Skinly: A novel handheld IoT device for validating biophysical skin characteristics.

BACKGROUND: Recent advancements in artificial intelligence have revolutionized dermatological diagnostics. These technologies, particularly machine learning (ML), including deep learning (DL), have shown accuracy equivalent or even superior to human experts in diagnosing skin conditions like melanoma. With the integration of ML, including DL, the development of at home skin analysis devices has become feasible. To this end, we introduced the Skinly system, a handheld device capable of evaluating various personal skin characteristics noninvasively. MATERIALS AND METHODS: Equipped with a moisture sensor and a multi-light-source camera, Skinly can assess age-related skin parameters and specific skin properties. Utilizing state-of-the-art DL, Skinly processed vast amounts of images efficiently. The Skinly system's efficacy was validated both in the lab and at home, comparing its results to established "gold standard" methods. RESULTS: Our findings revealed that the Skinly device can accurately measure age-associated parameters, that is, facial age, skin evenness, and wrinkles. Furthermore, Skinly produced data consistent with established devices for parameters like glossiness, skin tone, redness, and porphyrin levels. A separate study was conducted to evaluate the effects of two moisturizing formulations on skin hydration in laboratory studies with standard instrumentation and at home with Skinly. CONCLUSION: Thanks to its capability for multi-parameter measurements, the Skinly device, combined with its smartphone application, holds the potential to replace more expensive, time-consuming diagnostic tools. Collectively, the Skinly device opens new avenues in dermatological research, offering a reliable, versatile tool for comprehensive skin analysis.

A method to analyze the influence of mechanical strain on dermal collagen morphologies.

Collagen fibers and their orientation play a major role in the mechanical behavior of soft biological tissue such as skin. Here, we present a proof-of-principle study correlating mechanical properties with collagen fiber network morphologies. A dedicated multiphoton stretching device allows for mechanical deformations in combination with a simultaneous analysis of its collagen fiber network by second harmonic generation imaging (SHG). The recently introduced Fiber Image Network Evaluation (FINE) algorithm is used to obtain detailed information about the morphology with regard to fiber families in collagen network images. To demonstrate the potential of our method, we investigate an isotropic and an anisotropic ex-vivo dorsal pig skin sample under quasi-static cyclic stretching and relaxation sequences. Families of collagen fibers are found to form a partially aligned collagen network under strain. We find that the relative force uptake is accomplished in two steps. Firstly, fibers align within their fiber families and, secondly, fiber families orient in the direction of force. The maximum alignment of the collagen fiber network is found to be determined by the largest strain. Isotropic and anisotropic samples reveal a different micro structural behavior under repeated deformation leading to a similar force uptake after two stretching cycles. Our method correlates mechanical properties with morphologies in collagen fiber networks.

General method for classification of fiber families in fiber-reinforced materials: application to in-vivo human skin images.

Fiber structures play a major role for the function of fiber-reinforced materials such as biological tissue. An objective classification of the fiber orientations into fiber families is crucial to understand its mechanical properties. We introduce the Fiber Image Network Evaluation Algorithm (FINE algorithm) to classify and quantify the number of fiber families in scientific images. Each fiber family is characterized by an amplitude, a mean orientation, and a dispersion. A new alignment index giving the averaged fraction of aligned fibers is defined. The FINE algorithm is validated by realistic grayscale Monte-Carlo fiber images. We apply the algorithm to an in-vivo depth scan of second harmonic generation images of dermal collagen in human skin. The derived alignment index exhibits a crossover at a critical depth where two fiber families with a perpendicular orientation around the main tension line arise. This strongly suggests the presence of a transition from the papillary to the reticular dermis. Hence, the FINE algorithm provides a valuable tool for a reliable classification and a meaningful interpretation of in-vivo collagen fiber networks and general fiber reinforced materials.

Noise reduction and quantification of fiber orientations in greyscale images.

Quantification of the angular orientation distribution of fibrous tissue structures in scientific images benefits from the Fourier image analysis to obtain quantitative information. Measurement uncertainties represent a major challenge and need to be considered by propagating them in order to determine an adaptive anisotropic Fourier filter. Our adaptive filter method (AF) is based on the maximum relative uncertainty δcut of the power spectrum as well as a weighted radial sum with weighting factor α. We use a Monte-Carlo simulation to obtain realistic greyscale images that include defined variations in fiber thickness, length, and angular dispersion as well as variations in noise. From this simulation the best agreement between predefined and derived angular orientation distribution is found for evaluation parameters δcut = 2.1% and α = 1.5. The resulting cumulative orientation distribution was modeled by a sigmoid function to obtain the mean angle and the fiber dispersion. A comparison to a state-of-the-art band-pass method revealed that the AF method is more suitable for the application on greyscale fiber images, since the error of the fiber dispersion significantly decreased from (33.9 ± 26.5)% to (13.2 ± 12.7)%. Both methods were found to accurately quantify the mean fiber orientation with an error of (1.9 ± 1.5)° and (2.3 ± 2.1)° in case of the AF and the band-pass method, respectively. We demonstrate that the AF method is able to accurately quantify the fiber orientation distribution in in vivo second-harmonic generation images of dermal collagen with a mean fiber orientation error of (6.0 ± 4.0)° and a dispersion error of (9.3 ± 12.1)%.

Mitochondrial Morphologies Driven by Energy-Consuming Cell Sites in a Spatially and Time-Resolved Quality Model.

Mitochondria are the energy plants of eukaryotic cells. Mitochondrial network morphologies are essential for the energy supply of eukaryotic cells. However, the associated dynamics are not yet fully understood. They behave as a dynamic network that adapts to the cell's environment and its energetic needs. Various processes such as mitochondrial fission and fusion, mitochondrial recycling, repair mechanisms, and oxidative stress influence the state of the mitochondrial network. Here, we introduce a novel time-dependent and spatially resolved quality model on mitochondrial morphology. The interplay between the mitochondrial network and energy-consuming cell sites is modeled by biophysical interactions of quality-dependent mitochondrial clusters in the presence of adenosine triphosphate (ATP) consumers represented by Mie potentials. Mitochondria are modeled as simplified ballistic particles that move within the cytoplasm of a virtual cell, and connect and divide by inelastic collisions. With this model, we investigate the coupling of mitochondrial dynamics with oscillating cell functions, representing diverse global states of the energetic architecture in the cell. Our simulations based on a generalized cell reveal a perinuclear condensation of mitochondria during phases of high-energy demand. Furthermore, quality-increasing mechanisms disclose the benefits of high mitochondrial masses. Simulations reveal that varying energy demands modeled by oscillations of ATP consumers alter the morphology of the network. Phases of high-energy consumption lead to interconnected network structures and perinuclear condensation of mitochondria. The model explains quality-increasing benefits of high mitochondrial masses.

PhotoAgeClock: deep learning algorithms for development of non-invasive visual biomarkers of aging.

Aging biomarkers are the qualitative and quantitative indicators of the aging processes of the human body. Estimation of biological age is important for assessing the physiological state of an organism. The advent of machine learning lead to the development of the many age predictors commonly referred to as the "aging clocks" varying in biological relevance, ease of use, cost, actionability, interpretability, and applications. Here we present and investigate a novel non-invasive class of visual photographic biomarkers of aging. We developed a simple and accurate predictor of chronological age using just the anonymized images of eye corners called the PhotoAgeClock. Deep neural networks were trained on 8414 anonymized high-resolution images of eye corners labeled with the correct chronological age. For people within the age range of 20 to 80 in a specific population, the model was able to achieve a mean absolute error of 2.3 years and 95% Pearson and Spearman correlation.

Fragmentation of the mitochondrial network in skin in vivo.

Mitochondria form dynamic networks which adapt to the environmental requirements of the cell. We investigated the aging process of these networks in human skin cells in vivo by multiphoton microscopy. A study on the age-dependency of the mitochondrial network in young and old volunteers revealed that keratinocytes in old skin establish a significantly more fragmented network with smaller and more compact mitochondrial clusters than keratinocytes in young skin. Furthermore, we investigated the mitochondrial network during differentiation processes of keratinocytes within the epidermis of volunteers. We observe a fragmentation similar to the age-dependent study in almost all parameters. These parallels raise questions about the dynamics of biophysical network structures during aging processes.

Quality Saving Mechanisms of Mitochondria during Aging in a Fully Time-Dependent Computational Biophysical Model.

Mitochondria are essential for the energy production of eukaryotic cells. During aging mitochondria run through various processes which change their quality in terms of activity, health and metabolic supply. In recent years, many of these processes such as fission and fusion of mitochondria, mitophagy, mitochondrial biogenesis and energy consumption have been subject of research. Based on numerous experimental insights, it was possible to qualify mitochondrial behaviour in computational simulations. Here, we present a new biophysical model based on the approach of Figge et al. in 2012. We introduce exponential decay and growth laws for each mitochondrial process to derive its time-dependent probability during the aging of cells. All mitochondrial processes of the original model are mathematically and biophysically redefined and additional processes are implemented: Mitochondrial fission and fusion is separated into a metabolic outer-membrane part and a protein-related inner-membrane part, a quality-dependent threshold for mitophagy and mitochondrial biogenesis is introduced and processes for activity-dependent internal oxidative stress as well as mitochondrial repair mechanisms are newly included. Our findings reveal a decrease of mitochondrial quality and a fragmentation of the mitochondrial network during aging. Additionally, the model discloses a quality increasing mechanism due to the interplay of the mitophagy and biogenesis cycle and the fission and fusion cycle of mitochondria. It is revealed that decreased mitochondrial repair can be a quality saving process in aged cells. Furthermore, the model finds strategies to sustain the quality of the mitochondrial network in cells with high production rates of reactive oxygen species due to large energy demands. Hence, the model adds new insights to biophysical mechanisms of mitochondrial aging and provides novel understandings of the interdependency of mitochondrial processes.

Dermal penetration of creatine from a face-care formulation containing creatine, guarana and glycerol is linked to effective antiwrinkle and antisagging efficacy in male subjects.

BACKGROUND: The dermal extracellular matrix provides stability and structure to the skin. With increasing age, however, its major component collagen is subject to degeneration, resulting in a gradual decline in skin elasticity and progression of wrinkle formation. Previous studies suggest that the reduction in cellular energy contributes to the diminished synthesis of cutaneous collagen during aging. AIMS: To investigate the potential of topically applied creatine to improve the clinical signs of skin aging by stimulating dermal collagen synthesis in vitro and in vivo. PATIENTS/METHODS: Penetration experiments were performed with a pig skin ex vivo model. Effects of creatine on dermal collagen gene expression and procollagen synthesis were studied in vitro using cultured fibroblast-populated collagen gels. In a single-center, controlled study, 43 male Caucasians applied a face-care formulation containing creatine, guarana extract, and glycerol to determine its influence on facial topometric features. RESULTS: Cultured human dermal fibroblasts supplemented with creatine displayed a stimulation of collagen synthesis relative to untreated control cells both on the gene expression and at the protein level. In skin penetration experiments, topically applied creatine rapidly reached the dermis. In addition, topical in vivo application of a creatine-containing formulation for 6 weeks significantly reduced the sagging cheek intensity in the jowl area as compared to baseline. This result was confirmed by clinical live scoring, which also demonstrated a significant reduction in crow's feet wrinkles and wrinkles under the eyes. CONCLUSIONS: In summary, creatine represents a beneficial active ingredient for topical use in the prevention and treatment of human skin aging.

Folic acid and creatine improve the firmness of human skin in vivo.

BACKGROUND: The decrease in firmness is a hallmark of skin aging. Accelerated by chronic sun exposure, fundamental changes occur within the dermal extracellular matrix over the years, mainly impairing the collagenous network. AIMS: Based on the qualitative and quantitative assessment of skin firmness, in vitro and in vivo studies were carried out to elucidate the effects of topical folic acid and creatine to counteract this age-dependent reduction in the amount of collagen. PATIENTS/METHODS: Topical application of a commercially available formulation containing folic acid and creatine was performed to study effects on skin firmness in vivo using cutometric analysis. Imaging and quantification of collagen density were carried out using multiphoton laser scanning microscopy (MPLSM). To investigate the effects of these compounds on collagen gene expression, procollagen synthesis, and collagen fibril organization, complementary in vitro studies on cultured fibroblast-populated collagen gels were carried out. RESULTS: The underlying structural changes in the collagen network of young and aged sun-exposed facial skin in vivo were visualized by MPLSM. Topical application of a folic acid- and creatine-containing formulation significantly improved firmness of mature skin in vivo. Treatment of fibroblast-populated dermal equivalents with folic acid and creatine increased collagen gene expression and procollagen levels and improved collagen fiber density, suggesting that the in vivo effects are based on the overall improvement of the collagen metabolism. CONCLUSIONS: Employing MPLSM, dermal changes occurring in photo-aged human skin were visualized in an unprecedented manner and correlated to a loss of firmness. Treatment of aged skin with a topical formulation containing folic acid and creatine counteracted this age-dependent decline by exerting sustained effects on collagen metabolism. Our results support previous findings on the efficacy of these actives.

Validation of the body scanner as a measuring tool for a rapid quantification of body shape.

BACKGROUND: Currently, the body scanner, using laser-triangulation, is one of the most precise measuring tools for the rapid quantification of body shape. The VITUS body scanner is a laser-based system based on a principle called triangulation and the scan produced describes the distance to a surface at each point in the picture. The body scanner has multiple applications such as determining body measurements for tailoring, anthropometric investigations and cosmetic surgery. There are also intensive investigations into the effect of weight gain and thus body shape on health risks. In order to be of value, the body scanner needs to generate precise, accurate and reproducible data. AIMS: To determine the precision and reproducibility of the VITUS XXL 3D body scanner. METHODS: The measurements of geometric shapes (cones, columns) and human body parts (mid-thigh) were compared using a measuring tape and the body scanner. RESULTS: The precision of the measurements of the circumferences of a truncated cone and a column was within 1 mm of the actual values (0.29%). The reproducibility of the measurements was very good. The standard deviation in the measurement of a truncated cone was only 0.13% of the actual value. Likewise, the standard deviation of the thigh measurement of 12 human subjects was <1%. CONCLUSION: These results show that the body scanner can accurately, precisely and reproducibly measure the circumference of objects and human body parts.

A novel treatment option for photoaged skin.

BACKGROUND: DNA damage as a result of ultraviolet (UV) exposure plays an important role in the progression of cutaneous aging. Both folic acid and creatine have been linked to the process of DNA protection and repair. AIMS: This study aims to investigate the effects of a commercially available folic acid- and creatine-containing formulation to fight the clinical signs of premature skin aging. PATIENTS/METHODS: Both in vitro and in vivo home-in-use studies using a folic acid- and creatine-containing formulation were performed aiming to elucidate the efficacy in terms of improvement of skin regeneration, protection from UV-induced DNA damage (Comet assay), reduction of wrinkle volume, and skin visco-elasticity. Furthermore, clinical evaluation and photography were carried out to determine the improvement of clinically graded parameters after treatment. RESULTS: Cultured full-thickness epidermal skin models supplemented with folic acid and creatine after epithelial perturbation showed an accelerated skin regeneration compared to untreated control models. Similarly, application of a folic acid- and creatine-containing formulation significantly improved epidermal turnover in vivo as evidenced by smaller corneocytes derived from the treated sites relative to the vehicle-treated sides. In addition, topical in vivo application of this formulation significantly protected from UV-induced DNA lesions, increased skin firmness, and reduced wrinkle volume compared to untreated control areas. Expert grading confirmed a significant decrease of fine and coarse wrinkles in the periocular region as well as overall wrinkles, tactile roughness, and laxity. CONCLUSIONS: Taken together, these results show that the combination of folic acid and creatine significantly accelerates epidermal skin regeneration in vitro and in vivo. Together with the finding of improved biomechanical skin properties, we conclude that the described topical formulation provides an effective treatment option for (photo)-aged skin.

Novel aspects of intrinsic and extrinsic aging of human skin: beneficial effects of soy extract.

Biochemical and structural changes of the dermal connective tissue substantially contribute to the phenotype of aging skin. To study connective tissue metabolism with respect to ultraviolet (UV) exposure, we performed an in vitro (human dermal fibroblasts) and an in vivo complementary DNA array study in combination with protein analysis in young and old volunteers. Several genes of the collagen metabolism such as Collagen I, III and VI as well as heat shock protein 47 and matrix metalloproteinase-1 are expressed differentially, indicating UV-mediated effects on collagen expression, processing and degradation. In particular, Collagen I is time and age dependently reduced after a single UV exposure in human skin in vivo. Moreover, older subjects display a lower baseline level and a shorter UV-mediated increase in hyaluronan (HA) levels. To counteract these age-dependent changes, cultured fibroblasts were treated with a specific soy extract. This treatment resulted in increased collagen and HA synthesis. In a placebo-controlled in vivo study, topical application of an isoflavone-containing emulsion significantly enhanced the number of dermal papillae per area after 2 weeks. Because the flattening of the dermal-epidermal junction is the most reproducible structural change in aged skin, this soy extract appears to rejuvenate the structure of mature skin.

Topically applied vitamin C increases the density of dermal papillae in aged human skin.

BACKGROUND: The influence of ageing on the density of the functional entities of the papillae containing nutritive capillaries, here in terms as the papillary index, and the effect of topically applied vitamin C were investigated by confocal laser scanning microscopy (CLSM) in vivo. METHODS: The age dependency of the papillary index was determined by CLSM on 3 different age groups. Additionally, we determined the effect of a topical cream containing 3% vitamin C against the vehicle alone using daily applications for four months on the volar forearm of 33 women. RESULTS: There were significant decreases in the papillary index showing a clear dependency on age. Topical vitamin C resulted in a significant increase of the density of dermal papillae from 4 weeks onward compared to its vehicle. Reproducibility was determined in repeated studies. CONCLUSIONS: Vitamin C has the potential to enhance the density of dermal papillae, perhaps through the mechanism of angiogenesis. Topical vitamin C may have therapeutical effects for partial corrections of the regressive structural changes associated with the aging process.

Histometric data obtained by in vivo confocal laser scanning microscopy in patients with systemic sclerosis.

BACKGROUND: It would be a benefit if time-saving, non-invasive methods could give hints for diagnosing systemic sclerosis. To investigate the skin of patients with systemic sclerosis using confocal laser scanning microscopy in vivo and to develop histometric parameters to describe characteristic cutaneous changes of systemic sclerosis observed by this new technique, we conducted an exploratory study. MATERIALS AND METHODS: Fifteen patients with systemic sclerosis treated with extracorporal photopheresis were compared with 15 healthy volunteers and 10 patients with other disorders also treated with extracorporal photopheresis. All subjects were investigated using confocal laser scanning microscopy in vivo. RESULTS: Micromorphologic characteristics of skin of patients with systemic sclerosis and measuring parameters for melanisation, epidermal hypotrophy, and fibrosis for dislocation of capillaries by collagen deposits in the papillary dermis were evaluated. An interesting finding was an increased thickness of the tissue in the dermal papillae superior to the first dermal papilla vessel. It was also possible to reproduce characteristic histologic features by confocal laser scanning microscopy in vivo. Histometric parameters for fibrosis and vascular features developed in this study showed significant differences in patients with systemic sclerosis compared to controls. CONCLUSIONS: Although the predominant histopathological features in systemic sclerosis are findings of the reticular dermis and the subcutis, and in histopathological investigation the epidermis seems to remain unaffected by the disease, we have demonstrate some characteristic differences in the epidermis and papillary dermis by confocal laser scanning microscopy in vivo. Some of them have not been described so far. However, to use this technique as a tool for diagnosis and/or staging of systemic sclerosis, further studies are needed investigating the sensitivity and specificity of the histometric parameters developed in this study.

Age related changes of human skin investigated with histometric measurements by confocal laser scanning microscopy in vivo.

BACKGROUND/AIMS: The confocal laser scanning microscope Vivascope (Lucid, Henrietta) allows skin to be studied in real-time with a resolution of 0.5 microm horizontal and 1.3 microm vertical in vivo. In this study, we present the results of a comparison between the skin of an older and a younger group of volunteers by in vivo histometric measurements. METHODS: To investigate changes caused by age, 13 young (18-25years) and 13 older (>65years) volunteers were examined. The following parameters were measured using the Vivascope at the volar forearm: minimal thickness of the epidermis (E(min)), size of cells in the granular layer (A(gran)), thickness of the horny layer (DSC), thickness of the basal layer (DSB) and number of dermal papillae per area (Papl). The image analysis program image tool was used to measure the size of the cells and the thickness of the basal layer. RESULTS: The older group of volunteers showed a significant increase in E(min), no significant change in DSC, a significant decrease in dermal papillae and in the thickness of the basal layer, and an increase in A(gran) compared to the younger group. CONCLUSIONS: Histometric measurements by in vivo confocal laser scanning microscopy are a sensitive and non-invasive tool for characterizing and quantifying histological changes of the epidermis and papillary dermis due to ageing.