Tag Archives: diabetic wounds

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.

Shape-conforming hydrogel and the body’s own healing mechanisms

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A June 11, 2018 news item on ScienceDaily announces a development of interest to people with diabetes or those who treat them,

A simple scrape or sore might not cause alarm for most people. But for diabetic patients, an untreated scratch can turn into an open wound that could potentially lead to a limb amputation or even death.

A Northwestern University team has developed a new device, called a regenerative bandage, that quickly heals these painful, hard-to-treat sores without using drugs. During head-to-head tests, Northwestern’s bandage healed diabetic wounds 33 percent faster than one of the most popular bandages currently on the market.

A June 11, 2018 Northwestern University news release by Amanda Morris, which originated the news item, provides more detail,

“The novelty is that we identified a segment of a protein in skin that is important to wound healing, made the segment and incorporated it into an antioxidant molecule that self-aggregates at body temperature to create a scaffold that facilitates the body’s ability to regenerate tissue at the wound site,” said Northwestern’s Guillermo Ameer, who led the study. “With this newer approach, we’re not releasing drugs or outside factors to accelerate healing. And it works very well.”

Because the bandage leverages the body’s own healing power without releasing drugs or biologics, it faces fewer regulatory hurdles. This means patients could see it on the market much sooner.

The research was published today, June 11 [2018], in the Proceedings of the National Academy of Sciences. Although Ameer’s laboratory is specifically interested in diabetes applications, the bandage can be used to heal all types of open wounds.

An expert in biomaterials and regenerative engineering, Ameer is the Daniel Hale Williams Professor of Biomedical Engineering in the McCormick School of Engineering, professor of surgery in the Feinberg School of Medicine and director of Northwestern’s new Center for Advanced Regenerative Engineering (CARE).

The difference between a sore in a physically healthy person versus a diabetic patient? Diabetes can cause nerve damage that leads to numbness in the extremities. People with diabetes, therefore, might experience something as simple as a blister or small scratch that goes unnoticed and untreated because they cannot feel it to know it’s there. As high glucose levels also thicken capillary walls, blood circulation slows, making it more difficult for these wounds to heal. It’s a perfect storm for a small nick to become a limb-threatening — or life-threatening — wound.

The secret behind Ameer’s regenerative bandage is laminin, a protein found in most of the body’s tissues including the skin. Laminin sends signals to cells, encouraging them to differentiate, migrate and adhere to one another. Ameer’s team identified a segment of laminin — 12 amino acids in length — called A5G81 that is critical for the wound-healing process.

“This particular sequence caught our eye because it activates cellular receptors to get cells to adhere, migrate and proliferate,” Ameer said. “Then we cut up the sequence to find the minimum size that we needed for it to work.”

By using such a small fragment of laminin rather than the entire protein, it can be easily synthesized in the laboratory — making it more reproducible while keeping manufacturing costs low. Ameer’s team incorporated A5G81 into an antioxidant hydrogel bandage that it previously developed in the laboratory.

The bandage’s antioxidant nature counters inflammation. And the hydrogel is thermally responsive: It is a liquid when applied to the wound bed, then rapidly solidifies into a gel when exposed to body temperature. This phase change allows it to conform to the exact shape of the wound — a property that helped it out-perform other bandages on the market.

“Wounds have irregular shapes and depths. Our liquid can fill any shape and then stay in place,” Ameer said. “Other bandages are mostly based on collagen films or sponges that can move around and shift away from the wound site.”

Patients also must change bandages often, which can rip off the healing tissue and re-injure the site. Ameer’s bandage, however, can be rinsed off with cool saline, so the regenerating tissue remains undisturbed.

Not only will the lack of drugs or biologics make the bandage move to market faster, it also increases the bandage’s safety. So far, Ameer’s team has not noticed any adverse side effects in animal models. This is a stark difference from another product on the market, which contains a growth factor linked to cancer.

“It is not acceptable for patients who are trying to heal an open sore to have to deal with an increased risk of cancer,” Ameer said.

Next, Ameer’s team will continue to investigate the bandage in a larger pre-clinical model.

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

Potent laminin-inspired antioxidant regenerative dressing accelerates wound healing in diabetes by Yunxiao Zhu, Zdravka Cankova, Marta Iwanaszko, Sheridan Lichtor, Milan Mrksich, and Guillermo A. Ameer. PNAS [Proceedings of the National Academy of Science] June 11, 2018. 201804262; published ahead of print June 11, 2018. https://doi.org/10.1073/pnas.1804262115

This paper is behind a paywall.