Reduction of wrinkles: From a computational hypothesis to a clinical, instrumental, and biological proof.

BACKGROUND: Facial wrinkles are clear markers of the aging process, being chronological, photo-induced, or reflecting repetitive facial expressions. The aim of this study is to provide new insights into the biophysical and biological mechanisms involved in the formation, prevention, or elimination of the expression wrinkles. MATERIALS AND METHODS: We use a computational model to get a better understanding of the wrinkle mechanical behavior and evolution after skin softening and suggesting a possible antiaging mechanism. Then, we provide a clinical demonstration of the anti-wrinkle effect of a long-term application of a 20% glycerol in a moisturizer formula (GBM) versus its vehicle on crow's feet. Skin hydration, elasticity, and wrinkles visibility were evaluated by a combination of clinical and instrumental in vivo data, inverse finite element analysis, and proteomic data. RESULTS: The computational model shows a predominantly compressive stress beneath the wrinkle and its significant decrease by the softening of stratum corneum. The associated clinical study confirmed a significant increase of skin hydration and elasticity as well as a decrease of wrinkle visibility after 2 and 4 months as application for both formulas; this effect being stronger for GBM. A softening effect on stratum corneum and dermis was also observed for the GBM. Furthermore, proteomic data revealed an effect of upregulation of four proteins associated with desquamation, cell-glycan extracellular interactions, and protein glycation/oxidation, functions related to the tissue mechanics and adhesion. CONCLUSIONS: We provide an in vivo demonstration of the anti-ageing benefit of glycerol at high dose (20%) reflected by a cumulative skin surface softening effect. The use of high moisturizing potent formulations should bring additional performance to other conventional moisturizing formulations.

Controlled mechanical vibration and impacts on skin biology.

BACKGROUND AND OBJECTIVE: Different biological models have shown how mechanical stimulation may induce physiological responses from solicited cells, tissues, or organs. In models of cultured skin cells, the frequency of the mechanical stress appears to be a paramount parameter, generating a biological response in some cells, particularly from dermal fibroblasts. Our objective was to explore in ex vivo human skin explants the effects of mechanical stimulation. MATERIALS AND METHODS: Mechanical stimulations were provided by a torque test device, with different end effectors, able to generate cyclic strains at different frequencies (from 40 to 120 Hz). Skin explant samples were stimulated twice daily by the device for one minute, over 10 days. RESULTS: At days 0, 5, and 10, samples were processed by immunohistological procedures, allowing some structural dermal proteins to be quantified (fluorescence). As compared to untreated skin explant samples, the stimulation procedure clearly led some proteins of the dermal-epidermal and some dermal proteins to be overexpressed. This stimulation was found to be frequency-dependent, with the greatest overall increases occurring at 60 and 90 Hz. CONCLUSION: For the first time, ultrafast ultrasound imaging in vitro (phantom mimicking skin mechanical properties) was used to analyze mechanical waves transmitted to the skin layers as a function of end effector shape.

The effect of age on skin color and color heterogeneity in four ethnic groups.

BACKGROUND: Few comparative data are available on age-related changes in skin color among different ethnic groups. The aim of the study was to measure and analyze the skin color and color heterogeneity in four different ethnic groups living in the same local environment and to determine the effects of age on these skin color characteristics. METHODS: Female volunteers (385) from four ethnic populations (African-American, Caucasian, Chinese and Mexicans) living in the same city were enrolled after informed consent. Skin color was measured on two facial areas, forehead and cheek. The subjects were further divided into six age ranges: 19-30, 31-40, 41-50, 51-60, 61-70 and 71-87 years to determine any age-related effects on the skin color and color heterogeneity in both areas. RESULTS: According to the L(*)a(*)b(*) CIE system, clarity (fairness/lightness) was found to be lower in the African-American group whereas the hue was lower in Caucasians, which means more red skin. A clear, statistically significant darkening of the skin with age was observed in all ethnic groups, while evidence of yellowing of the skin was shown in the Chinese volunteers. Overall, the skin color of the face of African-Americans was more heterogeneous than in the other ethnic groups, but showed the least increase with age. CONCLUSION: Our study revealed interesting differences in skin color and color heterogeneity with respect to ethnicity and age-related alterations. Data obtained are very useful in improving our knowledge about the skin of people of different origins and helps in the development of specific cosmetic products that are well adapted to all these populations.

Skin from various ethnic origins and aging: an in vivo cross-sectional multimodality imaging study.

BACKGROUND: Ethnic differences in skin structural features have not been thoroughly investigated, and the few reported studies are contradictory. Thus, we have carried out a set of in vivo measurements on the skin of about 400 volunteers from various ethnic origins living in the same environment. METHODS: Female subjects were distributed into four ethnic groups: African Americans, Mexicans, Caucasians, and Chinese. Inter- and intra-ethnic skin structural differences, according to age and anatomic site, were investigated using three non-invasive skin-imaging methods: ultrasound (US) at 25 and 150 MHz, and optical coherence tomography (OCT). RESULTS: The thickness of the skin is higher on the cheek compared with the dorsal and ventral forearm, with no ethnic or age-related specificity. We confirm that the sub-epidermal non-echogenic band is a sensitive marker of skin aging, and reveal for the first time that it is less pronounced in African Americans. From OCT images, we bring out evidence that the thickness of the dermal-epidermal junction (DEJ) decreased with age, and was higher in African Americans than in Caucasians. Finally, by comparing US images at 150 MHz with OCT images, we show that papillary dermis thickness can be measured and appears to be quite constant irrespective of age or ethnic group. CONCLUSION: Our study confirms that skin imaging is very attractive to further our knowledge of the morphology of skin from various ethnic origins. Regarding age effects, quantitative parameters have shown that they would be delayed in African Americans compared with all other ethnic populations.

Neural basis of sensitive skin: an fMRI study.

BACKGROUND/PURPOSE: About 50% of women declare themselves to have sensitive skin. However, sensitive skin still appears to be a questionable problem not corresponding to a specific physiological pattern. To objectivate the neural basis of sensitive skin, we measured cerebral response to cutaneous provocative tests in self-perceived sensitive and non-sensitive skin subjects using functional magnetic resonance imaging (fMRI). METHODS: Subjects were divided into two groups according to their self-perceived characterization by using a dedicated questionnaire about their skin reactivity. Event-related fMRI was used to measure cerebral activation associated with skin discomfort induced by a simultaneous split-face application of lactic acid and of its vehicle. RESULTS AND DISCUSSION: In both groups, skin discomfort due to lactic acid increased activity in the primary sensorimotor cortex contralateral to application site and in a bilateral fronto-parietal network including parietal cortex, prefrontal areas around the superior frontal sulcus, and the supplementary motor area. However, activity was significantly larger in the sensitive skin group. Most remarkably, in the sensitive skin group only, activity spreaded into the ipsilateral primary sensorimotor cortex and the bilateral peri-insular secondary somatosensory area. Our results demonstrate that, compared with control subjects, self-perceived sensitive skin subjects have a specific cerebral activation during skin irritative test, which allows us to hypothesize that self-perceived sensitive skin is intrinsically linked to a specific neurophysiologic pattern for these subjects. CONCLUSION: This study demonstrates that fMRI is an effective objective method for measuring cerebral processes underlying skin reactivity and contributes to a better understanding of the neural basis of the sensitive skin phenomenon.

Comparative study of the hydration of the stratum corneum between four ethnic groups: influence of age.

BACKGROUND: Several recent overviews have reported that significant work remains to be performed to understand and quantify the ethnic differences in skin properties. In this way, we have carried out a set of in vivo biophysical experiments on the skin of American women from different ethnic populations living in the same environment. Inter- and intraethnic skin micro relief results were already published, skin hydration differences are now reported here. METHODS: The skin water content was evaluated taking advantage of the new skin capacitance imaging technique which allows to study stratum corneum hydration without suffering of the influence of the skin micro-relief and hair on the measurement. Three hundred and eleven American women from four ethnic groups were enrolled in this study. The investigation was performed during the summer season of 2004 on the major relatively distinct ethnic groups of Chicago, which is to say: African American, Chinese, Caucasian and Mexican. The hydration of the skin was investigated on the dorsal and ventral forearm sites as a function of ethnicity and age. RESULTS: Skin dryness is higher on sun exposed sites for lighter skin tones, such as in Chinese and Caucasian women, than on sites that are primarily out of the sun; while, no skin dryness differences are seen on either site for African American and Mexican women whose skin is darker. The skin dryness does not change as a function of ethnicity for the younger group for either the ventral and dorsal site of the forearm. With age, however, the dryness of the skin is higher for African American and Caucasian women than for the two other ethnic groups, with a higher percentage increase in Caucasian women. CONCLUSIONS: This study has revealed that the hydration of the skin is different according to ethnicity and that the age effects are influenced by ethnicity, suggesting anatomical or physiological property differences in ethnic skin. This study has also pointed out that the SkinChip seems to be a convenient and fast way to investigate both the micro relief as previously published and the dryness of the skin on a large number of subjects, and in this way will be very useful to improve our knowledge about skin of people from different ethnic groups and helping to develop specific products that are customized to all these populations.

Advances in MR imaging of the skin.

MR imaging of the skin is challenging because of the small size of the structures to be visualized. By increasing the gradient amplitude and/or duration, skin layers can be visualized with a voxel size of the order of 20 microm, clearly the smallest obtained for in vivo images in a whole-body imager. Currently, the gradient strength of most commercial systems enables acquisition of such a small voxel size, and the main difficulty has thus become to achieve sufficient detection sensitivity. The signal-to-noise ratio (SNR) can be increased either by increasing the magnetic field strength or by minimizing noise with small coils; cooling copper coils or superconducting coils can enhance the SNR by a factor of 3 or more. MR imaging, because of the large number of parameters it is able to measure, can provide more than the microscopic architecture of the skin: physical parameters such as relaxation times, magnetization transfer or diffusion, and chemical parameters such as the water and fat contents or phosphorus metabolism. In spite of the amount of information they have provided to date, MR imaging and spectroscopy have had limited clinical applications, mainly because cutaneous pathologies are easily accessible to the naked eye and surgery. However, MR technologies indeed represent powerful research tools to study normal and diseased skin.

Assessment of elastic parameters of human skin using dynamic elastography.

Sonoelastography and transient elastography are two ultrasound-based techniques that facilitate noninvasive characterization of the viscoelastic properties of soft tissues by investigating their response to shear mechanical excitation. Young's modulus is the principle assessment parameter. Because it defines local tissue stiffness, it is of major interest for the medical imaging and cosmetic industries as it could replace subjective palpation by yielding local, quantitative information. In this paper, we describe a new high-resolution device capable of measuring local Young's modulus in very thin layers (1-5 mm) and devoted to the in vivo evaluation of the elastic properties of human skin. It uses an ultrasonic probe (50 MHz) for tracking the displacements induced by a 300 Hz shear wave generated by a ring surrounding the transducer. The displacements are measured using a conventional cross-correlation technique between successive ultrasonic back-scattered echoes. First, this noninvasive technique has been experimentally proven to be accurate for investigating elasticity in different skin-mimicking phantoms. Second, data were acquired in vivo on human forearms. As expected, Young's modulus was found to be higher in the dermis than in the hypodermis and other soft tissues.

Magnetic resonance imaging and spectroscopy of skin and subcutis.

Amongst in vivo skin imaging methods, magnetic resonance (MR) imaging and spectroscopy is of high interest not only for its ability to distinguish structures at a submillimetre scale but also for its ability to describe the physiology of the different skin layers through the measurement of their intrinsic MR parameters. High spatial resolution MR imaging allows the differentiation of epidermis, dermis and hypodermis. Cutaneous appendages such as hair follicles are also clearly visible. By measuring proton relaxation times and proton density, it is possible to go a step further in the description of skin physiology in vivo through the analysis of water-macromolecular interactions within the dermis as an example. Finally, quantification of water and lipid components in healthy and diseased adipose tissue by localized spectroscopy is also described. Even if MR imaging is of little interest for dermatological diagnosis, some preliminary studies have shown interesting results for preoperative staging, postoperative follow-up, and assessment of the efficacy of new dermatological products. In healthy skin, MR imaging and spectroscopy is a very promising method for the study of chronological and photoageing effects.

SkinChip, a new tool for investigating the skin surface in vivo.

BACKGROUND/AIMS: Non-invasive methods used for characterizing skin micro-relief and skin surface hydration were developed in the 1980s. Although they allowed some progress in the knowledge of skin properties, they are not completely satisfactory in many aspects. Today, new technologies are emerging that may address such issues. METHODS: We adapted the technology produced by the ST Microelectronics Company for sensing fingerprint for the measurement of skin surface properties. Accordingly, we developed acquisition software for obtaining routinely the distribution of skin surface capacitance along different body sites. Image analysis softwares were also processed for collecting both the main orientations of the micro-relief lines and their density. The average value of skin capacitance is also obtained. RESULTS: The images allow a highly precise observation of the skin topography that can be easily quantified in terms of line density and line orientation. The mean gray levels of the images appear much closely correlated to the Corneometer values. CONCLUSION: This new device appears to be a very convenient way for characterizing the properties of the skin surface. With regard to hydration, it usefully provides both the average value and the hydration chart of the investigated skin zones.

Influence of age on the wrinkling capacities of skin.

BACKGROUND: Comparisons of clinical assessment with measurement of physical parameters are rare. OBJECTIVE: To standardize the horizontal wrinkling of the skin in order to define a reference chart of the different wrinkling grades and to propose an interpretation of the clinical pattern in terms of skin layers thickness and mechanical parameters. METHODS: A device allowing reproducible wrinkling of the skin was made. The skin folds created in this way were clinically assessed on women of different ages. Measurements of the mechanical properties of the skin were carried out by using a Torquemeter. Skin layers' thicknesses were measured by using in vivo Confocal Microscopy (CM) and Ultrasound Imaging (B mode). RESULTS: Skin wrinkling grades increase versus age. Skin elasticity, extensibility and echogenicity decrease also versus age and the wrinkling grade. Wrinkling appears to be related to skin rigidification (for both stratum corneum and dermis) coupled to a certain weakening of the upper dermis (loss of echogenicity). CONCLUSION: This study points out the key role of the age-related alterations of the upper dermis in skin wrinkling capacities.

A computational skin model: fold and wrinkle formation.

This paper presents a computational model for studying the mechanical properties of skin with aging. In particular, attention is given to the folding capacity of skin, which may be manifested as wrinkles. The simulation provides visual results demonstrating the form and density of folds under the various conditions. This can help in the consideration of proper measures for a cosmetic product for the skin.