R. Randall Wickett

Effect of dermal thickness, tissue composition, and body site on skin biomechanical properties.

Background/Purpose: Quantitative measurement of skin biomechanical properties has been used effectively in the investigation of physiological changes in tissue structure and function and to determine treatment efficacy. As the methods are applied to new questions, tissue characteristics that may influence the resultant biomechanical properties are important considerations in the research design. For certain applications, variables such as dermal thickness and subdermal tissue composition, as well as age and/or solar exposure, may influence the skin biomechanics.

Mechanisms Regulating Skin Pigmentation: The Rise and Fall of Complexion Coloration

Skin pigmentary abnormalities are seen as aesthetically unfavorable and have led to the development of cosmetic and therapeutic treatment modalities of varying efficacy. Hence, several putative depigmenting agents aimed at modulating skin pigmentation are currently being researched or sold in commercially available products. In this review we will discuss the regulation of processes that control skin complexion coloration. This includes direct inhibition of tyrosinase and related melanogenic enzymes, regulation of melanocyte homeostasis, alteration of constitutive and facultative pigmentation and down-regulation of melanosome transfer to the keratinocytes. These various processes, in the complex mechanism of skin pigmentation, can be regulated individually or concomitantly to alter complexion coloration and thus ameliorate skin complexion diseases.

Effective inhibition of melanosome transfer to keratinocytes by lectins and niacinamide is reversible.

Abstract:  Skin pigmentation results in part from the transfer of melanized melanosomes synthesized by melanocytes to neighboring keratinocytes. Plasma membrane lectins and their glycoconjugates expressed by these epidermal cells are critical molecules involved in this transfer process. In addition, the derivative of vitamin B3, niacinamide, can inhibit melanosome transfer and induce skin lightening. We investigated the effects of these molecules on the viability of melanocytes and keratinocytes and on the reversibility of melanosome‐transfer inhibition induced by these agents using an in vitro melanocyte–keratinocyte coculture model system. While lectins and neoglycoproteins could induce apoptosis in a dose‐dependent manner to melanocytes or keratinocytes in monoculture, similar dosages of the lectins, as opposed to neoglycoproteins, did not induce apoptosis to either cell type when treated in coculture. The dosages of lectins and niacinamide not affecting cell viability produced an inhibitory effect on melanosome transfer, when used either alone or together in cocultures of melanocytes–keratinocytes. Cocultures treated with lectins or niacinamide resumed normal melanosome transfer in 3 days after removal of the inhibitor, while cocultures treated with a combination of lectins and niacinamide demonstrated a lag in this recovery. Subsequently, we assessed the effect of niacinamide on facial hyperpigmented spots using a vehicle‐controlled, split‐faced design human clinical trial. Topical application of niacinamide resulted in a dose‐dependent and reversible reduction in hyperpigmented lesions. These results suggest that lectins and niacinamide at concentrations that do not affect cell viability are reversible inhibitors of melanosome transfer.

Effect of weight loss on cellulite: gynoid lypodystrophy.

Background: Gynoid lipodystrophy (cellulite) affects most women, and many seek plastic surgery consultation to improve appearance. Various products are offered, but the literature on the cause and treatment is limited. Understanding the biological and biophysical factors that affect severity may facilitate the development of effective therapies. There has been a dramatic increase in the number of people who have lost significant weight as a result of bariatric surgery or medically supervised weight programs. The effect of weight loss on cellulite severity has not been systematically studied and remains a common patient concern. The authors hypothesized that cellulite severity would decrease with weight loss and subsequent decrease in subcutaneous fat in most subjects. Methods: The authors examined the cellulite changes in female subjects who were enrolled in medically supervised weight loss programs using quantitative surface roughness by three-dimensional laser surface scanning, tissue composition by dual energy x-ray absorptiometry, dermal-subcutaneous structure with three-dimensional ultrasound, and tissue elasticity with biomechanical measurements. Results: The majority of subjects had an improvement in cellulite with weight loss, but the condition worsened for others. Improvement was associated with significant reductions in weight and percentage of thigh fat, significantly higher starting body mass index, and significantly greater initial severity. Cellulite worsened with a significantly smaller starting body mass index, smaller reductions in weight accompanied by no change in percentage of thigh fat, and significant increases in tissue compliance. Conclusions: Cellulite is a complex condition, and treatments such as weight loss have variable effects on the improvement or worsening of this condition. Additional studies are required to understand how the factors that influence and modulate cellulite severity, particularly those at the level of the subcutaneous tissue septa, can be manipulated to improve this condition.

Effect of semipermeable membranes on skin barrier repair following tape stripping

Abstract  Reports in the literature suggest that the permeability of a wound dressing to water transport is an important variable in the healing of superficial wounds. Factors that influence skin hydration during barrier repair, therefore, are important in the optimization of wound treatments. In this study, the effects of semipermeable films on human skin following a standardized wound (tape stripping) were evaluated using measurements of transepidermal water loss (TEWL), skin hydration, rate of moisture accumulation, and erythema. Wounds treated with semipermeable films underwent more rapid barrier recovery than either unoccluded wounds or wounds under complete occlusion. Barrier films that produced intermediate levels of skin hydration during recovery produced the highest barrier repair rates. The results support the hypothesis that semipermeable wound dressings augment barrier repair and skin quality by providing an optimized water vapor gradient during the wound healing process. The choice of wound dressing is discussed within the larger context of the design of vapor-permeable fabrics (smart materials) and the new fields of corneotherapy and comfort science.

Human Newborn Skin: The Effect of Isopropanol on Skin Surface Hydrophobicity

ABSTRACT: The development of a hydrophobic skin surface in newborn mammals such as the rat plays an important role in promoting adaptation to the abrupt change in the environment that occurs at birth. To determine whether the skin surface plays a similar role in the human neonate, we performed tests of water sorption and desorption on the chest wall of 13 term newborns. These tests were performed within the first 24 h of life on unperturbed skin (controls) and after perturbation of a contralateral site with isopropanol. The degree of surface hydration was determined by measurement of skin surface electrical capacitance, and desorption rates were calculated by 1st-order kinetic analysis. The unperturbed surface of the newborn skin exhibited a peak sorption value (change from baseline after water loading) of 435 ± 83 pF (mean ± SEM) and a desorption rate of 0.048 ± 0.009 s−1. After exposure to isopropanol, the peak sorption value increased to 594 ± 79 pF (p < 0.05) and the desorption rate decreased to 0.024 ± 0.004 s−1 (p < 0.01). Paired sorption values were positively correlated (r2 = 0.8, p < 0.001). These results support the hypothesis that the skin surface of the human newborn, by limiting the sorption of water (or amniotic fluid) on the skin, may play a role in the adaptation to the change in environment at birth.

Assessment with the dermal torque meter of skin pliability after treatment of burns with cultured skin substitutes.

The assessment of visco-elastic (V-E) properties in cutaneous scars is critical to reduction of impairment and restoration of function after grafting of excised burns. Cultured skin substitutes (CSS) that consist of autologous keratinocytes and fibroblasts attached to biopolymer substrates are alternatives for permanent closure of excised, full-thickness burns, but assessment of scarring has been subjective. V-E properties of CSS were measured with a Dia-Stron Dermal Torque Meter (DTM 310, Dia-Stron, Ltd, Broomall, Pa), which applies a constant torque (10 mNm) for a fixed interval (10 seconds) and measures rotational deformation and recovery. Parameters of skin deformation were measured in patients (n = 10) after grafting of CSS or meshed skin autograft. Native human skin (NHS) of healthy volunteers (n = 13) served as the control. Skin healed after treatment with CSS or autograft was evaluated for 1 year or longer after grafting. Elastic stretch (Ue), viscous stretch (Uv), total extensibility (Uf), elastic recovery (Ur), total recovery (Ua), and residual plasticity (R) were measured as degrees of rotation, were tested for significance (P < .05) by Student t test comparisons between treatment groups and controls, and were subjected to regression analysis. Assessment of burn scar with the Dermal Torque Meter detected time-dependent increases of all individual parameters of V-E properties for both CSS and autograft during the first year after grafting. At 1 year or later, no statistical differences were found between CSS and autograft for individual parameters, but Ue and Ur for autograft were significantly lower than for NHS. At 1 year or longer, autograft was significantly different from CSS or NHS, with a greater ratio of Uv to Ue, and both graft types had a lower ratio of Ur to Uf than NHS had. These results suggest that instrumental measurement of scar pliability may increase objectivity in assessment of patient recovery and establish an absolute scale for quantitative analysis of V-E properties in skin after grafting of conventional or alternative skin substitutes.

Incubation of cultured skin substitutes in reduced humidity promotes cornification in vitro and stable engraftment in athymic mice.

Cultured skin substitutes have been used successfully for adjunctive treatment of excised burns and chronic skin wounds. However, limitations inherent to all models of cultured skin include deficient barrier function in vitro, and delayed keratinization after grafting in comparison to native skin autografts. Experimental conditions for incubation of skin substitutes were tested to stimulate barrier development before grafting, and measure responses in function and stability after grafting. Cultured skin substitutes consisted of human keratinocytes and fibroblasts attached to collagen‐glycosaminoglycan biopolymer substrates. Parallel cultured skin substitutes were incubated at the air–liquid interface in ambient (48–61%) or saturated (79–91%) relative humidity, and grafted to athymic mice on culture day 14. Additional cultured skin substitutes were incubated in the experimental conditions for a total of 28 days. Cadaveric human skin and acellular biopolymer substrates served as controls. Epidermal barrier was evaluated as the change in surface hydration by surface electrical capacitance with the NOVA™ Dermal Phase Meter. Cultured skin substitutes and cadaveric skin incubated in ambient humidity had lower baseline surface electrical capacitance and less change in surface electrical capacitance than parallel samples incubated in saturated humidity at all time points in vitro. Data from healing cultured skin substitutes at 2, 4, 8 and 12 weeks after grafting showed an earlier return to hydration levels comparable to native human skin, and more stable engraftment for skin substitutes from ambient humidity. The data indicate that cultured skin substitutes in ambient humidity have lower surface electrical capacitance and greater stability in vitro, and that they reform epidermal barrier more rapidly after grafting than cultured skin substitutes in saturated humidity. These results suggest that restoration of functional epidermis by cultured skin substitutes is stimulated by incubation in reduced humidity in vitro.

Interaction Between Pulmonary Surfactant and Vernix: A Potential Mechanism for Induction of Amniotic Fluid Turbidity

The development of amniotic fluid turbidity during the third trimester is a known marker of fetal lung maturity. We hypothesized that this turbidity results from detachment of vernix caseosa from the fetal skin secondary to interaction with pulmonary-derived phospholipids in the amniotic fluid. To test this hypothesis, we exposed vernix to bovine-derived pulmonary surfactant over a physiologically relevant concentration range. Ten milligrams of vernix was evenly applied to the interior walls of 1.5-mL polypropylene microfuge tubes. Surfactant phospholipids were added to the tubes followed by slow rotation at 37°C overnight. The liquid was decanted and spectrophotometrically analyzed at 650 nm to detect solution turbidity due to vernix detachment and/or emulsification. Increasing concentrations of surfactant phospholipids produced a dose-dependent increase in solution turbidity. A phospholipid mixture closely approximating natural pulmonary surfactant but devoid of surfactant-associated proteins yielded no increase. In other studies, the flow properties of vernix were studied in a Haake flow rheometer at 23°C and 37°C. There was a marked temperature-dependent effect with lower stress required to elicit flow at 37°C compared with 23°C. This temperature dependence was also demonstrated in the turbidity assay with a 124% increase in turbidity at body temperature compared with room temperature. We conclude that under in vitro conditions, pulmonary surfactant interacts with vernix resulting in detachment from a solid phase support. We speculate that in utero, this phenomenon contributes to the increase in amniotic fluid turbidity that is observed near term.

Surface free energy characterization of vernix caseosa. Potential role in waterproofing the newborn infant

Background/aims: Vernix caseosa is a proteolipid biofilm synthesized by the human fetus, which progressively covers the fetal skin surface during the last trimester of pregnancy. The exact physiological functions of vernix are unclear. Hypothetically, it serves a role in “waterproofing” the fetus during the critical period of epidermal barrier development before birth. Vernix may also play a role in adaptation of the fetal skin surface to the dry, cool extrauterine environment after birth. Given the strategic position of vernix on the fetal skin surface and the rapidly changing environment encountered by the skin at birth, we proposed that investigation of vernix surface characteristics would facilitate understanding its putative physiological roles.