EpiDerm

Evaluation of the medical devices benchmark materials in the controlled human patch testing and in the RhE in vitro skin irritation protocol

Several irritants were used in the in vitro irritation medical device round robin. The objective of this study was to verify their irritation potential using the human patch test (HPT), an in vitro assay, and in vivo data. The irritants were lactic acid (LA), heptanoic acid (HA), sodium dodecyl sulfate (SDS), Genapol® X-80 (GP), and Y-4 polymer. Dilute saline and sesame seed oil (SSO) solutions of each […]

Human keratinocyte caspase-14 expression is altered in human epidermal 3D models by dexamethasone and by natural products used in cosmetics

Caspase-14 is a cysteinyl-aspartate-specific proteinase that is specifically expressed in epidermal keratinocytes. Dysregulation of caspase-14 expression is implicated in impaired skin barrier formation. To elucidate the regulation of caspase-14 in differentiated keratinocytes, we characterized the expression of caspase-14 in normal human epidermal keratinocytes (NHEKs) and two types of three-dimensional (3D) human epidermis culture models, EPI-200 […]

Hydrophobic binary mixtures containing amphotericin B as lipophilic solutions for the treatment of cutaneous leishmaniasis

Cutaneous leishmaniasis, caused by Leishmania parasites, requires treatments with fewer side effects than those currently available. The development of a topical solution based on amphotericin B (AmB) was pursued. The considerable interest in deep eutectic solvents (DESs) and their remarkable advantages inspired the search for a suitable hydrophobic excipient. Various mixtures based on commonly used […]

Cytotoxicity and Bioimmunological Activity of Poly(2-Isopropenyl-2- oxazoline) Conjugates with Ibuprofen Using 3D Reconstructed Tissue Models

Poly(2-isopropenyl-2-oxazoline) (PIPOx) represents a universal polymer platform with pendant 2-oxazoline groups, allowing the preparation of biomaterials for various biomedical applications. However, there is a lack of information on PIPOx concerning the effect of molar mass (Mn) on cytotoxicity and bioimmunological properties. Here, aqueous copper(0)-mediated reversible-deactivation radical polymerization (Cu0-RDPR) was used for the preparation of PIPOx […]

Evaluation of skin irritation potentials of different cosmetic products in Turkish market by reconstructed human epidermis model

Human skin is a protective barrier against the toxic effects of cosmetics. Marketing of cosmetic products with ingredients tested on animals was prohibited in 2013. Since then, safety evaluation of cosmetic products is performed by using alternative in vitro toxicity tests. In vitro 3-D reconstructed human epidermis (RhE) tissue models are now used to define […]

Development of an in vitro Functional Assay to Evaluate the Occlusive Properties of Moisturizers on Dry Skin

Introduction: Dry skin is a hallmark of impaired skin barrier function. Moisturizers are a mainstay of treatment to help the skin retain moisture, and there is a high consumer demand for effective products. However, the development and optimization of new formulations are hampered due to lack of reliable efficacy measures using in vitro models. Methods: […]

Assessment of Skin Toxicity in an in Vitro Reconstituted Human Epidermis Model Using Deep Learning

Skin toxicity is a common safety concern associated with drugs that inhibit epidermal growth factor receptors as well as other targets involved in epidermal growth and differentiation. Recently, the use of a three-dimensional reconstructed human epidermis model enabled large-scale drug screening and showed potential for predicting skin toxicity. Although a decrease in epidermal thickness was […]

An Evaluation of the EpiDerm™ Corrosivity and Corrositex® Assays for Predicting Skin Corrosivity of Chemical Products with Extreme Alkaline pH

The purpose of this study was to evaluate the EpiDerm™ Corrosivity (OECD 431) and Corrositex® Time Monitor (OECD 435) as in vitro methods to predict skin corrosivity for extreme pH (≥ 11.5) products. Extreme pH can be a useful predictor of irritation but may lead to over classification in weakly buffered systems. Hazard classification guidelines […]

In Vitro Irritation Assay and Regulatory Acceptance Two Years after ISO 10993-23:2021 Release

Medical device biological safety testing is transitioning away from the use of animals to more technologically advanced and reliable in vitro alternative methods. The irritation potential of medical devices has historically been evaluated by rabbit testing; however, ISO 10993-23:2021 offers a validated alternative by using reconstructed human epidermis (RhE) as the first consideration. Regulatory agencies […]

Arctigenin-Enriched Burdock Seed Oil (ABSO): A New Skin Brightening Botanical Extract

The Arctium lappa L. plant, commonly known as burdock, has been used therapeutically for hundreds of years. Arctigenin (ATG) is an active ingredient in burdock, albeit at low quantities or mostly in the form of acrtiin (arctigenin-4-glucoside). ATG has been touted for its anti-inflammatory properties in many cell types and disease states; however, its role […]

Health safety of parabens evaluated by selected in vitro methods

Seven selected parabens (4 allowed, 3 banned in cosmetics) were tested in order to confirm and expand historical data on their toxicological properties and safety. The aim was to apply novel in vitro methods, which have been sufficiently technically and scientifically validated for the purposes of toxicological testing of chemicals. The study included several toxicological […]

Protective effects of a comprehensive topical antioxidant against ozone‑induced damage in a reconstructed human skin model

Tropospheric ozone (O3) is a source of oxidative stress. This study examined the ability of a topical antioxidant (WEL-DS) to inhibit O3-mediated damage in a human epidermal skin model. Four groups of tissues (N = 24) were compared: Group 1 (control) were untreated and unexposed; Group 2 were untreated and exposed to O3 (0.4 ppm, […]

Investigating the sonophoresis effect on the permeation of diclofenac sodium using 3D skin equivalent

Ultrasound temporally increases skin permeability by altering stratum corneum SC function (sonophoresis). The objective of this study was to evaluate the effect of variable ultrasound conditions on the permeation of diclofenac sodium DS with range of physicochemical properties through EpiDerm™. Permeation studies were carried out in vitro using Franz diffusion cell. HPLC method was used […]

Correlation of In Vitro and In Vivo Skin Irritation Assays in Medical Devices: A Case Study

Biocompatibility testing is moving away from animal-based assays in favor of technologically advanced and reliable in silico and in vitro alternative approaches. While irritation has traditionally been assessed in a rabbit animal model, validated reconstructed human epidermis(RhE) models have been introduced in ISO 10993-23:2021. This standard describes a step-wise approach to evaluating the potential for […]

p38 MAP Kinase Inhibition Reduces Propionibacterium acnes-Induced Inflammation in Vitro

Introduction: Propionibacterium acnes, a ubiquitous skin bacterium, stimulates keratinocytes to produce a number of proinflammatory cytokines and may contribute to inflammatory acne. The aim of the study was to investigate whether P. acnesinduced proinflammatory cytokine release is mediated by P. acnes-induced activation of p38mitogen-activated protein kinase (p38 MAPK or p38) in human keratinocytes. Methods: Immunohistochemistry […]

Characterization of application scenario-dependent pharmacokinetics and pharmacodynamic properties of permethrin and hyperforin in a dynamic skin and liver multi-organ-chip model

 Microphysiological systems (MPS) aim to mimic the dynamic microenvironment and the interaction between tissues. While MPS exist for investigating pharmaceuticals, the applicability of MPS for cosmetics ingredients is yet to be evaluated. The HUMIMIC Chip2 (“Chip2′′ ), is the first multi-organ chip technology to incorporate skin models, allowing for the topical route to be tested. […]

Can Performance and Gentleness Be Reconciled? A Skin Care Approach for Sensitive Skin

People with self-reported sensitive skin may reluctantly use performing anti-ageing skin care products as it could elicit skin discomfort. We thus aimed to design and test an anti-ageing skin care routine that is suitable for people reporting sensitive skin. Key principles for developing products for sensitive skin were applied and formulas were screened for their […]

Cytokine induction in the 3D EpiDerm™ skin model used as an in vitro preclinical screening tool for formulations with anti-inflammatory action

Abnormal cytokine profiles represent the hallmark of inflammatory skin conditions such as psoriasis, acne, atopic dermatitis, irritant and allergic contact dermatitis. Damage to skin keratinocytes induces the release of primary cytokine interleukin (IL)-1α which further stimulates the release of secondary cytokines (e.g., IL-8) involved in the mediation of inflammatory reactions. Animal models have been historically […]

Use of the EpiDerm 3D reconstructed skin micronucleus assay for fragrance materials

In order to evaluate the utility of the 3D reconstructed skin micronucleus assay (3DRSMN) to assess clastogenic/aneugenic potential of the fra- grance chemicals, a set of 22 fragrance materials were evaluated in 3DRSMN assay. These materials evaluated were also evaluated in an in vitro as well as in vivo micronucleus assay, conducted as per Organisation […]

In Vitro and Clinical Safety Assessment of the Multiple W/O/W Emulsion Based on the Active Ingredients from Rosmarinus officinalis L., Avena sativa L. and Linum usitatissimum L.

The multiple W/O/W emulsion supplemented with the extracts of Rosmarinus officinalis L., Avena sativa L. and Linum usitatissimum L. was prepared in the study, its active compounds were determined by HPLC and its safety was evaluated in vitro by the means of reconstituted human skin model EpiDerm™ for the assessment of its irritation, phototoxicity and […]

Skin phototoxicity of cosmetic formulations containing photounstable and photostable UV-filters and vitamin A palmitate

The aim of this study was to evaluate the in vitro skin phototoxicity of cosmetic formulations containing photounstable and photostable UV-filters and vitamin A palmitate, assessed by two in vitro techniques: 3T3 Neutral Red Uptake Phototoxicity Test and Human 3-D Skin Model In Vitro Phototoxicity Test. For this, four different formulations containing vitamin A palmitate […]

Use of alternative test methods in a tiered testing approach to address photoirritation potential of fragrance materials

The safety assessment of fragrance materials for photoirritation utilized by The Research Institute for Fragrance Materials has recently been modified and is described in detail. Materials demonstrating significant absorbance in the ultraviolet and visible light (UV/VIS) range (290–700 nm) may present a concern for photoirritation and require further investigation. If there are no photoirritation data […]

Small Molecule IL-36γ Antagonist as a Novel Therapeutic Approach for Plaque Psoriasis

IL-36 cytokines are pro-inflammatory members of the IL-1 family that are upregulated in inflammatory disorders. Specifically, IL-36γ is highly expressed in active psoriatic lesions and can drive pro inflammatory processes in 3D human skin equivalents supporting a role for this target in skin inflammation. Small molecule antagonists of interleukins have been historically challenging to generate. […]

The 3D reconstructed skin micronucleus assay using imaging flow cytometry and deep learning: A proof-of-principle investigation

The reconstructed skin micronucleus (RSMN) assay was developed in 2006, as an in vitro alternative for genotoxicity evaluation of dermally applied chemicals or products. In the years since, significant progress has been made in the optimization of the assay, including publication of a standard protocol and extensive validation. However, the diverse morphology of skin cells […]

Topical treatments with acylceramide dispersions restored stratum corneum lipid lamellar structures in a reconstructed human epidermis model

Long-periodicity phase (LPP) lamellar structures in intercellular lipid matrixes of the stratum corneum (SC) are considered important for maintenance of skin permeability barriers. Acylceramides are essential components of LPP structures, and their absence influences skin barriers under physiological and pathological conditions, such as atopic dermatitis and dry skin. Although topical applications of acylceramide have been […]

Round robin study to evaluate the reconstructed human epidermis (RhE) model as an in vitro skin irritation test for detection of irritant activity in medical device extracts

Assessment of skin irritation is an essential component of the safety evaluation of medical devices. OECD Test Guideline 439 describes the use of reconstructed human epidermis (RhE) as an in vitro test system for classification of skin irritation by neat chemicals. An international round robin study was conducted to evaluate the RhE method for determination […]

A mixed community of skin microbiome representatives influences cutaneous processes more than individual members

Skin, the largest organ of the human body by weight, hosts a diversity of microorganisms that can influence health. The microbial residents of the skin are now appreciated for their roles in host immune interactions, wound healing, colonization resistance, and various skin disorders. Still, much remains to be discovered in terms of the host pathways […]

Demonstration of the first-pass metabolism in the skin of the hair dye, 4-amino-2-hydroxytoluene, using the Chip2 skin–liver microphysiological model

We used TissUse’s HUMIMIC Chip2 microfluidic model, incorporating reconstructed skin models and liver spheroids, to investigate the impact of consumer-relevant application scenarios on the metabolic fate of the hair dye, 4-amino-2-hydroxytoluene (AHT). After a single topical or systemic application of AHT to Chip2 models, medium was analysed for parent and metabolites over 5 days. The […]

Experiments in the EpiDerm 3D Skin In Vitro Model and Minipigs In Vivo Indicate Comparatively Lower In Vivo Skin Sensitivity of Topically Applied Aneugenic Compounds

Risk management of in vitro aneugens for topically applied compounds is not clearly defined because there is no validated methodology to accurately measure compound concentration in proliferating stratum basale keratinocytes of the skin. Here, we experimentally tested several known aneugens in the EpiDerm reconstructed human skin in vitro micronucleus assay and compared the results to […]

Retrospective review on in vitro phototoxicity data generated in 3D skin models to support the development of new OECD Test Guideline

Phototoxicity (also photo-irritation), is a light-induced skin reaction that occurs when photoreactive chemicals are activated to produce cytotoxic effects. Phototoxicity testing of chemicals is mostly conducted in vitro, following the methods described in the OECD test guideline (OECD TG 432), using the Balb/c 3T3 mouse fibroblast cell line. The test is highly sensitive, but low […]

Validation of the 3D reconstructed human skin micronucleus (RSMN) assay: an animal-free alternative for following-up positive results from standard in vitro genotoxicity assays

In vitro test batteries have become the standard approach to determine the genotoxic potential of substances of interest across industry sectors. While useful for hazard identification, standard in vitro genotoxicity assays in 2D cell cultures have limited capability to predict in vivo outcomes and may trigger unnecessary follow-up animal studies or the loss of promising […]

In vitro evaluation of immunobiological activity of simple mannolipids

Immunomodulation, cytotoxicity and anti-cancer activity of selected amphiphilic non-ionic (thio)alkyl α-Dmannosides (with aglycone of C6-C12) were investigated in vitro in human cervix epitheloid carcinoma cell line HeLa, murine melanoma cancer cells B16, murine lymphocytic leukemia cell line L1210, murine fibroblast cell line NIH 3 T3 and murine macrophage cell line RAW 264.7. Toxicological studies revealed […]

Novel cytokine marker available for skin irritation testing of medical devices using reconstructed human epidermis models

In biological safety evaluation of medical devices, false-negative results have been observed during skin irritation testing using the reconstructed human epidermis (RhE) model when measuring cell viability as a single marker. Therefore, to improve testing accuracy, this study conducted a comprehensive survey and performance evaluation of cytokines to identify a second marker. In addition to […]

The 3D reconstructed skin micronucleus assay: considerations for optimal protocol design

Implementation of the seventh amendment to the EU Cosmetics Directive has driven much research into suitable in vitro alternative assays to support satisfactory risk assessments. One such assay is the reconstructed skin micronucleus (RSMN) assay. First reported in 2006, further development occurred and a standard protocol was published in 2011. To evaluate and optimize the […]

Evaluation of phototoxicity of tattoo pigments using the 3 T3 neutral red uptake phototoxicity test and a 3D human reconstructed skin model

Phototoxicity due to dermally impregnated compounds exposed to ultraviolet radiation is associated with skin inflammation. The phototoxicity potential of active substances applied to the skin should be evaluated. Pigments are widely used for tattoos, and hypersensitivity reactions, such as photoallergic dermatitis, are possible tattoo related complications. However, the phototoxicity of these chemicals is not well […]

Nicotinamide Metabolism Modulates the Proliferation/Differentiation Balance and Senescence of Human Primary Keratinocytes

Nicotinamide (NAM) is the main precursor of nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for DNA repair, glycolysis, and oxidative phosphorylation. NAM has anti-aging activity on human skin, but the underlying mechanisms of action are unclear. Using 3-dimensional organotypic skin models, we show that NAM inhibits differentiation of the upper epidermal layers and maintains proliferation […]

Evaluation of Phototoxic and Cytotoxic Potential of TiO2 Nanosheets in a 3D Reconstructed Human Skin Model

Despite a continuous increase in commercial products containing nanoparticles, only few materials are currently used in such large amounts, forms and sizes as titanium dioxide – TiO2. Besides their use in cosmetics, the food industry and biomedicine, TiO2 nanoparticles (NPs) are also used as highly efficient photocatalysts due to their unique ability to convert complex […]

Pre-validation of an in vitro skin irritation test for medical devices using the reconstructed human tissue model EpiDerm™

Assessment of dermal irritation is an essential component of the safety evaluation of medical devices. Reconstructed human epidermis (RhE) models have replaced rabbit skin irritation testing for neat chemicals and their mixtures (OECD Test Guideline 439). However, this guideline cannot be directly applied to the area of medical devices (MD) since their non-toxicity assessment is […]

In vitro RHE skin sensitization assays: Applicability to challenging substances

In the last 20 years, alternative approaches to the identification of skin sensitization hazards have been at the forefront of the 3Rs and have helped refine the validation and acceptance processes. However, experience with the local lymph node assay showed that, post-validation, challenges still occurred, particularly when a wider diversity of chemical substances was addressed, […]

Unlocking Mother Nature’s Building Blocks

Just as the foundation of water is hydrogen and oxygen, the foundation of plants and trees are cellulose and lignin. These universal materials act as Mother Nature’s building blocks and have proven critical to botanical viability, enabling growth and protecting against environmental stresses. Historically, scientists have failed to extract cellulose and lignin in the form […]

Vibrational spectroscopy and microscopic imaging: novel approaches for comparing barrier physical properties in native and human skin equivalents

Vibrational spectroscopy and imaging have been used to compare barrier properties in human skin, porcine skin, and two human skin equivalents, Epiderm 200X with an enhanced barrier and Epiderm 200 with a normal barrier. Three structural characterizations were performed. First, chain packing and conformational order were compared in isolated human stratum corneum (SC), isolated porcine […]

Propionibacterium acnes-Derived Extracellular Vesicles Promote Acne-Like Phenotypes in Human Epidermis

Acne vulgaris is an inflammatory disease occurring in the pilosebaceous unit and is the most common skin condition in young people. A gram-positive bacterium, Propionibacterium acnes, has been suspected to contribute to the development of acne. Here, we report that P. acnes, constitutively releases extracellular vesicles (EVs) exhibiting typical EV morphology and size. Moreover, the […]

Reconstructed Human Epidermis Predicts Barrier-Improving Effects of Lactococcus lactis Emulsion in Humans

Background/Aims: The skin provides protection against chemical, physical, and biological stressors, yet the skin morphology changes over the course of life. These changes might affect the skin barrier function and facilitate the onset of age-related diseases. Since orally applied lactic acid bacteria ameliorate signs of aged and atopic skin, we investigated the effects of a […]

Modulation of cutaneous scavenger receptor B1 levels by exogenous stressors impairs “in vitro” wound closure

Scavenger receptor B1 (SR-B1) is a trans-membrane protein, involved in tissue reverse cholesterol transport. Several studies have demonstrated that SR-B1 is also implicated in other physiological processes, such as bacteria and apoptotic cells recognition and regulation of intracellular tocopherol and carotenoids levels. Among the tissues where it is localized, SR-B1 has been shown to be […]

Basket-weave structure in the stratum corneum is an important factor for maintaining the physiological properties of human skin as studied using reconstructed human epidermis and tape stripping of human cheek skin

The normal stratum corneum (SC) has an upper basket-weave (BW) pattern layer and a lower compact layer. The transition from compact to BW SC is well associated with a transition from diffuse to peripheral distributions of corneodesmosomes (CDs). The loss of transition from compact SC to BW SC appears to cause structural and barrier-function impairments.

In vitro biocompatibility study approaches to evaluate the safety profile of electrolyzed water for skin and eye

Electrolyzed water (EW) is a widely used disinfectant agent with high oxidation–reduction potential (ORP). Although EW has been used in many areas, such as food hygiene, agriculture, and animal husbandry, the studies presented in the literature are not enough to clarify the toxic effects of EW. The aim of this study is, therefore, to produce […]

A series of in vitro and human studies of a novel lip cream formulation for protecting against environmental triggers of recurrent herpes labialis

Purpose: These studies describe the testing of a novel, daily-use lip cream designed for individuals with lips prone to recurrent herpes labialis (RHL) that protects against environmental triggers. Subjects and methods: In vitro occlusive and in vitro and in vivo photoprotection analyses, a characterization of normal vs dry lips, and a randomized, evaluator-blinded, clinical trial […]

Genetic toxicity assessment of engineered nanoparticles using a 3D in vitro skin model (EpiDerm™)

Background: The rapid production and incorporation of engineered nanomaterials into consumer products alongside research suggesting nanomaterials can cause cell death and DNA damage (genotoxicity) makes in vitro assays desirable for nanosafety screening. However, conflicting outcomes are often observed when in vitro and in vivo study results are compared, suggesting more physiologically representative in vitro models […]

Skin Damage Mechanisms Related to Airborne Particulate Matter Exposure

Epidemiological studies suggest a correlation between increased airborne particulate matter (PM) and adverse health effects. The mechanisms of PM-health effects are believed to involve oxidative stress and inflammation. To evaluate the ability of PM promoting skin tissue damage, one of the main organs exposed to outdoor pollutants, we analyzed the effect of concentrated ambient particles (CAPs) in a […]

Validation of the In Vitro Reconstructed Skin Micronucleus Assay as a Potential Animal Alternative for Fragrance Materials

The in vitro reconstructed skin micronucleus assay is a skin-based assay which measures the clastogenicity and aneugenicity potential of chemical materials and mixtures. Reconstructed skin models are prepared from primary human cells and are expected to have DNA repair and cell cycle control mechanisms similar to in vivo systems. They are also expected to exhibit a human metabolic capability that is […]

The EpiDerm Skin Irritation Test 3 (EpiDerm SIT)

Skin irritation is defined in vivo as the reversible damage to the skin following the application of a test chemical for up to 4 h [as defined by the United Nations (UN) Globally Harmonized System of Classification and Labeling of Chemicals (GHS)]. The potential of chemicals to induce skin irritation (hazard) is an important consideration in establishing […]

The EpiDerm Phototoxicity Test (EpiDerm H3D-PT)

Phototoxicity is defined as a toxic response from a substance applied to the body which is either elicited or increased (apparent at lower dose levels) after exposure to light, or that is induced by skin irradiation after systemic administration of a substance. Identification of the phototoxic potential of topically or systemically applied test chemicals is a […]

The EpiDerm Skin Corrosion Test (EpiDerm SCT)

The potential for chemical induced skin corrosion is an important consideration in establishing procedures for the safe handling, packing and transport of chemicals. Various systems for classification of corrosive potential are included in international regulatory requirements. The EpiDermTM Skin Corrosion Test (SCT) is based on the experience that corrosive chemicals are cytotoxic after a short-term […]

Anthralin modulates the expression pattern of cytokeratins and antimicrobial peptides by psoriatic keratinocytes

Background: Psoriasis is an inflammatory skin disease with aberrant keratinocyte proliferation, presumably as a result of immune cell activation. Th17 cytokines like IL-17A and IL-22 are critically implicated in epidermal thickening, altered keratinocyte differentiation and production of innate factors such as antimicrobial peptides. Psoriasis treatment options include modern targeted therapies using anti-cytokine antibodies and traditional […]

In Vitro Skin Models and Their Predictability in Defining Normal and Disease Biology, Pharmacology, and Toxicity

In vitro skin model systems are increasingly being used both in the early evaluation of therapeutic drug candidates and in confirmatory mechanistic studies. The most commonly used of these in vitro model systems are reconstituted human epidermis (RHE) models. These RHE skin models consist solely of epidermal keratinocytes, which comes with some limitations but also with the advantage […]

In Vitro Assessment of Skin Irritation Potential of Surfactant-based Formulations by Using a 3-D Skin Reconstructed Tissue Model and Cytokine Response

Summary — The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to […]

Application of Mattek In Vitro Reconstructed Human Skin Models for Safety, Efficacy Screening, and Basic Preclinical Research

During the past three decades, great progress has been achieved in the development of in vitro reconstructed human epidermal (RhE) tissue models. This technology is now available via various manufacturers of commercially available tissue models, and has provided opportunities for researchers worldwide to reduce or even completely avoid in vivo experimentation for screening and prediction of cutaneous […]

The EpiDerm 3D human reconstructed skin micronucleus (RSMN) assay: Historical control data and proof of principle studies for mechanistic assay adaptations

The in vitro human reconstructed skin micronucleus (RSMN) assay in EpiDerm is a promising novel animal alternative for evaluating genotoxicity of topically applied chemicals. It is particularly useful for assessing cosmetic ingredients that can no longer be tested using in vivo assays. To advance the use of this test especially for regulatory decision-making, we have […]

Antibacterial modification of an injectable, biodegradable, non-cytotoxic block copolymer-based physical gel with body temperature-stimulated sol-gel transition and controlled drug release

Biomaterials are being extensively used in various biomedical fields; however, they are readily infected with microorganisms, thus posing a serious threat to the public health care. We herein presented a facile route to the antibacterial modification of an important A-B-A type biomaterial using poly (ethylene glycol) methyl ether (mPEG)- poly(-caprolactone) (PCL)-mPEG as a typical model. […]

The effect of low dose ionizing radiation on homeostasis andfunctional integrity in an organotypic human skin model

Outside the protection of Earth’s atmosphere, astronauts are exposed to low doses of high linear energy transfer (LET) radiation. Future NASA plans for deep space missions or a permanent settlement on the moon are limited by the health risks associated with space radiation exposures. There is a paucity of direct epidemiological data for low dose […]

A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents

Systemic absorption and metabolism of drugs in the small intestine, metabolism by the liver as well as excretion by the kidney are key determinants of efficacy and safety for therapeutic candidates. However, these systemic responses of applied substances lack in most in vitro assays. In this study, a microphysiological system maintaining the functionality of four organs over 28 […]

Evaluation of an In Vitro Human Dermal Sensitization Test for Use with Medical Device Extracts

In accordance with ISO 10993-10, the guinea pig maximization test, Buehler test, or murine local lymph node assay are used to assess the dermal sensitization potential of medical devices. The goal of our study was to determine if the in vitro SenCeeTox assay could be an acceptable alternative. The SenCeeTox assay has previously been shown to accurately […]

Chip-based human liver–intestine and liver–skin co-cultures – A first step toward systemic repeated dose substance testing in vitro

Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called human-on-a-chip concepts are […]

ELUCIDATION OF XENOBIOTIC METABOLISM PATHWAYS IN HUMAN SKIN AND HUMAN SKIN MODELS BY PROTEOMIC PROFILING.

Background: Human skin has the capacity to metabolise foreign chemicals (xenobiotics), but knowledge of the various enzymes involved is incomplete. A broad-based unbiased proteomics approach was used to describe the profile of xenobiotic metabolising enzymes present in human skin and hence indicate principal routes of metabolism of xenobiotic compounds. Several in vitro models of human […]

NIACINAMIDE DIMINISHED UVB INDUCED STRESS RESPONSE IN HUMAN EPIDERMAL EQUIVALENT MODEL.

Niacinamide (vitamin B3) is used in various skin care formulation, since it has been shown to photoprotective  activities  and  effectiveness on sallowness, wrinkling, red blotchiness and hyperpigmented  spots in aging skin. In order to investigate the molecular mechanism of this effect of niacinamide, we used EPI-201, a human skin equivalent model with partially formed stratified, […]

EFFECTS OF GALACTOMYCES FERMENT FILTRATE ON EPIDERMAL BARRIER MARKER CASPASE-14 IN HUMAN SKIN CELLS.

BACKGROUND: The stratum corneum of human epidermis is composed of terminally differentiated keratinocytes serving as an essential barrier to environmental stresses, such as UV induced photodamage, and water loss. The regulatory and proteolytic events that coordinate barrier formation are tightly controlled. Caspase-14 belongs to a conserved family of aspartate-specific proteases. Its epidermal expression is restricted […]

TOPICALLY APPLIED LACTIC ACID INCREASES SPONTANEOUS SECRETION OF VASCULAR ENDOTHELIAL GROWTH FACTOR BY HUMAN RECONSTRUCTED EPIDERMIS.

Background: Alpha-hydroxy acids (AHAs) are widely used for the treatment of hyperkeratotic skin disorders and photodamaged skin. Objectives: To investigate the effect of lactic acid (LA) on the secretion of cytokines by keratinocytes (KCs) of human reconstructed epidermis. Methods: Creams containing 1•5%, 3% or 5% LA or vehicle controls were topically applied on to human […]

INHIBITION OF UV INDUCED MMP-1 IN EPIDERMAL EQUIVALENTS BY ANTIOXIDANTS.

Chronic exposure to sunlight has been shown to induce matrix metalloproteinase (MMP) synthesis in human skin, resulting in elevated levels of MMPs and contributing towards photoagng. Reactive oxygen species (ROS) are believed to be important second messengers in this process resulting in an up-regulation of c-fos and c-jun which bind to form the transcription factor […]

NUCLEOTIDE EXCISION REPAIR IS REDUCED IN ORAL EPITHELIAL TISSUES COMPARED WITH SKIN.

Ultraviolet radiation (UVR) exposure to internal tissues for diagnostic, therapeutic and cosmetic procedures has increased dramatically over the past decade. The greatest increase in UVR exposure of internal tissues occurs in the cosmetic industry where it is combined with oxidizing agents for teeth whitening, often in conjunction with indoor tanning. To address potential carcinogenic risks […]

EVALUATION OF THE EFFECTS OF GOLDEN SILK-DERIVED EXTRACT ON EPIDERMAL BARRIER MARKERS, CASPASE-14 AND RELATED GENES IN HUMAN SKIN EQUIVALENT MODELS.

Glucocorticoids are widely used for their anti-inflammatory effects but the mechanism of their action in skin has not been fully understood. Bayo et al reported that glucocorticoid receptor is required for skin barrier competence(1) and Cirillo et al reported that epidermal keratinocyte synthesize and activate cortisol(2). Caspase-14 is a cystenyl-aspartate-specific proteinase that is specifically expressed […]

NICOTINIC ACETYLCHOLINE RECEPTOR STIMULATION IMPAIRS EPIDERMAL PERMEABILITY BARRIER FUNCTION AND RECOVERY AND MODULATES CORNIFIED ENVELOPE PROTEINS.

Aim:  To characterize how nicotinic acetylcholine receptors (nAChRs) influence epidermal barrier function and recovery following prolonged stress or direct nAChR activation or antagonism. Main methods:  Mice were subjected to physiological stress or treated topically with nAChR agonist or antagonist for three days. We assessed barrier permeability recovery by measuring transepidermal water loss (TEWL) before and […]

ULTRASTRUCTURAL AND HISTOLOGICAL EFFECTS OF EXPOSURE TO CEES OR HEAT IN A HUMAN EPIDERMAL MODEL.

Ultrastructural and terminal deoxynucleotidyl transferase nick end labeling (TUNEL) studies were conducted to compare mechanisms of 2-chloroethyl ethyl sulfide (CEES) and heat-induced injury to EpiDerm™. Twenty-two hours after 2-h exposure to the mono-functional alkylating agent CEES, budding of cytoplasm, clumping of nuclear chromatin, disintegration of nuclear membranes and cytoplasmic structures, and cytoplasmic vacuolization were detected, […]

VISUALISING FREE RADICAL INHIBITION FROM TOPICALLY APPLIED ANTIOXIDANTS.

The destructive role of free radicals in biological systems is well recognised and is manifested most commonly in ultraviolet (UV) light-induced skin damage, so-called photoaging. Sources of free radicals or reactive oxygen species (ROS) include not only UV from sunlight but also other environmental stresses, such as ozone or smog. We present data showing how […]

INVESTIGATING THE PROTECTIVE PROPERTIES OF MILK PHOSPHOLIPIDS AGAINST ULTRAVIOLET LIGHT EXPOSURE IN A SKIN EQUIVALENT MODEL.

Current research on bioactive molecules in milk has documented health advantages of bovine milk and its components. Milk Phospholipids, selected for this study, represent molecules with great potential benefit in human health and nutrition. In this study we used confocal reflectance and multiphoton microscopy to monitor changes in skin morphology upon skin exposure to ultraviolet […]

CONTRIBUTION OF UVB AND UVA TO UV- DEPENDENT STIMULATION OF CYCLOOXYGENASE-2 EXPRESSION IN ARTIFICIAL EPIDERMIS.

Both UVB (280–320 nm) and UVA (320–400 nm) radiation lead to an enhanced expression of cyclooxygenase-2 (COX-2) in epidermal cells in various in-vitro and in-vivo models. It is demonstrated here that the expression of COX-2 is induced in artificial human epidermis exposed to simulated solar light (>290 nm). Employing filters eliminating specified regions from the […]

REGULATION OF ANGIOGENESIS FACTORS BY ULTRAVIOLET RADIATION OR HYDROGEN PEROXIDE IN THE EPIDERM IN VITRO SKIN EQUIVALENT.

Vascular endothelial growth factors (VEGF) released by epidermis in response to environmental stimuli modulate new blood vessel growth (angiogenesis), a critical step in skin tumor progression and metastasis. Placenta growth factor (PlGF), a related angiogenic member of the VEGF family, is also expressed by epidermal keratinocytes. In order to evaluate the relative importance of VEGF […]

MOLECULAR RESPONSE OF NASAL MUCOSA TO THERAPEUTIC EXPOSURE TO BROAD-BAND ULTRAVIOLET RADIATION.

This study by researchers at MD Anderson Cancer Center (USA), the University of Szeged (Hungary), the Hungarian Academy of Sciences (Hungary), McGill University (Canada) and Victor Babes University (Romania) demonstrated that Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent and EpiDerm in vitro human skin tissue equivalent can be used to model the UV-induced DNA […]

WOUND HEALING AND EXPRESSION OF ANTIMICROBIAL PEPTIDES/ POLYPEPTIDES IN HUMAN KERATINOCYTES, A CONSEQUENCE OF COMMON GROWTH FACTORS.

In addition to acting as a physical barrier against microorganisms, the skin produces antimicrobial peptides and proteins. After wounding, growth factors are produced to stimulate the regeneration of tissue. The growth factor response ceases after regeneration of the tissue, when the physical barrier protecting against microbial infections is re-established. We found that the growth factors […]

WOUNDING UPREGULATES VASCULAR ENDOTHELIAL GROWTH FACTOR PRODUCTION BY KERATINOCYTES OF IN VITRO RECONSTRUCTED HUMAN EPIDERMIS.

Vascular endothelial growth factor (VEGF) is produced by keratinocytes and has been implicated in the past in animal models as the major factor involved in wound healing associated angiogenesis. In the present study we investigated the effects of wounding on the VEGF production by human keratinocytes of in vitro reconstructed epidermis (EpiDerm™). For this purpose […]

ARTIFICIAL HUMAN SKIN: CYTOKINE, PROSTAGLANDIN, HSP7O AND HISTOLOGICAL RESPONSES TO HEAT EXPOSURE.

INITIAL RESULTS WITH EPI-201, A DEVELOPING IN VITRO MODEL OF HUMAN EPIDERMIS.

MICROVESICATING EFFECTS OF SULFUR MUSTARD ON AN IN VITRO HUMAN SKIN MODEL.

This study by scientists at the US Army Medical Research Institute of Chemical Defense, University of Iowa, Harvard Medical School and Mattek Corp. demonstrated that Mattek’s EpiDermFT full-thickness in vitro 3-D human skin tissue equivalent with a well-developed basement membrane structure is a useful tool for in vitro mechanistic studies of sulfur mustard vesicant (blistering) […]

FULL THICKNESS EPIDERM™, A DERMAL-EPIDERMAL SKIN MODEL TO STUDY EPITHELIAL-MESENCHYMAL INTERACTIONS.

It has long been recognized that significant paracrine signaling occurs between dermal fibroblasts and epidermal keratinocytes. Further, it is understood that such interactions likely modulate the response of skin to materials which may lead to contact irritant or allergic responses. Also, dermis related phenomena such as photo-aging and photo-damage, wound healing and cancer progression are […]

TOPICAL DELIVERY OF SIRNA-BASED SPHERICAL NUCLEIC ACID NANOPARTICLE CONJUGATES FOR GENE REGULATION

Topical application of nucleic acids offers many potential therapeutic advantages for suppressing genes in the skin, and potentially for systemic gene delivery. However, the epidermal barrier typically precludes entry of gene-suppressing therapy unless the barrier is disrupted. We now show that spherical nucleic acid nanoparticle conjugates (SNA-NCs), gold cores surrounded by a dense shell of […]

IN VITRO APPROACHES FOR PREDICTING IRRITATION POTENTIAL OF TOPICAL EXPOSURES TO THE SKIN AND EYES.

Outline: Focus on topical exposure toxicity measures …Skin ……Corrosion ……Irritation –Chemicals ……Mildness –Formulations …Eye ……Physiology and modes of action –eye irritation ……Human Reconstructed Tissues ………Ingredients ………Mild formulation assessment …BCOP ……Moderate formulation assessment histology Conclusions: Skin Irritation/Corrosion …Validated methods are in place for testing chemicals for corrosion and irritation (EU). …Methods for determining mildness of formulations […]

EVALUATION OF IN VITRO MODELS FOR REACH TOXICITY TESTING: INDUCIBILITY OF XENOBIOTIC METABOLIZING ENZYME (XME) ACTIVITY IN IN VITRO HUMAN AIRWAY (EPIAIRWAY™) AND EPIDERMAL (EPIDERM™) MODELS.

Dermal and airway epithelia contain XMEs including phase I (oxidative) and phase II (conjugative) activities. These XMEs may play a role in biotransformation of drugs and chemicals, leading to altered drug activity or formation of toxic/mutagenic metabolites. Consideration of metabolic activity is therefore important for development of in vitro toxicity/genotoxicty assays required by REACH and […]

NON-ANIMAL METHODS FOR TOXICITY TESTING: EMERGING RESEARCH, METHODS & POLICIES.

Areas of emerging skin research include: studies on skin regeneration and the mechanisms involved in skin irritation and wound healing; modifying existing in vitro methods to make them acceptable for a broader range of testing applications; and, development of new methods for in vitro culture of skin cells, including co-cultures (keratinocytes + another type of […]

NON-ANIMAL APPROACHES FOR CONSUMER SAFETY RISK ASSESSMENTS: UNILEVER’S SCIENTIFIC RESEARCH PROGRAMME.

Non-animal based approaches to risk assessment are now routinely used for assuring consumer safety for some endpoints (such as skin irritation) following considerable investment in developing and applying new methods over the past 20 years. Unilever’s research programme into non-animal approaches for safety assessment is currently focused on the application of new technologies to risk […]

RECONSTITUTED 3-DIMENSIONAL HUMAN SKIN OF VARIOUS ETHNIC ORIGINS AS AN IN VITRO MODEL FOR STUDIES OF PIGMENTATION.

Reconstituted 3-dimensional human skin equivalents containing melanocytes and keratinocytes on an artifcial dermal substitute are gaining popularity for studies of skin metabolism because they exhibit morphological and growth characteristics similar to human epidermis. In this study, we show that such a pigmented epidermis model can be used to assess the regulation of pigmentation by known […]

FORSKOLIN PROTECTS KERATINOCYTES FROM UVB-INDUCED APOPTOSIS AND INCREASES DNA REPAIR INDEPENDENT OF ITS EFFECTS ON MELANOGENESIS.

This study by researchers in the Laboratory of Cell Biology, National Cancer Institute (National Institutes of Health) demonstrated that Mattek’s melanocyte/keratinocyte-containing MelanoDerm in vitro human skin tissue equivalent can be used to investigate the ability of a topically applied compound to prevent UVB-induced DNA damage in keratinocytes independent of melanin production in melanocytes. Melanin pigments […]

INFLAMMATORY ACTIVITY OF PARTHENOLIDE-DEPLETED FEVERFEW (TANACETUM PARTHENIUM).

This study by researchers at Johnson and Johnson demonstrated that Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent can be used to measure the effectiveness of a new topical formulation to inhibit TPA-induced release of PGE2 (Prostaglandin E2). Extracts of Tanacetum parthenium (L.) Sch. Bip., a plant known under the common name “Feverfew”, contains […]

IDENTIFICATION OF QUINOLINES THAT INHIBIT MELANOGENESIS BY ALTERING TYROSINASE FAMILY TRAFFICKING.

This study by scientists at the New York University School of Medicine and PTC Therapeutics demonstrated how Mattek’s MelanoDerm in vitro human skin tissue equivalent can be used to measure the depigmenting effects of human skin lightening agents. A series of quinolines, including chloroquine and quinine, were identified as potent pigmentation inhibitors through screening a […]

EVALUATION OF RECONSTRUCTED HUMAN EPIDERMIS KITS FOR THE IN VITRO ASSESSMENT OF COSMETIC SAFETY.

Reconstructed human epidermis is one of the most promising tools for in vitro evaluation of cosmetics. In recent years, their availability as kits offered to users practical models for the assessment of safety and efficacy of ingredients and finished products. However, the evaluation of their reproducibility, reliability and the relevance of the data obtained with […]

THE USE OF STANDARDIZED HUMAN SKIN MODELS FOR CUTANEOUS PHARMACOTOXICOLOGY STUDIES.

Reconstructed skin and epidermis models are finding increasingly numerous applications in cosmetology and dermatology. In particular, they are currently employed to assess the tolerability and efficacy of raw materials and formulations, in conditions approaching those of normal use. Importantly, the use of such models greatly reduces the need for animal testing. Various models of reconstructed […]

RECONSTRUCTED HUMAN EPIDERMIS EQUIVALENTS.

Special Section. (See Mattek TR’s 276 thru 283.)

UPDATE ON VALIDATION STATUS AND INDUSTRY UTILIZATION OF NORMAL HUMAN 3D (NHU-3D) ANIMAL ALTERNATIVE MODELS.

Progress in in vitro tissue engineering over the last several decades has contributed to a significant decrease in animal use for industrial risk and safety assessment of products and ingredients. Mattek Corporation has a long-standing involvement in development, production and validation of animal alternative in vitro models produced from normal human cells (NHu-3D models). The […]

PRESENCE OF HYDROCORTISONE DRAMATICALLY AFFECTS CYTOKINE PRODUCTION FOLLOWING UV IRRADIATION IN 3-DIMENSIONAL SKIN MODEL EPIDERM.

Dating back to work originally done by Rheinwald and Green, hydrocortisone (HC) is commonly used in culture media for epithelial cells, especially keratinocytes. In the culture of EpiDerm™, a highly differentiated, three-dimensional model of the human epidermis, this additive is included in the culture media. However, HC is a glucocorticoid, known for its anti-inflammatory efficacy. […]

Skin irritation and potential efficacy of a novel compound for localized treatment of psoriasis

Psoriasis is a chronic condition characterized by formation of white scaly patches on the skin. Current treatment options include topical glucocorticoids which have several side effects. Pentaerythritol tetrakis (3,5-di-tert-butyl-4-hydroxyhydrocinnamate) (PTTC) is a cinnamate tetraester which may be used as a novel topical treatment for psoriasis with less side effects. The purpose of this study was […]

NON-ANIMAL METHODS FOR TOXICITY TESTING: SKIN IRRITATION/CORROSION.

Skin toxicity refers to the local toxic effects resulting from a topical exposure of the skin to a substance. Skin toxicities include skin irritation and skin corrosion. The Globally Harmonized System of Classification and Labeling of Chemicals (GHS) defines skin irritation as “the production of reversible damage to the skin following the application of a […]

EVALUATION OF EPIDERM™ AS A MODEL TO STUDY IRRITATION AFTER EXPOSURE TO VARIOUS ALIPHATIC HYDROCARBONS FOUND IN JET FUELS.

This study by scientists at Florida A&M University College of Pharmacy, Auburn University Harrison School of Pharmacy, and Mattek Corp. demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent is an excellent in vitro alternative to animal testing for evaluating the skin irritation potential of chemicals and jet fuels. JP-8 has been recognized as […]

AN IN VITRO METHOD FOR SCREENING ANTI-IRRITANTS ON UV AND CHEMICALLY TREATED, RECONSTITUTED, THREE DIMENSIONAL HUMAN SKIN.

A great need exists in the cosmetics industry for in vitro screening methods that can provide accurate predictions of potential product or ingredient irritation. A variety of in vitro methods exist that utilize cell cultures, some of these focusing on the effects of irritants on specific cytokine release. However, these are not suitable for the […]

USE OF DIFFERENTIAL DISPLAY-POLYMERASE CHAIN REACTION TO IDENTIFY GENES SELECTIVELY MODULATED BY CHEMICAL ALLERGENS IN RECONSTITUTED HUMAN EPIDERMIS.

In the screening of topical drugs, cosmetics and other chemicals for human use, it is very important, both from a safety and an economic point of view, to have biological markers to discriminate irritant and allergic contact dermatitis that have different impacts on human health. Owing to their anatomical location, keratinocytes are among the first […]

IN VITRO AND IN VIVO COMPARISON OF DERMAL IRRITANCY OF JET FUEL EXPOSURE USING EPIDERM (EPI-200) CULTURED HUMAN SKIN AND HAIRLESS RATS.

This study by researchers at the Schools of Pharmacy at Florida A&M University and Auburn University demonstrated that Mattek’s EpiDerm human skin tissue equivalent can be used as an alternative to animals in evaluating the dermal irritation potential of several jet fuel formulations. The purpose of this study was to evaluate the EpiDerm™ in vitro […]

DEVELOPMENT OF AN IN VITRO MODEL FOR THE PREDICTION OF SKIN IRRITATION POTENTIAL.

Cytokines important to the inflammatory cascade were measured both at the level of transcription and secreted protein, from skin equivalents topically exposed to a panel of relevant consumer products. The response of a full thickness model, consisting of both keratinocytes and fibroblasts (Advanced Tissue Sciences’ SKIN2™), was compared to a keratinocyte only equivalent (Mattek’s Epi-Derm™) […]

EVALUATION OF PRO-INFLAMMATORY BIOMARKERS OF IRRITATION IN HUMAN SKIN MODEL USING MULTIPLEXED IMMUNOASSAY.

INITIAL IN VITRO SCREENING APPROACH TO INVESTIGATE THE POTENTIAL HEALTH AND ENVIRONMENTAL HAZARDS OF ENVIROX™ – A NANOPARTICULATE CERIUM OXIDE DIESEL FUEL ADDITIVE.

This study by scientists at Oxonica, Product Assessment & Regulatory Compliance, and SafePharm Laboratories Ltd. demonstrated that Mattek’s EpiDerm in vitro tissue model system can be used to determine the skin irritation potential of formulations containing nanoparticles. Nanotechnology is the new industrial revolution of the 21st Century as the various processes lead to radical improvements […]

COMPARISONS OF IN VITRO AND IN VIVO SKIN RESPONSES TO SURFACTANTS WITH A RANGE OF IRRITANCY POTENTIAL.

Scientists at Procter & Gamble Co. previously reported the development of a battery of endpoints in human skin cultures that correlate with human skin irritation responses to selected prototype surfactants. The purpose of the present study was to directly compare dose-response characteristics for surfactant-induced irritation in intact human skin exposed in vivo with the responses […]

INTER-AND INTRALABORATORY REPRODUCIBILITY OF A THREE DIMENSIONAL HUMAN EPIDERMAL MODEL – EPIDERM.

EpiDerm™ is a model of the human epidermis grown from normal human epidermal keratinocytes (foreskin-derived) seeded onto Millicell® CM (Millipore Corp., Bedford, MA) cell culture inserts. The inserts are placed at the air/culture medium interface allowing the cells to differentiate into a three dimensional model which consists of a basal layer of epidermal keratinocytes covered […]

LOT-TO-LOT VARIABILITY OF EPIDERM, AN EPIDERMAL MODEL FOR DERMAL IRRITANCY TESTING.

A model of the human epidermis, EpiDerm™, cultured from neonatal fore-skin-derived normal human epidermal keratinocytes (NHEK) was introduced by Mattek Corporation in April 1993. Using highly controlled tissue culture techniques, weekly batches of EpiDerm are produced and shipped domestically and internationally for dermal irritancy testing, percutaneous absorption studies, and basic skin research, amongst other uses. […]

DESIGN PRINCIPLES OF CHEMICAL PENETRATION ENHANCERS FOR TRANSDERMAL DRUG DELIVERY.

This study by researchers at the University of California at Santa Barbara demonstrated how Mattek’s EpiDerm human skin tissue equivalent can be used to measure the irritation potential of chemical penetration enhancers (CPEs) present in a large number of transdermal, dermatological, and cosmetic products. Chemical penetration enhancers (CPEs) are present in a large number of […]

INTRA- AND INTERLABORATORY REPRODUCIBILITY (ET-50) OF EPIDERM, AN IN VITRO MODEL FOR DERMAL IRRITANCY TESTING.

An in vitro model of the human epidermis, EpiDerm™, cultured from normal human epidermal keratinocytes (NHEK), was introduced by Mattek Corporation in April 1993. Using highly controlled tissue culture techniques, weekly batches of EpiDerm are produced for dermal irritancy testing, percutaneous absorption studies, and basic skin research. Histology, sterility, and the toxicological behavior are rigorously […]

LIPID AND ULTRASTRUCTURAL CHARACTERIZATION OF A NEW EPIDERMAL MODEL SHOWS GOOD CORRESPONDENCE TO NORMAL HUMAN EPIDERMIS.

A model of the human epidermis, EpiDerm, based on neonatal foreskin-derived normal human epidermal keratinocytes (NHEK), has recently been characterized by scientists at the University of Iowa College of Dentistry in terms of stratum corneum (SC) lipids and ultrastructure. Cultured using serum free media, the model allows determination of the effects of defined media additives […]

LIPID CHARACTERIZATION OF A NEW EPIDERMAL MODEL FOR SKIN IRRITANCY AND PENETRATION STUDIES.

A model of human epidermis, EpiDerm™, based on neonatal, foreskin-derived normal human epidermal keratinocytes (NHEK) has recently been characterized by scientists at the University of Iowa College of Dentistry in terms of stratum corneum lipids, ultrastructure, and barrier properties. Cultured using serum free media, the EpiDerm model allows determination of the effects of defined media […]

EVALUATION OF THE USEFULNESS OF 3-D MODELS OF RECONSTITUTED HUMAN SKIN AND EPIDERMIS IN APPLICATIONS OF REGULATORY SKIN TOXICOLOGY: PREVALIDATION, VALIDATION, CATCH-UP VALIDATION, AND REGULATORY ACCEPTANCE.

In 1991 we evaluated a model of full human skin (Skin2, ATS, La Jolla) for phototoxicity testing. The test developed showed promising results as an adjunct to a test performed with Balb/c 3T3 cells. While it detected acute phototoxins correctly, it classified those chemicals negative, that are known photoallergic in humans, but are not phototoxic […]

MODULATION OF CYTOKINE MESSAGE IN THE EPIDERM IN VITRO SKIN MODEL FOLLOWING TREATMENT WITH CONTACT ALLERGENS AND SKIN IRRITANTS.

Previous studies have demonstrated that EpiDerm™ (Mattek Corporation) in vitro skin model constitutively expresses message for several cytokines (Limardi et al., 1996 JID 106, 939). The objective of research presented here is to assess the ability of irritants and contact allergens to modulate cytokine message in the EpiDerm model. Total RNA was isolated at 2 […]

NEW PERSPECTIVES ON SKIN-COMPATIBLE DETERGENTS FOR SENSITIVE SKIN.

An interdisciplinary working group comprising manufactures of washing machines and household detergents (IKW/ZVEI) has studied whether or not household detergents today can provoke skin reactions. The results showed that modern technologies (washing machines and detergents) do not generally lead to higher levels of residues on washed textiles than the technologies of the 1980s. Consumer perception […]

PROGRAM TO REDUCE ANIMAL TESTING FOR EPA REGISTRATIONS OF ANTIMICROBIAL PRODUCTS.

This study by scientists at Proctor & Gamble, S.C. Johnson, the Institute for In Vitro Sciences (IIVS) and The Accord Group, in conjunction with the US EPA, documented how Mattek’s EpiDerm in vitro human skin tissue equivalent and EpiOcular in vitro human corneal tissue equivalent can be used to assess the dermal and eye irritation […]

THE USE OF Mattek EPIDERMAL EQUIVALENTS FOR PREDICTION OF IRRITATION POTENTIAL.

The need exists for a rapid, accurate in vitro screening protocol, predictive for human skin irritation in response to topically applied products. The EPI-100, EpiDerm™ Human Skin Model System produced by Mattek Corp. (Ashland, MA) is being investigated for this purpose. This system consists of normal, human-derived epidermal keratinocytes (NHEK), grown on permeable cell culture […]

DEVELOPMENT OF IN VITRO METHODS FOR EVALUATING THE EPIDERMAL AND DERMAL EFFECTS OF ALPHA HYDROXY AND AMIDES.

Several in vitro methods for their ability to replicate in vivo effects of selected alpha hydroxy acids and amides on the epidermis and dermis have been investigated. Cytotoxicity, prostaglandin release, morphology and histology on single cells and on tissue models were studied. Cytotoxicity, PGE-2 release in a commercial full skin model (ZK1300) correlated better with […]

PREDICTIVE TESTING: UNDERSTANDING THE ROLE OF IN VITRO AND IN VIVO TESTING.

Understanding predictive in vitro testing of topically applied materials is especially important to the pharmacologist who works with the skin since this technology is applied for basic research and product development. This exhibit presents information and data on traditional and relatively new in vitro assays, i.e. both human clinical data and innovative three dimensional, artificially […]

A COMPARISON OF THREE DIMENSIONAL HUMAN SKIN MODELS TO EVALUATE THE DERMAL IRRITATION OF SELECTED PETROLEUM PRODUCTS.

The in vitro evaluation of the dermal irritation potential of volatile or water insoluble petroleum products has generally proved difficult. Scientists at ARCO and Microbiological Associates utilized three human skin constructs (Living Skin Equivalent [LSE], Organogenesis, Inc., Cambridge, MA; Skin2 Model ZK1300, Advanced Tissue Sciences, La Jolla, CA; and EpiDerm™, Mattek Corporation, Ashland, MA) to […]

EVALUATION OF TWO IN VITRO HUMAN SKIN EQUIVALENTS (THE EPIDERM™ AND SKIN²™ MODEL ZK1300) FOR ASSESSING THE SKIN IRRITATION POTENTIAL OF PERSONAL CARE PRODUCTS AND CHEMICALS.

Living, three-dimensional human skin substrates were used to assess the relative skin irritation potential of selected chemicals and prototype shampoo formulations. Scientists at Clairol Inc. and Thomas Stephens Associates exposed two full-thickness skin equivalent models (EpiDerm™ from Mattek Corp. and Skin2™ from Advanced Tissue Sciences, Inc.) topically to the test materials for periods ranging from […]

CHARACTERIZATION AND COMPARISON OF RECONSTRUCTED SKIN MODELS: MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL EVALUATION.

Reconstructed human skin equivalents are currently being investigated as in vitro models for the prediction of human skin toxicity and irritation responses. Three different industrial reconstructed skin models (EpiDerm, Episkin and SkinEthic) and one in-house equivalent were characterized and compared using light microscopy, immunohistochemistry and reduction of (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyl tetrazolium bromide) (MTT). Their inter- and intra-batch […]

USE OF DIFFERENTIATED EPIDERMAL CULTURES FOR THE EXAMINATION OF INFANT-FECES-INDUCED SKIN IRRITATION.

Infant feces (BM) is known to possess a multitude of skin irritants. The aim of this study was to examine an in vitro model for BM-induced skin irritation, and determine if BM-induced skin irritation can be patterned in the laboratory. Infant BM was examined by diluting in water as individual samples or by pooling samples […]

IL-1α AND IL-1ra SECRETION FROM EPIDERMAL EQUIVALENTS AND THE PREDICTION OF THE IRRITATION POTENTIAL OF MILD SOAP AND SURFACTANT-BASED CONSUMER PRODUCTS.

Scientists at Johnson & Johnson Consumer Products and Neutrogena Corp. previously evaluated the measurement of viability and cytokine release from skin equivalents for predicting the skin irritation potential of topically applied surfactants, and demonstrated that IL-1a and interleukin-1 receptor antagonist (IL-1ra) release from epidermal skin equivalents correlates with skin irritation potential. In this study, the […]

THE INFLUENCE OF THE RESPONSE OF SKIN EQUIVALENT SYSTEMS TO TOPICALLY APPLIED CONSUMER PRODUCTS BY EPITHELIAL-MESENCHYMAL INTERACTIONS.

A number of diverse in vitro model systems have been employed for the prediction of irritation potential of test articles. Monolayer systems have proven to be useful for preliminary screening but are not always capable of distinguishing mild effects or adaptable to fully formulated product. Three-dimensional reconstructed skin equivalents integrate cellular toxicity with the kinetics […]

HUMAN IN VITRO AND IN VIVO CUTANEOUS RESPONSES TO SOAP SUSPENSIONS: ROLE OF SOLUTION BEHAVIOR IN PREDICTING POTENTIAL IRRITANT CONTACT DERMATITIS.

Over the years a number of methods have been developed to assess the potential contact irritancy of cosmetic-related surfactants. These methods include in vitro exposure using skin equivalent cultures, proteins, enzymes, etc. These methods are exaggerated in so far as the time of exposure, concentration of material tested, and/or material composition do not represent typical […]

COMPARISON OF IN VITRO AND IN VIVO HUMAN SKIN RESPONSES TO CONSUMER PRODUCTS AND INGREDIENTS WITH A RANGE OF IRRITANCY POTENTIAL.

Human skin equivalent cultures were investigated as possible pre-clinical skin irritation screens to aid safety assessments for chemicals and product formulations, and to facilitate design of safe and efficient human studies. In vitro responses in human skin equivalent cultures were compared directly to in vivo human skin responses from historic or concurrent skin tests for […]

DEVELOPMENT OF AN IN VITRO METHOD FOR SCREENING ANTI-IRRITANTS.

The development of an in vitro method for testing unknown anti-irritant ingredients can provide preliminary estimate of material safety and it is fast and economical before testing on humans. We utilized the Mattek EpiDerm skin model and a primary culture of keratinocytes to screen a variety of anti-irritants. EpiDerm partially mimics human skin morphologically and […]

EFFECT OF A NEW BOTANICAL EXTRACT BASED ON THE RED ALGAE, PIKEA ROBUSTA, ON IN VIVO REDUCTION OF SURFACTANT-INDUCED SKIN IRRITATION.

Through millions of years of evolution, organisms have developed various biochemical mechanisms to combat environmental pollutants and insure cell viability. Today, we exist under a constant barrage of damaging elements. Some are external and environmental; some are internal and result from natural metabolic processes. These processes result in the formation of dangerous free radical species […]

EVALUATION OF A NEW ALTERNATIVE TO PRIMARY DRAIZE SKIN IRRITATION TESTING USING THE EPIDERM SKIN MODEL.

EpiDerm™ is a commercially available human skin model consisting of normal human-derived epidermal keratinocytes (NHEK), which have been cultured to form a multilayered, highly differentiated model of the human epidermis. We evaluated this model as an alternative to the primary Draize skin irritation test using rabbits. Eighteen cosmetic products were tested using a new assay […]

ASSESSMENT OF HUMAN SKIN IRRITATION: VALIDATION OF IN VITRO MODELS.

BIOCONVERSION OF TOCOPHERYL ACETATE TO TOCOPHEROL IN HUMAN SKIN ORGAN CULTURE MODELS.

There is substantial interest in delivering the antioxidant benefits of vitamin E (tocopherol) to the skin. Since free tocopherol is inherently unstable, it is usually delivered to the skin in the form of tocopheryl acetate. The premise behind this approach is that the skin’s enzymes (esterases/lipases) would bioconvert the pro-vitamin E to the active vitamin. […]

USE OF PROTEOMIC TECHNOLOGIES FOR DISCOVERY OF NEW MARKERS OF SKIN IRRITATION IN VITRO.

Analysis of epidermal proteins from irritant-treated in vitro epidermal models by proteomics is a promising approach to detect new markers of human skin irritation. These data provide a more comprehensive understanding of the mechanisms involved in the skin irritation response. It is possible that some of these may provide novel markers of skin irritation.

SKIN IRRITATION POTENTIAL OF SURFACTANT MIXTURES: USING RELEVANT DOSES IN IN VITRO SYSTEMS.

Simple in vitro cell culture methods are often inappropriate for investigating the cytotoxicity of high concentration test substances. The relevance of these assays for assessing skin irritation potential substances such as surfactants or surfactant mixtures, where the toxicity of the substance is related to its physicochemical state which is in turn dependent on its concentration, […]

RECONSTRUCTED SKIN KITS: REPRODUCIBILITY OF CUTANEOUS IRRITANCY TESTING.

The aim of this study was to determine the reproducibility of data obtained from in vitro irritation testing using three industrial reconstructed human epidermis models, EpiDerm™, Episkin™ and SkinEthic(R), and one in-house model developed at Wella/Cosmital. A common protocol was established based on the measurement of cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and […]

A REPRODUCIBLE, STRUCTURALLY APPROPRIATE SKIN MODEL FOR DERMAL IRRITANCY AND EFFICACY TESTING.

The ability to determine, in vitro, the efficacy and irritancy of materials contacting the skin critically depends on the accuracy of the skin model in emulating native epidermis’ structure and biochemistry. In addition, for any toxicology or efficacy model to be useful, it is important to know that the model is reproducible both within a […]

PREDICTIVE ABILITY OF RECONSTRUCTED HUMAN EPIDERMIS EQUIVALENTS FOR THE ASSESSMENT OF SKIN IRRITATION OF COSMETICS.

The goal of this study by researchers at Cosmital SA (Wella AG) and L’Oreal (Life Sciences Research, Centre) was to examine the concordance between human in vivo and in vitro skin irritation classifications of cosmetic products and to evaluate the correlations between the different parameters. For that purpose, 22 formulations from product development test series, […]

PROTEOMIC AND MICROARRAY INVESTIGATION TO IDENTIFY POTENTIAL IN VITRO ENDPOINTS FOR SKIN IRRITATION.

There is a need to investigate the mechanistic basis of the human skin irritation response if relevant in vitro test systems for the predictive identification of skin irritation are to be developed. The aim of this work was to identify proteins (and genes encoding proteins) which may be regulated in response to skin irritation, following […]

IDENTIFICATION OF POTENTIAL IN VITRO ENDPOINTS FOR SKIN IRRITATION USING PROTEOMIC AND MICROARRAY ANALYSIS.

Understanding the mechanistic basis of the human skin irritation response is key to the development of relevant in vitro test systems for the predictive identification of skin irritation hazards. Recent progress in the development of proteomic and microarray technologies means that tools for the identification and investigation of important biochemical events in the processes of […]

GENE EXPRESSION ANALYSIS OF EPIDERM™ FOLLOWING EXPOSURE TO SLS USING cDNA MICROARRAYS.

There is a need to investigate the mechanistic basis of the human skin irritation response if relevant in vitro test systems for the predictive identification of skin irritation hazards are to be developed. Recent progress in genomics technologies mean that tools for the identification and investigation of important biochemical events in the processes of skin […]

RECONSTRUCTED HUMAN SKIN EQUIVALENTS-THEIR VALUE FOR SCREENING OF SKIN IRRITATION.

Advances in techniques for culturing human skin cells have led to the development of reconstructed human skin equivalents that closely resemble native human skin. These in vitro models offer a variety of approaches to investigate wound healing, skin ageing, pigmentation, skin penetration, transdermal drug delivery, cutaneous metabolism and toxicity. Skin corrosion and irritation due to […]

AN IN VITRO SKIN IRRITATION TEST (SIT) USING THE EPIDERM RECONSTRUCTED HUMAN EPIDERMAL (RHE) MODEL. (VIDEO Protocol)

This peer-reviewed, PubMed-indexed VIDEO technical article produced by scientists at Mattek Corp. and published in JoVE (Journal of Visualized Experiments) provides detailed instructions on how to perform the ECVAM-Validated EpiDerm Skin Irritation Test (SIT) Method, a stand-alone full replacement for traditional animal-based skin irritation tests. NOTE: This 20 MINUTE video protocol is ONLY to be […]

FOLLOW-UP VALIDATION OF THE EPIDERM SKIN IRRITATION TEST (SIT): RESULTS OF A MULTI-CENTRE STUDY OF TWENTY REFERENCE TEST SUBSTANCES.

This multi-center validation study performed by scientists at BfR (ZEBET), BASF SE, the Institute for In Vitro Sciences, Inc., the Centre for Alternative and Complementary Methods to Animal Testing (zet–LSL) and Mattek Corp. demonstrated that the modified Skin Irritation Test (SIT) based on Mattek’s EpiDerm in vitro human skin tissue equivalent can be used to […]

COMPARISON OF HUMAN PATCH TEST AND 3D HUMAN SKIN MODEL RESULTS WITH CLASSIFICATION OF CHEMICALS BASED ON RABBIT DRAIZE TEST.

As stated in the “Conclusions” section, this study by scientists at the National Institute of Public Health (CZ), St. John’s Institute of Dermatology, Unilever SEAC, ZEBET, and Mattek Corp. demonstrated that in vitro 3D models derived from human skin cells (Mattek’s EpiDerm), if used in appropriate test designs and optimized by reference to human hazard […]

A REPRODUCIBLE SKIN MODEL FOR DERMAL SAFETY AND EFFICACY TESTING.

The utility of any toxicological test system or method critically depends on the short and long term reproducibility of the method. Over the past 6 years, histological observations and quantitative quality control test methods utilizing the MTT assay have established a high level of intra-lot and inter-lot reproducibility for Mattek’s organotypic skin model, EpiDerm™. Interestingly, […]

IN VITRO SKIN IRRITATION TEST: INCREASING THE SENSITIVITY OF THE EPIDERM SKIN IRRITATION PROTOCOL EVALUATED IN THE ECVAM SKIN IRRITATION VALIDATION STUDY.

This study by scientists at Mattek Corp. demonstrated that a modification of the common Skin Irritation protocol that extended the exposure time from 15 minutes to 60 minutes for Mattek’s EpiDerm in vitro human skin tissue model produced a significant increase in sensitivity without decreasing the specificity of the method. During 2001-2004, refined EPISKIN and […]

A REPRODUCIBLE, STRUCTURALLY APPROPRIATE SKIN MODEL FOR DERMAL SAFETY AND EFFICACY TESTING.

The ability to determine, in vitro, the safety and efficacy profile for a material contacting the skin critically depends on the skin model’s structure and biochemistry. In addition, to be useful, the model must have a high level of intra-lot and inter-lot reproducibility. For this reason, the structure, biochemical nature, and reproducibility of the organotypic […]

AN IN VITRO SYSTEM FOR PREDICTING SKIN IRRITATION OF LIQUID ANTIPERSPIRANTS.

This study by scientists at Procter & Gamble demonstrated the ability to use Mattek’s EpiDerm in vitro human tissue equivalent as a preclinical test to confirm the mildness of prototype liquid antiperspirant formulations prior to beginning human clinical evaluations. Topical skin care products differ substantially in their composition, yet all need to be acceptably mild […]

IN VITRO HUMAN SKIN IRRITATION TEST FOR EVALUATION OF MEDICAL DEVICE EXTRACTS.

Purpose: The aim of this study was to determine if the EpiDerm™ reconstructed human skin model (Mattek Corp.) could be an acceptable alternative to the ISO 10993-required rabbit skin irritation test for assessing medical device biocompatibility. Eleven medical device polymers were tested. Four extracts were prepared per polymer, two each with saline and sesame oil; half […]

PROTEOMIC ANALYSIS OF THE RESPONSE OF EPIDERM™ CULTURES TO SODIUM LAURYL SULPHATE.

This study by researchers at Unilever’s Safety and Environmental Assurance Centre (SEAC) demonstrated how Mattek’s EpiDerm in vitro human skin tissue equivalent was used to identify a number of proteins that could be used as general markers for skin irritation. Scientists at Unilever’s Safety and Environmental Assurance Centre (UK) performed an analysis of EpiDerm™ cultures […]

EVALUATION OF AN IN VITRO HUMAN SKIN IRRITATION TEST FOR USE WITH MEDICAL DEVICE EXTRACTS

In accordance with ISO 10993, the rabbit skin irritation test is used to assess medical device biocompatibility, however, this method is time-consuming and expensive.  Our study’s goal was to determine if the EpiDerm™ reconstructed human skin model (Mattek Corp.) could be an acceptable alternative. To that end, eleven medical device polymers and adhesives were selected […]

USE OF HUMAN SKIN EQUIVALENT CULTURES FOR COSMETIC BENEFIT SCREENING.

This study by scientists at Procter and Gamble and CyberDERM demonstrated that Mattek’s EpiDerm fully developed and EpiDerm-201 underdeveloped in vitro human skin tissue equivalents, and EpiOcular in vitro human corneal tissue equivalent could be used to develop methodologies for measurement of transepidermal water loss (TEWL) from human epithelial tissue equivalent cultures, and that TEWL […]

CLASSIFICATION AND LABELING OF INDUSTRIAL PRODUCTS WITH EXTREME PH BY MAKING USE OF IN VITRO METHODS FOR THE ASSESSMENT OF SKIN AND EYE IRRITATION AND CORROSION IN A WEIGHT OF EVIDENCE APPROACH.

Classification and labeling of products with extreme pH values (62 or P11.5) is addressed in chemicals legislation. Following determination of pH and alkaline/acid reserve, additional in vitro tests are needed, especially to substantiate results less than corrosive. However, only limited experience with the practical application of in vitro methods to determine appropriate classifications for pH […]

IN VITRO ASSESSMENT OF SKIN IRRITATION POTENTIAL OF SURFACTANT BASED FORMULATIONS USING 3-D SKIN RECONSTRUCTED TISSUES AND CYTOKINE EXPRESSION ANALYSIS.

A goal of personal care products manufacturers is to develop increasingly milder formulations. To this end, reproducible  in vitro systems can accurately assess the irritation potential of the products, thus avoiding the use of animals for  testing. The three-dimensional EpiDermTM model (Mattek Corp.) provides a testing platform for Johnson & Johnson’s  skin irritation assessment program […]

MEETING REQUIREMENTS OF OECD TG 404 FOR IN VITRO SKIN IRRITATION TESTING: REPRODUCIBILITY OF EPIDERM SKIN IRRITATION TEST (EPIDERM-SIT) FOLLOWING ECVAM VALIDATION AND ACCEPTANCE AS A FULL REPLACEMENT METHOD.

In autumn 2007, an international validation study was performed to evaluate the reproducibility and confirm the predictive ability of the EpiDerm Skin Irritation Test (SIT) method (1, 2). In November 2008, ECVAM endorsed the EpiDerm SIT as a full replacement method for the in vivo rabbit skin irritation test. As reflected draft OECD guidelines for […]

SCREENING SOFT MATERIALS FOR THEIR EFFECT ON SKIN BARRIER FUNCTION BY HIGH THROUGHPUT EXPERIMENTATION.

Some of the challenges in applying high throughput experimentation (HTE) to materials in contact with natural media or tissues are outlined, with an emphasis on soft materials applied to biological surfaces, such as skin. We overview approaches to soft materials development and to assaying, in high throughput, how such soft materials affect skin barrier properties […]

ASSESSMENT OF SKIN ABSORPTION AND IRRITATION POTENTIAL OF ARACHIDONIC ACID AND GLYCERYL ARACHIDONATE USING IN VITRO DIFFUSION CELL TECHNIQUES.

Arachidonic acid (AA), a precursor of pro-inflammatory mediators, and its glycerin ester, glyceryl arachidonate (GA), are reportedly used in cosmetic products. In vitro skin penetration of AA and GA and GA’s ester hydrolysis was determined in flow-through diffusion cells. AA penetration with human and rat skin was 19.5% and 52.3% of the applied dose respectively, […]

NON-ANIMAL METHODS FOR TOXICITY TESTING: THE WAY FORWARD FOR IN VITRO SKIN IRRITATION TESTING.

A major milestone for in vitro skin irritation testing was achieved with the recent release of the Statement on the Validity of In-Vitro Tests for Skin Irritation by the European Centre for the Validation of Alternative Methods (ECVAM) Scientific Advisory Committee (ESAC). The statement endorsed the use of in vitro skin models and the MTT […]

IRRITANCY AND ALLERGIC RESPONSES INDUCED BY TOPICAL APPLICATION OF ORTHO-PHTHALALDEHYDE.

Although ortho-phthalaldehyde (OPA) has been suggested as an alternative to glutaraldehyde for the sterilization and disinfection of hospital equipment, the toxicity has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of OPA. The EpiDerm Skin Irritation Test was used to evaluate in vitro irritancy potential of […]

FURTHER DEVELOPMENT OF AN EPIDERM™ IN VITRO SKIN IRRITATION TEST FOR THE GLOBALLY HARMONIZED SYSTEM (GHS-SIT) OF CLASSIFICATION AND LABELING OF CHEMICALS.

Determination of skin irritation potential is an international regulatory requirement to ensure safe handling, packaging, labeling and transport of chemicals and evaluation of cosmetics and household products. Recent REACH legislation and a ban on animal testing for cosmetics have heightened the need for validated in vitro SITs. A UN treaty endorsed by the US, EU, […]

IN VITRO SKIN IRRITATION TESTING: IMPROVING THE SENSITIVITY OF THE EPIDERM SKIN IRRITATION TEST PROTOCOL.

This paper details the effort by Mattek scientists to increase the sensitivity of the Skin Irritation Test (SIT) method based on Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent. This effort led to the EpiDerm SIT method being validated by ECVAM as a full replacement for the rabbit skin irritant test in November 2008. […]

VALIDATION OF HUMAN SKIN MODELS FOR SKIN CORROSIVITY TESTS IN JAPAN.

This study by scientists at NIHS, Nihon Nohyaku Co., Ltd., Nippon Soda Co., Ltd., The Inst. Of Environmental Toxicology, Nippon Menard Cosmetic Co., Ltd., Sumitomo Chemical Co., Ltd., Kyoto University, and Tokyo University demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent can be used to reliably determine the dermal corrosivity potential of chemicals. […]

LONG TERM REPRODUCIBILITY OF EPIDERM, AN EPIDERMAL MODEL FOR DERMAL TESTING AND RESEARCH.

This technical reference summarizes Mattek’s 10-plus YEAR EpiDerm tissue reproducibility data. Long-term reproducibility is important not only to Mattek Customers, but also to European (ECVAM) and US (ICCVAM) regulators. Regulators constantly stress the need for superior reproducibility of in vitro tissue equivalents, not only during a specific validation program, but also long after the initial […]

ASSESSMENT OF THE IN-HOUSE PERFORMANCE OF THE EPIDERM™ AND EPISKIN™ IN VITRO CORROSIVITY TESTS.

The purpose of this study, conducted by scientists at Unilever’s Safety and Environmental Assurance Centre, was to assess the in-house performance of the EpiDerm and EPISKIN corrosivity tests using materials of known corrosive potential (six corrosives and six non-corrosives), as recommended in the draft OECD test guideline (TG) 431. Determination of the labelling requirements for […]

HUMANE ENDPOINTS AND ACUTE TOXICITY TESTING.

Evidence of acute toxicity for specific materials was originally provided using large numbers of animals in tests that often resulted in pain, suffering, and/or death to the experimental subjects. Recent research has been directed toward development of alternatives that remove or significantly reduce these effects while providing data indicative of the acute toxicity of the […]

DEVELOPMENT OF AN IN VITRO METHOD FOR SKIN CORROSION TESTING.

Scientists from The Procter and Gamble Company investigated the feasibility of an in-vitro skin corrosion test method using commercially available human skin cultures. Skin2 from Advanced Tissue Sciences and EpiDerm from Mattek were evaluated for their responses to 24 corrosive and non-corrosive materials. The multilayered epidermis of the Skin2 cultures contained a basal layer of […]

THE Mattek STORY – HOW THE THREE Rs PRINCIPLES LED TO 3-D TISSUE SUCCESS!

FRAME, the UK-based Fund for the Replacement of Animals in Medical Experiments, asked Mattek to contribute an article to a special edition of ATLA, FRAME’s scientific journal, commemorating FRAME’s 40th anniversary. FRAME asked Mattek to focus the article on the successful development of our in vitro 3-D tissues, produced from normal (non-transformed) human cells, as […]

THE ECVAM PREVALIDATION STUDY ON THE USE OF EPIDERM FOR SKIN CORROSIVITY TESTING.

In 1996 and 1997, ECVAM supported a formal validation study on in vitro methods for predicting skin corrosivity. Two of the in vitro tests included in the study employed human skin models, the Skin ZK1350 and EPISKIN™ models. In the ECVAM validation study, BASF, Huntingdon Life Sciences (HLS) and ZEBET tested the Skin human skin […]

DEVELOPMENT OF HISTOPATHOLOGIC CRITERIA FOR ASSESSING IN VITRO SKIN CORROSION.

The United States Department of Transportation recently granted an exemption for use of the in vitro Skin2 Model ZK1350 Corrosivity Assay as a replacement to rabbit skin corrosion testing for 6 chemical classes. The in vitro skin corrosion test is based on methods scientists at Procter & Gamble Co. previously developed in which test substances […]

APPLICATION OF AN IN VITRO METHOD FOR SKIN CORROSION TESTING TO A VARIETY OF COMMERCIALLY AVAILABLE SKIN CULTURES.

National and international regulations require that chemicals must be properly classified, labeled, packaged, and transported based on their ability to damage or destroy tissue, e.g., skin. Traditional rabbit tests for assessing skin irritation or corrosion are based on the methods of Draize et al. (1944). Scientists at Procter & Gamble Co. previously reported an in […]

USE OF AN IN VITRO SKIN MODEL TO PREDICT CHEMICAL CORROSIVITY.

The U.S. Department of Transportation now requires companies to assess the skin corrosivity of raw materials and products in order to insure their safe transport. The United Nations has issued guidelines and assigned packaging groups to materials based on how quickly corrosion of skin occurs in animal studies: I: less than 3 minutes, II: 3 […]

REGULATORY REQUIREMENTS FOR IN VITRO SYSTEMS TO MEET PERFORMANCE STANDARDS OVER TIME AS WELL AS DURING VALIDATION.

This technical poster by scientists at Mattek Corp. summarized 12-PLUS YEARS (1996-2007) of commercial production QC data for Mattek’s EpiDerm and EpiOcular in vitro human tissue equivalents, and how that data addresses regulatory concerns regarding performance standards of alternative in vitro testing methods over time. In vitro models are being proposed as alternatives to animal […]

PREVALIDATION OF TESTS FOR PREDICTING SKIN CORROSIVITY AND PHOTOTOXICITY USING AN IN VITRO MODEL OF HUMAN EPIDERMIS.

Tests for prediction of skin corrosivity and dermal phototoxicity using the model EpiDerm™ were evaluated at ZEBET in a prevalidation study funded by the European Centre for the Validation of Alternative Methods (ECVAM). The study comprised an interlaboratory method transfer, a refinement of test protocols and prediction models, and a blind trial involving three laboratories […]

DEVELOPMENT OF AN IN VITRO CORROSION/IRRITATION PREDICTION ASSAY USING THE EPIDERM™ SKIN MODEL.

This study by scientists at Covance Laboratories and the University of York demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent can be used to accurately predict the dermal corrosivity and skin irritation potential of 12 test chemicals. A validation of the in vitro skin corrosion method using the EpiDerm™ skin model was performed […]

ENSURING QUALITY OF IN VITRO ALTERNATIVE TEST METHODS: ISSUES AND ANSWERS.

This report by scientists at the US EPA, the US Consumer Product Safety Commission, the European Center for the Validation of Alternative Methods (ECVAM) and the Institute for In Vitro Sciences (IIVS) discussed the importance of having specific quality control safeguards in place during and long after formal in vitro test method validation is completed, […]

EVALUATION OF A TISSUE ENGINEERED HUMAN SKIN EPIDERM 3-D CULTURE AS A MODEL TO STUDY IRRITATION AFTER JET FUEL EXPOSURE.

This study by researchers at Florida A&M University demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent is a “valuable model to evaluate the skin irritation potential of jet fuels and hydrocarbon chemicals”. The purpose of the present study was to evaluate human skin Epiderm™ 3-D culture, EPI-200 (Mattek Corp, Ashland, MA) as a […]

IN VITRO AND HUMAN TESTING STRATEGIES FOR SKIN IRRITATION.

Prior to the manufacture, transport, and marketing of chemicals or products, it is critical to assess their potential for skin toxicity (corrosion or irritation), thereby protecting the worker and consumer from adverse skin effects due to intended or accidental skin exposure. Traditionally, animal testing procedures have provided the data needed to assess the more severe […]

STRATEGIES FOR THE ASSESSMENT OF ACUTE SKIN IRRITATION POTENTIAL.

The manufacture, transport, and marketing of chemicals and finished products requires the prior toxicologic evaluation and assessment of skin reactivity (corrosion and irritation) that may result from intended or accidental skin exposure. Procedures for the skin testing of new chemicals and finished products is rapidly evolving in the face of technologic advancements and political pressures. […]

ALTERNATIVE METHODS FOR SKIN IRRITATION TESTING: THE CURRENT STATUS.

The ECVAM Skin Irritation Task Force was established in November 1996, primarily to prepare a report on the current status of the development and validation of alternative tests for skin irritation and corrosion and, in particular, to identify any appropriate non-animal tests for predicting human skin irritation which were sufficiently well-developed to warrant ECVAM supporting […]

INCORPORATION OF RECONSTRUCTED HUMAN EPIDERMAL TISSUES INTO A CORPORATE TOXICOLOGY LABORATORY: USE OF IN VITRO TEST DATA FOR DIVERSE SAFETY AND RISK ASSESSMENT APPLICATIONS.

The 3M Strategic Toxicology Laboratory (STL) is an internal corporate resource providing toxicology support to 3M businesses. An objective in the STL is to routinely incorporate in vitro test methods, with a recent focus on the use of reconstructed human epidermis (RhE) tissues.. The first model utilized has been EpiDerm™, which is currently validated for […]

UVB IRRADIATION OF AN ORGANOTYPIC SKIN MODEL, EPIDERM™, RESULTS IN SIGNIFICANT RELEASE OF CYTOKINES.

Ultraviolet light, especially UVB (290-320 nm), is believed to be responsible for most of the immediate and long term effects of excessive exposure to sunlight. In many cases, the initial stages of these UV induced changes are the release of cytokines. Although cytokine release from human keratinocytes in monolayer cultures following UV exposure has been […]

RETROSPECTIVE ANALYSIS OF THE EPIDERM 3-MINUTE PREDICTION MODEL FOR ASSESSMENT OF GHS SKIN CORROSION PACKING GROUP SUB-CATEGORY 1A.

OECD has adopted several ECVAM-validated reconstructed human skin models (EpiDerm and EPISKIN/SkinEthic) for testing skin corrosion as OECD TG 431(1). However, OECD TG 431 does not satisfy international (GHS) labeling guidelines for transport of dangerous goods. GHS package labeling guidelines utilize 3 corrosion sub-categories (1A: very dangerous, 1B: medium danger, and 1C: minor danger). Labeling […]

SURFACTANT-LIKE PROPERTIES OF ALKALINE EXTRACTS FROM WASTEWATER BIOSOLIDS.

In order to assess the potential for utilizing wastewater biosolids as a source of useful substances, the surface activity of materials extracted from wastewater biosolids (activated sludge) by simple incubation with sodium hydroxide solutions at room temperature was assessed. The surface activity, measured by surface and interfacial tension methods, of the extracts was shown to […]

IN VITRO SKIN CORROSION TEST: LONG TERM REPRODUCIBILITY AND RELIABILITY FOR A REGULATORY ACCEPTED METHOD.

This study by scientists at the Institute for In Vitro Sciences (IIVS) and Mattek Corp. demonstrated the long term reproducibility and reliability of Mattek’s EpiDerm tissue model and the EpiDerm Dermal Corrosion assay protocol, as required by regulators. The EpiDerm skin corrosion test was repeated with the commercially available test substances previously used in both […]

COMPARISON OF CORROSITEX AND EPIDERM IN VITRO SKIN CORROSION SCREENING ASSAYS TO IN VIVO CORROSIVITY RESULTS.

This study by researchers at Dow Chemical Co. demonstrated that Mattek’s EpiDerm human skin tissue equivalent gave near-perfect concordance with in vivo corrosivity data for a panel of 12 reference chemicals recommended in OECD Guideline 431. In this study, Dow Chemical scientists objectively compared a battery of chemicals in the EpiDerm™ (Mattek Corp., Ashland, MA) […]

HIGHLY DIFFERENTIATED IN VITRO SKIN MODEL FOR HIGH THROUGHPUT SCREENlNG OF TOPICAL THERAPEUTICS.

THE EFFECTS OF TROPOSPHERIC OZONE ON A HUMAN EPIDERMAL SKIN MODEL (EPIDERM).

Recent reports suggest that exposure to tropospheric ozone (O3) poses an oxidative stress to murine skin. So far, no data is available on human skin. Monolayers of human keratinocytes cannot serve as a model of human skin for O3 exposure, since O3 mainly reacts within the stratified stratum corneum (SC). We chose a organotypic model […]

TOPICALLY APPLIED LACTIC ACID INCREASES SPONTANEOUS SECRETION OF VASCULAR ENDOTHELIAL GROWTH FACTOR/VASCULAR PERMEABILITY FACTOR (VEGF/VPF) BY HUMAN RECONSTRUCTED EPIDERMIS.

Background: Alpha-hydroxy acids (AHAs) are widely used for the treatment of hyperkeratotic skin disorders and photodamaged skin. Objectives: To investigate the effect of lactic acid (LA) on the secretion of cytokines by keratinocytes (KCs) of human reconstructed epidermis. Methods: Creams containing 1.5%, 3% or 5% LA or vehicle controls were topically applied on to human […]

TISSUE ABLATION WITH 100-fs AND 200-ps LASER PULSES.

We used water and human skin tissue to compare the surgical potential of 100-fs and 200-ps laser pulses. For investigation of threshold behavior of 100-fs and 200-ps pulses, we use water as a model for tissue. In addition to having a lower threshold, we find that energy deposition is much more consistent with 100-fs pulses. […]

ALAMAR BLUE DISCLOSES LATENT TOXICITY OF VESICANT IN HUMAN EPIDERMAL MODEL AND CELLS.

A new metabolic activity indicator, alamar blue (AB), was used by researchers at the United States Army Medical Research Institute of Chemical Defense and the State University of New York at Binghamton to estimate cell counts and to observe toxicity in the same human cells at several time points. AB permitted accurate estimates of cell […]

A SYNTHETIC HUMAN EPIDERMAL MODEL CAN DIFFERENTIATE ACUTE FROM LATENT EFFECTS OF THE MONOFUNCTIONAL MUSTARD ANALOGUE, 2-CHLOROETHYLETHYL SULFIDE.

In this study, researchers at the United States Army Medical Research Institute of Chemical Defense and the State University of New York at Binghamton used the metabolic indicator alamar blue (AB) as a noninvasive, fluorescent probe to analyze the toxic effects of the monofunctional sulfur mustard analogue, 2-chloroethylethyl sulfide (CEES). Data from normal human epidermal […]

PHOTOPROTECTIVE EFFECT OF ISOFLAVONE GENISTEIN ON ULTRAVIOLET B-INDUCED PYRIMIDINE DIMER FORMATION AND PCNA EXPRESSION IN HUMAN RECONSTITUTED SKIN AND ITS IMPLICATIONS IN DERMATOLOGY AND PREVENTION OF CUTANEOUS CARCINOGENESIS.

This study by researchers at Mount Sinai School of Medicine demonstrated that Mattek’s EpiDermFT epidermal/dermal human skin tissue equivalent can be used to investigate the photoprotective efficacy of compounds by exposing treated and untreated EpiDermFT tissues to UVB radiation. Genistein, the most abundant isoflavone of the soy derived phytoestrogen compounds, is a potent antioxidant and […]

EFFECTS IN UNIRRADIATED HUMAN TISSUE INDUCED BY RADIATION DAMAGE UP TO 1 MM AWAY.

This study by researchers at Columbia University’s Center for Radiological Research, Finland’s Radiation and Nuclear Safety Authority, and New York City’s Stuyvesant High School demonstrated how Mattek’s EpiDerm in vitro human skin tissue equivalent and EpiDermFT full-thickness in vitro human skin tissue equivalent can be used in vitro to study “bystander effects” of ionizing radiation […]

DETECTING REACTIVE OXYGEN SPECIES IN SKIN USING TWO-PHOTON FLUORESCENCE IMAGING MICROSCOPY.

Reactive oxygen species (ROS) contribute to skin photodamage including photoaging, immunomodulation, actinic keratosis and skin cancers. Because these highly-reactive derivatives of molecular oxygen are extremely short-lived and essentially non-emissive, they are difficult to detect directly. In addition, until recently with the realization of two-photon excited fluorescence (TPEF) imaging, the opaque and heterogeneous environment of the […]

EFFECT OF LAUNDERING ON ABILITY OF GLOVE FABRICS TO DECREASE THE PENETRATION OF ORGANOPHOSPHATE INSECTICIDES THROUGH IN VITRO EPIDERMAL SYSTEMS.

Researchers at Virginia Tech University examined two knit glove fabrics, one of 100% cotton and one of 100% polypropylene, for their capability to decrease the penetration of the organo-phosphate insecticides (OPs), azinphos-methyl and paraoxon after 4 h at field concentrations (3000 and 15 ppm, respectively) through an in vitro epidermal system (Skin2, Advanced Tissue Systems, […]

FLAVONOIDS DIFFERENTIALLY REGULATE IFN-GAMMA-INDUCED ICAM-1 EXPRESSION IN HUMAN KERATINOCYTES: MOLECULAR MECHANISMS OF ACTION.

The effect of plant flavonoids on intercellular adhesion molecule-1 (ICAM-1) expression in human keratinocyte was investigated. ICAM-1 is known to mediate skin inflammation. Among the flavonoids tested, taxifolin was the most potent in inhibiting interferon γ (IFN γ)-induced ICAM-1 protein as well as mRNA expression in human keratinocytes. Much smaller dosages of taxifolin were required […]

QUALITY ASSURANCE FOR IN VITRO ALTERNATIVE TEST METHODS: QUALITY CONTROL ISSUES IN TEST KIT PRODUCTION.

In vitro toxicology methods are being adopted by regulatory agencies worldwide. Many of these methods have been validated by using proprietary materials, often in the form of test kits. Guidelines for the use of Good Laboratory Practice methods for in vitro methods have been proposed. However, users of the data from these methods also need […]

GENE EXPRESSION PROFILING OF SKIN CARCINOGENSIS IN MICE.

This study by researchers at the University of Leicester and Unilever’s Safety Environmental Assurance Centre (SEAC) demonstrated that Mattek’s EpiDerm human skin tissue equivalents can be kept in a viable state for up to 23 DAYS. The overall goal of this project, conducted by researchers at the University of Leicester and Unilever’s Safety Environmental Assurance […]

ROLE OF TAURINE ACCUMULATION IN KERATINOCYTE HYDRATION.

Epidermal keratinocytes are exposed to a low water concentration at the stratum corneum stratum granulosum interface. When epithelial tissues are osmotically perturbed, cellular protection and cell volume regulation is mediated by accumulation of organic osmolytes such as taurine. Previous studies reported the presence of taurine in the epidermis of several animal species. Therefore, we analyzed […]

EVIDENCE THAT NITRIC OXIDE IS AN UPSTREAM MEDIATOR OF FASL-MEDIATED KERATINOCYTE APOPTOSIS IN TOXIC EPIDERMAL NECROLYSIS.

Toxic epidermal necrolysis (TEN or Lyell’s syndrome) is a severe adverse drug reaction that results in extensive necrolysis of the skin due to large scale Fas-FasL mediated keratinocyte apoptosis. The signaling pathways leading to the rapid upregulation of keratinocyte FasL expression in TEN are unknown. Here we show that FasL and inducible nitric oxide synthase […]

NOTCH-1 MEDIATED SIGNALING INCREASES IKKα LEVELS – A CRITICAL DETERMINANT CONTROLLING KERATINOCYTE TERMINAL DIFFERENTIATION AND CELL SURVIVAL.

Epidermal formation depends on a balance between cell proliferation, differentiation, and death. While deletion of IKKα gene blocks terminal differentiation in mice, biochemical pathways regulating IKKα in epidermis are unknown. Notch receptors regulate cell fate in response to ligands such as Jagged-1. In normal skin, Jagged-1 is expressed by keratinocytes (KCs) in basal cells and […]

JAGGED-1 MEDIATED ACTIVATION OF NOTCH SIGNALING INDUCES COMPLETE MATURATION OF HUMAN KERATINOCYTES THROUGH NF-B AND PPARγ.

Establishing an effective epidermal barrier requires a series of coordinated molecular events involving keratinocytes (KCs) within a stratified epithelium. Epidermal maturation depends on convergence of pathways involving components of NF-B and peroxisome proliferator activated receptor (PPAR) signaling systems that promote terminal differentiation and production of a stratum corneum. The Notch-1 receptor and its ligand Delta-1 […]

CHARACTERIZATION OF RECONSTRUCTED SKIN MODELS.

The aim of the present study was to evaluate tissue architecture and lipid composition of commercially available reconstructed human skin models; EpiDerm™, SkinEthic™ and Episkin™ in comparison to in-house reconstructed epidermis on a de-epidermized dermis (RE-DED) model and native tissue. For this purpose, the tissue architecture was examined using light microscopy, electron microscopy and immunohistochemistry; […]

EXPRESSION OF CYCLOOXYGENASE IN THE EPIDERM™ HUMAN SKIN MODEL: REGULATION BY ULTRAVIOLET RADIATION AND CYTOKINES.

Cyclooxygenase-2 (COX-2) appears to play an important role in skin carcinogenesis caused by solar ultraviolet radiation (UVR): UVR induces COX-2 expression in human skin, COX-2 activity is upregulated in skin cancers and COX inhibitors reduce UVR-induced tumor formation. In this report, we use RT-PCR, Western blotting and ELISA to study the effect of UVR on […]

ACTIVATION OF NOTCH SIGNALING IN KERATINOCYTES (KC’S) IS NECESSARY AND SUFFICIENT TO CREATE MATURE HUMAN EPIDERMIS.

The signaling system regulating the highly coordinated and programmed series of molecular events that generate a mature, fully differentiated and cornified epidermis is unknown. To determine if Notch ligands and receptors that regulate cell fate decisions in other organ systems may be operative in epidermis, normal human skin was initially examined by immunostaining and Western […]

CROSS-TALK BETWEEN NOTCH SIGNALING AND TWO PATHWAYS REGULATING EPIDERMAL DIFFERENTIATION.

Recently we established that peptides derived from the Notch ligand-Jagged-1 could trigger complete epidermal differentiation using submerged living epidermal equivalents (EEs). Moreover, using a selective inhibitor designed to block Notch receptor activity, epidermal differentiation was also blocked when submerged EEs were raised to an air/liquid interface. To determine the molecular basis by which Notch signaling […]

CHARACTERIZATION OF APOPTOTIC MACHINERY CONTROLLING CELL DEATH IN EPIDERMIS.

Ironically, the functional integrity of epidermis is dependent on a “planned cell death” pathway by which keratinocytes (KCs) undergo terminal differentiation, and then die producing comeocytes. To explore the molecular basis for crucial steps regulating epidermal KC cell death, normal human skin was examined by immunostaining and Western blot analysis. Fractionating KCs by state of […]

HIGHLY DIFFERENTIATED SKIN EQUIVALENT MODEL FOR HIGH THROUGHPUT SCREENING OF TOPICAL THERAPEUTICS.

EpiDerm™ is an in vitro organotypic human skin model cultured at the air/liquid interface to produce a three-dimensional tissue with a stratum corneum possessing a barrier function similar to native epidermis. The model is suitable for topical application of creams or lotions, and has found use in applications including cytotoxicity, irritation, and/or efficacy screening of […]

TERMINAL DIFFERENTIATION OF HUMAN KERATINOCYTES AND STRATUM CORNEUM FORMATION IS ASSOCIATED WITH CASPASE-14 ACTIVATION.

Programmed cell death of epidermal keratinocytes (KC) results in the formation of cornified cells, which constitute the outermost skin layer, the stratum corneum. Here we show by reverse transcription-polymerase chain reaction, western blot, and immunohistochemistry that epidermal KC express caspase-14, a member of the caspase family of pro-apoptotic proteases, in a tissue-specific manner. Caspase-14 protein […]

THREE DIMENSIONAL (3D) RECONSTRUCTED PSORIATIC TISSUE MODEL.

Psoriasis is a chronic skin disease that affects about 2% of the global population. Availability of well characterized in vitro psoriatic tissue model will enhance our understanding of the disease and the development of therapeutic strategies.  In this study, an in vitro three-dimensional psoriatic-like tissue model was reconstructed, culture conditions were optimized, and the model […]

LACK OF PHOTOTOXICITY OF COSMETIC FORMULATIONS CONTAINING GLYCOLIC ACID IN AN IN VITRO HUMAN SKIN MODEL.

Glycolic acid (GA) is a naturally occurring product found in sugar cane and is a member of a class of chemicals known as alpha-hydroxy acids. GA has been widely used in cosmetic and dermatological formulations for over a decade. These formulations are often used in dermal applications where they may be sub-ject to ultraviolet radiation […]

THE SERINE PROTEASE MARAPSIN IS EXPRESSED IN STRATIFIED SQUAMOUS EPITHELIA AND IS UP-REGULATED IN THE HYPERPROLIFERATIVE EPIDERMIS OF PSORIASIS AND REGENERATING WOUNDS.

The trypsin-like serine protease marapsin is a member of the large protease gene cluster at human chromosome 16p13.3, which also contains the structurally related proteases testisin, tryptase €, tryptase γ, and EOS. To gain insight into the biological functions of marapsin, we undertook a detailed gene expression analysis. It showed that marapsin expression was restricted […]

PREVALIDATION OF THE EPIDERM PHOTOTOXICITY TEST (ED-PT).

The EpiDerm™ phototoxicity test was chosen for prevalidation within ECVAM’s tiered prevalidation procedure. In phase 1, ZEBET drafted an SOP and project plan for conducting the study. ZEBET’s task in phase I was to adapt the existing Skin2 methodology to the specific needs of the epidermal model EpiDerm. UVA sensitivity experiments revealed 6J/cm2 as the […]

INHIBITION OF TUMOUR NECROSIS FACTOR-Á SECRETION FROM EPIDERM TISSUES BY A NOVEL SMALL MOLECULE, UTL-5D.

This study by scientists at Unitech Pharmaceuticals, Wayne State University, BioInnovation Laboratories, and the Taiwan National Defense Medical Center demonstrated that Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent could be used to study the dose-dependent reduction of TNF-á by a specific small molecule, UTL-5d, as well as study the feasibility of using this […]

PREVALIDATION OF THE EPIDERM PHOTOTOXCITY TEST.

The EpiDerm™ phototoxicity test was chosen for prevalidation within ECVAM’s tiered prevalidation procedure, since production of the full human in vitro skin model Skin2™ had been ceased in October 1996. ZEBET had developed a test protocol of a Skin2 phototoxicity test and had obtained promising results with a refined version of this test in the […]

PROTECTING THE SKIN AGAINST EXOGENOUS NOXES.

The authors have monitored various parameters to evaluate the protection of skin against oxidative damage by antioxidants. Chemoluminescence and liposomal preoxidation determined the efficiency of several antioxidants.

EPIDERMAL STRATIFICATION REDUCES THE EFFECTS OF UVB (BUT NOT UVA) ON KERATINOCYTE CYTOKINE PRODUCTION AND CYTOTOXICITY.

Ultraviolet (UV) radiation induced cytokine release from cultured keratinocytes as well as from epidermis in vivo. The purpose of this study was to determine whether differentiation of cultured keratinocytes into stratified epithelium decreases the effects of UVA and UVB radiation on cytokine release. Interleukin-1 IL-1á, IL-1â and tumor necrosis factor (TNF)-á release from human keratinocytes […]

DEVELOPMENT OF A NEW IN VITRO TEST FOR DERMAL PHOTOTOXICITY USING A MODEL OF RECONSTITUTED HUMAN EPIDERMIS (EPIDERM).

Results are reported using the human epidermis model (EpiDerm™) in a test protocol that was adopted from the method developed by ZEBET for phototoxicity testing with the model Skin2. In the new phototoxicity test the cytotoxicity of test materials applied topically to EpiDerm™ is determined at five concentrations in the absence and presence of a […]

AN IN VITRO METHOD TO EVALUATE THE ANTIOXIDANT EFFICACY OF TOPICAL FORMULATIONS.

We have developed a method of evaluating antioxidant efficacy in vitro using a three dimensional epidermal construct (Mattek EPI-100, Mattek Corpora-tion, Ashland, MA) which contains a well defined stratum corneum with a lipid profile similar to human skin. The EPI-100 allows direct application of test products to the stratum corneum. This method was used to […]

A COMPARISON STUDY OF FOUR IN VITRO PHOTOTOXICITY SYSTEMS.

Four in vitro phototoxicity systems were evaluated to determine how closely each method would reproduce the others. Eleven materials were used to evaluate these methods. All eleven materials were run in each system. Phototoxicity was evaluated using the Mattek EPI-100 dermal construct, the Advanced Tissues Sciences’ model 2K1300 dermal construct, and a monolayer of neonatal […]

USE OF THE Mattek EPI-100 IN VITRO SYSTEM TO SCREEN ANTIOXIDANT EFFICACY.

In this study, scientists at R. Thomas Stephens & Associates present an in vitro method to evaluate the efficacy of antioxidants and antioxidant formulations. The premise of this research is that exposure of human skin equivalents, specifically the commercially available Mattek EpiDerm EPI-100 skin model, to ultraviolet B (UVB) irradiation stimulates the production of oxygen […]

RECONSTITUTED 3-DIMENSIONAL HUMAN SKIN, A NEW IN VITRO MODEL FOR SKIN CARCINOGENESIS STUDY.

EpiDerm (Mattek Co., MA) is a newly developed reconstituted human skin equivalent that exhibits human skin-like morphological and growth characteristics. It has been utilized to evaluate the cytotoxicity and irritant potential of various cosmetic and household products. In this study, we found that EpiDerm can also be used to evaluate the genotoxicity of carcinogenic agents […]

THE FIBROBLAST-DERIVED PARACRINE FACTOR NEUREGULIN-1 HAS A NOVEL ROLE IN REGULATING THE CONSTITUTIVE COLOR AND MELANOCYTE FUNCTION IN HUMAN SKIN.

Interactions between melanocytes and neighboring cells in the skin are important in regulating skin color in humans. We recently demonstrated that the less pigmented and thicker skin on the palms and soles is regulated by underlying fibroblasts in those areas, specifically via a secreted factor (DKK1) that modulates Wnt signaling. In this study, we tested […]

HYPERPIGMENTATION IN HUMAN SOLAR LENTIGO IS PROMOTED BY HEPARANASE-INDUCED LOSS OF HEPARAN SULFATE CHAINS AT THE DERMAL–EPIDERMAL JUNCTION.

Background:  Skin pigmentation induced by ultraviolet B radiation is caused in part by inflammation mediated by cytokines secreted from keratinocytes and fibroblasts in the irradiated area. Heparanase is also activated in the irradiated skin, and this leads to loss of heparan sulfate at the dermal–epidermal junction (DEJ), resulting in uncontrolled diffusion of heparan sulfate-binding cytokines […]

FGF2 REGULATES MELANOCYTES VIABILITY THROUGH THE STAT3-TRANSACTIVATED PAX3 TRANSCRIPTION.

PAX3 (paired box 3) is known to have an important role in melanocyte development through modulation of microphthalmia­associated transcription factor transcription. Here we found that PAX3 transcriptional activity could be regulated through FGF2 (basic fibroblast growth factor)-STAT3 (signal transducer and activator of transcription 3) signaling in the pigment cells. To study its function in vivo, […]

DEVELOPMENT AND CHARACTERIZATION OF 3D PSORIATIC TISSUE MODEL.

Psoriasis is an inflammatory skin disease marked by hyperproliferation and abnormal keratinocyte differentiation that affects about 2% of the global population.  In this study, we developed a human cell based in vitro psoriatic tissue model from psoriatic fibroblasts and normal keratinocytes using an optimized serum-free culture medium.  When compared to normal skin reconstructs, confocal microscopic […]

DELPHINIDIN INDUCES EPIDERMAL DIFFERENTIATION AND INHIBITS PROLIFERATION AND INFLAMMATION IN A THREE-DIMENSIONAL RECONSTITUTED SKIN MODEL OF PSORIASIS.

Psoriasis is a chronic, inflammatory skin disease characterized by epidermal hyperproliferation and aberrant keratinocyte differentiation. Several lines of evidence suggest that intrinsic alterations of the epidermis may play an important role in the pathogenesis of psoriasis. Identification of natural agents that possess the ability to abrogate these effects could be useful for the treatment of […]

NALTREXONE ESTER PRODRUG BIOCONVERSION IN A HUMAN EPIDERMIS EQUIVALENT.

IN VITRO TESTING FOR PHOTOTOXIC POTENTIAL USING THE EPIDERM 3-D RECONSTRUCTED SKIN MODEL.

An in vitro photocytotoxicity model using mouse 3T3 fibroblasts (the 3T3 NRU PT) has recently been validated for the detection of the phototoxic potential of test substances. Although the 3T3 NRU PT has been demonstrated to detect the phototoxic potential of both strong and weak phototoxins, irrespective of their aqueous solubility, in cases of low […]

IMPROVEMENTS IN EPIDERM, A HIGHLY DIFFERENTIATED SKIN MODEL, FOR DRUG DELIVERY STUDIES.

The ability to produce skin in vitro with barrier properties equivalent to those of native epidermis remains a much sought after goal. This study by scientists in the Department of Pharmacology and Physiology, UMDNJ-NJMS and Mattek Corp. involves the use of a highly differentiated skin model, EpiDerm™, which has been shown to be useful in […]

PHOTOTOXICITY OF BERGAMOT OIL ASSESSED BY IN VITRO TECHNIQUES IN COMBINATION WITH HUMAN PATCH TESTS.

The aim of this study was to clarify the differences in the phototoxicity of bergamot oil obtained from four different suppliers. Spectral and chemical analyses were performed to identify presence of photoactive compounds in the test samples. The phototoxicity was assessed in vitro by the 3T3 NRU phototoxicity test (PT) and subsequently in a phototoxicity […]

ALTERNATIVE METHODS FOR PHOTOTOXICITY TEST USING RECONSTRUCTED HUMAN SKIN MODEL.

This study by researchers at the Korea Food and Drug Administration (KFDA) demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent can be used to determine the phototoxic potency of chemicals. Phototoxicity is defined as a skin inflammatory reaction elicited by topical or systemic administration of chemicals and subsequent exposure to light, particu-larly UVA […]

COMPARISON OF IN VITRO PHOTOTOXICITY TEST METHODS: 3T3 NRU PT VS. ENHANCED PHOTOTOXICITY SCREENING ASSAY IN RECONSTITUTED SKIN (EPARS).

This study by scientists at MB Research Labs demonstrated that Mattek’s EpiDerm in vitro human tissue equivalent provided more in vivo-like test results for phototoxicity testing than the 3T3 Neutral Red Uptake Phototoxicity Test. Currently, only the 3T3 Neutral Red Uptake Phototoxicity Test (3T3-NRU PT) has been approved as a non-animal phototoxicity test by governmental […]

IN VITRO SCREEN FOR PHOTOTOXICITY OPTIMIZED DRUG DEVELOPMENT USING A HIGHLY DIFFERENTIATED SKIN MODEL.

This study by Mattek Corp. scientists demonstrated that Mattek’s EpiDerm human skin tissue equivalent can be used to determine the phototoxicity of systemically administered drugs, significantly improving the drug development process. PURPOSE: Both topically applied and systemically administered medications can induce photosensitivity. Photosensitivity includes both photo-allergic (immunologically mediated) reactions, and phototoxic effects, which occur following […]

ECVAM FEASIBILITY STUDY: CAN THE PRE-VALIDATED IN VITRO SKIN MODEL PHOTOTOXICITY ASSAY BE UPGRADED TO QUANTIFY PHOTOTOXIC POTENCY OF TOPICAL PHOTOTOXINS?

This study by scientists at ZEBET (Germany) and the Czech Republic National Institute of Public Health (SZU) demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent can be used in place of animals to accurately predict the phototoxicity of topically applied formulations. The determination of phototoxicity of a chemical in the 3T3-NRU-PT test according […]

AN ASSESSMENT OF THE PHOTOTOXIC HAZARD OF A PERSONAL PRODUCT INGREDIENT USING IN VITRO ASSAYS.

Where substances are intended for use in personal products applied to the skin an assessment of potential phototoxic hazard is required. This report describes a tiered testing strategy involving in vitro assays used for the phototoxic hazard assessment of a personal product ingredient (Ingredient X). The initial assay was measurement of a UV/visible absorption spectrum […]

A TIERED STRATEGY FOR IN VITRO PHOTOTOXICITY TESTING.

Of the materials used to demonstrate the value of the 3-D Skin Assay (in supporting and interpreting 3T3 NRU PT results), all of those predicted phototoxic in the 3T3 NRU PT were confirmed phototoxic in the 3-D Skin Assay, with the exception of one (material coded 10). This material was clearly defined as phototoxic to […]

DERMATACS™ IN SITU APOTOSIS DETECTION KIT FOR SKIN CELLS AND TISSUES.

Trevigen announces the release of a new in situ apoptosis detection kit for skin cells and tissues, DermaTACS, and the companion products, EpiDerm™ Control Slides. DermaTACS was developed for the scientist working in skin research seeking distinct identification of cells with fragmented DNA and unprecedented low background interference. DermaTACS is ideal for the novice user […]

CHANGES IN CANCER-RELATED GENE EXPRESSION IN AN IN VITRO HUMAN SKIN MODEL FOLLOWING UVB-IRRADIATION.

UV-irradiation causes initiation and promotion of skin cancers, photoaging and immunosuppression. To further our understanding of these processes at the molecular level, we utilized cDNA array technology to examine changes in gene expression in the EpiDerm™ in vitro human skin model following irradiation with UVB (175 ml per cm2). Viability of irradiated EpiDerm tissue, as […]

ASSESSMENT OF PHOTOTOXICITY, SKIN IRRITATION, AND SENSITIZATION POTENTIAL OF POLYSTYRENE AND TiO2 NANOPARTICLES.

The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO2 nanoparticles using cultured keratinocytes, an HSEM, and an animal […]

INITIAL CHARACTERIZATION OF AN EPIDERMAL MODEL CONTAINING FUNCTIONAL MELANOCYTES.

A model of the human epidermis, EpiDerm™, cultured from foreskin derived normal human epidermal keratinocytes (NHEK) has been shown to reproduce many of the histological and ultrastructural properties of native epidermis. In an effort to extend the utility and complexity of these cultures, normal human melanocytes (NHM) have recently been incorporated. Both melanocyte free and […]

THE PROTEASE-ACTIVATED RECEPTOR 2 REGULATES PIGMENTATION VIA KERATINOCYTE-MELANOCYTE INTERACTIONS.

Close association exists between melanocytes, the pigment melanin-producing cells in the body, and their neighboring keratinocytes. Keratinocytes are the pigment recipients and skin pigmentation is the result of this interaction. While the chemical basis of melanin production (melanogenesis) is well documented, the molecular mechanism of melanosome transfer needs to be elucidated. We are now providing […]

NEW RESULTS WITH MELANODERM™, AN EPIDERMAL MODEL CONTAINING FUNCTIONAL MELANOCYTES.

We have previously reported on the successful incorporation of normal human melanocytes (NHM) into a highly differentiated, three-dimensional tissue culture model of human epidermis (JID, 104(4), 616, 1995). Melanocytes exhibited dendritic morphology, were localized in the basal cell layer, and converted 1-dopa to melanin. Previously, spontaneous pigmentation of the melanocytes could not be observed using […]

DERMAL PENETRATION OF PESTICIDES AND POLYCHLORINATED BIPHENYLS FROM HOUSE DUST.

This study demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalents were the most in vivo-like for performing percutaneous penetration experiments in vitro. Indoor contamination has been rated as a high environmental risk, as people living in industrialized countries spend about 80-90% of their individual live time indoors. Several epidemiological studies showed a link […]

EFFECTS OF ANTIOXIDANT INGREDIENTS ON HUMAN SKIN: FROM CELL CULTURE TESTING TO HUMAN CLINICAL TRIALS.

Cosmetic chemists have included Vitamins A, C, and 12 and other similar ingredients into skin care and cosmetic products for many years now. These ingredients and their derivatives were originally incorporated into those products for their effects in improving the appearance and feel of the skin. It has been well documented that Vitamins A and […]

USE OF NORMAL HUMAN 3D (NHU-3D) TISSUE MODELS (EPIDERM™, EPIAIRWAY™) FOR NANOTOXICOLOGY APPLICATIONS

Nanomaterials are increasingly utilized in numerous commercial applications where dermal contact, inhalation, or oral ingestion is likely. However, their toxicological properties are largely unknown. Potential adverse effects of nanoparticle exposure include allergenicity, cytotoxicity, and genotoxicity. Nanomaterials may enter the body by interacting with, and eventually crossing, epithelial barriers including skin, airway, and intestinal epithelium. Once […]

THE STATE OF NANO-SIZED TITANIUM DIOXIDE (TIO2) MAY AFFECT SUNSCREEN PERFORMANCE.

In the past several years, there has been a trend in the sunscreen/cosmetics industry to replace micron-sized titanium dioxide (TiO2) particles with nanoscale materials. The increased use of nanoscale TiO2 has resulted in questions about these and other nanoproducts. This study examines the effects of using nanoscale TiO2 on ultraviolet (UV) attenuation in simple to […]

ASSESSMENT OF PENETRATION OF QUANTUM DOTS THROUGH IN VITRO AND IN VIVO HUMAN SKIN USING THE HUMAN SKIN EQUIVALENT MODEL AND THE TAPE STRIPPING METHOD.

Quantum dots (QDs) are rapidly emerging as an important class of nanoparticles (NPs) with potential applications in medicine. However, little is known about penetration of QDs through human skin. This study investigated skin penetration of QDs in both in vivo and in vitro human skin. Using the tape strip- ping method, this study demonstrates for […]

PARTICLE SIZE AND BILAYER RIGIDITY EFFECTS ON SKIN DIFFUSION OF NANOSOMES.

ASSESSMENT OF DERMAL TOXICITY OF NANOSILICA USING CULTURED KERATINOCYTES, A HUMAN SKIN EQUIVALENT MODEL AND AN IN VIVO MODEL.

This study by researchers at Korea University College of Medicine and the National Institute of Toxicological Research (Korea) demonstrated how Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent can be used to test the skin irritation potential of nanosilica and “provided more useful screening data than the conventional cell culture model on the relative […]

IL-18 SECRETION AS A MARKER FOR IDENTIFICATION OF CONTACT SENSITIZERS IN THE EPIDERM IN VITRO HUMAN SKIN MODEL.

Assessment of the allergic potential of chemicals has traditionally been conducted in animal models such as the local lymph node assay (LLNA). However, recent legislation has prohibited the use of animals for conducting such tests on cosmetics or cosmetic ingredients. Thus, animal alternative tests for contact sensitization are urgently needed. Interluekin-18 (IL-18) secretion has recently […]

NAD(P)H:QUINONE REDUCTASE ACTIVITY IN HUMAN EPIDERMAL KERATINOCYTES AND RECONSTRUCTED EPIDERMAL MODELS.

Reconstructed epidermal models may provide a suitable and relevant model for screening compounds such as quinones, which affect the activities of phase I and II enzymes involved in epidermal detoxification. Reconstructed epidermis may also allow the study of the metabolism of topically applied compounds by the phase I and II enzymes. We demonstrate that NAD(P)H:quinone […]

COMPARISON OF ACTIVITIES DEPENDENT ON GLUTATHIONE S-TRANSFERASE AND CYTOCHROME P-450 IA1 IN CULTURED KERATINOCYTES AND RECONSTRUCTED EPIDERMAL MODELS.

There is an increasing need for in vitro testing of compounds for topical application. Reconstructed epidermal models may provide a suitable and relevant model for screening compounds that may affect the activities of phase I and II enzymes involved in epidermal detoxification. In this study, we measured the activity of a phase I enzyme, cytochrome […]

TGF-á REGULATES TLR EXPRESSION AND FUNCTION ON EPIDERMAL KERATINOCYTES.

This study by researchers at the UCLA School of Medicine and the University of Iowa Hospitals and Clinics demonstrated that Mattek’s EpiDerm human skin tissue equivalent can be used to investigate how TGF-á, a growth and differentiation factor present during wound healing and in psoriasis, up-regulates toll-like receptor (TLR) expression and function on keratinocytes, thereby […]

EFFECTS OF CEES ON INFLAMMATORY MEDIATORS, HEAT SHOCK PROTEIN 70A, HISTOLOGY AND ULTRASTRUCTURE IN TWO SKIN MODELS.

Chemical warfare threats require the development of diverse models for the assessment of countermeasures. Human skin products, Skin2 (differentiating keratinocytes on a fibroblast-collagen matrix) and EpiDerm (differentiating keratinocytes) were exposed (2 h) to the sulfur mustard 2-chloroethyl ethyl sulfide (CEES. 1-2 mg l(-1) min(-1)) in humidified air or to humidified air alone. Tissues were evaluated […]

INHIBITION OF CRYSTALLIZATION IN DRUG-IN-ADHESIVE-TYPE TRANSDERMAL PATCHES.

In this study the ability of various additives to inhibit crystallization of two model drugs, captopril and levonorgestrel, in acrylate and silicone adhesives was investigated. Among the various additives tested, PVP was found to be the most effective in inhibiting the crystallization of both drugs. Incorporation of PVP in patches (PVP stabilized patches) allowed incorporation […]

OPTIMISATION OF THE EPIDERM TEST PROTOCOL FOR THE UPCOMING ECVAM VALIDATION STUDY ON IN VITRO SKIN IRRITATION TESTS.

*An ECVAM-funded prevalidation study (PV) was conducted during 1999 and 2000 to identify in vitro tests capable of reliably distinguishing between skin irritants (I) and non-irritants(NI) according to European Union risk phrases (“R38” or no classification). The tests evaluated were EpiDerm™, EPISKIN™, PREDISKIN™, the non-perfused pig ear method, and the mouse skin integrity function test […]

INITIAL CHARACTERIZATION OF A NEW MODEL FOR DERMAL IRRITANCY TESTING.

A model of the human epidermis, EpiDerm™, based on neonatal foreskin-derived normal human epidermal keratinocytes (NHEK) has recently been introduced by Mattek Corporation. Cultured using serum free media in easily handled Millicell® CM (Millipore Corp.) cell culture inserts, the model allows application of liquid and solid test materials (potential dermal irritants) directly to the apical […]

NEW EPIDERMAL MODEL FOR DERMAL IRRITANCY TESTING.

A model of the human epidermis, EpiDerm™, based on neonatal, foreskin-derived normal human epidermal keratinocytes (NHEK) has been developed over the past 18 months at Mattek Corporation. Cultured in easily handled Millicell® CM (Millipore Corp.) cell culture inserts, the model allows application of liquid and solid test materials (potential dermal irritants) directly to the stratum […]

SAFETY TESTING OF REMERGENT™ SKINCARE PRODUCTS.

Remergent products are manufactured by AGI Dermatics under rigorous quality control procedures to ensure safety. Testing begins with the important functional ingredients, which are subjected to the most stringent tests in the industry. The finished Remergent products were subjected to safety testing by two in vitro tests to screen for dermal and ocular irritancy, and […]

PARP-1 ACTIVITY IS INVOLVED IN THE SOLAR UV-INDUCED CUTANEOUS INFLAMMATORY RESPONSE IN THE EPIDERM-FT IN VITRO HUMAN SKIN MODEL.

Poly (ADP-ribose) polymerase 1 (PARP-1) is known to be activated under conditions of genotoxic stress.  In the presence of DNA damage, PARP-1, a nuclear zinc-finger DNA-binding protein, is activated and catalyzes the transfer of ADP-ribose from NAD+ to itself (automodification) and a range of other nuclear proteins (1,2,3).  UV-induced cutaneous inflammation has been demonstrated in […]

RANTES, GRO-α, TNF-α RELEASE FROM IN VITRO EPIDERMIS MODELS FOLLOWING TREATMENT OF STAPHLOCOCCAL ENTEROTOXIN A.

Human skin equivalent cultures are currently being investigated as in vitro models to predict the cytokine expression. The object of the research presented here is to evaluate the production of panel of immunomodulatory cytokines under the Staphylococcus infection and to determine the modulation of these cytokines following exposure to Staphylococcal enterotoxin in the Mattek EpiDerm […]

DIFFERENTIAL REGULATION OF â-DEFENSIN EXPRESSION IN HUMAN SKIN BY MICROBIAL STIMULI.

This study by researchers at UCLA’s David Geffen School of Medicine and Lund University (Sweden) demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent can be used to study the pathways that connect infection and inflammation with the induction of antimicrobial peptides in epithelia. In response to infection, epithelia mount an innate immune response […]

CYTOKINE RELEASE OF A KERATINOCYTE MODEL AFTER INCUBATION WITH TWO DIFFERENT VISCUM ALBUM L EXTRACTS.

This study by researchers at several institutions including the International Institute for Oncological and Immunological Research and the University of California at San Francisco demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent is an excellent in vitro model for measuring the specific pro-inflammatory cytokines released in the skin when exposed to pro-inflammatory compounds, […]

ATTENUATION OF SURFACTANT-INDUCED INTERLEUKIN 1α EXPRESSION BY ZINC PYRITHIONE.

Background: Dandruff is believed to be a fungus-mediated disease which responds to the topical delivery of antifungal agents. Although the primary causative factor is fungus related, distal events include an inflammatory cascade that eventually expresses itself as corneocyte flakes. The most common vehicle for dandruff treatment includes surfactants (i.e. shampoos), which as a chemical group […]

AVOCADO PHYTOSTEROLS DECREASE UVB-INDUCED PRO-INFLAMMATORY MEDIATORS.

Exposure of skin to UVB radiation can cause the production of pro-inflammatory cytokines and prostanoids. Changes in the production of these mediators in the skin can decrease or increase the potentially damaging effects of UVB irradiation. In this series of experiments we investigated the effects of avocado-derived sterols on the production of pro-inflammatory mediators IL-1α, […]

EXPRESSION OF PLACENTA GROWTH FACTOR CYCLOOXYGENASE AND THYMUS-AND ACTIVATION-REGULATED CHEMOKINE IN THE EPIDERM IN VITRO HUMAN SKIN EQUIVALENT.

In vitro skin equivalent models are finding increased utility as tools in basic skin research, safety assessment and product development processes. To further utilization for these purposes, we are currently defining a growing list of physiologically significant molecular endpoints to monitor the effects of experimental treatments on EpiDerm™ in vitro human skin tissue. In the […]

ULTRAVIOLET B RADIATION UPREGULATES THE PRODUCTION OF MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) IN HUMAN EPIDERMAL KERATINOCYTES.

Human epidermal cells are capable of secreting various cytokines with immunologic, inflammatory, and proliferative properties. In a previous study, by reverse transcription-polymerase chain reaction and immunohistochemical analysis, we have shown that human epidermal keratinocytes express macrophage migration inhibitory factor and identified its presence in the cytoplasm. In this study, we detected an increased serum macrophage […]

USE OF EPIDERM™ AS AN INFLAMMATORY MODEL FOR PRE-CLINICAL SCREENING.

Organotypic skin models are becoming widely used by the pharmaceutical and cosmetics industries as an alternative to animal testing for screening cosmetics and potential therapeutics for safety and efficacy. The purpose of this study was to test if Mattek’s EpiDerm organotypic skin model can be induced at the molecular level to initiate an inflammatory response. […]

IL-1-RELATED CYTOKINE RESPONSES OF NONIMMUNE SKIN CELLS SUBJECTED TO CEES EXPOSURE WITH AND WITHOUT POTENTIAL VESICANT ANTAGONISTS.

Sulfur mustard provokes an acute inflammatory response in skin. To determine if keratinocytes regulate this response and whether three potential vesicant antagonists can counteract adverse changes, specimens of EpiDerm™ (Mattek Corp., Ashland, MA), a human skin model of differentiating keratinocytes, were exposed 2 h to humidified air with or without 2-chloroethyl ethyl sulfide (CEES. 1.72-4.73 […]

INJURY-INDUCED INNATE IMMUNE RESPONSE IN HUMAN SKIN MEDIATED BY TRANSACTIVATION OF THE EPIDERMAL GROWTH FACTOR RECEPTOR.

This study by researchers at the UCLA School of Medicine (USA) and Lund University (Sweden) demonstrated that sterile wounding of Mattek’s EpiDerm human skin tissue equivalent initiates an in vivo-like innate immune response that increases resistance to overt infection and microbial colonization. Researchers found that sterile wounding of human skin induced epidermal expression of the […]

IN HUMAN EPIDERMIS, BETA-DEFENSIN 2 IS PACKAGED IN LAMELLAR BODIES.

The skin presents a mechanical, as well as an immunological barrier to infection, and displays considerable innate immune capacity. Recently, cultured human keratinocytes were described to produce and export a microbicidal peptide human-defensin 2 (HBD-2). Immunogold was used to label ultrathin cryosections of stimulated, cultured human epidermis. HBD-2 was found to be stored in the […]

INJURY ENHANCES TLR2 FUNCTION AND ANTIMICROBIAL PEPTIDE EXPRESSION THROUGH A VITAMIN D–DEPENDENT MECHANISM.

This study by researchers at UCSD, UCLA, UCSF, the University of Michigan and Schering AG demonstrated that Mattek’s EpiDerm human skin tissue equivalent can be used to study the effects of vitamin D3 on the human epidermis, specifically on keratinocytes, enabling them to recognize and respond to microbes, and to protect wounds against infection. An […]

RECONSTITUTED 3-DIMENSIONAL HUMAN SKIN AS A NOVEL IN VITRO MODEL FOR STUDIES OF CARCINOGENESIS.

EpiDerm (Mattek Co., MA) is a reconstituted human skin equivalent which exhibits morphological and growth characteristics similar to human skin. This model has previously been utilized to evaluate the cytotoxicity and irritant potential of various cosmetic and household products. In this study, we show for the first time that EpiDerm can be used successfully to […]

STUDIES OF BYSTANDER EFFECTS IN ARTIFICIAL HUMAN 3D TISSUE SYSTEMS USING A MICROBEAM IRRADIATION.

According to the target theory of radiation-induced effects (1), a central tenet of radiation biology, DNA damage occurs during or very shortly after irradiation of the nuclei in targeted cells, and the potential for biological consequences can be expressed within one or two cell generations. A range of evidence has now emerged that challenges the […]

THE EFFECTS OF IL-20 SUBFAMILY CYTOKINES ON RECONSTITUTED HUMAN EPIDERMIS SUGGEST POTENTIAL ROLES IN CUTANEOUS INNATE DEFENSE AND PATHOGENIC ADAPTIVE IMMUNITY IN PSORIASIS.

This study by researchers at Genentech demonstrated that Mattek’s EpiDerm human skin tissue equivalent can be used to study the immunopathology of psoriasis. IL-19, IL-20, IL-22, IL-24, and IL-26 are members of the IL-10 family of cytokines that have been shown to be up-regulated in psoriatic skin. Contrary to IL-10, these cytokines signal using receptor […]

THE COLIPA STRATEGY FOR THE DEVELOPMENT OF IN VITRO ALTERNATIVES: GENOTOXICITY.

This report by the COLIPA Genotoxicity Task Force, comprised of researchers from Wella AG, L’Oreal, Procter & Gamble, Henkel, and Unilever, presents details of a concept developed for testing dermally exposed substances, including the use of Mattek’s EpiDerm human skin tissue equivalent, that will be part of a strategy for replacement of animal genotoxicity experiments. […]

CHARACTERIZATION OF THE EPIDERM™ HUMAN 3-D SKIN MODEL FOR GENOTOXICITY TESTING.

This study by scientists at Procter & Gamble, the Institute for In Vitro Sciences (IIVS) and Mattek Corp. demonstrated that a micronucleus assay based on Mattek’s EpiDerm in vitro human skin tissue equivalent shows great promise as a new genotoxicity test for cosmetic products and their ingredients. To meet the requirements of the EU 7th […]

DEVELOPMENT OF A NOVEL MICRONUCLEUS ASSAY USING THE HUMAN 3-D SKIN MODEL, EPIDERM™.

This study by scientists at Procter & Gamble Co. and the Institute for In Vitro Sciences (IIVS) demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent is an excellent candidate for use in an in vitro micronucleus assay because micronuclei can be reproducibly induced in EpiDerm, the first step in developing a routine “in […]

DEVELOPMENT OF A MICRONUCLEUS ASSAY IN THE EPIDERM HUMAN 3D SKIN MODEL.

This study by scientists at Procter & Gamble Co. and the Institute for In Vitro Sciences (IIVS) demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent is an excellent potential candidate for use in an in vitro micronucleus assay because scientists were able to reliably obtain a reasonably-sized population of binucleated cells. To meet […]

COLIPA VALIDATION OF THE RECONSTRUCTED HUMAN SKIN MICRONUCLEUS ASSAY (RSMN): A NOVEL MICRONUCLEUS ASSAY IN A 3D HUMAN SKIN MODEL.

This COLIPA-funded study by scientists at Procter and Gamble, Henkel AG and Co KGaA, L’Oreal, the Institute for In Vitro Sciences (IIVS), Unilever, Beiersdorf AG, KPSS (Kao Professional Salon Services), GlaxoSmithKline (GSK) and Pierre Fabre demonstrated that Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent, when used as the basis for a human skin […]

ANALYSIS OF IONIZING RADIATION-INDUCED DNA DAMAGE AND REPAIR IN THREE-DIMENSIONAL HUMAN SKIN MODEL SYSTEM.

This study by researchers in the Columbia University College of Physicians and Surgeons Center for Radiological Research demonstrated that Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent and EpiDermFT full-thickness in vitro 3-D human skin tissue equivalent can be used to study the damaging effects to DNA of ionizing radiation exposure. Knowledge of cellular […]

THE DEVELOPMENT OF AN IN VITRO SCREENING STRATEGY FOR TOPICALLY APPLIED PRODUCTS.

The objective of this study was the pharmaco-toxicological understanding of the constituents of an authenticated herbal mixture. The mixture was prepared by maceration in ethanol and subsequent dilution to produce a topically applied lotion, for which the intended target conditions are psoriasis and eczema. A three-tiered in vitro screening strategy was adopted for evaluating this […]

DERMAL PENETRATION AND METABOLISM OF p-AMINOPHENOL AND p-PHENYLENEDIAMINE: APPLICATION OF THE EPIDERM HUMAN RECONSTRUCTED EPIDERMIS MODEL.

This study by scientists at Procter & Gamble Co. demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent showed excellent correlation to in vivo results for skin penetration and metabolism of two hair dye ingredients, further strengthening the evidence for the use of the EpiDerm reconstructed human skin micronucleus assay as a replacement for […]

FURTHER DEVELOPMENT OF A MICRONUCLEUS ASSAY USING THE HUMAN 3-D SKIN MODEL, EPIDERM™.

COMPARATIVE STUDIES ON THE BIOTRANSFORMATION OF BENZO[A]PYRENE IN HUMAN KERATINOCYTES, IN VITRO SKIN MODELS, AND SKIN EX VIVO: METABOLITE PATTERNS AS INDICATOR FOR THE METABOLIC CAPACITY OF SKIN EQUIVALENTS.

In vitro skin models are increasingly important for toxicological testing strategies to facilitate risk assessment and classification of chemicals. The reliability of these tests depends on the capacity of skin equivalents to metabolize xenobiotics in a similar way as found for human skin. So far, studies aimed at characterizing the metabolic competence of in vitro […]

A TIERED APPROACH TO THE USE OF ALTERNATIVES TO ANIMAL TESTING FOR THE SAFETY ASSESSMENT OF COSMETICS: GENOTOXICITY. A COLIPA ANALYSIS.

For the assessment of genotoxic effects of cosmetic ingredients, a number of well-established and regulatory accepted in vitro assays are in place. A caveat to the use of these assays is their relatively low specificity and high rate of false or misleading positive results. Due to the 7th amendment to the EUCosmetics Directive ban on […]

IMPROVING GENOTOXICITY TESTING: COMET ASSAY WITH 3D SKIN MODELS.

This study by scientists at Henkel, ECVAM, TNO, L’Oreal, COLIPA, Procter and Gamble – Cosmital SA, Unilever, Procter and Gamble US, Beiersdorf, KPSS (Kao Professional Salon Services), GlaxoSmithKline (GSK) and Pierre Fabre demonstrated that Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent can be used in a test system of higher biological relevance compared […]

FURTHER DEVELOPMENT OF THE EPIDERM 3D RECONSTRUCTED HUMAN SKIN MICRONUCLEUS (RSMN) ASSAY.

This study by scientists at Procter & Gamble Co., the Institute for In Vitro Sciences (IIVS), Advanced Testing Laboratory and Mattek Corp. demonstrated that an in vitro human reconstructed skin micronucleus assay (RSMN) based on Mattek’s EpiDerm in vitro human skin tissue equivalent has a higher predictive value than currently available in vitro genotoxicity tests. […]

INTRALABORATORY AND INTERLABORATORY EVALUATION OF THE EPIDERM 3D HUMAN RECONSTRUCTED SKIN MICRONUCLEUS (RSMN) ASSAY.

This study by scientists at Procter & Gamble Co., the Institute for In Vitro Sciences (IIVS), Advanced Testing Laboratory and Mattek Corp. demonstrated that an in vitro human reconstructed skin micronucleus assay (RSMN) based on Mattek’s EpiDerm in vitro human skin tissue equivalent exhibited the required intra and interlaboratory reproducibility with tissues produced from cells […]

GENOTOXICITY TESTING USING THE MICRONUCLEUS ASSAY IN THE EPIDERM™ HUMAN 3D SKIN MODEL.

This study by scientists at Procter & Gamble, the Institute for In Vitro Sciences (IIVS), and Mattek Corp. demonstrated that the Micronucleus Assay that utilizes Mattek’s EpiDerm in vitro human skin tissue equivalent with inherent metabolic activity holds excellent promise to predict genotoxicity while avoiding animal welfare issues. Safety assessment of new products for human […]

AUTOMATION AND VALIDATION OF MICRONUCLEUS DETECTION IN THE 3D EPIDERM™ HUMAN RECONSTRUCTED SKIN ASSAY AND CORRELATION WITH 2D DOSE RESPONSES.

Recent restrictions on the testing of cosmetic ingredients in animals have resulted in the need to test the genotoxic potential of chemicals exclusively in vitro prior to licensing. However, as current in vitro tests produce some misleading positive results, sole reliance on such tests could prevent some chemicals with safe or beneficial exposure levels from […]

USE OF THE COMET ASSAY TO DETECT GENOTOXIC EFFECTS IN RECONSTITUTED HUMAN SKIN.

This study by scientists at Procter & Gamble and Wella-Cosmital SA demonstrated that Mattek’s EpiDerm in vitro human tissue equivalent may provide an excellent platform for performing comet (genotoxicity) assays of dermally applied cosmetics and their constituents because EpiDerm is produced from primary (non-transformed) human keratinocytes and it possesses a human skin-like barrier function. Current […]

COLIPA VALIDATION OF THE RECONSTRUCTED HUMAN SKIN MICRONUCLEUS ASSAY (RSMN): FURTHER PRE-VALIDATION STUDIES AND INVESTIGATIONS IN INCREASING TIME EFFICIENCY.

The European Cosmetics Association (COLIPA) has initiated a multi-laboratory project to establish and evaluate more predictive in vitro genotoxicity assays using 3D human tissues as replacements for current mammalian cell in vitro genotoxicity assays, which induce high levels of false positives. The reconstructed skin (RS) model, EpiDermTM, was combined with the micronucleus (MN) and comet […]

THE USE OF 3D SKIN MODELS IN THE MICRONUCLEUS AND COMET ASSAYS: FURTHER PRE-VALIDATION STUDIES AND INVESTIGATIONS INTO INCREASING THROUGHPUT.

The European Cosmetic Association (COLIPA) has initiated a multi-laboratory project to establish and evaluate more predictive in vitro genotoxicity assays using 3D human tissues as replacements for current mammalian cell in vitro genotoxicity assays, which induce high levels of “false” positives. The reconstructed skin (RS) model, EpiDermTM, was combined with the micronucleus (MN) and Comet […]

THE USE OF HUMAN 3D EPIDERMAL MODELS FOR GENOTOXICITY TESTING: RESULTS WITH THE COMET ASSAY.

EU policy, including REACH and the Cosmetics Directive, implies the urgent need for reliable in vitro strategies with regards to the safety evaluation of chemicals. Currently used in vitro assays are not sufficiently suitable to reliably evaluate substances, for example cosmetic ingredients, for which the skin is the primary route of exposure. Therefore, genotoxicity assays […]

THE RECONSTRUCTED SKIN COMET ASSAY SHOWS GOOD INTRA- AND INTER-LABORATORY REPRODUCIBILITY: RESULTS FROM THREE LABORATORIES.

EU policy marks the need for a broad replacement of animal tests in relation to the 7th Amendment to the Cosmetics Directive. For cosmetics ingredients as well as many chemicals, the skin is the main route of exposure. The currently used standard in vitro genotoxicity assays, if used in a test battery approach, show a […]

IN VITRO GENOTOXICITY TESTING USING THE MICRONUCLEUS ASSAY IN CELL LINES, HUMAN LYMPHOCYTES AND 3D HUMAN SKIN MODELS.

The toxicological relevance of the micronucleus (MN) testis well defined: it is a multi-target genotoxic endpoint,assessing not only clastogenic and aneugenic events butalso some epigenetic effects, which is simple to score,accurate, applicable in different cell types. In addition, it ispredictive for cancer, amenable for automation and allowsgood extrapolation for potential limits of exposure orthresholds and […]

THE RECONSTRUCTED SKIN MICRONUCLEUS ASSAY (RSMN) IN EPIDERM™: DETAILED PROTOCOL AND HARMONIZED SCORING ATLAS.

The European Cosmetic Toiletry and Perfumery Association (COLIPA), along with contributions from the European Centre for the Validation of Alternative Methods (ECVAM), initiated a multi-lab international prevalidation project on the reconstructed skin micronucleus (RSMN) assay in EpiDerm™ for the assessment of the genotoxicity of dermally applied chemicals. The first step of this project was to […]

γ-H2AX FORMATION IN THREE-DIMENSIONAL HUMAN SKIN AND CELL MODELS FOLLOWING INVITRO EXPOSURE TO SULFUR MUSTARD.

Sulfur mustard (2-2’-dichlorodiethyl sulfide, SM) is a cytotoxic chemical warfare agent known for its vesicating properties. SM exposure to human tissue results in DNA damage, eventually leading to cell and tissue death. To elucidate the genotoxic effects of SM, the presence of γ-H2AX foci was determined in several skin models. These included normal human epidermal […]

CHARACTERIZATION OF ENZYME ACTIVITIES OF CYTOCHROME P450 ENZYMES, FLAVIN-DEPENDENT MONOOXYGENASES, N-ACETYLTRANSFERASES AND UDP-GLUCURONYLTRANSFERASES IN HUMAN RECONSTRUCTED EPIDERMIS AND FULL-THICKNESS SKIN MODELS.

With the perspective to use human reconstructed skin models for genotoxicity testing which require metabolic activation of xenobiotics, this study aimed to characterize activities of biotransforming enzymes within two human reconstructed skin models, the epidermis model EpiDerm™ (Mattek) and the Phenion_Full-Thickness skin model Phenion_FT (Henkel). According to existing gene expression profiles, Cytochrome P450 (CYP) enzymes, […]

INVESTIGATION OF THE BIOTRANSFORMING CAPACITY OF HUMAN RECONSTRUCTED SKIN MODELS FOR GENOTOXICITY TESTING.

Skin penetration is a route of xenobiotic uptake in the body, however, less information is available about the fate of the penetrated xenobiotic in regard of metabolic turn over. The presence of xenobiotic metabolizing enzymes in skin has previously been shown by transcriptional expression analysis including CYPs, Flavin-dependent monooxygenases (FMO), Alcohol- (ADH) and Aldehyde-Dehydrogenases (ALDH), […]

ANALYSIS OF GLOBAL GENE EXPRESSION PROFILE CHANGES DURING THE DIFFERENTIATION OF THE EPIDERM™ IN VITRO HUMAN SKIN EQUIVALENT.

This study by researchers at Oxford University’s Wellcome Trust Centre for Human Genetics and the Oxford Centre for Gene Function demonstrated how Mattek’s EpiDerm in vitro human skin tissue equivalent can be used to provide a working knowledge of normal (human) epidermal differentiation at the gene level that could prove useful for advancing the understanding […]

CYTOKINE GENE EXPRESSION IN THE Mattek EPIDERM™ CULTURES.

Human skin equivalent cultures are currently being investigated as in vitro models to predict the contact sensitization potential of chemicals. The objective of the research presented here is to evaluate the constitutive expression of a panel of immunomodulatory cytokine genes and to determine the modulation of these genes following exposure to phorbol myristic acetate (PMA) […]

MICROARRAY ANALYSIS OF GENE EXPRESSION FOLLOWING EXPOSURE TO SKIN IRRITANTS.

Understanding of the mechanistic basis of the human skin irritation response is key to the development of relevant in vitro test systems for the predictive identification of skin irritation hazards. Recent progress in genomic technologies means that tools for the identification and investigation of important biochemical events in the processes of skin irritation are now […]

GENE EXPRESSION PROFILE OF TISSUE ENGINEERED SKIN SUBJECTED TO ACUTE BARRIER DISRUPTION.

The main function of the skin is to protect the body from infection, dehydration, and other environmental insults by creating an impermeable barrier of cornified cell layers, the stratum corneum. In contrast to cells in culture, tissue-engineeried skin equivalents contain well-developed basal, spinous, granular, and cornified cell layers providing an excellent model to study the […]

GENOTOXICITY TESTING USING THE NORMAL HUMAN CELL BASED 3D EPITHELIAL MODELS.

Safety assessment of new products for human use requires genotoxicity testing to ensure their non-carcinogenicity. Current in vitro genotoxicity assays have low specificity resulting in unacceptably high rates of false positives. Moreover, starting in 2009, in vivo genotoxicity testing was banned by the 7th Amendment to the Cosmetics Directive. Since epithelial tissues have the highest […]

The Cosmetics Europe strategy for animal-free genotoxicity testing: project status up-date

The Cosmetics Europe (formerly COLIPA) Genotoxicity Task Force has driven and funded three projects to help address the high rate of misleading positives in in vitro genotoxicity tests: The completed “False Positives” project optimized current mammalian cell assays and showed that the predictive capacity of the in vitro micronucleus assay was improved dramatically by selecting […]

COLGATE-PALMOLIVE’S PROGRAM – VALIDATE THE EPlOCULAR HUMAN TISSUE CONSTRUCT MODEL (OCL-200).

The objective of this corporate-based program was to formally validate the EpiOcular™ model’s ability to predict the eye irritation potential of surfactants and surfactant-based formulations, As defined by the Interagency Coordinating Committee on the Validation of Alternative Methods (NIH Publication No.97-3981), a validated method is one for which the reliability and relevance for a specific […]

DEVELOPMENT OF A NEW IN VITRO GENETIC TOXICOLOGY MODEL USING RECONSTRUCTED HUMAN SKIN.

Choosing the Approach: • Procter & Gamble, a major cosmetics company, had excellent genetox personnel and expertise….and the idea to use a reconstructed skin model as a target tissue. • IIVS had extensive experience in using 3D skin models and in developing regulatory compliant in vitro assay systems. • IIVS is a non-profit company with […]

XENOBIOTIC METABOLIZING CAPABILITIES OF THE EPIDERM IN VITRO HUMAN SKIN EQUIVALENT.

This study by scientists at Procter and Gamble, the Institute for In Vitro Sciences (IIVS), and Mattek Corp. demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent possesses numerous in vivo-like Xenobiotic Metabolizing Enzyme (XME) activities and is therefore useful for evaluating the dermal metabolism of drugs, cosmetics and environmental chemicals. The EpiDerm in […]

PROTECTING THE SKIN AGAINST OZONE.

This study by researchers at Arch Personal Care Products and Bioinnovation Laboratories demonstrated that Mattek’s EpiDerm and MelanoDerm in vitro human skin tissue equivalents could be used to prove that topical application of ozone stressed yeast extract protected the EpiDerm tissues against oxidative damage to both DNA and cholesterol, but not to the degradation of […]

IN VITRO SKIN EQUIVALENT MODELS FOR TOXICITY TESTING.

This technical paper by Mattek scientists documented how Mattek’s EpiDerm, EpiDermFT and MelanoDerm in vitro human skin tissue equivalents can be used to assess the safety of topically applied pharmaceutical and cosmetic products. Prior to human use of new cosmetic or therapeutic products, in vivo animal tests are often conducted in order to screen for […]

HIGH-THROUGHPUT IN VITRO MODELS OF HUMAN EPIDERMIS AND OCULAR EPITHELIUM FOR PRECLINICAL SAFETY AND EFFICACY TESTING OF CONSUMER PRODUCTS AND PHARMACEUTICALS.

This study by scientists at Mattek Corp. demonstrated that Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent and Mattek’s EpiOcular in vitro 3-D human corneal tissue equivalent can be produced in a 96-well high-throughput microwell plate format in a highly reproducible manner, enabling the use of this format to help eliminate sample throughput bottlenecks […]

MATTEK’S TISSUE MODELS: NEW DEVELOPMENTS.

Mattek commercially offers three organotypic tissue models for irritancy and mechanistic studies: 1) EpiDerm™, a highly differentiated, keratinocyte-only model of the epidermis, 2) MelanoDerm™, a second generation version of EpiDerm in which functioning melanocytes have been incorporated, and 3) EpiOcular™, a three-dimensional, non-cornified epithelial tissue model which has been useful in predicting ocular irritancy in […]

INITIAL CHARACTERIZATION OF A NEW MODEL FOR OCULAR IRRITANCY TESTING.

A three dimensional, tissue culture construct, EpiDerm-SCA (EpiOcular™), based on neonatal foreskin-derived normal human epidermal keratinocytes (NHEK) is under development by Mattek Corporation. Cultured using serum free media in easily handled Millicell® CM (Millipore Corp.) cell culture inserts, the model allows application of liquid and solid test materials (potential ocular irritants) directly to the apical […]

RETAINING CELL INTEGRITY DURING ORGANOTYPIC MODEL VIABILITY ASSAYS: ALTERNATIVES TO MTT.

This study by researchers at the State University of New York (SUNY) at Stony Brook documents the effort to the develop an alternative tissue viability endpoint analysis using a non-lytic agent (MTS, Alamar Blue or CalceinAM) in place of the industry-standard MTT for Mattek’s EpiAirway in vitro 3-D human tracheal/bronchial tissue equivalent and Mattek’s EpiDerm […]

VALIDATING MTS AS AN ALTERNATIVE VIABILITY ASSAY TO MTT ON THE HUMAN 3-D TISSUE MODELS, EPIAIRWAY AND EPIDERM.

This study by researchers at the State University of New York (SUNY) at Stony Brook documents the development of an alternative tissue viability endpoint analysis using the non-lytic agent MTS in place of the industry-standard MTT for Mattek’s EpiAirway in vitro 3-D human tracheal/bronchial tissue equivalent and Mattek’s EpiDerm in vitro 3-D human skin tissue […]

DISCOVERY OF TRANSDERMAL PENETRATION ENHANCERS BY HIGH-THROUGHPUT SCREENING.

Although transdermal drug delivery is more attractive than injection, it has not been applied to macromolecules because of low skin permeability. Here scientists at UC Santa Barbara describe particular mixtures of penetration enhancers that increase skin permeability to macromolecules (~1-10 kDa) by up to ~100-fold without inducing skin irritation. The discovery of these mixtures was […]

NALTREXONE AND NALTREXONE-3-O-VALERATE DIFFUSION AND BIOCONVERSION IN A HUMAN EPIDERMIS EQUIVALENT.

Transdermal naltrexone delivery may help improve patient compliance in the treatment of narcotic dependence and alcoholism. Lipophilic alkyl ester prodrugs increase the delivery rate of naltrexone across human surgical waste skin in vitro. Human skin equivalent models can be useful tools for assessing epidermal drug metabolism and topical/transdermal prodrug metabolic conversion. The purpose of this […]

BARRIER FUNCTION COMPARISON BETWEEN IN VITRO SKIN, ORAL (BUCCAL), AND OCULAR TISSUE MODELS – IMPLICATIONS FOR DRUG DELIVERY STUDIES.

Purpose: Due to the barrier properties of skin, transdermal delivery of therapeutic compounds is often not feasible. As an alternative, delivery through buccal or gingival tissues has been investigated. The current presentation involves use highly differentiated, in vitro tissue models of the epidermis (EpiDerm™), oral tissue (EpiOral™), and cornea tissue (EpiOcular™). The purpose of this […]

BIOCONVERSION OF NALTREXONE AND ITS 3-O-ALKYL-ESTER PRODRUGS IN A HUMAN SKIN EQUIVALENT.

This study by scientists at the University of Kentucky College of Pharmacy and Mattek Corp. demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent can be used as an alternative experimental system to human skin for the prediction of topical/transdermal drug/prodrug bioconversion. The purpose of this study was to compare the percutaneous absorption and […]

LINKER-BASED LECITHIN MICROEMULSIONS FOR TRANSDERMAL DELIVERY OF LIDOCAINE.

This study by researchers at the University of Toronto demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent is an excellent in vitro alternative for examining the transdermal permeation and cytotoxicity characteristics of novel microemulsions. In this work, researchers at the University of Toronto introduce alcohol-free lecithin microemulsions formulated with linkers to produce transdermal […]

IN VITRO SKIN ABSORPTION AND DRUG RELEASE – A COMPARISON OF SIX COMMERCIAL PREDNICARBATE PREPARATIONS FOR TOPICAL USE.

This study by researchers at the Freie Universitat Berlin and Charite–Universitatsmedizin Berlin demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent is an excellent in vitro model to study the potential skin metabolism of drugs designed to be applied to and/or penetrate human skin. Reconstructed human epidermis is a useful tool for in vitro […]

COMPARISON OF CUTANEOUS BIOAVAILABILITY OF COSMETIC PREPARATIONS CONTAINING CAFFEINE OR ALPHA-TOCOPHEROL APPLIED ON HUMAN SKIN MODELS OR HUMAN SKIN EX VIVO AT FINITE DOSES.

The use of human skin models for performing cutaneous bioavailability studies has been little investigated. For instance, only few studies have been reported on human skin models dealing with vehicle effects on percutaneous penetration. The present study aimed at evaluating the influence on caffeine’s and α-tocopherol’s cutaneous bioavailability of cosmetic vehicles such as a water-in-oil […]

THE COLIPA SKIN METABOLISM PROJECT: DO IN VITRO ALTERNATIVES COMPRISE ADEQUATE DETOXIFICATION CAPACITIES FOR CHEMICAL TESTING IN SKIN?

Background: The aim of this study is to characterize the specific enzymatic activity of Phase I and II detoxification enzymes in human ex vivo skin compared to skin cell-derived in vitro models. Emphasis was here put on the determination of basal enzyme activity. Conclusions: Basal CYP1A, 1B1 and CYP2B activity is below detection limit in […]

INTERNATIONAL PREVALIDATION STUDIES OF THE EPIDERM™ 3D HUMAN RECONSTRUCTED SKIN MICRONUCLEUS (RSMN) ASSAY: TRANSFERABILITY AND REPRODUCIBILITY.

Recently, a novel in vitro reconstructed skin micronucleus (RSMN) assay incorporating the EpiDermTM 3D human skin model (Curren et al., Mutat. Res. 607 (2006) 192–204; Mun et al., Mutat. Res. 673 (2009) 92–99) has been shown to produce comparable data when utilized in three different laboratories in the United States (Hu et al., Mutat. Res. […]

INCREASED HYALURONAN PRODUCTION AND DECREASED E-CADHERIN EXPRESSION BY CYTOKINE-STIMULATED KERATINOCYTES LEAD TO SPONGIOSIS FORMATION.

The pathogenesis of spongiosis, which is a well-known hallmark of acute eczema, is not fully understood. We sought to clarify the mechanism for the influx of tissue fluid into the epidermis and the loss of cohesion between keratinocytes in acute eczema that result in spongiosis. We first demonstrated increased intercellular accumulation of hyaluronan (HA) in […]

Gamma-H2AX AS A BIOMARKER OF DNA DAMAGE INDUCED BY IONIZING RADIATION IN HUMAN PERIPHERAL BLOOD LYMPHOCYTES AND ARTIFICIAL SKIN.

This study by researchers at the National Cancer Institute (USA) demonstrated that Mattek’s EpiDermFT full-thickness in vitro 3-D human skin tissue equivalent is an excellent tissue model for performing experiments that measure the DNA damage caused by exposure to ionizing radiation because the tissue is derived from normal (non-transformed) human keratinocyes and fibroblasts. Ionizing radiation […]

REGULATION OF TIGHT JUNCTION PERMEABILITY BY SODIUM CAPRATE IN HUMAN KERATINOCYTES AND RECONSTRUCTED EPIDERMIS.

This study by researchers at Pola Chemical Industries Inc. and Jikei University School of Medicine used Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent to investigate the effects of a known intestinal tissue tight junction dialator (sodium caprate) on human skin tissue tight junctions. Tight junctions (TJs) restrict paracellular flux of water and solutes […]

THE TRANSPORT PROFILE OF CYTOKINES IN EPIDERMAL EQUIVALENTS SUBJECTED TO MECHANICAL LOADING.

This study by researchers at Eindhoven University of Technology and the University of London demonstrated how Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent can be used to study the use of soft tissue cytokine release as potential biochemical markers for pressure ulcer risk assessment. Pressure ulcer risk assessment might be optimized by incorporating […]

AN IN VITRO MODEL SYSTEM TO STUDY THE DAMAGING EFFECTS OF PROLONGED MECHANICAL LOADING OF THE EPIDERMIS.

This study by scientists at the Eindhoven University of Technology demonstrated that Mattek’s EpiDerm human skin tissue equivalent can be used to improve insight in the epidermal damage process due to prolonged mechanical loading, and can serve as a sound basis for effective clinical identification and prevention of pressure ulcers. Pressure ulcers are areas of […]

SUNSCREEN ENHANCEMENT OF UV-INDUCED REACTIVE OXYGEN SPECIES IN THE SKIN.

This study by scientists at UC Riverside and UC Irvine demonstrated that two-photon fluorescence microscopy can be successfully used to image UV-induced ROS generation in both ex vivo skin and the EpiDerm human skin tissue equivalent. Both types of tissues gave identical results for the experimental protocol used, but the EpiDerm tissues provide the added […]

CHARACTERIZATION OF THE EFFECT OF URINE ON MECHANICALLY INDUCED SKIN DAMAGE.

As stated in the “Conclusions” section, the main experiment in this study by researchers at Eindhoven University of Technology was performed to determine whether urine makes the skin more susceptible for mechanical loading, and that to make this determination, an experimental setup was successfully developed that made use of (Mattek’s) EpiDerm, s-urine and a custom-built […]

CYTOKINE AND CHEMOKINE RELEASE UPON PROLONGED MECHANICAL LOADING OF THE EPIDERMIS.

This study by researchers at the Eindhoven University of Technology and the VU University Medical Center Dept. of Dermatology demonstrated that Mattek’s EpiDerm human epidermal tissue equivalent can be used to study the damage caused by subjecting these epidermal tissues to increasing pressures for 24 hours, and that the resulting epidermal tissue damage could be […]

EXPRESSION OF STRATUM CORNEUM LIPID PATHWAYS IN HUMAN SKIN EQUIVALENT CULTURES.

This study by scientists at Procter & Gamble Beauty demonstrated that gene pathways involved in stratum corneum lipid formation are expressed in Mattek’s EpiDermFT full-thickness in vitro 3-D human skin tissue equivalent, suggesting that ths culture system is an appropriate in vitro approach for studying stratum corneum biology. Human skin equivalent cultures contain living human […]

XENOBIOTIC METABOLISM GENE EXPRESSION IN THE EPIDERM™ IN VITRO 3D HUMAN EPIDERMIS MODEL COMPARED TO HUMAN SKIN.

There is an urgent need to validate in vitro human skin models for use in safety testing. An important component of validation is characterizing the metabolizing capacity of these models. We report comparison of the expression of 139 genes encoding xenobiotic metabolizing enzymes in the EpiDerm™ model and human skin. In microarray analysis, the expression […]

PROTECTIVE EFFECT OF POMEGRANATE-DERIVED PRODUCTS ON UVB-MEDIATED DAMAGE IN HUMAN RECONSTITUTED SKIN.

Solar ultraviolet (UV) radiation, particularly its UVB (290–320 nm) component, is the primary cause of many adverse biological effects including photoageing and skin cancer. UVB radiation causes DNA damage, protein oxidation and induces matrix metalloproteinases (MMPs). Photochemoprevention via the use of botanical antioxidants in affording protection to human skin against UVB damage is receiving increasing […]

TRANSCUTANEOUS IMMUNIZATION USING COMMON CHEMICALS.

Transcutaneous immunization, topical application of vaccines on skin, provides several advantages over needle based immunization. However, simple topical application of vaccines does not generate sufficient immune response due to limited transport of vaccines across the stratum corneum of skin. Here we report that chemicals used in common skin products can enhance the immunogenicity of topically […]

DIFFUSION MEASUREMENTS IN EPIDERMAL TISSUES WITH FLUORESCENT RECOVERY AFTER PHOTOBLEACHING.

Background/Purpose: Pressure ulcers are areas of soft tissue breakdown, resulting from sustained mechanical loading of the skin and underlying tissues. Measuring biochemical markers that are released upon mechanical loading by the epidermis seems a promising method for objective risk assessment of the development of pressure ulcers. This risk assessment method will better determine the risk […]

DYNAMIC AND PHYSICAL CLUSTERING OF GENE EXPRESSION DURING EPIDERMAL BARRIER FORMATION IN DIFFERENTIATING KERATINOCYTES.

The mammalian epidermis is a continually renewing structure that provides the interface between the organism and an innately hostile environment. The keratinocyte is its principal cell. Keratinocyte proteins form a physical epithelial barrier, protect against microbial damage, and prepare immune responses to danger. Epithelial immunity is disordered in many common diseases and disordered epithelial differentiation […]

REINFORCEMENT OF INNATE HOST DEFENSE VIA INDUCTION OF ANTI-MICROBIAL PEPTIDES.

Anti-microbial peptides are an important weapon of the innate immune response arsenal. The large surface area of the skin provides an easy target for microbial colonization. Keratinocytes monitor the surface of the skin for potential hazards. When a potential pathogen is encountered, keratinocytes release anti-microbial peptides. We investigated a battery of substances for inducing NHEKs […]

HUMAN β-DEFENSIN-2 PRODUCTION IN KERATINOCYTES IS REGULATED BY INTERLEUKIN-1, BACTERIA, AND THE STATE OF DIFFERENTIATION.

Intact human epidermis resists invasion by pathogenic microbes but the biochemical basis of its resistance is not well understood. Recently, an antimicrobial peptide, human β-defensin-2, was discovered in inflamed epidermis. We used a recombinant baculovirus/insect cell system to produce human β-defensin-2 and confirmed that at micromolar concentrations it has a broad spectrum of antimicrobial activity, […]

NVC-422: TOWARDS DEVELOPING PRECLINICAL INFECTED TISSUE MODELS.

Background: P. aeruginosa and S. aureus are opportunistic human pathogens implicated in many clinical diseases of the eye and skin, including keratitis and impetigo, respectively. Infection can involve destruction of underlying tissue by toxins to exacerbate tissue damage, leading to erosive disease. Developing infected tissue models provide a platform for assessing antimicrobial efficacy and toxicity […]

ASSESSMENT OF THE IRRITATION POTENTIAL OF TOPICAL SKIN ANTISEPTICS BY IN VIVO AND IN VITRO METHODS.

The development of an in vitro irritation assay producing results which correlate well with those obtained from in vivo animal studies would be a valuable tool for the evaluation of topical products. Human skin equivalent cultures are currently used as in vitro models to predict the topical irritation potential of actives, excipients, and formulations. These […]

INHIBITING THE EFFECTS OF OXIDATIVE STRESS VIA TOPICALLY APPLIED ANTIOXIDANT FORMULATIONS.

VISUALIZATION AND CHARACTERIZATION OF UVB-INDUCED REACTIVE OXYGEN SPECIES IN A HUMAN SKIN EQUIVALENT MODEL.

This study by researchers at Procter and Gamble, Kyoto University and Kyoto Pharmaceutical University demonstrated that Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent is useful for visualizing the production of UVB-induced Reactive Oxygen Species (ROS) in real-time, and for evaluating the efficacy of topically applied anti-oxidative compounds to suppress ROS generation and attenuate […]

REGULATION OF APOPTOSIS BY P53 IN UV-IRRADIATED HUMAN EPIDERMIS, PSORIATIC PLAQUES AND SENESCENT KERATINOCYTES.

This study by researchers at Loyola University Medical Center demonstrated that Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent can be used to study the sensitivity and resistance of human epidermal keratinocytes to apoptosis when exposed to UV radiation. The carcinogenic effects of sunlight in human epidermis may be thwarted by either: transient growth […]

HISTAMINE MAY INDUCE AIRWAY REMODELING THROUGH RELEASE OF EPIDERMAL GROWTH FACTOR RECEPTOR LIGANDS FROM BRONCHIAL EPITHELIAL CELLS

Asthma is a chronic inflammatory disease that is associated with airway remodeling, including hyperplasia of airway epithelial cells and airway smooth muscle cells, and goblet cell differentiation. We wished to address the potential role of histamine, a key biogenic amine involved in allergic reactions, in airway remodeling through the epidermal growth factor receptor (EGFR) pathway. […]

FOLLOW-UP TO THE ECVAM PREVALIDATION STUDY ON IN VITRO TESTS FOR ACUTE SKIN IRRITATION.

The European Centre for the Validation of Alternative Methods (ECVAM) Skin Irritation Task Force was established in 1996, to review the status of the development and validation of alternative tests for skin irritation and corrosion, and to identify appropriate non-animal tests for predicting human skin irritation that were sufficiently well-developed to be prevalidated and validated […]

DC DETOXDEFENSE™ STIMULATES SKIN’S OWN SOD ANTIOXIDANT PROTECTION AND DETOXIFICATION.

Objective: The objective of this experiment was to determine whether the results previously obtained DC Detoxdefense in enzymatic and cell-based assays are corroborated by modulation of gene expression in EpiDerm human skin substitute model. Methods: EpiDerm tissues were obtained from Mattek (Ashland, MA) and cultured according to the manufacturer’s instructions. The test materials – Upregulex […]

ANTIOXIDANT CAPACITY OF 3D HUMAN SKIN EPIDERM MODEL: EFFECTS ON SKIN MOISTURIZERS.

This study by researchers at North Dakota State University, the University of North Dakota and the Plastic Surgery Institute demonstrated how Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent can be used to better understand the mechanisms of the effects of skin moisturizers containing antioxidant ingredients on skin function at the tissue level, and […]

USE OF EPIDERM FULL THICKNESS TISSUE FOR ANTI-AGING STUDIES.

This study by scientists at Arch Personal Care Products demonstrated that Mattek’s EpiDermFT full-thickness in vitro human skin tissue equivalent can be used to measure the effect of a new topically applied formulation on the elastin content in human skin’s extracellular matrix. Mattek’s EpiDerm and EpiOcular in vitro tissues were also used to show this […]

UNDERSTANDING METABOLIC PATHWAYS FOR SKIN ANTI-AGING.

Global gene expression profiling provides a useful means to identify key aspects of the skin aging process, and provides Information to help develop new skin technologies. Important aspects of skin aging that can be addressed Include skin hydration, barrier, matrix, pigmentation and antioxidant capacity. Human skin equivalent cultures allow topical application of test compounds, combinations […]

IN VITRO SCREENING TECHNIQUES IN DERMATOLOGY.

To avoid skin irritation and allergies from cosmetic products, the raw materials should be screened during product development. In vivo screening techniques are best. The author describes two in vitro models (cell culture and living skin equivalent) and several in vitro tests (percutaneous absorption, toxicity, melanogenesis, wound healing, antiaging, and cell proliferation and differentiation).

BY IL-1 SIGNALING, MONOCYTE-DERIVED CELLS DRAMATICALLY ENHANCE THE EPIDERMAL ANTIMICROBIAL RESPONSE TO LIPOPOLYSACCHARIDE.

Epithelia react to microbial pathogens by mounting a defensive response that includes the production of antimicrobial peptides. In this study, we show that, in human epidermal cultures, Escherichia coli LPS was a very weak direct inducer of human β-defensin (HBD)-2 mRNA and peptide, but the induction was greatly amplified when monocyte-derived cells (MoDeC) acted as […]

DEVELOPMENT OF A NEW RECONSTRUCTED HUMAN EPIDERMIS (RHE)-BASED SCREENING ASSAY FOR CONTACT ALLERGENS.

Recent changes in regulatory restrictions and social views against animal testing called for the development of reliable in vitro tests for predicting skin sensitizing potential of a broad range of cosmetic raw materials. Also, many of these raw materials include lipophilic compounds and complex mixtures, which could be out of the applicability domain for known […]

IN VITRO PERCUTANEOUS ABSORPTION USING THE Mattek EPI-606X SKIN CONSTRUCT AND HUMAN SKIN.

The rates of absorption of chemicals in human skin can be modeled in the in vitro percutaneous absorption assay. Moreover, the impact of various vehicles on the permeation rates of chemicals can also be evaluated. The reference material, benzoic acid (BA), was prepared in two vehicles (acetone and petrolatum) and was tested in duplicate trials […]

ASSESSMENT OF HUMAN CADAVER AND RECONSTRUCTED SKIN MODELS TO PREDICT PHARMACOKINETICS OF TESTOSTERONE TRANSDERMAL DRUG DELIVERY PATCHES.0

Testosterone TDD patches were compared for in-vitro skin permeation characteristics and in the clinic for in-vivo pharmacokinetic parameters. In-vitro evaluations were conducted using both human cadaver and reconstructed skin models in order to determine a model predictive of in-vivo delivery. HCS was chosen at the model most predictive of testosterone in-vivo delivery. The preliminary IVIVC […]

INTERRELATION OF PERMEATION AND PENETRATION PARAMETERS OBTAINED FROM IN VITRO EXPERIMENTS WITH HUMAN SKIN AND SKIN EQUIVALENTS.

In a comparative study, two different in vitro cutaneous test systems were examined: (1) The Franz diffusion cell (FD-C), a test system to study drug permeation through the skin and to obtain data like steady state flux and lag time as well as permeability and diffusion coefficients. (2) The Saarbruecken penetration model (SB-M), a test […]

COMPARISON OF CUTANEOUS BIOAVAILABILIY OF COSMETIC PREPARATIONS CONTAINING CAFFEINE OR α-TOCOPHEROL APPLIED ON HUMAN SKIN MODELS OR HUMAN SKIN EX VIVO AT FINITE DOSES.

The use of human skin models for performing cutaneous bioavailability studies has been little investigated. For instance, only few studies have been reported on human skin models dealing with vehicle effects on percutaneous penetration. The present study aimed at evaluating the influence on caffeine’s and α-tocopherol’s cutaneous bioavailability of cosmetic vehicles such as a water-in-oil […]

TESTING AND IMPROVEMENT OF RECONSTRUCTED SKIN KITS IN ORDER TO ELABORATE EUROPEAN STANDARDS: FIRST RESULTS.

Cosmetics, safety testing, Cutaneous irritancy, Cutaneous irritation, Cutaneous metabolism, Cutaneous toxicity, Cytoplasmic enzymes, Dermal absorption, Dermal irritancy, Dermal irritancy testing, Dermal irritation, Dermal penetration, Dermal permeation, ECVAM, EpiDerm, EpiSkin, European standards, Glutamate-oxaloacetate transferase, Glutathione-S-transferase, IL-1a, Interleukin (IL), Lactate dehydrogenase, Lauric acid, MTT, MTT ET-50 tissue viability assay, MTT assay, Mannitol, Metabolism, NADPH quinone reductase, Penetration, […]

EFFECT OF SIZE AT THE NANOSCALE AND BILAYER RIGIDITY ON SKIN DIFFUSION OF LIPOSOMES.

This study by researchers at Drexel University’s School of Biomedical Engineering and the Dept. of Dermatology and Cutaneous Biology at Jefferson Medical College (Thomas Jefferson Univ.) demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent can be used to determine the permeation characteristics of liposomes by their particle size at the nanoscale level. This […]

APPROACHES FOR THE DEVELOPMENT OF CELL-BASED IN VITRO METHODS FOR CONTACT SENSITIZATION.

Allergic contact dermatitis (ACD) is a cell-mediated immune response to small molecular weight chemicals that contact and penetrate the skin. There are a variety of characteristics that determine whether a chemical can function as a contact sensitizer (or allergen) including the ability to penetrate into the skin, react with protein and be recognized as antigenic […]

CHARACTERIZATION AND EVALUATION OF CD34+ GENERATED LANGERHANS CELLS FOR TISSUE ENGINEERING.

Specialized antigen-presenting cells (APC), particularly Langerhans cells (LC) residing in the skin, mucosa, and lymphoid tissues play a key role in sensitization and other immunological reactions of the body. However, difficulty in harvesting, short survival time in culture, and variability in cytokine production of cultured LC has prevented researchers from widespread use of LC for […]

NORMAL HUMAN DENDRITIC CELLS: A TOOL TO STUDY ALLERGIC AND IMMUNOLOGICAL REACTIONS IN VITRO.

Dendritic cells (DC) or Langerhans cells (LC) are immunological cells of the body which play a key role in allergic reactions and infectious diseases. However, widespread experimental use of DC has not occurred since previously-used methods of harvesting DC directly from tissue result in poor yields, short survival time, and rapid phenotypic changes. Currently, we […]

CYTOKINE AND LIPID MEDIATOR RELEASE FROM IN VITRO SKIN MODELS FOLLOWING DETERGENT TREATMENT OR PHYSICAL WOUNDING.

The purpose of the present work is to characterize two in vitro skin mod-els with regard to release of inflammatory cytokines and lipids under basal conditions and following chemical or physical damage. The two models evaluated are Skin2 (Advanced Tissue Sciences) and EpiDerm (Mattek Corporation). Model tissues were topically treated with SDS or were slice-wounded […]

CYTOKINE RESPONSE OF THE EPIDERM SKIN MODEL TO TOPICALLY APPLIED IRRITANTS AND TOXICANTS.

EpiDerm™, Mattek Corporation’s in vitro reproduction of the human epidermis provides a convenient way in which toxicity and irritation potential of chemicals and physical stresses can be assessed. Derived from single strains of human keratinocytes, the model contains layers of cells which have differentiated into easily recognizable component strata of human epidermis. These include basal, […]

VISUALIZATION OF IONTOPHORETIC TRANSPORT PATHS IN CULTURED AND ANIMAL SKIN MODELS.

Physiological structures associated with iontophoretic paths in hairless mouse skin and two cultured skin models (“EpiDerm” by Mattek, Corp., and “SKIN” by Advanced Tissue Sciences, Inc.) are reported. Visualization of ionic paths at current densities between 20 and 100 uA/cm2 is accomplished by the counterdirectional transport of Fe(CN)64- and Fe3+, resulting in the controlled precipitation […]

THE USE OF RECONSTRUCTED HUMAN EPIDERMIS FOR SKIN ABSORPTION TESTING: RESULTS OF THE VALIDATION STUDY.

This formal validation study by scientists at the Freie Universität Berlin, Across Barriers GmbH, Beiersdorf AG, BASF Aktiengesellschaft, Technische Universität Carolo-Wilhelmina zu Braunschweig, Stiftung Tierärztliche Hochschule Hannover, Ludwig-Maximilians-Universität München, Cognis Deutschland GmbH & Co. KG, Universität des Saarlandes and ZEBET demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent is an appropriate alternative to […]

LOCALIZATION OF β-GLUCOCEREBROSIDASE ACTIVITY IN MAMMALIAN EPIDERMIS BY IN SITU ZYMOGRAPHY.

A critical, late step in epidermal barrier formation is the transformation of secreted lamellar body contents into mature extracellular lamellar unit structures. Although previous studies have demonstrated a crucial role for the enzyme β-glucocerebrosidase (GlcCer’ase) in the final steps of membrane structural maturation, the precise in vivo localization of GCase activity and protein is not […]

ASSESSMENT OF SKIN ABSORPTION AND METABOLISM OF ARACHIDONIC ACID & GLYCERYL ARACHIDONATE USING IN VITRO DIFFUSION CELL TECHNIQUES.

Arachidonic acid (AA), has been used in cosmetics as a surfactant-cleansing and emulsifying agent. Glyceryl arachidonate (GA), a skin conditioning agent and emollient, may be partially metabolized by ester hydrolysis in skin to AA. Based on the Cosmetic Ingredient Review (CIR) Panel’s concern that there was a lack of dermal absorption data for AA, in […]

COMPARISON OF AN IN VITRO HUMAN SKIN EQUIVALENT MODEL TO NORMAL HUMAN SKIN FOR DERMATOLOGICAL RESEARCH.

EpiDerm, an in vitro human skin equivalent (HSE), was compared to normal human breast skin (NHS) to morphologically and biochemically assess its feasibility for dermatological research. Intralot and interlot variability was studied in day 0, 1, 2, and 3 in vitro cultures and in day 0, 3, 5, and 7 NHS. For NHS, light microscopy […]

RECONSTRUCTED HUMAN EPIDERMIS FOR SKIN ABSORPTION TESTING: RESULTS OF THE GERMAN PREVALIDATION STUDY.

This study by scientists at the Freie Universität Berlin, Across Barriers GmbH, BASF Aktiengesellschaft Experimental Toxicology and Ecology, the Institut für Pharmakologie, Ludwig-Maximilians-Universität München, Cognis Deutschland GmbH & Co. KG, Universität des Saarlandes, ZEBET (Berlin, Germany), and Henkel KGaA demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent can be used to predict the […]

INTRA- AND INTER-LOT VARIABILITY OF EPIDERM™, AN EPIDERMAL MODEL FOR DERMAL RESEARCH AND TESTING.

A model of the human epidermis, EpiDerm, cultured from neonatal, nor-mal human epidermal keratinocytes has been sold commercially by Mattek Cor-poration since April 1993. Using serum free media, weekly batches of EpiDerm are produced and shipped for dermal irritancy, product efficacy, percutaneous absorption, and basic skin research studies. For all applications, it is important to […]

RECONSTRUCTED SKIN EQUIVALENTS FOR ASSESSING PERCUTANEOUS DRUG ABSORPTION FROM PHARMACEUTICAL FORMULATIONS.

Excised human skin has so far been considered to be one of the most suitable in vitro methods to evaluate the penetration of dermatologically applied substances. The limited supply and the relatively high donor variability stimulated many research groups to use animal skin as a substitute for human skin. Since nowadays reconstructed skin equivalents are […]

EVALUATION OF HUMAN BIO-ENGINEEREED SKIN EQUIVALENT FOR DRUG PERMEATION STUDIES.

PURPOSE: To test the barrier function of a bio-engineered human skin (BHS) using three model drugs (caffeine, hydrocortisone, and tamoxifen) in vitro. To investigate the lipid composition and microscopic structure of the BHS. METHODS: The human skin substitute was composed of both epidermal and dermal layers, the latter having a bovine collagen matrix. The permeability […]

NEW DRUG DELIVERY SYSTEMS: VALIDATION OF IN VITRO MODELS.

IN VITRO PERMEATION AND IRRITATION OF BENZOYL PEROXIDE – CONTAINING PRODUCTS.

Two in vitro models to measure release of benzoyl peroxide (BPO) from formulations were presented. Franz-type diffusion cells and acetonitrile/water receptor mediums were used in both models. The barrier in one model was silicone sheeting and in the other was cultured human epidermis. The similarity in release profiles, rates of permeation, and diffusion coefficients obtained […]

COMPARISON OF IN VITRO MODELS OF PERCUTANEOUS ABSORPTION.

As part of a Colgate-Palmolive sponsored program to validate an in vitro percutaneous absorption model, three reference materials with extensive in vivo human and in vitro (animal and human) data were evaluated in three in vitro models. The objective of this study was to determine if the results are consistent with data published in the […]

IMPROVEMENT OF THE EXPERIMENTAL SETUP TO ASSESS CUTANEOUS BIOAVAILABILITY ON HUMAN SKIN MODELS: DYNAMIC PROTOCOL.

Human skin models, such as EpiDerm® and Episkin® are not easily mounted into static or dynamic diffusion cells that are commonly used to perform bioavailability studies with human skin ex vivo. For various reasons, such as fragility, small sample size, and other morphological constraints, skin absorption studies with human skin models are often carried out […]

PERMEATION AND SKIN ABSORPTION: REPRODUCIBILITY OF VARIOUS INDUSTRIAL RECONSTRUCTED HUMAN SKIN MODELS.

Human reconstructed skin models could be very useful tools to quantify percutaneous permeation and absorption. Before using such models, the reproducibility in the same batch and/or various batches, i.e. the relevance of the results obtained, must be verified. The reproducibility of 3 industrial models – EpiDerm™, Episkin® and SkinEthic® – was tested regarding the permeation […]

THE INFLUENCE OF COSMETIC PRODUCTS ON THE STRATUM CORNEUM BY INFRARED AND RAMAN SPECTROSCOPY.

The stratum corneum is the outermost layer of the skin and as such represents the decisive barrier between the body and the environment. The combination of horny cells and lamellar lipid layers prevents water loss from the body and protects it against penetration by exogenous substances. For selective investigation of the thin outermost stratum corneum […]

APPLICATION OF A HUMAN SKIN TISSUE CULTURE MODEL IN DERMAL ABSORPTION STUDIES OF 3,3’,4,4-TETRACHLOROBIPHENYL (TCB).

TCB, one of the dioxin-like PCBs, demands much research and regulatory attention. To evaluate an in vitro generated human skin tissue culture model, cutaneous disposition of TCB under different exposure scenarios was investigated. Occlusive or non-occlusive doses of 14C-TCB were applied at 4 or 40 µg/cm2 in different vehicles including acetone, methylene chloride, a water-acetone […]

PERCUTANEOUS PERMEATION OF ZINC FROM NON-WOVEN FABRICS IMPREGNATED WITH ZINC SULFATE MONOHYDRATE FORMULATIONS USING EPIDERM™.

Zinc sulfate monohydrate is a widely used agent in the pharmaceutical industry. It can be applied on the skin in the form of a solution, ointment, or lotion, and recently in the form of non-woven fabrics impregnated with zinc sulfate monohydrate formulations. Topical zinc preparations have been found to accelerate wound healing and relieve chronic […]

LIPID AND ULTRA-STRUCTURAL CHARACTERIZATION OF RECONSTRUCTED SKIN MODEL.

The study aimed at evaluating tissue architecture and quality of the permeability barrier in commercially available reconstructed human skin models; EpiDerm™, SkinEthic™ and Episkin™ in comparison to native tissue. For this purpose, tissue architecture was examined by electron microscopy and epidermal lipid composition was analyzed by HPTLC. Stratum corneum lipid organization was investigated by electron […]

RECONSTRUCTED EPIDERMAL MODELS AS A POSSIBLE ALTERNATIVE TO THE USE OF EXCISED HUMAN SKIN FOR ASSESSING IN VITRO PERCUTANEOUS ABSORPTION.

Until now there is no general guideline to study the penetration of foreign substances into the skin and there are several in vitro models to study topical dermatological dosage forms. Excised human skin has proven to be one of the most suitable models, but because of its limited availability and the high donor rariability it […]

Dermatophytes Activate Skin Keratinocytes via Mitogen-Activated Protein Kinase Signaling and Induce Immune Responses

Dermatophytes cause superficial and cutaneous fungal infections in immunocompetent hosts and invasive disease in immunocompromised hosts. However, the host mechanisms that regulate innate immune responses against these fungi are largely unknown. Here, we utilized commercially available epidermal tissues and primary keratinocytes to assess (i) damage induction by anthropophilic, geophilic, and zoophilic dermatophyte strains and (ii) […]