Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption

Proper skin barrier function is paramount for our survival, and, suffering injury, there is an acute need to restore the lost barrier and prevent development of a chronic wound. We hypothesize that rapid wound closure is more important than immediate perfection of the barrier, whereas specific treatment may facilitate perfection. The aim of the current project was therefore to evaluate the quality of restored tissue down to the molecular level. We used Göttingen minipigs with a multi-technique approach correlating wound healing progression in vivo over three weeks, monitored by classical methods (e.g., histology, trans-epidermal water loss (TEWL), pH) and subsequent physicochemical characterization of barrier recovery (i.e., small and wide-angle X-ray diffraction (SWAXD), polarization transfer solid-state NMR (PTssNMR), dynamic vapor sorption (DVS), Fourier transform infrared (FTIR)), providing a unique insight into molecular aspects of healing. We conclude that although acute wounds sealed within two weeks as expected, molecular investigation of stratum corneum (SC) revealed a poorly developed keratin organization and deviations in lipid lamellae formation. A higher lipid fluidity was also observed in regenerated tissue. This may have been due to incomplete lipid conversion during barrier recovery as glycosphingolipids, normally not present in SC, were indicated by infrared FTIR spectroscopy. Evidently, a molecular approach to skin barrier recovery could be a valuable tool in future development of products targeting wound healing.

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Investigating the Early Events after Skin-Barrier Disruption Using Microdialysis—A Human Ex Vivo Skin Model

Dermato ◽

10.3390/dermato1020008 ◽

2021 ◽

Vol 1 (2) ◽

pp. 47-58

Author(s):

Katrine Baumann ◽

Niels Peter Hell Knudsen ◽

Anne-Sofie Østergaard Gadsbøll ◽

Anders Woetmann ◽

Per Stahl Skov

Keyword(s):

Interstitial Fluid ◽

Ex Vivo ◽

Skin Barrier ◽

Microdialysis Sampling ◽

Sample Analysis ◽

Skin Model ◽

Barrier Disruption ◽

Gm Csf ◽

Tnf Α ◽

Subsequent Sample

Skin-barrier restoration following abrasive trauma is facilitated by mediator release from skin-resident cells, a process that has been investigated primarily in mice or simplified human systems with previous studies focusing on a limited number of biomarkers. Here, we demonstrate how early events caused by skin-barrier disruption can be studied in a human ex vivo skin model. Ten relevant biomarkers were recovered from the interstitial fluid by skin microdialysis with subsequent sample analysis using a multiplex platform. As a control, the biomarker profiles obtained from microdialysis sampling were compared to profiles of skin biopsy homogenates. We found that nine (GM-CSF, CXCL1/GROα, CXCL8/IL-8 CXCL10/IP-10, IL-1α, IL-6, MIF, TNF-α, and VEGF) of the 10 biomarkers were significantly upregulated in response to abrasive trauma. Only dialysate levels of CCL27/CTACK were unaffected by skin abrasion. Biomarker levels in the homogenates corresponded to dialysate levels for CCL27/CTACK, CXCL1/GROα, CXCL8/IL-8, and IL-6. However, IL-1α showed an inverse trend in response to trauma, and biopsy levels of MIF were unchanged. GM-CSF, CXCL10/IP-10, TNF-α, and VEGF were not detected in the biopsy homogenates. Our results suggest that the human ex vivo skin model is a reliable approach to study early events after disruption of the skin barrier.

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A nontoxic ionic liquid composition for the delivery of biological macromolecular anions across the skin barrier

Pharmaceutical Patent Analyst ◽

10.4155/ppa-2021-0012 ◽

2021 ◽

Author(s):

Neeraj Kumar ◽

Balraj Saini ◽

Rajwinder Kaur

Keyword(s):

Ionic Liquids ◽

Ex Vivo ◽

Skin Permeation ◽

Skin Barrier ◽

Skin Penetration ◽

Liquid Composition ◽

Cell Internalization ◽

Dermal Delivery ◽

In Vivo Cytotoxicity

The development of biocompatible ionic liquids is needed in order to explore their vastly underutilized pharmaceutical potential. US10912834 patent discloses ionic liquids comprising macromolecular biological anions and alkylated cations, which provides enhanced dermal delivery and cell internalization of the large biological anions. The studies of ex vivo permeation through excised pig skin indicated significantly higher skin penetration of percent dose and enhanced drug internalization was achieved using these ionic liquids. Although, the patent advances an infant field of biological macromolecule-based ionic liquids, the evaluation of these claimed ionic liquids relies only on the in vivo cytotoxicity data and ex vivo skin permeation behavior. Exhaustive studies, including dermatokinetic evaluation and long-term animal toxicity experiments, should be performed in order to unravel the potential of the aforementioned ionic liquids.

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The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000116 ◽

2012 ◽

Vol 82 (3) ◽

pp. 228-232 ◽

Cited By ~ 7

Author(s):

Mauro Serafini ◽

Giuseppa Morabito

Keyword(s):

Antioxidant Capacity ◽

Dietary Intervention ◽

Ex Vivo ◽

The Body ◽

Dietary Polyphenols ◽

Enzymatic Antioxidant ◽

Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

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