Self-Assembled Nanomaterials for Chronic Skin Wound Healing

Schematic of self-assembled nanomaterials on skin wounds

Chronic wounds can be caused by several underlying molecular and cellular pathophysiological mechanisms, including poor vascularization, excessive extracellular matrix (ECM) degradation by proteases, decreased growth factor activity, and bacterial infection. More effective wound therapies need to address one or more of these mechanisms to significantly advance wound care.

Self-assembled nanomaterials may provide new therapeutic options for chronic wound healing applications as those materials generally exhibit excellent biocompatibility and can bear multiple functionalities, such as ECM-mimicking properties, drug delivery capabilities, and tunable mechanics. Furthermore, self-assembled nanomaterials can be produced at low cost, and owing to their ability to self-organize, generate complex multifunctional structures that can be tailored to the varying sizes and shapes of chronic wounds. Self-assembled nanomaterials have been engineered to serve as wound dressings, growth factor delivery systems, and antimicrobials.

As there are many different types of self-assembled nanomaterials, which in turn have different mechanisms of self-assembly and physiochemical properties, one type of self-assembled nanomaterials may not be sufficient to address all underlying mechanisms of chronic wounds. However, self-assembled nanomaterials can be easily tailored, and developing multifunctional self-assembled nanomaterials that can address various targets in chronic wounds will be needed.

Future studies should investigate combinations of various self-assembled nanomaterials to take full advantage of their multifunctional properties.

 

Read the full article to know more.

Defense or repair: How immune cells are controlled during wound healing

Credit: CNRI/ SCIENCE PHOTO LIBRARY

A Cologne-based research team has discovered that the metabolism of mitochondria, the energy suppliers of cells, in macrophages coordinate wound healing to a significant degree. Macrophages belong to the white blood cells and are also known as scavenger cells. Professor Dr. Sabine Eming and her collaborators and colleagues at the CECAD Cluster of Excellence for Aging Research at the University of Cologne showed that wound macrophages undergo different metabolic programs during tissue repair, which are required to support the successive phases for skin reconstruction after injury.

For more on this subject: https://www.sciencedaily.com/releases/2021/12/211208123417.htm   

Full article link: http://dx.doi.org/10.1016/j.cmet.2021.10.004

 

Research Uncovers New Mechanism that Promotes Wound Healing in Skin

A University of California, Irvine-led study identifies a new molecular pathway that promotes the healing of wounds in the skin. Titled, “GRHL3 activates FSCN1 to relax cell-cell adhesions between migrating keratinocytes during wound re-epithelialization,” the study was published in JCI Insight.

Credits to Dinesh C Sharma

The molecular pathway identified is controlled by an evolutionary conserved gene called a Grainyhead like 3 (GRHL3), which is a gene required for mammalian development. Without this gene, several abnormalities may occur, including spina bifida, defective epidermal barrier, defective eyelid closure and soft-tissue syndactyly, a condition in which children are born with fused or webbed fingers.

The study reveals how during wound healing, GRHL3 works to activate a protein coding gene called Fascin Actin-Bundling Protein 1 (Fscn1), to loosen the adhesion between wounded skin cells so they can migrate efficiently to close the wound. Researchers also found that alterations in this process may result in chronic, non-healing wounds, such as diabetic ulcers that affect millions of patients every year.

“What’s exciting about our findings is that we have identified a molecular pathway that is activated in normal acute wounds in humans, and altered in diabetic wounds in mice,” said Ghaidaa Kashgari, PhD, a postdoctoral researcher in the UCI School of Medicine Department of Medicine. “This finding strongly indicates clinical relevance and may improve our understanding of wound healing biology and could lead to new therapies.”

Acute skin wound healing progresses through four overlapping phases: hemostasis, inflammation, proliferation, and tissue remodeling. Although wounds close partially by dermal contraction, re-epithelialization occurring during the proliferation phase, is a key step in wound healing.

During re-epithelialization, keratinocytes, which are cells that make up the outermost layers of the skin, migrate on top of the underlying granulation tissue, which is the lumpy, pink tissue that forms around the edges of a wound. Ultimately, the keratinocytes meet migrating keratinocytes from the opposing margin to close the wound.

“Despite significant advances in treatment, much remains to be understood about the molecular mechanisms involved in normal wound healing,” said senior author Bogi Andersen, MD, a professor in the Departments of Biological Chemistry and Medicine at the UCI School of Medicine. Department of Biological Chemistry and Department of Medicine, Division of Endocrinology. “Our findings uncover how abnormalities in the GRHL3/FSCN1/E-cadherin pathway could play a role in non-healing wounds which needs to be further investigated.”

This work was supported by the National Institutes of Health and the Irving Weinstein Foundation.

DOI: http://dx.doi.org/10.1128/Spectrum.00562-21

 

Not all Acne is Equal: Scientists Reveal Strains of C. acnes that Promote Skin Health

A study led by Osaka City University and Okayama University researchers on Caenorhabditis elegans shows that certain strains of the bacteria Cutibacterium acnes actually prolong the nematode’s lifespan and help its innate immune system fight against the pathogen Staphylococcus aureus.

 

 

Cutibacterium acnes, a bacteria that is known to cause acne, is also widely spread on people with healthy skin. Recent advances in gene sequencing have shown that differences in the genetic background between strains of bacteria may lead to differing roles in the skin. A new study, done without animal (mammal) testing, shows that the nonpathogenic strain of C. acnes improves the skin’s resistance against the infection-causing bacteria Staphylococcus aureus.

“It is likely that C. acnes maintains skin health by inhibiting common pathogens like S. aureus from invading skin tissue,” said lead author Ayano Tsuru, a graduate student at the Graduate School of Human Life Science, Osaka City University. “Instead of using mammals, we explored this with Caenorhabditis elegans, a 1mm nematode that has basic animal parts like a nervous system, muscles, and digestive tract, as well as a body surface barrier equivalent to human skin.”

In this joint study between the Osaka City University and Okayama University, researchers used C. elegans to investigate the biological effects of several strains of C. acnes isolated from human skin.

Results showed that ribotype (RT) 4 and 8 strains, a classification of bacteria strains based on polymorphisms in rRNA, which are often detected in the skin of individuals suffering from acne, shortened the lifespan of the nematode, while RT6 strains that are often found in the skin of people without acne, did not.

“This means that,” explains supporting author Yumi Hamazaki also a graduate student at the OCU Graduate School of Human Life Science, “ribotype strains of C. acnes that cause acne in humans correlated with virulence, or a shortening the C. elegans lifespan.

The team further clarified this finding by investigating the effect of healthy skinassociated strains of C. acnes on the nematode’s susceptibility to S. aureus. Results showed the survival period of nematodes infected with the pathogen to be longer than the control group.

Also, RNA sequencing analysis of changes in the gene expression revealed that strains of C. acnes behind healthy skin activated a group of genes related to innate immunity and biological defense responses in C. elegans. “Further analysis of nematode gene mutants” states Professor Shuta Tomida of the Center for Comprehensive Genomic Medicine at Okayama University Hospital, “suggests this resistance to S. aureus was mediated by TIR-1 and p38 MAPK pathways that are responsible for innate immunity and not by suppressing the growth of the S. aureus pathogen.

The implications of this study are wide and exciting.

By focusing on ribotypes related to the absence of acne, this study revealed there are beneficial aspects of acne bacteria, which have had a generally negative image.

As advisor to the study, Eriko Kage-Nakadai, professor at the OCU Graduate School of Human Life Science puts it, “this reminds us that when evaluating the biological effects of certain bacteria, there is a need for a discussion at the strain level. Also,” the professor continues, “the fact that we succeeded in detecting the effects of skin indigenous bacteria using C. elegans illustrates the usefulness of this nematode as an alternative model in the field of epidemiology.”

Lastly, in the landscape of probiotic research currently dominated by bifidobacteria and lactobacillus, the team is excited at the expectation that this study may lead to the application of healthy skin-related strains of C. acnes as a “non-drinking probiotic.”

 

Journal Reference:
Ayano Tsuru, Yumi Hamazaki, Shuta Tomida, Mohammad Shaokat Ali, Tomomi Komura, Yoshikazu Nishikawa, Eriko Kage Nakadai. Nonpathogenic Cutibacterium acnes Confers Host Resistance against Staphylococcus aureus. Microbiology Spectrum, 2021; DOI: 10.1128/Spectrum.00562-21

Updated Treatment for Acne: Targeted Therapy Based on Pathogenesis

One of many topics which will discussed during the 12th International Conference on Skin Ageing and Challenges 2021 is Updated Treatment for Acne: Targeted Therapy Based on Pathogenesis.

Recent advances have further elucidated the pathogenesis of acne: it is now clear that immunological factors play an important role. To date, acne pathogenesis has implicated four major factors: androgen-dependent sebogenesis, hyperkeratinization of the infundibulum, Cutibacterium acnes (C. acnes) colonization, and inflammation. Successful targeted therapy for acne currently includes topical retinoids that normalize abnormal hyperkeratinization in the infundibulum and novel topical retinoids with anti-inflammatory properties. Topical and oral antimicrobials inhibit bacterial proliferation and reduce inflammation related to cytokines and extracellular enzymes. Topical benzoyl peroxide (BPO) is highly effective in reducing both sensitive and resistant strains of C. acnes and has some impact on hyperkeratinization in the infundibulum. Anti-androgens can regulate androgen metabolism, resulting in suppression of sebum excretion. Orally administered isotretinoin is currently the only agent that can affect all four main factors implicated in acne.

In this review, they summarize updated treatments facilitating potential novel approaches in acne treatment including immunology and wound healing. In particular, biological treatments targeting IL-1β, IL-17, IL-23, and TNFα could provide novel approaches for treating severe acne and related disorders. In addition, biological antibodies targeting TGFβ, IL-6, MMP, IGF-1, and B cells may be a potential strategy for the prevention and treatment of this type of scar in the future. Future treatment for acne should embrace approaches that target the main etiological factors of acne.

DOI: https://doi.org/10.1007/s13555-021-00552-6

Skin whitening products and their ingredients for safety, health risk, and the halal status

One of  study dedicated to the 12th International Conference on Skin Ageing and Challenges is Skin whitening products and their ingredients for safety, health risk, and the halal status published by Fatin Nur Majdina Nordin and al. 

This review paper aimed to shed light on the skin-whitening ingredients and their issues related to safety, health risk, and halal status: Skin-whitening products are in the high trend of demand for skin beautifying and lightening. Sources of ingredients for cosmetics could be natural, semi-synthetic, and synthetic that may affect the halal status of a product. The lack of scientific evidence on the safety and risks of such ingredients is a major concern to many consumers.

Based on the review, most of the common ingredients in the skin-whitening products are originated from plants, animals, microbes, and heavy metals. Health risk of the ingredients was evaluated based on the usage, chronic or acute adverse effect, frequency of incidence, and the hazardous chemical contents of a halal cosmetics. The halal status of the ingredients was investigated based on the sources of origin, safety evaluation, and associated health risk of the ingredients. This review shows that ingredients play a vital role in the halal status decision-making of a cosmetic product. Therefore, the categories of Halal-Safe, Haram-Prohibited, and Critical-Need further evaluation were suggested to integrate the sources of ingredients with safety.

DOI: https://doi.org/10.1111/jocd.13691

 

 

The Pathobiology of Skin Aging: New Insights into an Old Dilemma

One of the great topics that will be discussed during the 12th International Conference on Skin Ageing and Challenges 2021 is The Pathobiology of Skin Aging: New Insights into an Old Dilemma by Georges Murphy.

 

Long considered both physiologic and inevitable, skin aging is a degenerative phenomenon whereby both intrinsic and environmental factors conspire to produce an authentic disease. The consequences of this disorder are many and varied, ranging from atrophy and fragility to defective repair to deficient immunity and vulnerability to certain infections. The pathobiological basis for skin aging remains poorly understood. At a cellular level, stem cell dysfunction and attrition appear to be key events, and both genetic and epigenetic factors are involved in a complex interplay that over time results in deterioration of our main protective interface with the external environment. Past and current understanding of the cellular and molecular intricacies of skin aging provide a foundation for future approaches designed to thwart the aging phenotype.

This review has provided only a glimpse into the complex events that account for the disease of skin aging. Beyond UV light and infectious agents, there are numerous other factors that are likely to contribute to the aging skin phenotype. Krutmann and coworkers have recently emphasized the term skin exposome to describe the totality of potentially deleterious, age-inducing external factors to which skin is exposed during a lifetime. These factors include, in addition to UV radiation, environmental pollutants, stress, nutritional factors, tobacco, temperature-related factors, and even lack of sleep. Such factors, singly or in combination, may have the potential to conspire in a manner that affects the epigenome governing the transcriptional integrity of skin cell DNA, thus pathologically modifying cells, including physiologic stem cells, from the more pristine states that typified their youth. In this respect, it is important to remember that epigenomic alterations that reorganize chromatin and alter gene expression are known to contribute to cellular aging in organisms as basic as budding yeast.

Full article: https://doi.org/10.1016/j.ajpath.2020.03.007 

Apple cider vinegar soaks do not alter the skin bacterial microbiome in atopic dermatitis

Atopic dermatitis is a common skin disease characterized by altered cutaneous immunity in which patients often exhibit lower skin microbiota diversity compared to healthy skin and are prone to colonization by Staphylococcus aureus. Apple cider vinegar has been shown to have antibacterial effects; however, its effects on the skin microbiome have not previously been well-described.

The Conclusion: Results suggest that daily soaks in 0.5% apple cider vinegar are not an effective method of altering the skin bacterial microbiome in atopic dermatitis. Further studies are needed to explore the effects of different concentrations of apple cider vinegar on skin microflora and disease severity.

DOI: https://doi.org/10.1371/journal.pone.0252272

Authors: Lydia A. Luu, Richard H. Flowers, Yingnan Gao, Martin Wu, Sofia Gasperino, Ann L. Kellams, DeVon C. Preston, Barrett J. Zlotoff, Julia A. Wisniewski, Steven L. Zeichner

How to Access to Skin Ageing & Challenges 2020 Virtual Platform?

If you wish to visualize all talks (Major, Short oral presentations, and Posters), you can register and have access to our virtual platform for 1 month.
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Access to Skin Ageing & Challenges Platform  

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– Skin Ageing & Challenges  2020 Congress ( 40+ recorded presentations)

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– Workshop “How to Evaluate Mitochondria Function ?”

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Recorded Workshop only (without Workshop Report ) 275 €
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Best Image Contest – Skin Challenges 2020 Congress

Among the Best Images contest submitted images, the organizing committee selected Dr. Lia Mara Grosso Neves’s submission.

Dr. Neves also will present a short oral entitled “Polysaccharide‐rich hydrogel formulation combined with photobiomodulation repairs UV‐induced photodamage in mice skin” during the Skin Challenges 2020 Virtual Congress.

Summary of talk: The development of new therapies for the treatment of photoaging has gained importance in the last decades. In this scenario, natural products represent interesting tools for the prevention and treatment of skin aging. The therapy called photobiomodulation (PBM) refers to the use of photons, in a non-thermal irradiance, to alter the biological activity of cells and tissues. Non-ablative lasers have been increasingly used in the aesthetic treatment of fine wrinkles and skin photoaging. Will be demonstrated the biomodulatory effects of a polysaccharide-rich hydrogel formulation extracted from Lycium barbarum fruits combined with PBM repairing the UVR-induced photodamage on the skin of hairless mice.

If you wish to submit your images for Best Images contest, please follow the link here.