, 2023) by Emmanuel Barraud, describes the work in more detail,

When the spinal cords of mice and humans are partially damaged, the initial paralysis is followed by the extensive, spontaneous recovery of motor function. However, after a complete spinal cord injury, this natural repair of the spinal cord doesn’t occur and there is no recovery. Meaningful recovery after severe injuries requires strategies that promote the regeneration of nerve fibers, but the requisite conditions for these strategies to successfully restore motor function have remained elusive.

“Five years ago, we demonstrated that nerve fibers can be regenerated across anatomically complete spinal cord injuries,” says Mark Anderson, a senior author of the study. “But we also realized this wasn’t enough to restore motor function, as the new fibers failed to connect to the right places on the other side of the lesion.” Anderson is the director of Central Nervous System Regeneration at .NeuroRestore and a scientist at the Wyss Center for Bio and Neuroengineering.

Working in tandem with peers at UCLA [University of California at Los Angeles] and Harvard Medical School, the scientists used state-of-the-art equipment at EPFL’s Campus Biotech facilities in Geneva to run in-depth analyses and identity which type of neuron is involved in natural spinal-cord repair after partial spinal cord injury. “Our observations using single-cell nuclear RNA sequencing not only exposed the specific axons that must regenerate, but also revealed that these axons must reconnect to their natural targets to restore motor function,” says Jordan Squair, the study’s first author. The team’s findings appear in the 22 September 2023 issue of Science.

Towards a combination of approaches

Their discovery informed the design of a multipronged gene therapy. The scientists activated growth programs in the identified neurons in mice to regenerate their nerve fibers, upregulated specific proteins to support the neurons’ growth through the lesion core, and administered guidance molecules to attract the regenerating nerve fibers to their natural targets below the injury. “We were inspired by nature when we designed a therapeutic strategy that replicates the spinal-cord repair mechanisms occurring spontaneously after partial injuries,” says Squair.

Mice with anatomically complete spinal cord injuries regained the ability to walk, exhibiting gait patterns that resembled those quantified in mice that resumed walking naturally after partial injuries. This observation revealed a previously unknown condition for regenerative therapies to be successful in restoring motor function after neurotrauma. “We expect that our gene therapy will act synergistically with our other procedures involving electrical stimulation of the spinal cord,” says Grégoire Courtine, a senior author of the study who also heads .NeuroRestore together with Jocelyne Bloch. “We believe a complete solution for treating spinal cord injury will require both approaches – gene therapy to regrow relevant nerve fibers, and spinal stimulation to maximize the ability of both these fibers and the spinal cord below the injury to produce movement.”

While many obstacles must still be overcome before this gene therapy can be applied in humans, the scientists have taken the first steps towards developing the technology necessary to achieve this feat in the years to come.

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

Recovery of walking after paralysis by regenerating characterized neurons to their natural target region by Jordan W. Squair, Marco Milano, Alexandra de Coucy, Matthieu Gautier, Michael A. Skinnider, Nicholas D. James, Newton Cho, Anna Lasne, Claudia Kathe,Thomas H. Hutson, Steven Ceto, Laetitia Baud, Katia Galan, Viviana Aureli, Achilleas Laskaratos, Quentin Barraud, Timothy J. Deming, Richie E. Kohman, Bernard L. Schneider, Zhigang He, Jocelyne Bloch, Michael V. Sofroniew, Gregoire Courtine, and Mark A. Anderson. Science 21 Sep 2023 Vol 381, Issue 6664 pp. 1338-1345 DOI: 10.1126/science.adi641

This paper is behind a paywall.

This March 25, 2015 posting, “Spinal cords, brains, implants, and remote control,” features some research from EPFL researchers whose names you might recognize from this posting’s research paper.

Mentioned in the press release, the Swiss research centre website for NeuroRestore is here.

FrogHeart’s 2023 comes to an end as 2024 comes into view

My personal theme for this last year (2023) and for the coming year was and is: catching up. On the plus side, my 2023 backlog (roughly six months) to be published was whittled down considerably. On the minus side, I start 2024 with a backlog of two to three months.

2023 on this blog had a lot in common with 2022 (see my December 31, 2022 posting), which may be due to what’s going on in the world of emerging science and technology or to my personal interests or possibly a bit of both. On to 2023 and a further blurring of boundaries:

Energy, computing and the environment

The argument against paper is that it uses up resources, it’s polluting, it’s affecting the environment, etc. Somehow the part where electricity which underpins so much of our ‘smart’ society does the same thing is left out of the discussion.

Neuromorphic (brainlike) computing and lower energy

Before launching into the stories about lowering energy usage, here’s an October 16, 2023 posting “The cost of building ChatGPT” that gives you some idea of the consequences of our insatiable desire for more computing and more ‘smart’ devices,

In its latest environmental report, Microsoft disclosed that its global water consumption spiked 34% from 2021 to 2022 (to nearly 1.7 billion gallons , or more than 2,500 Olympic-sized swimming pools), a sharp increase compared to previous years that outside researchers tie to its AI research. [emphases mine]

“It’s fair to say the majority of the growth is due to AI,” including “its heavy investment in generative AI and partnership with OpenAI,” said Shaolei Ren, [emphasis mine] a researcher at the University of California, Riverside who has been trying to calculate the environmental impact of generative AI products such as ChatGPT.

Why it matters: Microsoft’s five WDM [West Des Moines in Iowa] data centers — the “epicenter for advancing AI” — represent more than $5 billion in investments in the last 15 years.

Yes, but: They consumed as much as 11.5 million gallons of water a month for cooling, or about 6% of WDM’s total usage during peak summer usage during the last two years, according to information from West Des Moines Water Works.

The focus is AI but it doesn’t take long to realize that all computing has energy and environmental costs. I have more about Ren’s work and about water shortages in the “The cost of building ChatGPT” posting.

This next posting would usually be included with my other art/sci postings but it touches on the issues. My October 13, 2023 posting about Toronto’s Art/Sci Salon events, in particular, there’s the Streaming Carbon Footprint event (just scroll down to the appropriate subhead). For the interested, I also found this 2022 paper “The Carbon Footprint of Streaming Media:; Problems, Calculations, Solutions” co-authored by one of the artist/researchers (Laura U. Marks, philosopher and scholar of new media and film at Simon Fraser University) who presented at the Toronto event.

I’m late to the party; Thomas Daigle posted a January 2, 2020 article about energy use and our appetite for computing and ‘smart’ devices for the Canadian Broadcasting Corporation’s online news,

For those of us binge-watching TV shows, installing new smartphone apps or sharing family photos on social media over the holidays, it may seem like an abstract predicament.

The gigabytes of data we’re using — although invisible — come at a significant cost to the environment. Some experts say it rivals that of the airline industry. 

And as more smart devices rely on data to operate (think internet-connected refrigerators or self-driving cars), their electricity demands are set to skyrocket.

“We are using an immense amount of energy to drive this data revolution,” said Jane Kearns, an environment and technology expert at MaRS Discovery District, an innovation hub in Toronto.

“It has real implications for our climate.”

Some good news

Researchers are working on ways to lower the energy and environmental costs, here’s a sampling of 2023 posts with an emphasis on brainlike computing that attest to it,

If there’s an industry that can make neuromorphic computing and energy savings sexy, it’s the automotive indusry,

On the energy front,

Most people are familiar with nuclear fission and some its attendant issues. There is an alternative nuclear energy, fusion, which is considered ‘green’ or greener anyway. General Fusion is a local (Vancouver area) company focused on developing fusion energy, alongside competitors from all over the planet.

Part of what makes fusion energy attractive is that salt water or sea water can be used in its production and, according to that December posting, there are other applications for salt water power,

More encouraging developments in environmental science

Again, this is a selection. You’ll find a number of nano cellulose research projects and a couple of seaweed projects (seaweed research seems to be of increasing interest).

All by myself (neuromorphic engineering)

Neuromorphic computing is a subset of neuromorphic engineering and I stumbled across an article that outlines the similarities and differences. My ‘summary’ of the main points and a link to the original article can be found here,

Oops! I did it again. More AI panic

I included an overview of the various ‘recent’ panics (in my May 25, 2023 posting below) along with a few other posts about concerning developments but it’s not all doom and gloom..

Governments have realized that regulation might be a good idea. The European Union has a n AI act, the UK held an AI Safety Summit in November 2023, the US has been discussing AI regulation with its various hearings, and there’s impending legislation in Canada (see professor and lawyer Michael Geist’s blog for more).

A long time coming, a nanomedicine comeuppance

Paolo Macchiarini is now infamous for his untested, dangerous approach to medicine. Like a lot of people, I was fooled too as you can see in my August 2, 2011 posting, “Body parts nano style,”

In early July 2011, there were reports of a new kind of transplant involving a body part made of a biocomposite. Andemariam Teklesenbet Beyene underwent a trachea transplant that required an artificial windpipe crafted by UK experts then flown to Sweden where Beyene’s stem cells were used to coat the windpipe before being transplanted into his body.

It is an extraordinary story not least because Beyene, a patient in a Swedish hospital planning to return to Eritrea after his PhD studies in Iceland, illustrates the international cooperation that made the transplant possible.

The scaffolding material for the artificial windpipe was developed by Professor Alex Seifalian at the University College London in a landmark piece of nanotechnology-enabled tissue engineering. …

Five years later I stumbled across problems with Macchiarini’s work as outlined in my April 19, 2016 posting, “Macchiarini controversy and synthetic trachea transplants (part 1 of 2)” and my other April 19, 2016 posting, “Macchiarini controversy and synthetic trachea transplants (part 2 of 2)“.

This year, Gretchen Vogel (whose work was featured in my 2016 posts) has written a June 21, 2023 update about the Macchiarini affair for Science magazine, Note: Links have been removed,

Surgeon Paolo Macchiarini, who was once hailed as a pioneer of stem cell medicine, was found guilty of gross assault against three of his patients today and sentenced to 2 years and 6 months in prison by an appeals court in Stockholm. The ruling comes a year after a Swedish district court found Macchiarini guilty of bodily harm in two of the cases and gave him a suspended sentence. After both the prosecution and Macchiarini appealed that ruling, the Svea Court of Appeal heard the case in April and May. Today’s ruling from the five-judge panel is largely a win for the prosecution—it had asked for a 5-year sentence whereas Macchiarini’s lawyer urged the appeals court to acquit him of all charges.

Macchiarini performed experimental surgeries on the three patients in 2011 and 2012 while working at the renowned Karolinska Institute. He implanted synthetic windpipes seeded with stem cells from the patients’ own bone marrow, with the hope the cells would multiply over time and provide an enduring replacement. All three patients died when the implants failed. One patient died suddenly when the implant caused massive bleeding just 4 months after it was implanted; the two others survived for 2.5 and nearly 5 years, respectively, but suffered painful and debilitating complications before their deaths.

In the ruling released today, the appeals judges disagreed with the district court’s decision that the first two patients were treated under “emergency” conditions. Both patients could have survived for a significant length of time without the surgeries, they said. The third case was an “emergency,” the court ruled, but the treatment was still indefensible because by then Macchiarini was well aware of the problems with the technique. (One patient had already died and the other had suffered severe complications.)

A fictionalized tv series ( part of the Dr. Death anthology series) based on Macchiarini’s deceptions and a Dr. Death documentary are being broadcast/streamed in the US during January 2024. These come on the heels of a November 2023 Macchiarini documentary also broadcast/streamed on US television.

Dr. Death (anthology), based on the previews I’ve seen, is heavily US-centric, which is to be expected since Adam Ciralsky is involved in the production. Ciralsky wrote an exposé about Macchiarini for Vanity Fair published in 2016 (also featured in my 2016 postings). From a December 20, 2023 article by Julie Miller for Vanity Fair, Note: A link has been removed,

Seven years ago [2016], world-renowned surgeon Paolo Macchiarini was the subject of an ongoing Vanity Fair investigation. He had seduced award-winning NBC producer Benita Alexander while she was making a special about him, proposed, and promised her a wedding officiated by Pope Francis and attended by political A-listers. It was only after her designer wedding gown was made that Alexander learned Macchiarini was still married to his wife, and seemingly had no association with the famous names on their guest list.

Vanity Fair contributor Adam Ciralsky was in the midst of reporting the story for this magazine in the fall of 2015 when he turned to Dr. Ronald Schouten, a Harvard psychiatry professor. Ciralsky sought expert insight into the kind of fabulist who would invent and engage in such an audacious lie.

“I laid out the story to him, and he said, ‘Anybody who does this in their private life engages in the same conduct in their professional life,” recalls Ciralsky, in a phone call with Vanity Fair. “I think you ought to take a hard look at his CVs.”

That was the turning point in the story for Ciralsky, a former CIA lawyer who soon learned that Macchiarini was more dangerous as a surgeon than a suitor. …

Here’s a link to Ciralsky’s original article, which I described this way, from my April 19, 2016 posting (part 2 of the Macchiarini controversy),

For some bizarre frosting on this disturbing cake (see part 1 of the Macchiarini controversy and synthetic trachea transplants for the medical science aspects), a January 5, 2016 Vanity Fair article by Adam Ciralsky documents Macchiarini’s courtship of an NBC ([US] National Broadcasting Corporation) news producer who was preparing a documentary about him and his work.

[from Ciralsky’s article]

“Macchiarini, 57, is a magnet for superlatives. He is commonly referred to as “world-renowned” and a “super-surgeon.” He is credited with medical miracles, including the world’s first synthetic organ transplant, which involved fashioning a trachea, or windpipe, out of plastic and then coating it with a patient’s own stem cells. That feat, in 2011, appeared to solve two of medicine’s more intractable problems—organ rejection and the lack of donor organs—and brought with it major media exposure for Macchiarini and his employer, Stockholm’s Karolinska Institute, home of the Nobel Prize in Physiology or Medicine. Macchiarini was now planning another first: a synthetic-trachea transplant on a child, a two-year-old Korean-Canadian girl named Hannah Warren, who had spent her entire life in a Seoul hospital. … “

Other players in the Macchiarini story

Pierre Delaere, a trachea expert and professor of head and neck surgery at KU Leuven (a university in Belgium) was one of the first to draw attention to Macchiarini’s dangerous and unethical practices. To give you an idea of how difficult it was to get attention for this issue, there’s a September 1, 2017 article by John Rasko and Carl Power for the Guardian illustrating the issue. Here’s what they had to say about Delaere and other early critics of the work, Note: Links have been removed,

Delaere was one of the earliest and harshest critics of Macchiarini’s engineered airways. Reports of their success always seemed like “hot air” to him. He could see no real evidence that the windpipe scaffolds were becoming living, functioning airways – in which case, they were destined to fail. The only question was how long it would take – weeks, months or a few years.

Delaere’s damning criticisms appeared in major medical journals, including the Lancet, but weren’t taken seriously by Karolinska’s leadership. Nor did they impress the institute’s ethics council when Delaere lodged a formal complaint. [emphases mine]

Support for Macchiarini remained strong, even as his patients began to die. In part, this is because the field of windpipe repair is a niche area. Few people at Karolinska, especially among those in power, knew enough about it to appreciate Delaere’s claims. Also, in such a highly competitive environment, people are keen to show allegiance to their superiors and wary of criticising them. The official report into the matter dubbed this the “bandwagon effect”.

With Macchiarini’s exploits endorsed by management and breathlessly reported in the media, it was all too easy to jump on that bandwagon.

And difficult to jump off. In early 2014, four Karolinska doctors defied the reigning culture of silence [emphasis mine] by complaining about Macchiarini. In their view, he was grossly misrepresenting his results and the health of his patients. An independent investigator agreed. But the vice-chancellor of Karolinska Institute, Anders Hamsten, wasn’t bound by this judgement. He officially cleared Macchiarini of scientific misconduct, allowing merely that he’d sometimes acted “without due care”.

For their efforts, the whistleblowers were punished. [emphasis mine] When Macchiarini accused one of them, Karl-Henrik Grinnemo, of stealing his work in a grant application, Hamsten found him guilty. As Grinnemo recalls, it nearly destroyed his career: “I didn’t receive any new grants. No one wanted to collaborate with me. We were doing good research, but it didn’t matter … I thought I was going to lose my lab, my staff – everything.”

This went on for three years until, just recently [2017], Grinnemo was cleared of all wrongdoing.

It is fitting that Macchiarini’s career unravelled at the Karolinska Institute. As the home of the Nobel prize in physiology or medicine, one of its ambitions is to create scientific celebrities. Every year, it gives science a show-business makeover, picking out from the mass of medical researchers those individuals deserving of superstardom. The idea is that scientific progress is driven by the genius of a few.

It’s a problematic idea with unfortunate side effects. A genius is a revolutionary by definition, a risk-taker and a law-breaker. Wasn’t something of this idea behind the special treatment Karolinska gave Macchiarini? Surely, he got away with so much because he was considered an exception to the rules with more than a whiff of the Nobel about him. At any rate, some of his most powerful friends were themselves Nobel judges until, with his fall from grace, they fell too.

The September 1, 2017 article by Rasko and Power is worth the read if you have the interest and the time. And, Delaere has written up a comprehensive analysis, which includes basic information about tracheas and more, “The Biggest Lie in Medical History” 2020, PDF, 164 pp., Creative Commons Licence).

I also want to mention Leonid Schneider, science journalist and molecular cell biologist, whose work the Macchiarini scandal on his ‘For Better Science’ website was also featured in my 2016 pieces. Schneider’s site has a page titled, ‘Macchiarini’s trachea transplant patients: the full list‘ started in 2017 and which he continues to update with new information about the patients. The latest update was made on December 20, 2023.

Promising nanomedicine research but no promises and a caveat

Most of the research mentioned here is still in the laboratory. i don’t often come across work that has made its way to clinical trials since the focus of this blog is emerging science and technology,

*If you’re interested in the business of neurotechnology, the July 17, 2023 posting highlights a very good UNESCO report on the topic.

Funky music (sound and noise)

I have couple of stories about using sound for wound healing, bioinspiration for soundproofing applications, detecting seismic activity, more data sonification, etc.

Same old, same old CRISPR

2023 was relatively quiet (no panics) where CRISPR developments are concerned but still quite active.

Art/Sci: a pretty active year

I didn’t realize how active the year was art/sciwise including events and other projects until I reviewed this year’s postings. This is a selection from 2023 but there’s a lot more on the blog, just use the search term, “art/sci,” or “art/science,” or “sciart.”

While I often feature events and projects from these groups (e.g., June 2, 2023 posting, “Metacreation Lab’s greatest hits of Summer 2023“), it’s possible for me to miss a few. So, you can check out Toronto’s Art/Sci Salon’s website (strong focus on visual art) and Simon Fraser University’s Metacreation Lab for Creative Artificial Intelligence website (strong focus on music).

My selection of this year’s postings is more heavily weighted to the ‘writing’ end of things.

Boundaries: life/nonlife

Last year I subtitled this section, ‘Aliens on earth: machinic biology and/or biological machinery?” Here’s this year’s selection,

Canada’s 2023 budget … military

2023 featured an unusual budget where military expenditures were going to be increased, something which could have implications for our science and technology research.

Then things changed as Murray Brewster’s November 21, 2023 article for the Canadian Broadcasting Corporation’s (CBC) news online website comments, Note: A link has been removed,

There was a revelatory moment on the weekend as Defence Minister Bill Blair attempted to bridge the gap between rhetoric and reality in the Liberal government’s spending plans for his department and the Canadian military.

Asked about an anticipated (and long overdue) update to the country’s defence policy (supposedly made urgent two years ago by Russia’s full-on invasion of Ukraine), Blair acknowledged that the reset is now being viewed through a fiscal lens.

“We said we’re going to bring forward a new defence policy update. We’ve been working through that,” Blair told CBC’s Rosemary Barton Live on Sunday.

“The current fiscal environment that the country faces itself does require (that) that defence policy update … recognize (the) fiscal challenges. And so it’ll be part of … our future budget processes.”

One policy goal of the existing defence plan, Strong, Secure and Engaged, was to require that the military be able to concurrently deliver “two sustained deployments of 500 [to] 1,500 personnel in two different theaters of operation, including one as a lead nation.”

In a footnote, the recent estimates said the Canadian military is “currently unable to conduct multiple operations concurrently per the requirements laid out in the 2017 Defence Policy. Readiness of CAF force elements has continued to decrease over the course of the last year, aggravated by decreasing number of personnel and issues with equipment and vehicles.”

Some analysts say they believe that even if the federal government hits its overall budget reduction targets, what has been taken away from defence — and what’s about to be taken away — won’t be coming back, the minister’s public assurances notwithstanding.

10 years: Graphene Flagship Project and Human Brain Project

Graphene and Human Brain Project win biggest research award in history (& this is the 2000th post)” on January 28, 2013 was how I announced the results of what had been a a European Union (EU) competition that stretched out over several years and many stages as projects were evaluated and fell to the wayside or were allowed onto the next stage. The two finalists received €1B each to be paid out over ten years.

Future or not

As you can see, there was plenty of interesting stuff going on in 2023 but no watershed moments in the areas I follow. (Please do let me know in the Comments should you disagree with this or any other part of this posting.) Nanotechnology seems less and less an emerging science/technology in itself and more like a foundational element of our science and technology sectors. On that note, you may find my upcoming (in 2024) post about a report concerning the economic impact of its National Nanotechnology Initiative (NNI) from 2002 to 2022 of interest.

Following on the commercialization theme, I have noticed an increase of interest in commercializing brain and brainlike engineering technologies, as well as, more discussion about ethics.

Colonizing the brain?

UNESCO held events such as, this noted in my July 17, 2023 posting, “Unveiling the Neurotechnology Landscape: Scientific Advancements, Innovations and Major Trends—a UNESCO report” and this noted in my July 7, 2023 posting “Global dialogue on the ethics of neurotechnology on July 13, 2023 led by UNESCO.” An August 21, 2023 posting, “Ethical nanobiotechnology” adds to the discussion.

Meanwhile, Australia has been producing some very interesting mind/robot research, my June 13, 2023 posting, “Mind-controlled robots based on graphene: an Australian research story.” I have more of this kind of research (mind control or mind reading) from Australia to be published in early 2024. The Australians are not alone, there’s also this April 12, 2023 posting, “Mind-reading prosthetic limbs” from Germany.

My May 12, 2023 posting, “Virtual panel discussion: Canadian Strategies for Responsible Neurotechnology Innovation on May 16, 2023” shows Canada is entering the discussion. Unfortunately, the Canadian Science Policy Centre (CSPC), which held the event, has not posted a video online even though they have a youtube channel featuring other of their events.

As for neurmorphic engineering, China has produced a roadmap for its research in this area as noted in my March 20, 2023 posting, “A nontraditional artificial synaptic device and roadmap for Chinese research into neuromorphic devices.”

Quantum anybody?

I haven’t singled it out in this end-of-year posting but there is a great deal of interest in quantum computer both here in Canada and elsewhere. There is a 2023 report from the Council of Canadian Academies on the topic of quantum computing in Canada, which I hope to comment on soon.

Final words

I have a shout out for the Canadian Science Policy Centre, which celebrated its 15th anniversary in 2023. Congratulations!

For everyone, I wish peace on earth and all the best for you and yours in 2024!

Nanoscientists speculate that artificial life forms could be medicine of the future

Even after all these years, my jaw is still capable of dropping but then I read the details. This looks a lot like ‘medical nanobots’ which researchers have been talking about for a long time. Nice twist on a familiar theme. From an October 5, 2023 news item on ScienceDaily,

Imagine a life form that doesn’t resemble any of the organisms found on the tree of life. One that has its own unique control system, and that a doctor would want to send into your body. It sounds like a science fiction movie, but according to nanoscientists, it can—and should—happen in the future.

Creating artificial life is a recurring theme in both science and popular literature, where it conjures images of creeping slime creatures with malevolent intentions or super-cute designer pets. At the same time, the question arises: What role should artificial life play in our environment here on Earth, where all life forms are created by nature and have their own place and purpose?

Associate professor Chenguang Lou from the Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, together with Professor Hanbin Mao from Kent State University, is the parent of a special artificial hybrid molecule that could lead to the creation of artificial life forms. They have now published a review in the journal Cell Reports Physical Science on the state of research in the field behind their creation. The field is called “hybrid peptide-DNA nanostructures,” and it is an emerging field, less than ten years old.

An October 5, 2023 University of Southern Denmark press release (also on EurekAlert) by Birgitte Svennevig, which originated the news item, shares the researcher’s (Chenguang Lou) vision for the research and more technical details about “hybrid peptide-DNA nanostructures” along with other international research efforts,

Lou’s vision is to create viral vaccines (modified and weakened versions of a virus) and artificial life forms that can be used for diagnosing and treating diseases.

“In nature, most organisms have natural enemies, but some do not. 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,” he says.

Similarly, he envisions such artificial life forms can act as vaccines against viral infection and can be used as nanorobots [also known as nanobots] or nanomachines loaded with medication or diagnostic elements and sent into a patient’s body.

“An artificial viral vaccine may be about 10 years away. 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,” he says.

What are the building blocks that Lou and his colleagues in this field will use to create viral vaccines and artificial life? 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. 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.

Recently, Hanbin Mao and Chenguang Lou have succeeded in linking designed three-stranded DNA structures with three-stranded peptide structures, thus creating an artificial hybrid molecule that combines the strengths of both. This work was published in Nature Communications in 2022. (read the article here “Chirality transmission in macromolecular domains” and the press release at https://www.sdu.dk/en/om_sdu/fakulteterne/naturvidenskab/nyheder-2022/supermolekyle)

Elsewhere in the world, 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.

At Oxford University, researchers have succeeded in building 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)

At 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)

At Northwest University [Northwestern 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)

At Ben-Gurion University of the Negev, scientists have used hybrid molecules to create an onion-like spherical structure containing cancer medication, which holds promise to be used in the body to target cancerous tumors. (Chotera et al., Chem. Eur. J., 2018, 24, 10128-10135)

“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 Chenguang Lou.

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

Peptide-DNA conjugates as building blocks for de novo design of hybrid nanostructures by Mathias Bogetoft Danielsen, Hanbin Mao, Chenguang Lou. Cell Reports Physical Science Volume 4, Issue 10, 18 October 2023, 101620 DOI: https://doi.org/10.1016/j.xcrp.2023.101620

This paper is open access.

Reducing toxicity of Alzheimer’s proteins with graphene oxide

Nobody really knows what causes Alzheimer’s disease (a form of dementia) so researchers continue to investigates the cause(s) and, also, possible remedies. An October 4, 2023 news item on ScienceDaily announces some of the latest research,

A probable early driver of Alzheimer’s disease is the accumulation of molecules called amyloid peptides. These cause cell death, and are commonly found in the brains of Alzheimer’s patients. Researchers at Chalmers University of Technology, Sweden, have now shown that yeast cells that accumulate these misfolded amyloid peptides can recover after being treated with graphene oxide nanoflakes.

An October 4, 2023 Chalmers University of Technology press release (also received via email and on EurekAlert) by Susanne Nilsson Lindh & Johanna Wilde, which originated the news item, delves into the topic,

Alzheimer’s disease is an incurable brain disease, leading to dementia and death, that causes suffering for both the patients and their families. It is estimated that over 40 million people worldwide are living with the disease or a related form of dementia. According to Alzheimer’s News Today, the estimated global cost of these diseases is one percent of the global gross domestic product.

Misfolded amyloid-beta peptides, Aβ peptides, that accumulate and aggregate in the brain, are believed to be the underlying cause of Alzheimer’s disease. They trigger a series of harmful processes in the neurons (brain cells) – causing the loss of many vital cell functions or cell death, and thus a loss of brain function in the affected area. To date, there are no effective strategies to treat amyloid accumulation in the brain.

Researchers at Chalmers University of Technology have now shown that treatment with graphene oxide leads to reduced levels of aggregated amyloid peptides in a yeast cell model.

“This effect of graphene oxide has recently also been shown by other researchers, but not in yeast cells”, says Xin Chen, Researcher in Systems Biology at Chalmers and first author of the study. “Our study also explains the mechanism behind the effect. Graphene oxide affects the metabolism of the cells, in a way that increases their resistance to misfolded proteins and oxidative stress. This has not been previously reported.”

Investigating the mechanisms using baker’s yeast affected by Alzheimer’s disease
In Alzheimer’s disease, the amyloid aggregates exert their neurotoxic effects by causing various cellular metabolic disorders, such as stress in the endoplasmic reticulum – a major part of the cell, in which many of its proteins are produced. This can reduce cells’ ability to handle misfolded proteins, and consequently increase the accumulation of these proteins.

The aggregates also affect the function of the mitochondria, the cells’ powerhouses. Therefore, the neurons are exposed to increased oxidative stress (reactive molecules called oxygen radicals, which damage other molecules); something to which brain cells are particularly sensitive.

The Chalmers researchers have conducted the study by a combination of protein analysis (proteomics) and follow-up experiments. They have used baker’s yeast, Saccharomyces cerevisiae, as an in vivo model for human cells. Both cell types have very similar systems for controlling protein quality. This yeast cell model was previously established by the research group to mimic human neurons affected by Alzheimer’s disease.

“The yeast cells in our model resemble neurons affected by the accumulation of amyloid-beta42, which is the form of amyloid peptide most prone to aggregate formation”, says Xin Chen. “These cells age faster than normal, show endoplasmic reticulum stress and mitochondrial dysfunction, and have elevated production of harmful reactive oxygen radicals.”

High hopes for graphene oxide nanoflakes
Graphene oxide nanoflakes are two-dimensional carbon nanomaterials with unique properties, including outstanding conductivity and high biocompatibility. They are used extensively in various research projects, including the development of cancer treatments, drug delivery systems and biosensors.

The nanoflakes are hydrophilic (water soluble) and interact well with biomolecules such as proteins. When graphene oxide enters living cells, it is able to interfere with the self-assembly processes of proteins.

“As a result, it can hinder the formation of protein aggregates and promote the disintegration of existing aggregates”, says Santosh Pandit, Researcher in Systems Biology at Chalmers and co-author of the study. “We believe that the nanoflakes act via two independent pathways to mitigate the toxic effects of amyloid-beta42 in the yeast cells.”

In one pathway, graphene oxide acts directly to prevent amyloid-beta42 accumulation. In the other, graphene oxide acts indirectly by a (currently unknown) mechanism, in which specific genes for stress response are activated. This increases the cell’s ability to handle misfolded proteins and oxidative stress.

How to treat Alzheimer’s patients is still a question for the future. However, according to the research group at Chalmers, graphene oxide holds great potential for future research in the field of neurodegenerative diseases. The research group has already been able to show that treatment with graphene oxide also reduces the toxic effects of protein aggregates specific to Huntington’s disease in a yeast model.

“The next step is to investigate whether it is possible to develop a drug delivery system based on graphene oxide for Alzheimer’s disease.” says Xin Chen. “We also want to test whether graphene oxide has beneficial effects in additional models of neurodegenerative diseases, such as Parkinson’s disease.”

More about: proteins and peptides
Proteins and peptides are fundamentally the same type of molecule and are made up of amino acids. Peptide molecules are smaller – typically containing less than 50 amino acids – and have a less complicated structure. Proteins and peptides can both become deformed if they fold in the wrong way during formation in the cell. When many amyloid-beta peptides accumulate in the brain, the aggregates are classified as proteins.

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

Graphene Oxide Attenuates Toxicity of Amyloid-β Aggregates in Yeast by Promoting Disassembly and Boosting Cellular Stress Response by Xin Chen, Santosh Pandit, Lei Shi, Vaishnavi Ravikumar, Julie Bonne Køhler, Ema Svetlicic, Zhejian Cao, Abhroop Garg, Dina Petranovic, Ivan Mijakovic. Advanced Functional Materials Volume 33, Issue 45 November 2, 2023 2304053 DOI: https://doi.org/10.1002/adfm.202304053 First published online: 07 July 2023

This paper is open access.

Robot that can maneuver through living lung tissue

Caption: Overview of the semiautonomous medical robot’s three stages in the lungs. Credit: Kuntz et al.

This looks like one robot operating on another robot; I guess the researchers want to emphasize the fact that this autonomous surgical procedure isn’t currently being tested on human beings.

There’s more in a September 21, 2023 news item on ScienceDaily,

Scientists have shown that their steerable lung robot can autonomously maneuver the intricacies of the lung, while avoiding important lung structures.

Lung cancer is the leading cause of cancer-related deaths in the United States. Some tumors are extremely small and hide deep within lung tissue, making it difficult for surgeons to reach them. To address this challenge, UNC -Chapel Hill and Vanderbilt University researchers have been working on an extremely bendy but sturdy robot capable of traversing lung tissue.

Their research has reached a new milestone. In a new paper, published in Science Robotics, Ron Alterovitz, PhD, in the UNC Department of Computer Science, and Jason Akulian, MD MPH, in the UNC Department of Medicine, have proven that their robot can autonomously go from “Point A” to “Point B” while avoiding important structures, such as tiny airways and blood vessels, in a living laboratory model.

Thankfully there’s a September 21, 2023 University of North Carolina (UNC) news release (also on EurekAlert), which originated the news item, to provide more information, Note: Links have been removed,

“This technology allows us to reach targets we can’t otherwise reach with a standard or even robotic bronchoscope,” said Dr. Akulian, co-author on the paper and Section Chief of Interventional Pulmonology and Pulmonary Oncology in the UNC Division of Pulmonary Disease and Critical Care Medicine. “It gives you that extra few centimeters or few millimeters even, which would help immensely with pursuing small targets in the lungs.”

The development of the autonomous steerable needle robot leveraged UNC’s highly collaborative culture by blending medicine, computer science, and engineering expertise. In addition to Alterovitz and Akulian, the development effort included Yueh Z. Lee, MD, PhD, at the UNC Department of Radiology, as well as Robert J. Webster III at Vanderbilt University and Alan Kuntz at the University of Utah.

The robot is made of several separate components. A mechanical control provides controlled thrust of the needle to go forward and backward and the needle design allows for steering along curved paths. The needle is made from a nickel-titanium alloy and has been laser etched to increase its flexibility, allowing it to move effortlessly through tissue.

As it moves forward, the etching on the needle allows it to steer around obstacles with ease. Other attachments, such as catheters, could be used together with the needle to perform procedures such as lung biopsies.

To drive through tissue, the needle needs to know where it is going. The research team used CT scans of the subject’s thoracic cavity and artificial intelligence to create three-dimensional models of the lung, including the airways, blood vessels, and the chosen target. Using this 3-D model and once the needle has been positioned for launch, their AI-driven software instructs it to automatically travel from “Point A” to “Point B” while avoiding important structures.

“The autonomous steerable needle we’ve developed is highly compact, but the system is packed with a suite of technologies that allow the needle to navigate autonomously in real-time,” said Alterovitz, the principal investigator on the project and senior author on the paper. “It’s akin to a self-driving car, but it navigates through lung tissue, avoiding obstacles like significant blood vessels as it travels to its destination.”

The needle can also account for respiratory motion. Unlike other organs, the lungs are constantly expanding and contracting in the chest cavity. This can make targeting especially difficult in a living, breathing subject. According to Akulian, it’s like shooting at a moving target.

The researchers tested their robot while the laboratory model performed intermittent breath holding. Every time the subject’s breath is held, the robot is programmed to move forward.

“There remain some nuances in terms of the robot’s ability to acquire targets and then actually get to them effectively,” said Akulian, who is also a member of the UNC Lineberger Comprehensive Cancer Center, “and while there’s still a lot of work to be done, I’m very excited about continuing to push the boundaries of what we can do for patients with the world-class experts that are here.”

“We plan to continue creating new autonomous medical robots that combine the strengths of robotics and AI to improve medical outcomes for patients facing a variety of health challenges while providing guarantees on patient safety,” added Alterovitz.

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

Autonomous medical needle steering in vivo by Alan Kuntz, Maxwell Emerson, Tayfun Efe Ertop, Inbar Fried, Mengyu Fu, Janine Hoelscher, Margaret Rox, Jason Akulian, Erin A. Gillaspie, Yueh Z. Lee, Fabien Maldonado, Robert J. Webster III, and Ron Alterovitz. Science Robotics 20 Sep 2023 Vol 8, Issue 82 DOI: 10.1126/scirobotics.adf7614

This paper is behind a paywall.

Scientists at Indian Institute of Science (IISc) created hybrid nanoparticles made of gold and copper sulfide that can kill cancer cells

It’s been a while since there was a theranostic (diagnosis and therapy combined in one treatment) story here.

Caption: Schematic indicating photo-theranostic potential of TSP-CA Credit: Madhavi Tripathi

A September 11, 2023 news item on phys.org announces the research, Note: A link has been removed,

Scientists at the Indian Institute of Science (IISc) have developed a new approach to potentially detect and kill cancer cells, especially those that form a solid tumor mass. They have created hybrid nanoparticles made of gold and copper sulfide that can kill cancer cells using heat and enable their detection using sound waves, according to a study published in ACS Applied Nano Materials.

A September 11, 2023 Indian Institute of Science (IISC) press release (also on EurekAlert), which originated the news item, provides more detail about the research,

Early detection and treatment are key in the battle against cancer. Copper sulphide nanoparticles have previously received attention for their application in cancer diagnosis, while gold nanoparticles, which can be chemically modified to target cancer cells, have shown anticancer effects. In the current study, the IISc team decided to combine these two into hybrid nanoparticles.  

“These particles have photothermal, oxidative stress, and photoacoustic properties,” says Jaya Prakash, Assistant Professor at the Department of Instrumentation and Applied Physics (IAP), IISc, and one of the corresponding authors of the paper. PhD students Madhavi Tripathi and Swathi Padmanabhan are co-first authors.

When light is shined on these hybrid nanoparticles, they absorb the light and generate heat, which can kill cancer cells. These nanoparticles also produce singlet oxygen atoms that are toxic for the cells. “We want both these mechanisms to kill the cancer cell,” Jaya Prakash explains.  

The researchers say that the nanoparticles can also help diagnose certain cancers. Existing methods such as standalone CT and MRI scans require trained radiology professionals to decipher the images. The photoacoustic property of the nanoparticles allows them to absorb light and generate ultrasound waves, which can be used to detect cancer cells with high contrast once the particles reach them. The ultrasound waves generated from the particles allow for a more accurate image resolution as sound waves scatter less when they pass through tissues compared to light. Scans created from the generated ultrasound waves can also provide better clarity and can be used to measure the oxygen saturation in the tumour, boosting their detection.

“You can integrate this with existing systems of detection or treatment,” says Ashok M Raichur, Professor at the Department of Materials Engineering, and another corresponding author. For example, the nanoparticles can be triggered to produce heat by shining a light on them using an endoscope that is typically used for cancer screening. 

Previously developed nanoparticles have limited applications because of their large size. The IISc team used a novel reduction method to deposit tiny seeds of gold onto the copper sulphide surface. The resulting hybrid nanoparticles – less than 8 nm in size – can potentially travel inside tissues easily and reach tumours. The researchers believe that the nanoparticles’ small size would also allow them to leave the human body naturally without accumulating, although extensive studies have to be carried out to determine if they are safe to use inside the human body.  

In the current study, the researchers have tested their nanoparticles on lung cancer and cervical cancer cell lines in the lab. They now plan to take the results forward for clinical development.  

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

Seed-Mediated Galvanic Synthesis of CuS–Au Nanohybrids for Photo-Theranostic Applications by Madhavi Tripathi, Swathi Padmanabhan, Jaya Prakash, and Ashok M. Raichur. ACS Appl. Nano Mater. 2023, 6, 16, 14861–14875 DOI: https://doi.org/10.1021/acsanm.3c02405 Publication Date:August 10, 2023 Copyright © 2023 American Chemical Society

This paper is behind a paywall.