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Human Skin Xenografts to Athymic Rodents as a System to Study Toxins Delivered to or Through Skin
Published in Rhoda G. M. Wang, James B. Knaak, Howard I. Maibach, Health Risk Assessment, 2017
Gerald G. Krueger, Lynn K. Pershing
It is intuitive that a very significant advance in clinical medicine would come with the ability to generate an artificial skin in vitro, also referred to as a skin-equivalent. This skin could be transplanted onto human subjects to replace burned skin, cover skin ulcers, or possibly even to correct a disorder inherent to skin. Such skin would, ideally, be non-immunogenic, functional, and persistent or slowly undergo resorption in the transplanted state. Current technology dictates that skin equivalents have an artificial dermis that can be impregnated with fibroblasts and covered with keratinocytes or an artificial barrier. The cellular constituents in such a skin-equivalent can be either allogeneic or, if they can be generated from the patient needing the artificial skin, autologous. In each scenario, there are questions as to the function, survival time, etc. of the artificial skin in the grafted state. Being able to observe such grafts in the in vivo state of the nude rat or mouse has and will answer at least some of the preclinical questions inherent to this technology.24-27
Alternative Methods in Dermatotoxicology
Published in Francis N. Marzulli, Howard I. Maibach, Vade Mecum, 2019
Mary A. Perkins, Michael K. Robinson, Rosemarie Osborne
Development of In Vitro Skin Corrosion Methods Using Normal Human Epidermal Keratinocytel Fibroblast Co-cultures with Stratum Corneum (NHEK/DF-SC). To develop an in vitro model to evaluate skin corrosion, we used the ATS Skin2 (Model ZK1300 and ZK1301) and the EpiDerm model (MatTek Corp.). These three-dimensional skin culture models are commercially available skin equivalent cultures that contain an epidermis, a stratum corneum, and in the case of the Skin2 model, a dermal component. The methods we used to develop the in vitro skin corrosion protocol were previously devised for an in vitro eye irritation assessment for “neat” (undiluted) test materials using the NHEK/DF as a tissue equivalent to rabbit cornea (Osborne et al., 1995). Before use, cultures were removed from shipping agar and placed dermis side down onto filter inserts in 6-well assay plates containing 1 ml/well of assay medium (DMEM) supplemented with serum. Cultures were maintained in a humidified atmosphere at 37°C and 5% CO2 except for brief treatment periods. Fresh assay medium (1 ml/well) was placed under each filter insert. The 24 chemicals screened in the experiments represent a range of skin irritancy potential, from relatively innocuous to severely corrosive materials that cause irreversible damage. Test materials used were reagent grade acids, bases, and other chemicals from Baker, Aldrich, and Sigma and some proprietary product formulations from the Procter & Gamble Company. All other components necessary for tissue culture, including assay and growth media, were supplied with the Skin2 (ATS) or the EpiDerm (MatTek) test kits .
Models for barrier understanding in health and disease in lab-on-a-chips
Published in Tissue Barriers, 2023
J. Ponmozhi, S. Dhinakaran, Dorottya Kocsis, Kristóf Iván, Franciska Erdő
The skin undergoes both intrinsic aging, caused by metabolic processes, and extrinsic aging, caused by environmental factors. However, replicating the intrinsic aging process in vitro is challenging due to its long-term progression. In a recent study, Jeong and colleagues accelerated aging on a full-thickness skin equivalent by applying periodic mechanical stimulation and mimicking the circadian rhythm for 28 days. They developed a full-thickness, three-dimensional skin equivalent by culturing human fibroblasts and keratinocytes and using a flexible skin-on-a-chip. Periodic compressive stress led to a reduction in epidermal layer thickness (as shown in Figure 6), contraction rate, and secretion of Myb, while increased galactosidase gene expression, secretion of reactive oxygen species, and transforming growth were observed. This in vitro aging skin model can be used to accelerate drug development for skin diseases and cosmetics that cannot be tested in animals142.
Revisiting techniques to evaluate drug permeation through skin
Published in Expert Opinion on Drug Delivery, 2021
Vamshi Krishna Rapalli, Arisha Mahmood, Tejashree Waghule, Srividya Gorantla, Sunil Kumar Dubey, Amit Alexander, Gautam Singhvi
Numerous in vitro and ex vivo techniques with human skin equivalents and synthetic membranes fill this void of the challenges above [19,20]. Numerous animal models such as snake, porcine, Guinea pigs, rodents (mice, rats) have been proposed as human skin alternatives and have been employed to assess permeation of the drug through the skin [19,21]. The hamster’s cheek pouch sheds, the snake’s skin, udder of the cow, and porcine ear are mostly used to perform the permeation studies. However, the animal model can overestimate a molecule’s permeability due to variation in thickness of SC, hair density, lipid content, and the layer of corneocytes. The animal skin is a cheap alternative, the drug permeability effect due to variation of age, sex, and race can be investigated [22]. To circumvent the problems associated with animal skin, many synthetic membranes and cultures of living skin equivalent have been developed by scientists. The problem of variability is not encountered with synthetic membranes however these membranes are devoid of lipid perturbation of the human skin [23]. These synthetic polymers fall under the category of non-human skin membranes and do not sufficiently provide information regarding the skin’s complex absorption process. These membranes are more useful for determining the release of the drug from formulation than determining skin diffusion.