Category: News & Media

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.

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

 

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

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