Deficient functional wound closure as measured by elevated trans-epidermal water loss predicts chronic wound recurrence: An exploratory observational study.

A single-center, prospective, observational pilot study was performed to evaluate wound healing endpoint and recurrence by measuring transepidermal water loss (TEWL) post-closure at the site of wound repair. Patients with clinically-defined chronic wounds (such as pressure ulcers, diabetic ulcers, and trauma wounds) who visited the Plastic Surgery outpatient department or were in-patients at the All India Institute of Medical Sciences, Rishikesh, India, and were referred for chronic wound management, were enrolled. Non-invasive point-of-care TEWL measurements were obtained, from closed wound-site and contralateral healthy skin site, starting from confirmation of closure (post-closure, V0) continuing every 2 weeks for a maximum of five visits or until the wound recurred. Statistical analyses of the data involved logistic regression and likelihood ratio chi-square tests to assess differences in TEWL at visit 0 (V0) between the closed wound site and reference skin, with the TEWL score as the sole predictor of recurrence. Of the 72 subjects that completed the study, 44 (61%) showed no recurrence and 28 (39%) had wounds that recurred over a period of 12 weeks. A significant association was found between the V0 (post-closure) TEWL score and the odds of wound recurrence, both in univariate analysis (OR [95%CI] = 1.26[1.14,1.42] (p < 0.001) and after adjusting for covariates in multivariable analysis (OR [95%CI] = 1.34[1.19,1.61] (p < 0.001). The likelihood ratio chi-square analysis demonstrated that the V0 TEWL score is a significant universal predictor of recurrence across all wound types studied. Cases of closed wounds with subsequent recurrence showed an overall higher post-closure V0 TEWL score, compared to those who did not have a wound recurrence, across visits. The TEWL score cut-off value predictive of recurrence was 24.1 g.m-2.h-1 (AUC = 0.967). The outcome of this pilot study on a wide range of chronic wounds leads to the hypothesis that post-closure TEWL at the site of wound healing is a reliable biomarker of wound recurrence. It also raises the question whether the clinical endpoint of wound closure should include re-establishment of skin barrier function as additional criterion. The current standard of care wound closure endpoint calls for re-epithelialization of the wound with no discharge for two consecutive weeks disregarding the functional parameter of restoration of skin barrier function at the wound-site.

Stratum corneum hydration levels are negatively correlated with HbA1c levels in the elderly Chinese.

Highlights Stratum corneum hydration levels are negatively correlated with HbA1c levels and positively correlated with skin surface pH. Individuals with type 2 diabetes display lower levels of stratum corneum hydration. Because low stratum corneum hydration levels can increase circulating levels of proinflammatory cytokines, which are linked to the pathogenesis of type 2 diabetes, improvement in stratum corneum hydration can be an alternative approach in the management of type 2 diabetes.

Changes in Skin Barrier Function in Neonates: Daily Variation and Impact of Bathing.

BACKGROUND: The skin barrier function is an important predictor of neonatal barrier defects. This study aimed to investigate the daily changes in skin barrier function and the impact of bathing on skin barrier function in neonates. METHODS: We assessed the transepidermal water loss (TEWL) and stratum corneum hydration (SCH) on the forehead, cheek, volar forearm, and chest from days 2 to 7 and at 1 month after birth. Additionally, we measured the values after bathing and compared them with the pre-bathing values. RESULTS: Sixty-six neonates were involved in the assessment, and each value at the four sites showed significant correlations. TEWL remained stable between days 2 and 7, but SCH significantly increased at most sites. Both significantly increased by 1.5-2 times in 1 month. After bathing, TEWL increased by more than 20% but decreased again after 3 h. CONCLUSIONS: TEWL did not change significantly with age during the first week of life. To minimize the effects of bathing, TEWL should be measured at least 3 h after bathing.

Omega-3 fatty acids mitigate skin damage caused by ultraviolet-B radiation.

Mice fed a diet containing an adequate amount of ω-3 fatty acids (ω-3 Adq) or a deficient diet (ω-3 Def) were irradiated with ultraviolet-B (UV-B) and were measured daily changes in transepidermal water loss (TEWL). TEWL was significantly increased in ω-3 Def mice with repeated UV-B irradiation, but this increase was significantly reduced in ω-3 Adq mice. The epidermal layers revealed thickening of the spinous and basal layers induced by UV-B irradiation in both groups. Moreover, the ω-3 Def mice had a disturbed epidermal structure and a coarser stratum corneum. And the granule cell layer is significantly reduced, and abnormal layer formation (parakeratosis) occurred in the stratum corneum. These results suggest that continuous UV-B irradiation promotes epidermal turnover and leads to epidermal thickening, but ω-3 fatty acids protect the body from UV-B-induced stress.

Intraday Variations in Skin Water Parameters.

INTRODUCTION: Three interrelated skin water assessments include stratum corneum hydration (SCH) via electrical measurements, skin water using tissue dielectric constant (TDC) measurements, and transepidermal water loss (TEWL). These are differentially used for skin physiology research, clinical assessments of dermatological conditions and to assess skin water in diabetes and lymphedema. Often volar forearm skin is used for assessments done at various times of day (TOD). The present goal was to assess the extent of intraday variability in SCH, TDC, and TEWL. METHODS: Twelve medical students self-measured SCH, TDC, and TEWL on their forearm every 2 h from 08:00 to 24:00 h on 2 consecutive days. All participants were well trained and pre-certified in all procedures. Tests for parameter differences among TOD were via the nonparametric Friedman test. RESULTS: No significant differences in SCH or TEWL were found among TOD over the 16-h interval for either day or combined. Contrastingly, TDC decreased slightly but significantly from morning through evening. There was no evidence of a diurnal pattern. Interestingly, a significant nonlinear relationship between TEWL and SCH was detected. CONCLUSION: Findings indicate only minor intraday variations with TOD trend except for TDC which decreases slightly from morning through evening. The clinical relevance relates to the confidence now gained associated with the parameter estimates when measured at different TOD during normal clinic hours or beyond. This should help in estimating the potential importance of small differences if measured at a different TOD. From a physiological viewpoint, the findings uncover and describe an interesting nonlinear relationship between TEWL and SCH which may serve to propel further investigations that might better characterize this process.

Restoration of Skin Barrier Abnormalities with IL4/13 Inhibitors and Jak Inhibitors in Atopic Dermatitis: A Systematic Review.

Background and Objectives: Atopic dermatitis is a chronic inflammatory skin disorder with a significant burden on patients' quality of life. This systematic review aims to evaluate the restoration of skin barrier abnormalities with interleukin-4/interleukin-13 (IL-4/IL-13) inhibitors and Janus kinase (JAK) inhibitors in atopic dermatitis. Materials and Methods: A comprehensive review of the literature was conducted, focusing on studies that assess the use of IL-4/IL-13 inhibitors and JAK inhibitors for atopic dermatitis. We identified eligible studies by searching Medline via PubMed with a special focus on their effect on the restoration of the epidermal barrier. Included studies evaluated the transepidermal water loss (TEWL), the reduction in epidermal thickness (ET), the improvement in ceramide synthesis, and the increase in stratum corneum hydration (SCH) with IL-4/IL-13 inhibitors and JAK inhibitors. The quality of included studies was assessed using the ROBINS-I and the RoB 2.0 tool for assessing the risk of bias. Results: Ten of the included studies concern dupilumab, while two concern JAK inhibitors. Ten were observational studies and two were randomized controlled trials (RCTs). The total number of included participants was 378 concerning dupilumab and 38 concerning JAK inhibitors. Five studies did not include any comparison group, three included healthy volunteers, two were conducted versus placebo, and two compared dupilumab with other treatments. The follow-up period ranged between 29 days and 32 weeks. The results demonstrated a significant decrease in transepidermal water loss (TEWL) and an increase in SCH on eczematous lesions for patients with sustained response to dupilumab treatment and observed improvements in ET and filaggrin (FLG) staining, which further support the efficacy of JAK inhibitors in enhancing skin barrier function. Conclusions: This review underscores the efficacy of IL-4/IL-13 inhibitors in improving skin barrier function. However, the limited number of studies focusing on JAK inhibitors and the overall lack of RCTs highlight the need for further research to establish the definitive role of IL-4/IL-13 inhibitors and JAK inhibitors in the restoration of the skin barrier.

Efficacy and Safety of Oral Administration of Wine Lees Extract (WLE)-Derived Ceramides and Glucosylceramides in Enhancing Skin Barrier Function: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Our search for plant-derived ceramides from sustainable sources led to the discovery of ceramides and glucosylceramides in wine lees. OBJECTIVE: This study evaluated the efficacy and safety of wine lees extract (WLE)-derived ceramides and glucosylceramides in enhancing skin barrier function. METHODS: A randomized, double-blind, placebo-controlled study was conducted with 30 healthy Japanese subjects aged 20-64. Subjects were allocated to receive either the WLE-derived ceramides and glucosylceramides (test group) or placebo for 12 weeks. The primary outcome was transepidermal water loss (TEWL), and secondary outcomes included skin hydration, visual analog scale (VAS) of itching sensation, and the Japanese Skindex-29. RESULTS: One participant withdrew for personal reasons, resulting in 29 subjects for data analysis (placebo n = 15; test n = 14). The test group showed a tendency of lower TEWL compared to the placebo after 8 weeks (p = 0.07). Furthermore, after 12 weeks of administration, the test group had significantly lower TEWL than the placebo (p = 0.04). On the other hand, no significant differences were observed in the secondary outcome parameters. No adverse events related to the supplements were reported. CONCLUSIONS: Oral supplementation of WLE-derived ceramides and glucosylceramides is a prominent and safe approach to enhancing skin barrier function and health. TRIAL REGISTRATION: (UMIN000050422).

The evidence from in vitro primary fibroblasts and a randomized, double-blind, placebo-controlled clinical trial of tuna collagen peptides intake on skin health.

BACKGROUND: Collagen peptides from various sources demonstrate benefits in health and well-being both in vitro and in clinical trials. However, there is a scarce study of collagen peptides from Tuna on skin health. AIMS: To investigate the impact of collagen peptides derived from Tuna (Katsuwonus pelamis and Thunnus albacares) on skin health, utilizing in vitro biological studies and a randomized controlled trial. METHODS: In vitro biological studies on human dermal primary fibroblasts were evaluated in terms of collagen and elastin synthesis and senescent cell inhibition. A randomized, placebo-controlled, double-blind clinical trial was conducted on 72 women who were randomly assigned to receive either tuna collagen peptides (n = 36) or a placebo (n = 36) orally for 8 weeks and 2 weeks post-ingestion by measuring skin hydration, transepidermal water loss (TEWL), skin elasticity, and skin density. RESULTS: In vitro biological effects demonstrated dose-dependent positive results in increasing collagen and elastin synthesis and reducing senescent cells. The effects on collagen and senescent cells plateaued at high concentrations. A clinical trial showed that the test group experienced a significant increase in skin hydration, elasticity, and density, along with a decrease in TEWL compared to the baseline. The test and placebo groups showed statistically significant differences at 8 weeks for all parameters except for the TEWL at the face. All positive effects were substantially retained even after 2 weeks of discontinuation. CONCLUSIONS: These findings demonstrate the significant potential of tuna collagen peptides to promote human skin health, warranting further investigation as a potential nutraceutical.

Study on percutaneous penetration of representative cosmetic ingredients in a baby wipe product in an in vitro diaper rash skin model.

Studying percutaneous penetration of various cosmetic ingredients through intact and compromised skin can provide insight on quantitative exposure assessment for baby products intended for diapered skin. We developed an in vitro model (tape-stripped human skin) designed to achieve the Trans-Epidermal Water Loss values measured in babies with various degrees of diaper dermatitis. Six reference compounds showed the impact of physicochemical properties on absorption through this "diaper rash" skin model. Under simulated diaper conditions, dermal absorption of cosmetic ingredients (phenoxyethanol, sodium benzoate, benzyl alcohol, disodium EDTA, and propylene glycol) was different, but <100%. Additionally, the effect of diaper rash on dermal absorption of well-absorbed ingredients (phenoxyethanol, sodium benzoate, and benzyl alcohol) was limited (enhancement of 1.1-1.3), while the enhancement for moderately absorbed compounds (disodium EDTA and propylene glycol) was 1.8-3.3. Absorption via skin with "diaper rash" is specific to individual ingredients and exposure conditions, so a fixed uncertainty factor is not appropriate for safety assessment. The data support that the default 100% dermal absorption commonly used in first-tier risk assessments for diapered skin is conservative. This diaper rash skin model provides a practical tool of estimating absorption of various ingredients in baby products intended for diapered skin.

Complexity in the timing of the first postnatal ecdysis in snakes.

Lepidosaurian reptiles, particularly snakes, periodically shed the outer epidermal layers of their skin (ecdysis) to restore or enhance vital functions such as regulating water and gaseous exchange, growth, and protection against insult, infection or physical injury. Although many studies have focused on the nature and mechanisms of skin shedding, little attention has been paid to the timing of the first ecdysis in neonates following birth or hatching. A recent study investigated patterns of the time to first postnatal ecdysis in snakes based on a large dataset taken from the literature. The analysis demonstrated patterns in the time to first postnatal ecdysis related to phylogeny as well as several life history traits. While this assessment provides important advances in our knowledge of this topic, data on known biophysical drivers of ecdysis - temperature and humidity - were largely unavailable and were not evaluated. The first postnatal ecdysis of neonatal snakes can be viewed as an adaptive adjustment to the transition from the aqueous environment of the embryo to the aerial environment of the newborn. Hence, the timing of the first postnatal ecdysis is logically influenced by the aerial environment into which a newborn snake or hatchling finds itself. Therefore, in this Commentary, we first emphasize the putative plasticity of ecdysis with respect to epidermal lipids that structure the water permeability barrier and are established or renewed during ecdysis to reduce transepidermal evaporative water loss. We then discuss the likely importance of biophysical variables as influential covariates that need future investigation as potential co-determinants of the timing of first postnatal ecdysis.

Effects of an ergothioneine-rich Pleurotus sp. on skin moisturizing functions and facial conditions: a randomized, double-blind, placebo-controlled trial.

Background: L-ergothioneine (EGT), an antioxidative and anti-inflammatory amino acid, is abundant in various mushroom fruiting bodies. Meanwhile, the effects of EGT-containing mushrooms on human skin are unknown. This study investigated the effects of oral ingestion of a novel EGT-rich strain of Pleurotus species (hiratake) on skin conditions in humans. Methods: We conducted a 12-week, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate skin moisturizing functions and facial conditions in 80 healthy women who were randomly assigned to either a group that was supplemented with hiratake tablets containing 25 mg of EGT/day or a placebo group. Skin moisture content, transepidermal water loss (TEWL), and facial scores (VISIA scores) were measured at baseline, 8 weeks, and 12 weeks of supplementation. Results: At 8 weeks, the skin moisture content was significantly higher on the temple in the hiratake group than in the placebo group. The hiratake group also exhibited a significant increase in skin moisture content on the arm at 8 and 12 weeks compared with baseline. At 12 weeks, wrinkle and texture scores were significantly better in the hiratake group than in the placebo group, and plasma EGT concentrations in the hiratake group were 4.7-fold higher than baseline (from 3.4 to 15.9 µM). Furthermore, EGT concentrations in plasma were significantly correlated with improvements in skin moisture content and TEWL on the arm, implying that these skin moisturizing benefits could be partly attributed to EGT. A stratified analysis of participants with a low baseline plasma EGT concentration (< 3.3 µM) revealed that skin moisture content on the temple was significantly higher at 8 and 12 weeks, and skin moisture content on the arm at 12 weeks tended to be higher (p = 0.074), in the hiratake group than in the placebo group. These findings suggested that oral ingestion of EGT-rich hiratake can improve skin moisturizing functions. Conclusion: EGT-rich hiratake may help maintain skin conditions in healthy women, and EGT may play a role in these beneficial effects.

Longitudinal Correlations between Molecular Compositions of Stratum Corneum and Breast Milk Factors during Infancy: A Prospective Birth Cohort Study.

Breast milk contains numerous factors that are involved in the maturation of the immune system and development of the gut microbiota in infants. These factors include transforming growth factor-ß1 and 2, immunoglobin A, and lactoferrin. Breast milk factors may also affect epidermal differentiation and the stratum corneum (SC) barrier in infants, but no studies examining these associations over time during infancy have been reported. In this single-center exploratory study, we measured the molecular components of the SC using confocal Raman spectroscopy at 0, 1, 2, 6, and 12 months of age in 39 infants born at our hospital. Breast milk factor concentrations from their mothers' breast milk were determined. Correlation coefficients for the two datasets were estimated for each molecular component of the SC and breast milk factor at each age and SC depth. The results showed that breast milk factors and molecular components of the SC during infancy were partly correlated with infant age in months and SC depth, suggesting that breast milk factors influence the maturation of the SC components. These findings may improve understanding of the pathogenesis of skin diseases associated with skin barrier abnormalities.

Atopic Dermatitis: Disease Background and Risk Factors.

Multiple risk factors have been associated with the development of atopic dermatitis (AD). Recent advances in understanding the role of genetics in this disease have been made, with discovery of the filaggrin (FLG) gene as the most notable so far. In addition to FLG gene mutations as a risk factor for AD, a positive family history of atopic or allergic disease in either parent has been shown to confer a greater risk of developing AD. Atopic dermatitis usually presents early in life and is thought to represent the initial step in the "atopic march," which is characterized by the development of other atopic diseases later in life such as asthma, allergic rhinitis, and/or rhinoconjunctivitis, food allergies, and hay fever. Other comorbid diseases that have been associated with AD include increase risk of viral and bacterial skin infections, neuropsychiatric diseases such as attention-deficit hyperactivity disorders (ADHD), and autistic spectrum disorder (ASD). Patients with AD have also been found to have worse sleep quality overall compared to patients without AD. In this chapter, we will discuss the risk factors associated with development of atopic dermatitis as well as the most commonly reported comorbidities in patients with this disease.

Clinical application of hempseed or flaxseed oil-based lyotropic liquid crystals: Evaluation of their impact on skin barrier function.

The principal function of skin is to form an effective barrier between the human body and its environment. Impaired barrier function represents a precondition for the development of skin diseases such as atopic dermatitis (AD), which is the most common inflammatory skin disease characterized by skin barrier dysfunction. AD significantly affects patients' quality of life, thus, there is a growing interest in the development of novel delivery systems that would improve therapeutic outcomes. Herein, eight novel lyotropic liquid crystals (LCCs) were investigated for the first time in a double-blind, interventional, before-after, single-group trial with healthy adult subjects and a twice-daily application regimen. LCCs consisted of constituents with skin regenerative properties and exhibited lamellar micro-structure, especially suitable for dermal application. The short- and long-term effects of LCCs on TEWL, SC hydration, erythema index, melanin index, and tolerability were determined and compared with baseline. LCCs with the highest oil content and lecithin/Tween 80 mixture stood out by providing a remarkable 2-fold reduction in TEWL values and showing the most distinctive decrease in skin erythema levels in both the short- and long-term exposure. Therefore, they exhibit great potential for clinical use as novel delivery systems for AD treatment, capable of repairing skin barrier function.

The water extracts from the oil cakes of Prinsepia utilis repair the epidermal barrier via up-regulating Corneocyte Envelope-proteins, lipid synthases, and tight junction proteins.

ETHNOPHARMACOLOGICAL RELEVANCE: Prinsepia utilis Royle, native to the Himalayan region, has a long history of use in traditional medicine for its heat-clearing, detoxification, anti-inflammatory, and analgesic properties. Oils extracted from P. utilis seeds are also used in cooking and cosmetics. With the increasing market demand, this extraction process generates substantial industrial biowastes. Recent studies have found many health benefits with using aqueous extracts of these biowastes, which are also rich in polysaccharides. However, there is limited research related to the reparative effects of the water extracts of P. utilis oil cakes (WEPUOC) on disruptions of the skin barrier function. AIM OF THE STUDY: This study aimed to evaluate the reparative efficacy of WEPUOC in both acute and chronic epidermal permeability barrier disruptions. Furthermore, the study sought to explore the underlying mechanisms involved in repairing the epidermal permeability barrier. MATERIALS AND METHODS: Mouse models with induced epidermal disruptions, employing tape-stripping (TS) and acetone wiping (AC) methods, were used. The subsequent application of WEPUOC (100 mg/mL) was evaluated through various assessments, with a focus on the upregulation of mRNA and protein expression of Corneocyte Envelope (CE) related proteins, lipid synthase-associated proteins, and tight junction proteins. RESULTS: The polysaccharide was the major phytochemicals of WEPUOC and its content was determined as 32.2% by the anthranone-sulfuric acid colorimetric method. WEPUOC significantly reduced transepidermal water loss (TEWL) and improved the damaged epidermal barrier in the model group. Mechanistically, these effects were associated with heightened expression levels of key proteins such as FLG (filaggrin), INV (involucrin), LOR (loricrin), SPT, FASN, HMGCR, Claudins-1, Claudins-5, and ZO-1. CONCLUSIONS: WEPUOC, obtained from the oil cakes of P. utilis, is rich in polysaccharides and exhibits pronounced efficacy in repairing disrupted epidermal barriers through increased expression of critical proteins involved in barrier integrity. Our findings underscore the potential of P. utilis wastes in developing natural cosmetic prototypes for the treatment of diseases characterized by damaged skin barriers, including atopic dermatitis and psoriasis.

Skin Barrier Function Assessment: Electrical Impedance Spectroscopy Is Less Influenced by Daily Routine Activities Than Transepidermal Water Loss.

BACKGROUND: Skin barrier function assessment is commonly done by measuring transepidermal water loss (TEWL). An important limitation of this method is the influence of intrinsic and extrinsic factors. Electrical impedance spectroscopy (EIS) is a lesser-established method for skin barrier function assessment. Some influential factors have been described, but no guidelines exist regarding the standardization of these measurements. OBJECTIVE: To evaluate the effect size of daily routine activities on TEWL and EIS, as well as their correlation with age and anatomical differences. METHODS: Healthy participants (n=31) were stratified into three age groups (18-29, 30-49, and ≥50 years). In a climate-controlled room, EIS and TEWL measurements were performed on the left and right volar forearm and abdomen. RESULTS: Body cream application decreased TEWL and EIS values after 15 and 90 minutes. Skin washing decreased TEWL for 15 minutes and EIS values for at least 90 minutes. TEWL was increased 5 minutes after moderate to intense exercise. Coffee intake increased TEWL on the abdomen after 60 minutes. TEWL and EIS values did not correlate with participants' age and no anatomical differences were observed. No correlation was observed between TEWL and EIS. CONCLUSION: Body cream application and skin washing should be avoided at least 90 minutes prior to measurements of TEWL and EIS. Exercise and coffee intake should also be avoided prior to TEWL measurements. EIS may be a promising tool for skin barrier function assessment as it is less affected by daily routine activities than TEWL.

Penetration rates into the stratum corneum layer: A novel quantitative indicator for assessing skin barrier function.

BACKGROUND: The stratum corneum (SC), the outermost layer of the skin epidermis, acts as an effective bi-directional barrier, preventing water loss (inside-outside barrier) and entry of foreign substances (outside-inside barrier). Although transepidermal water loss (TEWL) is a widely-used measure of barrier function, it represents only inside-outside protection. Therefore, we aimed to establish a non-invasive method for quantitative evaluation of the outside-inside barrier function and visually present a skin barrier model. MATERIALS AND METHODS: Skin barrier damage was induced by applying a closed patch of 1% sodium dodecyl sulfate to the forearms of eight participants; they were instructed to apply a barrier cream on a designated damaged area twice daily for 5 days. The SC barrier was evaluated by measuring TEWL and fluorescein sodium salt penetration rate before, immediately after, and 5 days after damage. The penetration rate was assessed using tape-stripping (TS) technique and fluorescence microscopy. RESULTS: The rates of fluorescein sodium salt penetration into the lower layers of SC differed significantly based on the degree of skin barrier damage. The correlation between penetration rate and TEWL was weak after two rounds of TS and became stronger after subsequent rounds. Five days after skin barrier damage, the penetration rate of all layers differed significantly between areas with and without the barrier cream application. CONCLUSION: Our findings demonstrated that the penetration rate was dependent on skin barrier conditions. The penetration rate and corresponding fluorescence images are suitable quantitative indicators that can visually represent skin barrier conditions.

Zinc oxide nanoparticles exacerbate skin epithelial cell damage by upregulating pro-inflammatory cytokines and exosome secretion in M1 macrophages following UVB irradiation-induced skin injury.

BACKGROUND: Zinc oxide nanoparticles (ZnONPs) are common materials used in skin-related cosmetics and sunscreen products due to their whitening and strong UV light absorption properties. Although the protective effects of ZnONPs against UV light in intact skin have been well demonstrated, the effects of using ZnONPs on damaged or sunburned skin are still unclear. In this study, we aimed to reveal the detailed underlying mechanisms related to keratinocytes and macrophages exposed to UVB and ZnONPs. RESULTS: We demonstrated that ZnONPs exacerbated mouse skin damage after UVB exposure, followed by increased transepidermal water loss (TEWL) levels, cell death and epithelial thickness. In addition, ZnONPs could penetrate through the damaged epithelium, gain access to the dermis cells, and lead to severe inflammation by activation of M1 macrophage. Mechanistic studies indicated that co-exposure of keratinocytes to UVB and ZnONPs lysosomal impairment and autophagy dysfunction, which increased cell exosome release. However, these exosomes could be taken up by macrophages, which accelerated M1 macrophage polarization. Furthermore, ZnONPs also induced a lasting inflammatory response in M1 macrophages and affected epithelial cell repair by regulating the autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. CONCLUSIONS: Our findings propose a new concept for ZnONP-induced skin toxicity mechanisms and the safety issue of ZnONPs application on vulnerable skin. The process involved an interplay of lysosomal impairment, autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. The current finding is valuable for evaluating the effects of ZnONPs for cosmetics applications.