Tag Archives: wound-healing

‘Origami organs’ for tissue engineering

This is a different approach to tissue engineering and its the consequence of a serendipitous accident.  From an Aug. 7, 2017 Northwestern University news release (also on EurekAlert),

Northwestern Medicine scientists and engineers have invented a range of bioactive “tissue papers” made of materials derived from organs that are thin and flexible enough to even fold into an origami bird. The new biomaterials can potentially be used to support natural hormone production in young cancer patients and aid wound healing.

The tissue papers are made from structural proteins excreted by cells that give organs their form and structure. The proteins are combined with a polymer to make the material pliable.

In the study, individual types of tissue papers were made from ovarian, uterine, kidney, liver, muscle or heart proteins obtained by processing pig and cow organs. Each tissue paper had specific cellular properties of the organ from which it was made.

The article describing the tissue paper and its function will be published Aug. 7 in the journal Advanced Functional Materials.

“This new class of biomaterials has potential for tissue engineering and regenerative medicine as well as drug discovery and therapeutics,” corresponding author Ramille Shah said. “It’s versatile and surgically friendly.”

Shah is an assistant professor of surgery at the Feinberg School of Medicine and an assistant professor of materials science and engineering at McCormick School of Engineering. She also is a member of the Simpson Querrey Institute for BioNanotechnology.

For wound healing, Shah thinks the tissue paper could provide support and the cell signaling needed to help regenerate tissue to prevent scarring and accelerate healing.

The tissue papers are made from natural organs or tissues. The cells are removed, leaving the natural structural proteins – known as the extracellular matrix – that then are dried into a powder and processed into the tissue papers. Each type of paper contains residual biochemicals and protein architecture from its original organ that can stimulate cells to behave in a certain way.

In the lab of reproductive scientist Teresa Woodruff, the tissue paper made from a bovine ovary was used to grow ovarian follicles when they were cultured in vitro. The follicles (eggs and hormone-producing cells) grown on the tissue paper produced hormones necessary for proper function and maturation.

“This could provide another option to restore normal hormone function to young cancer patients who often lose their hormone function as a result of chemotherapy and radiation,” Woodruff, a study coauthor, said.

A strip of the ovarian paper with the follicles could be implanted under the arm to restore hormone production for cancer patients or even women in menopause.

Woodruff is the director of the Oncofertility Consortium and the Thomas J. Watkins Memorial Professor of Obstetrics and Gynecology at Feinberg.

In addition, the tissue paper made from various organs separately supported the growth of adult human stem cells. Scientists placed human bone marrow stem cells on the tissue paper, and all the stem cells attached and multiplied over four weeks.

“That’s a good sign that the paper supports human stem cell growth,” said first author Adam Jakus, who developed the tissue papers. “It’s an indicator that once we start using tissue paper in animal models it will be biocompatible.”

The tissue papers feel and behave much like standard office paper when they are dry, Jakus said. Jakus simply stacks them in a refrigerator or a freezer. He even playfully folded them into an origami bird.

“Even when wet, the tissue papers maintain their mechanical properties and can be rolled, folded, cut and sutured to tissue,” he said.

Jakus was a Hartwell postdoctoral fellow in Shah’s lab for the study and is now chief technology officer and cofounder of the startup company Dimension Inx, LLC, which was also cofounded by Shah. The company will develop, produce and sell 3-D printable materials primarily for medical applications. The Intellectual Property is owned by Northwestern University and will be licensed to Dimension Inx.

An Accidental Spill Sparked Invention

An accidental spill of 3-D printing ink in Shah’s lab by Jakus sparked the invention of the tissue paper. Jakus was attempting to make a 3-D printable ovary ink similar to the other 3-D printable materials he previously developed to repair and regenerate bone, muscle and nerve tissue. When he went to wipe up the spill, the ovary ink had already formed a dry sheet.

“When I tried to pick it up, it felt strong,” Jakus said. “I knew right then I could make large amounts of bioactive materials from other organs. The light bulb went on in my head. I could do this with other organs.”

“It is really amazing that meat and animal by-products like a kidney, liver, heart and uterus can be transformed into paper-like biomaterials that can potentially regenerate and restore function to tissues and organs,” Jakus said. “I’ll never look at a steak or pork tenderloin the same way again.”

For those who like their news in a video,

As someone who once made baklava, that does not look like filo pastry, where an individual sheet is quite thin and rips easily. Enough said.

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

“Tissue Papers” from Organ-Specific Decellularized Extracellular Matrices by Adam E. Jakus, Monica M. Laronda, Alexandra S. Rashedi, Christina M. Robinson, Chris Lee, Sumanas W. Jordan, Kyle E. Orwig, Teresa K. Woodruff, and Ramille N. Shah. Advnaced Functional Materials DOI: 10.1002/adfm.201700992 Version of Record online: 7 AUG 2017

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Curcumin gel for burns and scalds

The curcumin debate continues (see my  Jan. 26, 2017 posting titled: Curcumin: a scientific literature review concludes health benefits may be overstated for more about that). In the meantime, scientists at the University of California at Los Angeles’ (UCLA) David Geffen School of Medicine found that curcumin gel might be effective as a treatment for burns. From a March 14, 2017 Pensoft Publishers news release on EurekAlert (Note: Links have been removed),

What is the effect of Topical Curcumin Gel for treating burns and scalds? In a recent research paper, published in the open access journal BioDiscovery, Dr. Madalene Heng, Clinical Professor of Dermatology at the David Geffen School of Medicine, stresses that use of topical curcumin gel for treating skin problems, like burns and scalds, is very different, and appears to work more effectively, when compared to taking curcumin tablets by mouth for other conditions.

“Curcumin gel appears to work much better when used on the skin because the gel preparation allows curcumin to penetrate the skin, inhibit phosphorylase kinase and reduce inflammation,” explains Dr Heng.

In this report, use of curcumin after burns and scalds were found to reduce the severity of the injury, lessen pain and inflammation, and improve healing with less than expected scarring, or even no scarring, of the affected skin. Dr. Heng reports her experience using curcumin gel on such injuries using three examples of patients treated after burns and scalds, and provides a detailed explanation why topical curcumin may work on such injuries.

Curcumin is an ingredient found in the common spice turmeric. Turmeric has been used as a spice for centuries in many Eastern countries and gives well known dishes, such as curry, their typical yellow-gold color. The spice has also been used for cosmetic and medical purposes for just as long in these countries.

In recent years, the medicinal value of curcumin has been the subject of intense scientific studies, with publication numbering in the thousands, looking into the possible beneficial effects of this natural product on many kinds of affliction in humans.

This study published reports that topical curcumin gel applied soon after mild to moderate burns and scalds appears to be remarkably effective in relieving symptoms and improved healing of the affected skin.

“When taken by mouth, curcumin is very poorly absorbed into the body, and may not work as well,” notes Dr. Heng. “Nonetheless, our tests have shown that when the substance is used in a topical gel, the effect is notable.”

The author of the study believes that the effectiveness of curcumin gel on the skin – or topical curcumin – is related to its potent anti-inflammatory activity. Based on studies that she has done both in the laboratory and in patients over 25 years, the key to curcumin’s effectiveness on burns and scalds is that it is a natural inhibitor of an enzyme called phosphorylase kinase.

This enzyme in humans has many important functions, including its involvement in wound healing. Wound healing is the vital process that enables healing of tissues after injury. The process goes through a sequence of acute and chronic inflammatory events, during which there is redness, swelling, pain and then healing, often with scarring in the case of burns and scalds of the skin. The sequence is started by the release of phosphorylase kinase about 5 mins after injury, which activates over 200 genes that are involved in wound healing.

Dr. Heng uses curcumin gel for burns, scalds and other skin conditions as complementary treatment, in addition to standard treatment usually recommended for such conditions.

Caption: These are results from 5 days upon application of curcumin gel to burns, and results after 6 weeks. Credit: Dr. Madalene Heng

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

Phosphorylase Kinase Inhibition Therapy in Burns and Scalds by Madalene Heng. BioDiscovery 20: e11207 (24 Feb 2017) https://doi.org/10.3897/biodiscovery.20.e1120

This paper is in an open access journal.

Antibiotic synthetic spider silk

I have a couple of questions, what is ‘click’ chemistry and how does a chance meeting lead to a five-year, interdisciplinary research project on synthetic spider silk? From a Jan. 4, 2017 news item on ScienceDaily,

A chance meeting between a spider expert and a chemist has led to the development of antibiotic synthetic spider silk.

After five years’ work an interdisciplinary team of scientists at The University of Nottingham has developed a technique to produce chemically functionalised spider silk that can be tailored to applications used in drug delivery, regenerative medicine and wound healing.

The Nottingham research team has shown for the first time how ‘click-chemistry’ can be used to attach molecules, such as antibiotics or fluorescent dyes, to artificially produced spider silk synthesised by E.coli bacteria. The research, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) is published today in the online journal Advanced Materials.

A Jan. 3, 2016 University of Nottingham press release (also on EurekAlert), which originated the news item, provides a few more details about ‘click’ chemistry (not enough for me) and more information about the research,

The chosen molecules can be ‘clicked’ into place in soluble silk protein before it has been turned into fibres, or after the fibres have been formed. This means that the process can be easily controlled and more than one type of molecule can be used to ‘decorate’ individual silk strands.

Nottingham breakthrough

In a laboratory in the Centre of Biomolecular Sciences, Professor Neil Thomas from the School of Chemistry in collaboration with Dr Sara Goodacre from the School of Life Sciences, has led a team of BBSRC DTP-funded PhD students starting with David Harvey who was then joined by Victor Tudorica, Leah Ashley and Tom Coekin. They have developed and diversified this new approach to functionalising ‘recombinant’ — artificial — spider silk with a wide range of small molecules.

They have shown that when these ‘silk’ fibres are ‘decorated’ with the antibiotic levofloxacin it is slowly released from the silk, retaining its anti-bacterial activity for at least five days.

Neil Thomas, a Professor of Medicinal and Biological Chemistry, said: “Our technique allows the rapid generation of biocompatible, mono or multi-functionalised silk structures for use in a wide range of applications. These will be particularly useful in the fields of tissue engineering and biomedicine.”

Remarkable qualities of spider silk

Spider silk is strong, biocompatible and biodegradable. It is a protein-based material that does not appear to cause a strong immune, allergic or inflammatory reaction. With the recent development of recombinant spider silk, the race has been on to find ways of harnessing its remarkable qualities.

The Nottingham research team has shown that their technique can be used to create a biodegradable mesh which can do two jobs at once. It can replace the extra cellular matrix that our own cells generate, to accelerate growth of the new tissue. It can also be used for the slow release of antibiotics.

Professor Thomas said: “There is the possibility of using the silk in advanced dressings for the treatment of slow-healing wounds such as diabetic ulcers. Using our technique infection could be prevented over weeks or months by the controlled release of antibiotics. At the same time tissue regeneration is accelerated by silk fibres functioning as a temporary scaffold before being biodegraded.”

The medicinal properties of spider silk recognised for centuries.

The medicinal properties of spider silk have been recognised for centuries but not clearly understood. The Greeks and Romans treated wounded soldiers with spider webs to stop bleeding. It is said that soldiers would use a combination of honey and vinegar to clean deep wounds and then cover the whole thing with balled-up spider webs.

There is even a mention in Shakespeare’s Midsummer Night’s Dream: “I shall desire you of more acquaintance, good master cobweb,” the character ‘Bottom’ said. “If I cut my finger, I shall make bold of you.”

The press release goes on to describe the genesis of the project and how this multidisciplinary team was formed in more detail,

The idea came together at a discipline bridging university ‘sandpit’ meeting five years ago. Dr Goodacre says her chance meeting at that event with Professor Thomas proved to be one of the most productive afternoons of her career.

Dr Goodacre, who heads up the SpiderLab in the School of Life Sciences, said: “I got up at that meeting and showed the audience a picture of some spider silk. I said ‘I want to understand how this silk works, and then make some.’

“At the end of the session Neil came up to me and said ‘I think my group could make that.’ He also suggested that there might be more interesting ‘tweaks’ one could make so that the silk could be ‘decorated’ with different, useful, compounds either permanently or which could be released over time due to a change in the acidity of the environment.”

The approach required the production of the silk proteins in a bacterium where an amino acid not normally found in proteins was included. This amino acid contained an azide group which is widely used in ‘click’ reactions that only occur at that position in the protein. It was an approach that no-one had used before with spider silk — but the big question was — would it work?

Dr Goodacre said: “It was the start of a fascinating adventure that saw a postdoc undertake a very preliminary study to construct the synthetic silks. He was a former SpiderLab PhD student who had previously worked with our tarantulas. Thanks to his ground work we showed we could produce the silk proteins in bacteria. We were then joined by David Harvey, a new PhD student, who not only made the silk fibres, incorporating the unusual amino acid, but also decorated it and demonstrated its antibiotic activity. He has since extended those first ideas far beyond what we had thought might be possible.”

David Harvey’s work is described in this paper but Professor Thomas and Dr Goodacre say this is just the start. There are other joint SpiderLab/Thomas lab students working on uses for this technology in the hope of developing it further.

David Harvey, the lead author on this their first paper, has just been awarded his PhD and is now a postdoctoral researcher on a BBSRC follow-on grant so is still at the heart of the research. His current work is focused on driving the functionalised spider silk technology towards commercial application in wound healing and tissue regeneration.

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

Antibiotic Spider Silk: Site-Specific Functionalization of Recombinant Spider Silk Using “Click” Chemistry by David Harvey, Philip Bardelang, Sara L. Goodacre, Alan Cockayne, and Neil R. Thomas. Advanced Materials DOI: 10.1002/adma.201604245 Version of Record online: 28 DEC 2016

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

This paper is behind a paywall.

I imagine Mr. Cockayne’s name has led to much teasing over the years. People who have names with that kind of potential tend to either change them or double down and refuse to compromise.

Eggshell-based bioplastics

Adding eggshell nanoparticles to a bioplastic (shown above) increases the strength and flexibility of the material, potentially making it more attractive for use in the packaging industry. Credit: Vijaya Rangari/Tuskegee University

Adding eggshell nanoparticles to a bioplastic (shown above) increases the strength and flexibility of the material, potentially making it more attractive for use in the packaging industry. Credit: Vijaya Rangari/Tuskegee University

A March 15, 2016 news item on Nanowerk describes the research,

Eggshells are both marvels and afterthoughts. Placed on end, they are as strong as the arches supporting ancient Roman aqueducts. Yet they readily crack in the middle, and once that happens, we discard them without a second thought. But now scientists report that adding tiny shards of eggshell to bioplastic could create a first-of-its-kind biodegradable packaging material that bends but does not easily break.

The researchers present their work today [March 15, 2016] at the 251st National Meeting & Exposition of the American Chemical Society (ACS).

A March 15, 2016 ACS news release (also on EurekAlert), which originated the news item, describes the work further,

“We’re breaking eggshells down into their most minute components and then infusing them into a special blend of bioplastics that we have developed,” says Vijaya K. Rangari, Ph.D. “These nano-sized eggshell particles add strength to the material and make them far more flexible than other bioplastics on the market. We believe that these traits — along with its biodegradability in the soil — could make this eggshell bioplastic a very attractive alternative packaging material.”

Worldwide, manufacturers produce about 300 million tons of plastic annually. Almost 99 percent of it is made with crude oil and other fossil fuels. Once it is discarded, petroleum-based plastics can last for centuries without breaking down. If burned, these plastics release carbon dioxide into the atmosphere, which can contribute to global climate change.

As an alternative, some manufacturers are producing bioplastics — a form of plastic derived from cornstarch, sweet potatoes or other renewable plant-based sources — that readily decompose or biodegrade once they are in the ground. However, most of these materials lack the strength and flexibility needed to work well in the packaging industry. And that’s a problem since the vast majority of plastic is used to hold, wrap and encase products. So petroleum-based materials continue to dominate the market, particularly in grocery and other retail stores, where estimates suggest that up to a trillion plastic bags are distributed worldwide every year.

To find a solution, Rangari, graduate student Boniface Tiimob and colleagues at Tuskegee University experimented with various plastic polymers. Eventually, they latched onto a mixture of 70 percent polybutyrate adipate terephthalate (PBAT), a petroleum polymer, and 30 percent polylactic acid (PLA), a polymer derived from cornstarch. PBAT, unlike other oil-based plastic polymers, is designed to begin degrading as soon as three months after it is put into the soil.

This mixture had many of the traits that the researchers were looking for, but they wanted to further enhance the flexibility of the material. So they created nanoparticles made of eggshells. They chose eggshells, in part, because they are porous, lightweight and mainly composed of calcium carbonate, a natural compound that easily decays.

The shells were washed, ground up in polypropylene glycol and then exposed to ultrasonic waves that broke the shell fragments down into nanoparticles more than 350,000 times smaller than the diameter of a human hair. Then, in a laboratory study, they infused a small fraction of these particles, each shaped like a deck of cards, into the 70/30 mixture of PBAT and PLA. The researchers found that this addition made the mixture 700 percent more flexible than other bioplastic blends. They say this pliability could make it ideal for use in retail packaging, grocery bags and food containers — including egg cartons.

In addition to bioplastics, Rangari’s team is investigating using eggshell nanoparticles to enhance wound healing, bone regeneration and drug delivery.

Wound healing with cellulose acetate nanofibres

This work on cellulose acetate nanofibres and wound healing (tested on mice) comes from Egypt according to an Aug. 10, 2015 news item on ScienceDaily,

People with diabetes mellitus often suffer from impaired wound healing. Now, scientists in Egypt have developed antibacterial nanofibres of cellulose acetate loaded with silver that could be used in a new type of dressing to promote tissue repair.

An Aug. 10, 2015 Inderscience Publishers press release on the Alpha Galileo website, which originated the news item, provides more detail about the research,

Thanaa Ibrahim Shalaby and colleagues, Nivan Mahmoud Fekry, Amal Sobhy El Sodfy, Amel Gaber El Sheredy and Maisa El Sayed Sayed Ahmed Moustafa, at Alexandria University, prepared nanofibres from cellulose acetate, an inexpensive and easily fabricated, semisynthetic polymer used in everything from photographic film to coatings for eyeglasses and even cigarette filters. It can be spun into fibres and thus used to make an absorbent and safe wound dressing. Shalaby and co-workers used various analytical techniques including scanning electron microscope (SEM) and Fourier-transform infrared (FTIR) spectroscopy to characterise their fibres in which they incorporated silver nanoparticles.

Having characterised the material the team then successfully tested its antibacterial activity against various strains of bacteria that might infect an open wound. They next used the material as a dressing on skin wounds on mice with diabetes and determined how quickly the wound healed with and without the nano dressing. The dressing absorbs fluids exuded by the wound, but also protects the wound from infectious agents while being permeable to air and moisture, the team reports. The use of this dressing also promotes collagen production as the wound heals, which helps to recreate normal skin strength and texture something that is lacking in unassisted wound healing in diabetes mellitus.

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

Preparation and characterisation of antibacterial silver-containing nanofibres for wound healing in diabetic mice by Thanaa Ibrahim Shalaby; Nivan Mahmoud Fekry; Amal Sobhy El Sodfy; Amel Gaber El Sheredy; Maisa El Sayed Sayed Ahmed Moustafa. International Journal of Nanoparticles (IJNP), Vol. 8, No. 1, p. 82 2015 DOI: 10.1504/IJNP.2015.070346

This paper is behind a paywall although there are some exceptions.

Kill bacterial biofilms and activate healing with cinnamon and peppermint

These compounds based on peppermint and cinnamon kill infection (bacterial biofilm) while helping the wound to heal according to a July 8, 2015 news item on ScienceDaily,

Infectious colonies of bacteria called biofilms that develop on chronic wounds and medical devices can cause serious health problems and are tough to treat. But now scientists have found a way to package antimicrobial compounds from peppermint and cinnamon in tiny capsules that can both kill biofilms and actively promote healing. The researchers say the new material could be used as a topical antibacterial treatment and disinfectant.

A July 8, 2015 American Chemical Society news release on EurekAlert, which originated the news item, provides more detail,

Many bacteria clump together in sticky plaques in a way that makes them difficult to eliminate with traditional antibiotics. Doctors sometimes recommend cutting out infected tissues. This approach is costly, however, and because it’s invasive, many patients opt out of treatment altogether. Essential oils and other natural compounds have emerged recently as alternative substances that can get rid of pathogenic bacteria, but researchers have had a hard time translating their antibacterial activity into treatments. Vincent M. Rotello and colleagues wanted to address this challenge.

The researchers packaged peppermint oil and cinnamaldehyde, the compound in cinnamon responsible for its flavor and aroma, into silica nanoparticles. The microcapsule treatment was effective against four different types of bacteria, including one antibiotic-resistant strain. It also promoted the growth of fibroblasts, a cell type that is important in wound healing.

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

Nanoparticle-Stabilized Capsules for the Treatment of Bacterial Biofilms by Bradley Duncan, Xiaoning Li, Ryan F. Landis, Sung Tae Kim, Akash Gupta, Li-Sheng Wang, Rajesh Ramanathan, Rui Tang, Jeffrey A. Boerth, and Vincent M. Rotello. ACS Nano, Article ASAP
DOI: 10.1021/acsnano.5b01696 Publication Date (Web): June 17, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

Wound healing is nature’s way of zipping up your skin

Scientists have been able to observe the healing process at the molecular scale—in fruit flies. From an April 21, 2015 news item on ScienceDaily,

Scientists from the Goethe University (GU) Frankfurt, the European Molecular Biology Laboratory (EMBL) Heidelberg and the University of Zurich explain skin fusion at a molecular level and pinpoint the specific molecules that do the job in their latest publication in the journal Nature Cell Biology.

An April 21, 2015 Goethe University Frankfurt press release on EurekAlert, which originated the news item, describes similarities between humans and fruit flies allowing scientists to infer the wound healing process for human skin,

In order to prevent death by bleeding or infection, every wound (skin opening) must close at some point. The events leading to skin closure had been unclear for many years. Mikhail Eltsov (GU) and colleagues used fruit fly embryos as a model system to understand this process. Similarly to humans, fruit fly embryos at some point in their development have a large opening in the skin on their back that must fuse. This process is called zipping, because two sides of the skin are fastened in a way that resembles a zipper that joins two sides of a jacket.

The scientists have used a top-of-the-range electron microscope to study exactly how this zipping of the skin works. “Our electron microscope allows us to distinguish the molecular components in the cell that act like small machines to fuse the skin. When we look at it from a distance, it appears as if skin cells simply fuse to each other, but if we zoom in, it becomes clear that membranes, molecular machines, and other cellular components are involved”, explains Eltsov.

“In order to visualize this orchestra of healing, a very high-resolution picture of the process is needed. For this purpose we have recorded an enormous amount of data that surpasses all previous studies of this kind”, says Mikhail Eltsov.

As a first step, as the scientists discovered, cells find their opposing partner by “sniffing” each other out. As a next step, they develop adherens junctions which act like a molecular Velcro. This way they become strongly attached to their opposing partner cell. The biggest revelation of this study was that small tubes in the cell, called microtubules, attach to this molecular Velcro and then deploy a self-catastrophe, which results in the skin being pulled towards the opening, as if one pulls a blanket over.

Damian Brunner who led the team at the University of Zurich has performed many genetic manipulations to identify the correct components. The scientists were astonished to find that microtubules involved in cell-division are the primary scaffold used for zipping, indicating a mechanism conserved during evolution.

“What was also amazing was the tremendous plasticity of the membranes in this process which managed to close the skin opening in a very short space of time. When five to ten cells have found their respective neighbors, the skin already appears normal”, says Achilleas Frangakis from the Goethe University Frankfurt, who led the study.

The scientists hope that their results will open new avenues into the understanding of epithelial plasticity and wound healing. They are also investigating the detailed structural organization of the adherens junctions, work for which they were awarded a starting grant from European Research Council (ERC).

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

Quantitative analysis of cytoskeletal reorganization during epithelial tissue sealing by large-volume electron tomography by Mikhail Eltsov, Nadia Dubé, Zhou Yu, Laurynas Pasakarnis, Uta Haselmann-Weiss, Damian Brunner, & Achilleas S. Frangakis. Nature Cell Biology (2015) doi:10.1038/ncb3159 Published online 20 April 2015

This paper is behind a paywall but there is a free preview available via ReadCube Access.

The researchers have provided an image illustrating ‘wound zipping’.

Caption: This is a perspective view of the zipping area with 17 skin cells. Credit: GU

Caption: This is a perspective view of the zipping area with 17 skin cells.
Credit: GU

Fish skin for wound healing

A Feb. 11, 2015 news item on Nanowerk features Chinese research on tilapia fish skin and possible applications for wound healing (Note: A link has been removed),

With a low price tag and mild flavor, tilapia has become a staple dinnertime fish for many Americans. Now it could have another use: helping to heal our wounds. In the journal ACS Applied Materials & Interfaces (“Development of Biomimetic Tilapia Collagen Nanofibers for Skin Regeneration through Inducing Keratinocytes Differentiation and Collagen Synthesis of Dermal Fibroblasts”), scientists have shown that a protein found in this fish can promote skin repair in rats without an immune reaction, suggesting possible future use for human patients.

A Feb. 11, 2015 American Chemical Society (ACS) news release, which originated the news item, provides a few more details about the work,

Jiao Sun, Xiumei Mo and colleagues explain that applying collagen — a major structural protein in animals — to wounds can help encourage skin to heal faster.  But when the protein dressing comes from mammals such as cows and pigs, it has the potential to transmit conditions such as foot-and-mouth disease. Searching for an alternative source of collagen, scientists recently turned to the ocean. Sun’s team wanted to test fish collagen’s potential as a more benign wound treatment.

The researchers developed nanofibers from tilapia collagen and used them to cover skin wounds on rats. The rats with the nanofiber dressing healed faster than those without it. In addition, lab tests on cells suggested that the fish collagen was not likely to cause an immune reaction. The researchers conclude that it could be a good candidate to develop for clinical use.

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

Development of Biomimetic Tilapia Collagen Nanofibers for Skin Regeneration through Inducing Keratinocytes Differentiation and Collagen Synthesis of Dermal Fibroblasts by Tian Zhou, Nanping Wang, Yang Xue, Tingting Ding, Xin Liu, Xiumei Mo, and Jiao Sun. ACS Appl. Mater. Interfaces, 2015, 7 (5), pp 3253–3262 DOI: 10.1021/am507990m Publication Date (Web): January 19, 2015

Copyright © 2015 American Chemical Society

This article is behind a paywall.

Wonders of curcumin: wound healing; wonders of aromatic-turmerone: stem cells

Both curcumin and turmerone are constituents of turmeric which has been long lauded for its healing properties. Michael Berger has written a Nanowerk Spotlight article featuring curcumin and some recent work on burn wound healing. Meanwhile, a ScienceDaily news item details information about a team of researchers focused on tumerone as a means for regenerating brain stem cells.

Curcumin and burn wounds

In a Sept. 22, 2014 Nanowerk Spotlight article Michael Berger sums up the curcumin research effort (referencing some of this previous articles on the topic) in light of a new research paper about burn wound healing (Note: Links have been removed),

Despite significant progress in medical treatments of severe burn wounds, infection and subsequent sepsis persist as frequent causes of morbidity and mortality for burn victims. This is due not only to the extensive compromise of the protective barrier against microbial invasion, but also as a result of growing pathogen resistance to therapeutic options.

… Dr Adam Friedman, Assistant Professor of Dermatology and Director of Dermatologic research at the Montefiore-Albert Einstein College of Medicine, tells Nanowerk. “For me, this gap fuels innovation, serving as the inspiration for my research with broad-spectrum, multi-mechanistic antimicrobial nanomaterials.”

In new work, Friedman and a team of researchers from Albert Einstein College of Medicine and Oregon State University have explored the use of curcumin nanoparticles for the treatment of infected burn wounds, an application that resulted in reduced bacterial load and enhancing wound healing.

It certainly seems promising as per the article abstract,

Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent by Aimee E. Krausz, Brandon L. Adler, Vitor Cabral, Mahantesh Navati, Jessica Doerner, Rabab Charafeddine, Dinesh Chandra, Hongying Liang, Leslie Gunther, Alicea Clendaniel, Stacey Harper, Joel M. Friedman, Joshua D. Nosanchuk, & Adam J. Friedman. Nanomedicine: Nanotechnology, Biology and Medicine (article in press) published online 19 September 2014.http://www.nanomedjournal.com/article/S1549-9634%2814%2900527-9/abstract Uncorrected Proof

Burn wounds are often complicated by bacterial infection, contributing to morbidity and mortality. Agents commonly used to treat burn wound infection are limited by toxicity, incomplete microbial coverage, inadequate penetration, and rising resistance. Curcumin is a naturally derived substance with innate antimicrobial and wound healing properties. Acting by multiple mechanisms, curcumin is less likely than current antibiotics to select for resistant bacteria.

Curcumin’s poor aqueous solubility and rapid degradation profile hinder usage; nanoparticle encapsulation overcomes this pitfall and enables extended topical delivery of curcumin.

In this study, we synthesized and characterized curcumin nanoparticles (curc-np), which inhibited in vitro growth of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in dose-dependent fashion, and inhibited MRSA growth and enhanced wound healing in an in vivo murine wound model. Curc-np may represent a novel topical antimicrobial and wound healing adjuvant for infected burn wounds and other cutaneous injuries.

Two things: This paper is behind a paywall and note the use of the term ‘in vivo’ which means they have tested on animals such as rats and mice for example, but not humans. Nonetheless, it seems a promising avenue for further exploration.

Interestingly, there was an attempt in 1995 to patent turmeric for use in wound healing as per my Dec. 26, 2011 posting which featured then current research on turmeric,

There has already been one court case regarding a curcumin patent,

Recently, turmeric came into the global limelight when the controversial patent “Use of Turmeric in Wound Healing” was awarded, in 1995, to the University of Mississippi Medical Center, USA. Indian Council of Scientific and Industrial Research (CSIR) aggressively contested this award of the patent. It was argued by them that turmeric has been an integral part of the traditional Indian medicinal system over several centuries, and therefore, is deemed to be ‘prior art’, hence is in the public domain. Subsequently, after protracted technical/legal battle USPTO decreed that turmeric is an Indian discovery and revoked the patent.

One last bit about curcumin, my April 22, 2014 posting featured work in Iran using curcumin for cancer-healing.


This excerpt from a Sept. 25, 2014, news item in ScienceDaily represents the first time that tumerone has been mentioned here,

A bioactive compound found in turmeric promotes stem cell proliferation and differentiation in the brain, reveals new research published today in the open access journal Stem Cell Research & Therapy. The findings suggest aromatic turmerone could be a future drug candidate for treating neurological disorders, such as stroke and Alzheimer’s disease.

A Sept. 25, 2014 news release on EurekAlert provides more information,

The study looked at the effects of aromatic (ar-) turmerone on endogenous neutral stem cells (NSC), which are stem cells found within adult brains. NSC differentiate into neurons, and play an important role in self-repair and recovery of brain function in neurodegenerative diseases. Previous studies of ar-turmerone have shown that the compound can block activation of microglia cells. When activated, these cells cause neuroinflammation, which is associated with different neurological disorders. However, ar-turmerone’s impact on the brain’s capacity to self-repair was unknown.

Researchers from the Institute of Neuroscience and Medicine in Jülich, Germany, studied the effects of ar-turmerone on NSC proliferation and differentiation both in vitro and in vivo. Rat fetal NSC were cultured and grown in six different concentrations of ar-turmerone over a 72 hour period. At certain concentrations, ar-turmerone was shown to increase NSC proliferation by up to 80%, without having any impact on cell death. The cell differentiation process also accelerated in ar-turmerone-treated cells compared to untreated control cells.

To test the effects of ar-turmerone on NSC in vivo, the researchers injected adult rats with ar-turmerone. Using PET imaging and a tracer to detect proliferating cells, they found that the subventricular zone (SVZ) was wider, and the hippocampus expanded, in the brains of rats injected with ar-turmerone than in control animals. The SVZ and hippocampus are the two sites in adult mammalian brains where neurogenesis, the growth of neurons, is known to occur.

Lead author of the study, Adele Rueger, said: “While several substances have been described to promote stem cell proliferation in the brain, fewer drugs additionally promote the differentiation of stem cells into neurons, which constitutes a major goal in regenerative medicine. Our findings on aromatic turmerone take us one step closer to achieving this goal.”

Ar-turmerone is the lesser-studied of two major bioactive compounds found in turmeric. The other compound is curcumin, which is well known for its anti-inflammatory and neuroprotective properties

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

Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo by Joerg Hucklenbroich, Rebecca Klein, Bernd Neumaier, Rudolf Graf, Gereon Rudolf Fink, Michael Schroeter, and Maria Adele Rueger. Stem Cell Research & Therapy 2014, 5:100  doi:10.1186/scrt500

This is an open access paper.

Make your carbon atoms stand taller to improve electronic devices

Scientists from Ireland ((Tyndall National Institute at University College Cork [UCC]) and Singapore (National University of Singapore [NUS]) have jointly published a paper about how they achieved a ten-fold increase in the switching efficiency of electronic devices by changing one carbon atom. From the Jan. 21, 2013 news item on ScienceDaily,

These devices could provide new ways to combat overheating in mobile phones and laptops, and could also aid in electrical stimulation of tissue repair for wound healing.

The breakthrough creation of molecular devices with highly controllable electrical properties will appear in the February [2013] issue of Nature Nanotechnology. Dr. Damien Thompson at the Tyndall National Institute, UCC and a team of researchers at the National University of Singapore led by Prof. Chris Nijhuis designed and created the devices, which are based on molecules acting as electrical valves, or diode rectifiers.

Dr. Thompson explains, “These molecules are very useful because they allow current to flow through them when switched ON and block current flow when switched OFF. The results of the study show that simply adding one extra carbon is sufficient to improve the device performance by more than a factor of ten. We are following up lots of new ideas based on these results, and we hope ultimately to create a range of new components for electronic devices.” Dr. Thompson’s atom-level computer simulations showed how molecules with an odd number of carbon atoms stand straighter than molecules with an even number of carbon atoms. This allows them to pack together more closely. Tightly-packed assemblies of these molecules were formed on metal electrode surfaces by the Nijhuis group in Singapore and were found to be remarkably free of defects. These high quality devices can suppress leakage currents and so operate efficiently and reliably. The device can be cleanly switched on and off purely on the basis of the charge and shape of the molecules, just like in the biological nanomachines that regulate photosynthesis, cell division and tissue growth.

The Jan. ??, 2013 University College Cork news release, which originated the news item, provides more details,

The combined experiments and simulations show for the first time that minute improvements in molecule orientation and packing trigger changes in van der Waals forces that are sufficiently large to dramatically improve the performance of electronic devices. Dr. Thompson explains: “These van der Waals forces are the weakest of all intermolecular forces and only become significant when summed over large areas. Hence, up until now, the majority of research into ultra-small devices has used stronger “pi-pi” interactions to stick molecules together, and has ignored the much weaker, but ubiquitous, van der Waals interactions. The present study shows how van der Waals effects, which are present in every conceivable molecular scale device, can be tuned to optimise the performance of the device.”

The devices are based on molecules that act as diodes by allowing current to pass through them when operated at forward bias and blocking current when the bias is reversed. Molecular rectifiers were first proposed back in 1974, and advances in scientific computing have allowed molecular‐level design to be used over the past decade to develop new organic materials that provide better electrical responses. However, the relative importance of the interactions between the molecules, the nature of the molecule-metal contact and the influence of environmental effects have been questioned. This new research demonstrates that dramatic improvements in device performance may be achieved by controlling the van der Waals forces that pack the molecules together. Simply changing the number of carbon atoms by one provides significantly more stable and more reproducible devices that exhibit an order of magnitude improvement in ON/OFF ratio. The research findings demonstrate the feasibility of boosting device performances by creating tighter seals between molecules.

Here a citation and a link to the paper,

The role of van der Waals forces in the performance of molecular diodes by Nisachol Nerngchamnong, Li Yuan, Dong-Chen Qi, Jiang Li, Damien Thompson, & Christian A. Nijhuis. Nature Nanotechnology (2013) doi:10.1038/nnano.2012.238 Advance online publication: Jan. 6, 2013.

This paper is behind a paywall.