Tag Archives: Ag nanoparticles

Nanomedicine: two stories about wound healing

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Different strokes for different folks or, in this case, somewhat different approaches to healing different wounds.

Infected wounds

A July 17, 2024 news item on Nanowerk highlights work from China’s Research Center for Neutrophil Engineering Technology (affiliated with Suzhou Hospital of Nanjing Medical University), Note: A link has been removed,

Infectious wounds represent a critical challenge in healthcare, especially for diabetic patients grappling with ineffective antibiotics and escalating drug resistance. Conventional therapies often inadequately address deep tissue infections, highlighting the need for more innovative solutions. Engineered nanovesicles (NVs) from activated neutrophils provide a precise mechanism to combat pathogens deeply embedded in tissues, potentially revolutionizing the management of complex infectious wounds and boosting overall treatment efficacy.

Researchers at the Research Center for Neutrophil Engineering Technology have achieved a significant advancement in medical nanotechnology. Their findings, published in the journal Burns & Trauma (“Engineered nanovesicles from activated neutrophils with enriched bactericidal proteins have molecular debridement ability and promote infectious wound healing”), detail the creation of novel neutrophil-engineered NVs.

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A July 17, 2024 Maximum Academic Press ‘press release’ on EurekAlert, which originated the news item, goes on to describe what the researchers discovered,

This study reveals that engineered NVs derived from activated neutrophils not only mimic the physical properties of exosomes but surpass them due to their rich content of bactericidal proteins. Extensively tested both in vitro and in vivo, these NVs effectively combat key pathogens like Staphylococcus aureus and Escherichia coli, which contribute to deep tissue infections. The NVs promote rapid debridement, significantly reduce bacterial populations, and boost collagen deposition, thus hastening the healing process. This research positions NVs as a formidable alternative to traditional antibiotics, introducing a novel method for treating resistant infections and advancing the field of wound care.

Dr. Bingwei Sun, the lead researcher, emphasized, “These engineered NVs mark a major advancement in the management of infectious diseases. By targeting the infection site with high levels of bactericidal proteins, we achieve swift and effective healing, thereby opening new paths for the treatment of chronic and resistant infections.”

The advent of activated neutrophil-derived NVs signifies a major leap in medical technology, potentially reducing healthcare costs and enhancing patient outcomes. This innovation not only promises to improve wound healing in diabetic and other chronic infection patients but also sets the stage for further development of biologically inspired therapeutic strategies.

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

Engineered nanovesicles from activated neutrophils with enriched bactericidal proteins have molecular debridement ability and promote infectious wound healing by Hangfei Jin, Xiao Wen, Ran Sun, Yanzhen Yu, Zaiwen Guo, Yunxi Yang, Linbin Li, and Bingwei Sun. Burns & Trauma, Volume 12, 2024, tkae018, DOI: https://doi.org/10.1093/burnst/tkae018 Published: 20 June 2024

This paper is open access.

Diabetic wounds

A July 17, 2024 news item on phys.org announces work from another team developing its own approach to healing wounds, albeit, a different category of wounds,

Diabetic wounds are notoriously challenging to treat, due to prolonged inflammation and a high risk of infection. Traditional treatments generally offer only passive protection and fail to dynamically interact with the wound environment.

In a new article published in Burns & Trauma on June 5, 2024, a research team from Mudanjiang Medical University and allied institutions assesses the effectiveness of PLLA nanofibrous membranes.

Infused with curcumin and silver nanoparticles, these membranes are designed to substantially enhance the healing processes in diabetic wounds by targeting fundamental issues like excessive inflammation and infection.

This research centered on developing PLLA/C/Ag nanofibrous membranes through air-jet spinning, achieving a consistent fiber distribution essential for effective therapeutic delivery. The membranes boast dual benefits: antioxidant properties that reduce harmful reactive oxygen species in wound environments and potent antibacterial activity that decreases infection risks.

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A July 17, 2024 Maximum Academic Press ‘press release‘ on EurekAlert provides more information about the research, Note 1: This press release appears to have originated the news item, which was then edited and rewritten; Note 2: Links have been removed,

In a pioneering study, researchers have developed a poly (L-lactic acid) (PLLA) nanofibrous membrane enhanced with curcumin and silver nanoparticles (AgNPs), aimed at improving the healing of diabetic wounds. This advanced dressing targets critical barriers such as inflammation, oxidative stress, and bacterial infections, which hinder the recovery process in diabetic patients. The study’s results reveal a promising therapeutic strategy that could revolutionize care for diabetes-related wounds.

Diabetic wounds are notoriously challenging to heal, with prolonged inflammation and a high risk of infection. Traditional treatments generally offer only passive protection and fail to dynamically interact with the wound environment. The creation of bioactive dressings like the poly (L-lactic acid) (PLLA) nanofibrous membranes incorporated with AgNPs and curcumin (PLLA/C/Ag) membranes signifies a crucial shift towards therapies that actively correct imbalances in the wound healing process, offering a more effective solution for managing diabetic wounds.

Published (DOI: 10.1093/burnst/tkae009) in Burns & Trauma on June 5, 2024, this trailblazing research by a team from Mudanjiang Medical University and allied institutions assesses the effectiveness of PLLA nanofibrous membranes. Infused with curcumin and silver nanoparticles, these membranes are designed to substantially enhance the healing processes in diabetic wounds by targeting fundamental issues like excessive inflammation and infection.

This research centered on developing PLLA/C/Ag nanofibrous membranes through air-jet spinning, achieving a consistent fiber distribution essential for effective therapeutic delivery. The membranes boast dual benefits: antioxidant properties that reduce harmful reactive oxygen species in wound environments and potent antibacterial activity that decreases infection risks. In vivo tests on diabetic mice demonstrated the membranes’ capability to promote crucial healing processes such as angiogenesis and collagen deposition. These findings illustrate that PLLA/C/Ag membranes not only protect wounds but also actively support and expedite the healing process, marking them as a significant therapeutic innovation for diabetic wound management with potential for broader chronic wound care applications.

Dr. Yanhui Chu, a principal investigator of the study, highlighted the importance of these developments: “The PLLA/C/Ag membranes are a significant breakthrough in diabetic wound care. Their ability to effectively modulate the wound environment and enhance healing could establish a new standard in treatment, providing hope to millions affected by diabetes-related complications.”

The deployment of PLLA/C/Ag nanofibrous membranes in clinical environments could transform the treatment of diabetic wounds, offering a more active and effective approach. Beyond diabetes management, this technology has the potential for extensive applications in various chronic wounds, paving the way for future breakthroughs in bioactive wound dressings. This study not only progresses our understanding of wound management but also paves new paths for developing adaptive treatments for complex wound scenarios.

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

Immunomodulatory poly(L-lactic acid) nanofibrous membranes promote diabetic wound healing by inhibiting inflammation, oxidation and bacterial infection by Yan Wu, Jin Zhang, Anqi Lin, Tinglin Zhang, Yong Liu, Chunlei Zhang, Yongkui Yin, Ran Guo, Jie Gao, Yulin Li, and Yanhui Chu. Burns & Trauma, Volume 12, 2024, tkae009, DOI: https://doi.org/10.1093/burnst/tkae009 Published: 05 June 2024

This paper is open access.

Science publishing

As I think most people know, publishing of any kind is a tough business, particularly these days. This instability has led to some interesting corporate relationships. E.g., Springer Nature (a German-British academic publisher) is the outcome of some mergers as the Springer Nature Wikipedia entry notes,

The company originates from several journals and publishing houses, notably Springer-Verlag, which was founded in 1842 by Julius Springer in Berlin[4] (the grandfather of Bernhard Springer who founded Springer Publishing in 1950 in New York),[5] Nature Publishing Group which has published Nature since 1869,[6] and Macmillan Education, which goes back to Macmillan Publishers founded in 1843.[7]

Springer Nature was formed in 2015 by the merger of Nature Publishing Group, Palgrave Macmillan, and Macmillan Education (held by Holtzbrinck Publishing Group) with Springer Science+Business Media (held by BC Partners). Plans for the merger were first announced on 15 January 2015.[8] The transaction was concluded in May 2015 with Holtzbrinck having the majority 53% share.[9]

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Now you have what was an independent science journal, Nature, owned by Springer. By the way, Springer Nature also acquired Scientific American, another major science journal.

Relatedly, seeing Maximum Academic Press as the issuer for the press releases mentioned here aroused my curiosity. I haven’t stumbled across the company before but found this on the company’s About Us webpage, Note: Links have been removed,

Maximum Academic Press (MAP) is an independent publishing company with focus on publishing golden open access academic journals. From 2020 to now, MAP has successfully launched 24 academic journals which cover the research fields of agriculture, biology, environmental sciences, engineering and humanities and social sciences.                    

Professor Zong-Ming (Max) Cheng, chief editor and founder of MAP, who earned his Ph.D from Cornell University in 1991 and worked as an Assistant, Associate and Professor at North Dakota State University and University of Tennessee for over 30 years. Prior to establishing MAP, Dr. Cheng launched Horticulture Research (initially published by Nature Publishing Group) in 2014, Plant Phenomics (published by American Association of Advancement of Sciences, AAAS) in 2019, and BioDesign Research (published by AAAS) in 2020, and served as the Editor-in-Chief, Co-Editors-in-Chief, and the executive editor, respectively. Dr. Cheng wishes to apply all successful experiences in launching and managing these three high quality journals to MAP-published journals with highest quality and ethics standards.

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It was a little bit of a surprise to see that MAP doesn’t publish the journal, Burns & Trauma, where the studies (cited here) were published. From the Burns & Trauma About the Journal webpage on the Oxford University Press website for Oxford Academic journals,

Aims and scope

Burns & Trauma is an open access, peer-reviewed journal publishing the latest developments in basic, clinical, and translational research related to burns and traumatic injuries, with a special focus on various aspects of biomaterials, tissue engineering, stem cells, critical care, immunobiology, skin transplantation, prevention, and regeneration of burns and trauma injury.

Society affiliations

Burns & Trauma is the official journal of Asia-Pacific Society of Scar Medicine, Chinese Burn Association, Chinese Burn Care and Rehabilitation Association and Chinese Society for Scar Medicine. It is sponsored by the Institute of Burn Research, Southwest Hospital (First Affiliated Hospital of Army Medical University), China.

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I don’t know what to make of it all but I can safely say scientific publishing has gotten quite complicated since the days that Nature first published its own eponymous journal.

Resisting silver’s microbial properties?

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Yes, it is possible for bacteria to become resistant to silver nanoparticles. However, that yes comes with some qualifications according to a July 13, 2021 news item on ScienceDaily (Note: Links have been removed),

Antimicrobials are used to kill or slow the growth of bacteria, viruses and other microorganisms. They can be in the form of antibiotics, used to treat bodily infections, or as an additive or coating on commercial products used to keep germs at bay. These life-saving tools are essential to preventing and treating infections in humans, animals and plants, but they also pose a global threat to public health when microorganisms develop resistance to them, a concept known as antimicrobial resistance.

One of the main drivers of antimicrobial resistance is the misuse and overuse of antimicrobial agents, which includes silver nanoparticles, [emphases mine] an advanced material with well-documented antimicrobial properties. It is increasingly used in commercial products that boast enhanced germ-killing performance — it has been woven into textiles, coated onto toothbrushes, and even mixed into cosmetics as a preservative.

The Gilbertson Group at the University of Pittsburgh [Pennsylvania, US} Swanson School of Engineering used laboratory strains of E.coli to better understand bacterial resistance to silver nanoparticles and attempt to get ahead of the potential misuse of this material. The team recently published their results in Nature Nanotechnology.

Caption: A depiction of hyper-motile E.coli, a strain of bacteria found to resist silver nanoparticles’ antimicrobial properties after repeated exposure. Credit: Lisa Stabryla/University of Pittsburgh.

A July 13, 2021 University of Pittsburgh news release (also on EurekAlert), which originated the news item, provides more insight into the research,

“Bacterial resistance to silver nanoparticles is understudied, so our group looked at the mechanisms behind this event,” said Lisa Stabryla, lead author on the paper and a recent civil and environmental PhD graduate at Pitt. “This is a promising innovation to add to our arsenal of antimicrobials, but we need to consciously study it and perhaps regulate its use to avoid decreased efficacy like we’ve seen with some common antibiotics.”

Stabryla exposed E.coli to 20 consecutive days of silver nanoparticles and monitored bacterial growth over time. Nanoparticles are roughly 50 times smaller than a bacterium.

“In the beginning, bacteria could only survive at low concentrations of silver nanoparticles, but as the experiment continued, we found that they could survive at higher doses,” Stabryla noted. “Interestingly, we found that bacteria developed resistance to the silver nanoparticles but not their released silver ions alone.”

The group sequenced the genome of the E.coli that had been exposed to silver nanoparticles and found a mutation in a gene that corresponds to an efflux pump that pushes heavy metal ions out of the cell.

“It is possible that some form of silver is getting into the cell, and when it arrives, the cell mutates to quickly pump it out,” she added. “More work is needed to determine if researchers can perhaps overcome this mechanism of resistance through particle design.”

The group then studied two different types of E.coli: a hyper-motile strain that swims through its environment more quickly than normally motile bacteria and a non-motile strain that does not have physical means for moving around. They found that only the hyper-motile strain developed resistance.

“This finding could suggest that silver nanoparticles may be a good option to target certain types of bacteria, particularly non-motile strains,” Stabryla said.

In the end, bacteria will still find a way to evolve and evade antimicrobials. The hope is that an understanding of the mechanisms that lead to this evolution and a mindful use of new antimicrobials will lessen the impact of antimicrobial resistance.

“We are the first to look at bacterial motility effects on the ability to develop resistance to silver nanoparticles,” said Leanne Gilbertson, assistant professor of civil and environmental engineering at Pitt. “The observed difference is really interesting and merits further investigation to understand it and how to link the genetic response – the efflux pump regulation – to the bacteria’s ability to move in the system.

“The results are promising for being able to tune particle properties for a desired response, such as high efficacy while avoiding resistance.”

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

Role of bacterial motility in differential resistance mechanisms of silver nanoparticles and silver ions by Lisa M. Stabryla, Kathryn A. Johnston, Nathan A. Diemler, Vaughn S. Cooper, Jill E. Millstone, Sarah-Jane Haig & Leanne M. Gilbertson. Nature Nanotechnology (2021) DOI: https://doi.org/10.1038/s41565-021-00929-w Published: 21 June 2021

This paper appears to be open access.

“Living” bandages made from biocompatible anti-burn nanofibers

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A February 16, 2018 news item on Nanowerk announces research from a Russian team about their work on “living” bandages,

In regenerative medicine, and particularly in burn therapy, the effective regeneration of damaged skin tissue and the prevention of scarring are usually the main goals. Scars form when skin is badly damaged, whether through a cut, burn, or a skin problem such as acne or fungal infection.

Scar tissue mainly consists of irreversible collagen and significantly differs from the tissue it replaces, having reduced functional properties. For example, scars on skin are more sensitive to ultraviolet radiation, are not elastic, and the sweat glands and hair follicles are not restored in the area.

The solution of this medical problem was proposed by the researchers from the NUST MISIS [National University of Science and Technology {formerly Moscow Institute of Steel and Alloys State Technological University})] Inorganic Nanomaterials Laboratory, led by PhD Anton Manakhov, a senior researcher. The team of nanotechnology scientists has managed to create multi-layer ‘bandages’ made of biodegradable fibers and multifunctional bioactive nanofilms, which [the bandages] prevent scarring and accelerate tissue regeneration.

A February 14, 2018 NUST MISIS press release, which originated the news item, provides more detail,

The addition of the antibacterial effect by the introduction of silver nanoparticles or joining antibiotics, as well as the increase of biological activity to the surface of hydrophilic groups (-COOH) and the blood plasma proteins have provided unique healing properties to the material.

A significant acceleration of the healing process, the successful regeneration of normal skin covering tissue, and the prevention of scarring on the site of burnt or damaged skin have been observed when applying these bandages made of the developed material to an injured area. The antibacterial components of multifunctional nanofibers decrease inflammation, and the blood plasma with an increased platelet level — vital and multi-purposed for every element in the healing process — stimulates the regeneration of tissues. The bandages should not be removed or changed during treatment as it may cause additional pain to the patient. After a certain period of time, the biodegradable fiber simply “dissolves” without any side effects.

“With the help of chemical bonds, we were able to create a stable layer containing blood plasma components (growth factors, fibrinogens, and other important proteins that promote cell growth) on a polycaprolactone base. The base fibers were synthesized by electroforming. Then, with the help of plasma treatment, to increase the material`s hydrophilic properties, a polymer layer containing carboxyl groups was applied to the surface. The resulting layer was enriched with antibacterial and protein components”, noted Elizabeth Permyakova, one of the project members and laboratory scientists.

The researchers have made images of their work available including this one,

Courtesy NUST MISS [downloaded from http://en.misis.ru/university/news/science/2018-02/5219/]

There is doesn’t appear to be an accompanying published paper.

Smaller (20nm vs 110nm) silver nanoparticles are more likely to absorbed by fish

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An Oct. 8, 2015 news item on Nanowerk offers some context for why researchers at the University of California at Los Angeles (UCLA) are studying silver nanoparticles and their entry into the water system,

More than 2,000 consumer products today contain nanoparticles — particles so small that they are measured in billionths of a meter.

Manufacturers use nanoparticles to help sunscreen work better against the sun’s rays and to make athletic apparel better at wicking moisture away from the body, among many other purposes.

Of those products, 462 — ranging from toothpaste to yoga mats — contain nanoparticles made from silver, which are used for their ability to kill bacteria. But that benefit might be coming at a cost to the environment. In many cases, simply using the products as intended causes silver nanoparticles to wind up in rivers and other bodies of water, where they can be ingested by fish and interact with other marine life.

For scientists, a key question has been to what extent organisms retain those particles and what effects they might have.

I’d like to know where they got those numbers “… 2,000 consumer products …” and “… 462 — ranging from toothpaste to yoga mats — contain nanoparticles made from silver… .”

Getting back to the research, an Oct. 7, 2015 UCLA news release, which originated the news item, describes the work in more detail,

A new study by the University of California Center for Environmental Implications of Nanotechnology has found that smaller silver nanoparticles were more likely to enter fish’s bodies, and that they persisted longer than larger silver nanoparticles or fluid silver nitrate. The study, published online in the journal ACS Nano, was led by UCLA postdoctoral scholars Olivia Osborne and Sijie Lin, and Andre Nel, director of UCLA’s Center for Environmental Implications of Nanotechnology and associate director of the California NanoSystems Institute at UCLA.

Nel said that although it is not yet known whether silver nanoparticles are harmful, the research team wanted to first identify whether they were even being absorbed by fish. CEIN, which is funded by the National Science Foundation, is focused on studying the effects of nanotechnology on the environment.

In the study, researchers placed zebrafish in water that contained fluid silver nitrate and two sizes of silver nanoparticles — some measuring 20 nanometers in diameter and others 110 nanometers. Although the difference in size between these two particles is so minute that it can only be seen using high-powered transmission electron microscopes, the researchers found that the two sizes of particles affected the fish very differently.

The researchers used zebrafish in the study because they have some genetic similarities to humans, their embryos and larvae are transparent (which makes them easier to observe). In addition, they tend to absorb chemicals and other substances from water.

Osborne said the team focused its research on the fish’s gills and intestines because they are the organs most susceptible to silver exposure.

“The gills showed a significantly higher silver content for the 20-nanometer than the 110-nanometer particles, while the values were more similar in the intestines,” she said, adding that both sizes of the silver particles were retained in the intestines even after the fish spent seven days in clean water. “The most interesting revelation was that the difference in size of only 90 nanometers made such a striking difference in the particles’ demeanor in the gills and intestines.”

The experiment was one of the most comprehensive in vivo studies to date on silver nanoparticles, as well as the first to compare silver nanoparticle toxicity by extent of organ penetration and duration with different-sized particles, and the first to demonstrate a mechanism for the differences.

Osborne said the results seem to indicate that smaller particles penetrated deeper into the fishes’ organs and stayed there longer because they dissolve faster than the larger particles and are more readily absorbed by the fish.

Lin said the results indicate that companies using silver nanoparticles have to strike a balance that recognizes their benefits and their potential as a pollutant. Using slightly larger nanoparticles might help make them somewhat safer, for example, but it also might make the products in which they’re used less effective.

He added that data from the study could be translated to understand how other nanoparticles could be used in more environmentally sustainable ways.

Nel said the team’s next step is to determine whether silver particles are potentially harmful. “Our research will continue in earnest to determine what the long-term effects of this exposure can be,” he said.

Here’s an image illustrating the findings,

Courtesy ACS Nano

Courtesy ACS Nano

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

Organ-Specific and Size-Dependent Ag Nanoparticle Toxicity in Gills and Intestines of Adult Zebrafish by Olivia J. Osborne, Sijie Lin, Chong Hyun Chang, Zhaoxia Ji, Xuechen Yu, Xiang Wang, Shuo Lin, Tian Xia, and André E. Nel. ACS Nano, Article ASAP DOI: 10.1021/acsnano.5b04583 Publication Date (Web): September 1, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.