Skin Pharmacology and Physiology最新文献

Background: This review summarizes published literature on in vitro and ex vivo test methods for preclinical evaluation of wound care products. There is currently no guidance from, e.g., authorities on how wound care products, especially antimicrobial wound care products, should be assessed regarding their cell toxic effects and their antimicrobial performance. Even though ISO 10993-1 gives clear guidance for biocompatibility evaluation of medical devices, the corresponding methods do not reflect wound conditions. Regarding antimicrobial efficacy, the first standard EN 17854 for wound dressings was published recently. For all other endpoints, no standards are available. In addition, there are increased ethical considerations that animal testing should be avoided. This was first practiced in cosmetic industry and is now implemented presenting a central part of ISO 10993-1 for toxicity assessment of medical devices. At the same time, there is increasing evidence that in vitro and ex vivo methods can replace animal testing for certain endpoints with the advantage that a partially difficult transfer of data from animals to humans may not be needed anymore. This review presents a comprehensive overview of methods that can be used for preclinical evaluation of wound care products.

Summary: In three tables, a new matrix for testing biocompatibility, healing, and antimicrobial endpoints for wound dressings, semi-liquid wound care products, as well as liquid products are presented. This matrix should give guidance to manufacturers during development and regulatory approval processes. Some of the methods, e.g., 3D wound models, may answer clinical questions in vitro, which are difficult to answer in a clinical study due to various reasons.

Key messages: We conclude that a broad range of in vitro and ex vivo methods are available and can be employed supporting development and regulatory approval of innovative wound care products ranging from dressing to semi-liquid and liquid products while at the same time reduce animal testing.

Introduction: In recent years, multicolored tattoos have gained popularity among young individuals. However, the behavior of tattoo inks in the skin, including their distribution, accumulation, and long-term effects, remains poorly understood, partly due to limited in vivo imaging techniques.

Methods: This study employs picosecond-pulsed two-photon excited fluorescence lifetime imaging microscopy (TPE-FLIM) to noninvasively visualize the deposition of colored tattoo ink pigments (blue, red, green, yellow, orange, purple, and black) in human skin in vivo at depths of up to ≈150 µm.

Results: The study reveals that tattoo ink agglomerates are present across various skin layers, ranging from the stratum corneum to the reticular dermis. Tattoo ink pigments were predominantly observed within dermal cells, including mast cells, macrophages, and fibroblasts, suggesting that these cells act as long-term reservoirs for the pigments. Additionally, ink residues were detected in epidermal cells, including keratinocytes, dendritic cells, and basal cells, indicating a continuous low-level release of the ink even in old tattoos. Furthermore, the analysis showed that melanin can be distinguished from certain tattoo ink pigments using phasor approach combined with TPE autofluorescence imaging.

Conclusion: The TPE-FLIM technique enables in vivo visualization of epidermal dendritic cells and dermal fibroblasts, which are otherwise undetectable using conventional optical methods without staining. This method holds significant potential for clinical dermatology by offering insights into cellular uptake, accumulation, and long-term effects of tattoo inks, thereby supporting the management of tattoo-related complications.

Introduction: Knowing thicknesses of skin-tissue layers within the depths of several hundred micrometers from the surface is highly important for numerous biomedical applications - cosmetology, treatment of wounds and burns, characterization of various lesions, etc. In this regard, optical coherence tomography (OCT) with its ability to noninvasively enable visualization depth of the order of 1 mm with a resolution of the order of several micrometers offers exceptional diagnostic possibilities largely unavailable to other techniques. This explains high interest to OCT utilization in dermatology.

Methods: This study demonstrates that appropriate physics-based processing of OCT data allows one to objectively reveal and automatically estimate thicknesses of morphological skin layers, even if they are not visible as optical layers with differing intensity in initial structural OCT scans. To this end, we apply recently developed efficient methods of spatially resolved estimation of the scattering coefficient µ_s to locally characterize the scattering strength of scatterers in the tissue. Another useful parameter termed speckle contrast (SC_I) characterizes fluctuations of scattering strengths of scatterers and their clustering. Mapping parameters µ_s and SC_I enable differentiation of morphological skin layers, although in structural OCT scans they cannot be clearly delineated even by experts.

Results: Analysis of parameters µs and SC_I for OCT data in vivo acquired in various localizations for women and man of various ages confirmed the possibility to clearly segment three medically significant skin layers: (i) stratum corneum, (ii) living-cell layer of epidermis, and (iii) upper dermis layer even if in the initial OCT scans these layers are hardly discernible. The present study is intentionally limited to healthy facial skin, for which significant variations in the layer thicknesses were demonstrated for various age groups, as well as in quite close localizations for the same person.

Conclusion: These findings underscore high potential of in vivo OCT imaging supplemented with the analysis of speckle features and optical attenuation parameter for objective real-time differentiation of morphological skin layers, which is critically important for numerous applications (surgical reconstruction of skin wounds and/or burn injuries, controlled drug delivery in targeted skin layers, choice of therapy). Similar approach may be extended for diagnosing various skin diseases/pathologies.

Introduction: The sacrum and posterior heel are two common areas where skin is exposed to pressure and shear forces which could lead to damage in the form of pressure ulcers. Despite their vulnerability, relatively few studies have explored their structural and physiological properties which predispose them to damage. The aim of this study was to characterise age and anatomical site differences in the skin epidermal properties and microvasculature using optical coherence tomography (OCT), in younger and older adults.

Methods: Twenty-two younger (18-35 years) and 19 older healthy adults (55-70 years) completed three experimental visits, comprising non-invasive OCT imaging to characterise skin epidermal properties and microvascular density. Extracted parameters from the captured images were optical attenuation coefficient, dermal brightness, epidermal thickness, surface roughness, microvascular plexus depth (µm), and vascular density (%).

Results: There were significant differences in the epidermal structural properties between the sacrum and heel across all parameters (p < 0.001), except for roughness (p > 0.05). The vascular density profiles plotted against skin depth were also significantly different between anatomical sites (p < 0.001), with peak vascular density being more superficial in the heel: ∼0.2 mm vs. sacrum: ∼0.4 mm (p < 0.001). The sacrum had a greater maximum vascular density (∼9%) compared to the heel (∼7%; p < 0.001). No significant differences were observed between the age groups (p > 0.05).

Conclusion: Distinct differences were observed for epidermal and vascular density measurements between heel and sacral skin sites. However, there were no age-related differences, which may be associated with the older adult range (55-70 years) and healthy status. The structural and microvasculature insights could aid in the design of therapeutic interventions to promote tissue viability and health such as site-specific dressing and textiles.

Introduction: Eczematous cheilitis is a common manifestation in patients with atopic dermatitis, and restoration of lip barrier function is essential for effective management. Wet wrap dressing is a widely used adjuvant therapy for atopic dermatitis lesions; a similar approach may be beneficial for treating atopic cheilitis. This study aimed to evaluate the short-term effects of saline gauze wet dressing on lip barrier function and to compare the clinical efficacy of this method, as an adjunct to standard therapy, in patients with eczematous cheilitis.

Methods: Patients with eczematous cheilitis and age-matched healthy volunteers were enrolled. Lip barrier function was assessed via transepidermal water loss, stratum corneum hydration (SCH), pH, and erythema values. Short-term changes were measured at 15, 30, and 60 min after application of saline gauze wet dressing. In addition, a case-control design was used to compare the 7-day efficacy of gauze wet dressing as adjuvant therapy combined with topical glucocorticoid and petroleum jelly versus standard therapy alone.

Results: Compared with healthy controls, patients with eczematous cheilitis demonstrated impaired lip barrier function. Application of saline gauze wet dressing significantly improved SCH and normalized pH within 30 min, with sustained barrier restoration over the 7-day treatment period. The adjuvant therapy group showed significantly greater clinical improvement than controls, including marked resolution of fissures and erythema and enhanced barrier function.

Conclusion: Saline gauze wet dressing, as an adjunct to standard topical therapy, provides a simple, convenient, and cost-effective option for improving lip barrier function and accelerating clinical recovery in eczematous cheilitis, thereby enhancing therapeutic outcomes and patient satisfaction.

Introduction: Skin senescence leads to decreased lipid and water levels, inducing xerosis with compromised barrier function. Xerosis affects ≈56% of the aging population, usually characterized by skin scaling, itching, and cracking predominating on the lower legs, causing discomfort, limited mobility, and increased risk of eczema/infections. With hydrating and barrier-strengthening properties, urea-based topical moisturizers are commonly used to manage skin dryness. This observational, open-label, single-group study, conducted in 59 participants (60-75 years), evaluated the effectiveness, tolerability, and patient benefits of a 10% urea-based emollient (U10%) in the management of moderate to severe senile xerosis of the lower legs.

Methods: Subjects applied U10% twice daily over 4 weeks. Clinical evaluations by physicians were conducted at baseline and day 28 to measure changes in hydration levels, barrier function, and skin texture. Patient-reported outcomes on treatment benefits and quality of life were recorded on day 7 and day 28.

Results: After 4 weeks of treatment, meaningful improvements were observed in the Global Clinical Assessment scores of xerosis, overall dry skin, skin roughness and dryness, total xerosis severity of the lower legs, xerosis severity for erythema, lichenification, desquamation, and body surface. Corneometry measurements showed decreased trans-epidermal water loss, in line with improvements in the skin barrier function. Patient-reported outcomes showed marked improvements, indicating enhancement in the overall patient perception of benefit and in the patients' quality of life resulting from treatment.

Conclusion: This study has provided strong evidence for the potential use of U10% emollient as a highly effective solution tailored to meet the unique needs of age-related xerosis and pruritus.

Introduction: Physical exercise influences the function of multiple organs, including the skin. Previous studies demonstrated an increase in transepidermal water loss rates (TEWL) after exercise. However, TEWL measured shortly after exercise may not truly reflect the epidermal permeability barrier function. And the limited sample size may also affect the generalizability of the findings. Therefore, we assessed the influence of physical exercise on epidermal biophysical properties in a larger cohort prior to exercise.

Participants and methods: A total of 327 university students without inflammatory skin disorders or other diseases which may affect epidermal function were enrolled in this study. Epidermal biophysical properties, including TEWL, stratum corneum hydration levels and skin surface pH on the volar site of the forearm and shin were measured with a multifunctional skin physiology monitor. The correlation between epidermal biophysical properties and duration of daily exercise were determined.

Results: This cohort included 168 females and 159 males with a mean age of 18.91 ± 0.04 years. On the forearm, TEWL were lower in females than in males, while on the shin, both stratum corneum hydration levels and skin surface pH were significantly higher in females than in males. No significant differences in other parameters were observed between males and females. Overall, there were no significant differences in epidermal biophysical properties among individuals with various daily exercise duration over the past month although there was a trend of higher stratum corneum hydration levels among individuals with longer duration of daily exercise. However, TEWL on the shin of females positively correlated with the daily exercise duration.

Conclusions: There are slight but significant differences in some epidermal biophysical properties between male and female university students. Overall, exercise does not dramatically affect TEWL, stratum corneum hydration levels and skin surface pH on both the shin and forearm except on the shin of females where shows a positive correlation between the daily exercise duration and TEWL.

Introduction: Since skin tissues feature highly inter- and intraindividual variable scattering properties, it is of interest for fluorescence spectroscopy applied to skin cancer diagnostic assistance to be combined with a device able to measure scattering properties of skin tissues in vivo and further correct fluorescence spectra. This study aimed to explore the interest of combining two devices previously used in vivo during clinical trials: line-field confocal optical coherence tomography (LC-OCT) for scattering property estimation and fluorescence spectroscopy for measuring the modification of endogenous fluorescence induced by carcinogenesis.

Methods: This study was performed on liquid phantoms and on commercially available in vitro-grown 3D human skin models. Bulk scattering properties of liquid fluorescent phantoms were estimated separately at 800 nm as a function of intralipid concentration from LC-OCT images using a model based on the modified Beer-Lambert law. These results were then compared with values obtained with double-integrating spheres and collimated transmittance measurements followed by inverse adding-doubling estimation of bulk scattering properties. Changes in the amplitude of the chlorin-e6 fluorescence peak were measured as a function of IL concentration using fluorescence spectroscopy. The results obtained on phantoms were then validated with the in vitro-grown skin model.

Results: Measurements performed on liquid phantoms showed that LC-OCT overestimates scattering coefficient and anisotropy factor by approximately 20-30% compared to values measured by a method (useable only ex vivo) considered here as the gold standard: double-integrating spheres-based optical bench. Fluorescence spectroscopy was employed to measure changes in chlorin-e6 fluorescence-measured intensity relative to varying intralipid concentration. Optical characterization of human skin models confirmed their similarity with in vivo human skin in terms of morphology and of autofluorescence signals. LC-OCT was used to detect dermal scattering coefficient increase induced by impregnating the artificial skin with a PEG-400/DMSO solution that usually acts as an optical clearing agent. However, the observed effect was opposite to the typically expected decrease in the scattering coefficient, which was likely attributable to specific morphological features of the artificial skin that hindered the clearing process, resulting in only hyperosmotic effect. Spectral measurements supported these findings.

Conclusion: These findings underscore the interest of combining both optical methods, LC-OCT imaging and autofluorescence spectroscopy, to assess pathology-related fluorophore and scattering alterations in vivo.

The human epidermis is the interface between the　human body and the environment. It is mainly comprised of keratinocytes. Since the beginning of this century, functional expression of a series of receptors for various environmental factors has been reported. Moreover, neurotransmitters and hormones originally found in the central nervous system are generated and released from keratinocytes. Thus, the pathophysiology of the epidermis is important not only for skin health but also for whole-body conditions. In outer space, humans must confront environmental factors different from those on Earth, such as electromagnetic fields, drastic changes in atmospheric pressure or humidity, and microgravity. In this review, the author discusses the potential effects of these factors on epidermal homeostasis and whole-body conditions.

Introduction: Stimulated skin wrinkling (SSW) reflects the integrity of the autonomic nervous system, eccrine sweat glands, and microcirculation. Specific stimuli, as water immersion or mechanical pressure usually elicit it. This study explored the influence of some physical, chemical, sympathetic stimuli, and circadian cycle on SSW.

Methods: Time required to achieve grade III finger wrinkling was assessed in 24 healthy adults. SSW induced by room-temperature filtered water (RTFW) for comparison across temperature variations: warm water (40°C) and iced water; tonicity: Distilled water and hypertonic saline (36% NaCl); pH variations: acidic and alkaline solution; oily medium: soybean oil; or pressure: immersion under hydrostatic pressure (30 cm water column). To evaluate the influence of sympathetic activity, SSW was assessed under caffeine stimulation: 30 min after ingestion of 60 mg caffeine (Ristretto espresso); diurnal variation: testing at 10 a.m. versus 10 p.m.; or ischemic influence: under sub-systolic ischemia induced by an arm cuff. Additionally, 12 participants underwent 10 min fingertip exposures to EMLA and room-temperature vinegar for comparison.

Results: The time to reach grade III SSW under RTFW varied widely across the sample (from 2.1 to 37.0 min). The acidic solution reduced the time to SSW compared to RTFW (mean: 6.4 vs. 13.9 min; p < 0.01), with a more pronounced effect observed with a warm (40°C) acidic solution (4.0 vs. 15.5 min; p < 0.01). Hot water, distilled water, and 30 cm hydrostatic pressure stimulation shortened the time to SSW compared to RTFW (p < 0.01). No SSW was observed after 30 min of immersion in the oily medium, iced water, alkaline solution, hypertonic solution, or following ischemia. A circadian influence on SSW was also observed, with morning measurements resulting in a faster response than at night (10.4 vs. 14.6 min; p < 0.01). SSW was also accelerated after coffee consumption (6.1 vs. 10.5 min; p < 0.01). After 10 min of stimulation with either EMLA or vinegar, 75% of participants reached grade III SSW (p = 1.00).

Conclusion: SSW is influenced by multiple factors, including solution temperature, pH, osmolarity, hydrostatic pressure, caffeine ingestion, and circadian timing. Warm vinegar elicited a faster and more consistent SSW response compared to other tested conditions, highlighting its use in experimental settings. No difference in SSW was observed between room-temperature vinegar and EMLA after 10 min, supporting its potential for clinical application.