Epidermal Biomarkers Research Articles

Revolutionizing wearable healthcare with solid-state epidermal biomarker monitoring

Revolutionizing wearable healthcare with solid-state epidermal biomarker monitoring

Stretchable ionic-electronic bilayer hydrogel electronics enable in situ detection of solid-state epidermal biomarkers.

Continuous and in situ detection of biomarkers in biofluids (for example, sweat) can provide critical health data but is limited by biofluid accessibility. Here we report a sensor design that enables in situ detection of solid-state biomarkers ubiquitously present on human skin. We deploy an ionic-electronic bilayer hydrogel to facilitate the sequential dissolution, diffusion and electrochemical reaction of solid-state analytes. We demonstrate continuous monitoring of water-soluble analytes (for example, solid lactate) and water-insoluble analytes (for example, solid cholesterol) with ultralow detection limits of 0.51 and 0.26 nmol cm-2, respectively. Additionally, the bilayer hydrogel electrochemical interface reduces motion artefacts by a factor of three compared with conventional liquid-sensing electrochemical interfaces. In a clinical study, solid-state epidermal biomarkers measured by our stretchable wearable sensors showed a high correlation with biomarkers in human blood and dynamically correlated with physiological activities. These results present routes to universal platforms for biomarker monitoring without the need for biofluid acquisition.

Metal Hydrogel‐Based Integrated Wearable Biofuel Cell for Self‐Powered Epidermal Sweat Biomarker Monitoring

AbstractWearable sensors for continuous monitoring of biomarkers in body fluids have gained significant attention for their potential in disease diagnostics and health management, but lack sustainable power supply and advanced sensing strategies. Herein, sweat wearable biofuel cells (w‐BFCs) based on metal hydrogels are demonstrated with high output and outstanding stability, which harvest energy directly from human sweat and simultaneously enable self‐powered sensing of epidermal biomarkers. Experimental and computational results elucidate that the highly porous and flexible metal hydrogels exhibit superior electrocatalytic capabilities for oxidizing ascorbic acid (AA), a sweat metabolite at the anode, and reducing O2 at the cathode. Consequently, the assembled AA/O2 BFC delivers a high and stable power output, with a maximum output power density of 35 µW cm−2 at an ultralow AA concentration and long‐term stability over 30 days, and a self‐powered, sensitive sensing for AA detection. When applied to the skin of the volunteers, this integrated w‐BFC powers the biosensor using human sweat AA as fuel and allowing real‐time monitoring of AA sensing signal via smartphone. This work not only advances energy harvesting for wearable sensors but also paves new avenues for real‐time, online monitoring of epidermal sweat biomarkers.

Stratum corneum and microbial biomarkers precede and characterize childhood atopic dermatitis.

Atopic dermatitis (AD) is the most common paediatric inflammatory skin disease. There are currently no robust biomarkers that could reliably predict its manifestation, and on the molecular level, it is less well characterized than adult AD. This study aimed to extend previous findings and provide evidence for distinct changes of the epidermal proteome and microbiome preceding the onset of AD as well as characterizing early AD. We longitudinally analysed epidermal biomarker levels and microbial profiles in a cohort of 50 neonates at high risk for AD, who had participated in a randomized controlled trial on early emollient use for AD prevention. About 26% of the infants developed AD until month 24 with an average age of 10 month at disease onset. In children with later AD, IL-1Ra, TNFβ, IL-8, IL-18, IL-22, CCL2, TARC, TSLP and VEGFa showed increased levels prior to disease manifestation with levels of IL-1Ra, TNFβ and VEGFa already increased shortly after birth. Further, children with later AD displayed a delayed maturation and differentially composed skin microbiome prior to AD onset. At manifestation, levels of multiple Th2, Th17/22 and Th1-associated biomarkers as well as innate immunity markers were elevated, and abundances of commensal Streptococcus species were reduced in favour of Staphylococcus epidermidis. Our results indicate that elevations of proinflammatory stratum corneum biomarkers and alterations of the skin microbiome precede paediatric AD and characterize the disease at onset.

Epidermal biomarkers of the skin barrier in atopic and contact dermatitis.

Dysfunction of the skin barrier plays a critical role in the initiation and progression of inflammatory skin diseases, such as atopic dermatitis and contact dermatitis. Epidermal biomarkers can aid in evaluating the functionality of the skin barrier and understanding the mechanisms that underlay its impairment. This narrative review provides an overview of recent studies on epidermal biomarkers associated with the function and integrity of the skin barrier, and their application in research on atopic dermatitis and contact dermatitis. The reviewed studies encompass a wide spectrum of molecular, morphological and biophysical biomarkers, mainly obtained from stratum corneum tape strips and biopsies. Lipids, natural moisturizing factors, and structural proteins are the most frequently reported molecular biomarkers. Additionally, corneocyte surface topography and elasticity show potential as biomarkers for assessing the physical barrier of the skin. In contact dermatitis studies, biomarkers are commonly employed to evaluate skin irritation and differentiate between irritant and allergic contact dermatitis. In atopic dermatitis, biomarkers are primarily utilized to identify differences between atopic and healthy skin, for predictive purposes, and monitoring response to therapies. While this overview identifies potential biomarkers for the skin barrier, their validation as epidermal biomarkers for atopic dermatitis and contact dermatitis has yet to be established.

390 Identification of early epidermal biomarkers in infants at risk of developing atopic dermatitis using minimally invasive methods

To investigate early disease biomarkers for atopic dermatitis (AD) we investigated epidermal cytokine levels and skin microbial profiles. We performed minimally invasive biosampling in a prospective cohort of 50 neonates at high risk for developing AD including tape strips and skin swabs from antecubital fossa, volar forearm and cheek at 3, 6, 12, 18 and 24 months after birth. 26% of the included new-borns developed AD until month 24. Multiplex ELISA analysis showed a significant increase of pro-inflammatory cytokines in the epidermis at AD onset (i.e.

The transcriptome of hand eczema assessed by tape stripping.

No biomarkers have been identified that can classify subtypes of hand eczema (HE). Although skin biopsies represent the gold standard for investigations of the skin, the invasive technique is not favorable when investigating skin from sensitive areas. Recent advances in the use of skin-tape strips for molecular investigations enable noninvasive investigations of HE. By using whole transcriptome sequencing (WTS), the molecular profile of HE according to different localizations on the hands, etiologies, and clinical/morphological subtypes was investigated. Thirty adult, Danish HE patients, 12 with and 18 without concurrent atopic dermatitis (AD), as well as 16 controls were included. Tape strip samples were collected from lesional, nonlesional, and healthy skin. Total RNA was extracted and WTS was performed. The largest molecular difference of HE patients with and without AD was found in nonlesional skin areas and included a downregulation of CXCL8 for HE patients without AD. Differences between allergic and irritant contact dermatitis included epidermal biomarkers such as EPHA1. Skin tape strip samples could be used to assess the gene expression profile of HE on different localizations of the hands. The skin tape strip method identified new molecular markers that showed promising result for the identification of HE subtypes.

143 Non-invasive skin sample collection: Comparing D-squame and the Smart Sticker

Collection of stratum corneum via tape stripping is a minimally invasive procedure applied in a number of fields, including identification of epidermal biomarkers in skin cancers and inflammatory disorders. Tape stripping is an established technique; however, the number and types of tapes used in different studies vary widely. As an example, the most commonly used tape, D-squame skin sampling disc (CuDerm), is applied between 10-35 consecutive times to the sampling site. Repeated tape stripping is likely to result in increased local inflammation, potentially complicating comparison and interpretation of gene expression changes.

Cytokine concentration across the stratum corneum in atopic dermatitis and healthy controls

Tape stripping is a promising technique for assessment of epidermal biomarkers in inflammatory skin diseases. However, to facilitate its implementation in the clinical practice, a thorough validation regarding sampling strategy is needed. Knowledge of biomarkers variation in concentration across stratum corneum is scarce. Therefore, this study aimed to assess the variability of cytokines across stratum corneum using tape stripping technique by consecutive application of 21 adhesive tapes (D-squame) to lesional and non-lesional skin from 15 patients with atopic dermatitis (AD) and 16 healthy controls. Concentration of cytokines (IL-1α, IL-1b, IL-5, IL-18, IFN-γ, CCL17, CCL22, CCL27, CXCL8, CXCL10, TNF-α, TSLP, VEGFA) was determined in five different depths, using multiplex immunoassay. Comparing tape 4 with tape 21, no cytokine changed significantly in concentration in AD lesional skin. In AD non-lesional skin a small decrease was found for CCL17, CXCL8 and CXCL10. For healthy controls, a decrease was found for IL-1a, IL-1b, VEGFA and an increase for IL-18. Differences were found between AD skin and healthy control skin. Concentration of cytokines was stable across stratum corneum, indicating that sampling of only one tape from the stratum corneum is reliable in reflecting the overall cytokine milieu. Differences between AD and healthy skin confirm robustness of tape stripping for measuring cytokine levels.

Stratum Corneum Biomarkers in Atopic Dermatitis: Biological and Spatial Variability

Background:Atopic dermatitis is a highly heterogeneous skin disease, mainly affecting children. Introduction of biological therapies has urged the development of biomarkers to facilitate personalized therapy. Stratum corneum biomarkers emerged as a promising non-invasive alternative to skin biopsy, yet validation of spatial and biological variability is essential for their application in clinical research.Objective:To assess spatial and biological variability of stratum corneum biomarkers for atopic dermatitis.Methods:Stratum corneum was collected from 17 atopic dermatitis patients by consecutive application of eight adhesive tapes to a lesional skin site and 2 cm and 4 cm from the lesion. Two non-lesional sites at a 2 cm distance from the same lesion were collected to determine biological variability. Filaggrin degradation products (NMF) were determined by liquid chromatography and thirteen cytokines (IL-4, IL-13, IL-18, IL-31, IL-33, CCL17, CCL22, CCL27, CXCL8, IL-1α, IL-RA, IL-18, IL-22) by multiplex immunoassay.Results:Biomarker levels showed gradual changes from lesional to non-lesional skin sites at 2 cm and 4 cm; magnitude and direction of change were biomarker-specific. Intra-subject variability ranged from 17.3% (NMF) to 85.1% (CXCL8). Biomarker levels from two stratum corneum depths were highly correlated; several biomarkers showed significant depth dependence.Conclusion:Stratum corneum enables non-invasive collection of relevant immune and epidermal biomarkers, but biomarker-specific spatial and biological variability emphasizes the importance of standardized procedures for stratum corneum collection.

Biomarkers for psoriasis skin lesions.

Psoriasis is a common, chronic skin disease, whose diagnosis is based mainly on clinical features but, in some cases, can be difficult. As the exact diagnosis of psoriasis and the differential diagnosis with other diseases are crucial for the therapeutic choice, several studies investigated the relevance of some genes and proteins as potential specific skin biomarkers. Despite a large number of reports, none of them has been tested in large studies and thus achieved regulatory approval and clinical application. Authors give an overview on the skin biomarkers (BMs) in psoriasis, distinguishing inflammatory and epidermal biomarkers, highlighting the most distinctive skin psoriasis BMs, that can help physicians and pathologists to recognize psoriasis among "psoriasiform dermatitis".

Molecular modifications of dermal and epidermal biomarkers following UVA exposures on reconstructed full-thickness human skin

Ultraviolet A (UVA) radiation adversely affects skin health and appearance via multiple molecular pathways. Biologically relevant UVA damage are classified as short-term effects (e.g. formation of reactive oxygen species [ROS], inflammation, photo-oxidation, DNA damage, immunosuppression, photoallergy and cell-mediated contact hypersensitivity) or long-term effects (elastosis, photoageing and photocarcinogenesis). Single and chronic experimental exposure to UVA are limited in humans by ethical concerns, and furthermore it is impossible to quantify long-term endpoints such as photoageing over the life-span of a human volunteer. The aim of the present study was to investigate the biological relevance of the Phenion FT skin model for use in photobiological studies. Biological responses to acute and repeated UVA exposures were investigated by monitoring the kinetics of gene expression during the post-irradiation period. By using a dynamic approach, we were able to define early and stable markers of UVA-induced effects that could be predictive of UVA damage in vivo. The transcriptomic approach applied to 3D human tissues appears to be an encouraging method for gaining a deeper understanding of the UVA effects on skin and for studying the dermal response with non-invasive techniques.

Use of RT-PCR and DNA microarrays to characterize RNA recovered by non-invasive tape harvesting of normal and inflamed skin.

We describe a non-invasive approach for recovering RNA from the surface of skin via a simple tape stripping procedure that permits a direct quantitative and qualitative assessment of pathologic and physiologic biomarkers. Using semi-quantitative RT-PCR we show that tape-harvested RNA is comparable in quality and utility to RNA recovered by biopsy. It is likely that tape-harvested RNA is derived from epidermal cells residing close to the surface and includes adnexal structures and present data showing that tape and biopsy likely recover different cell populations. We report the successful amplification of tape-harvested RNA for hybridization to DNA microarrays. These experiments showed no significant gene expression level differences between replicate sites on a subject and minimal differences between a male and female subject. We also compared the array generated RNA profiles between normal and 24 h 1% SLS-occluded skin and observed that SLS treatment resulted in statistically significant changes in the expression levels of more than 1,700 genes. These data establish the utility of tape harvesting as a non-invasive method for capturing RNA from human skin and support the hypothesis that tape harvesting is an efficient method for sampling the epidermis and identifying select differentially regulated epidermal biomarkers.