Abstract
Epidermal equivalents prepared with passaged keratinocytes are typically 10–20 μm thick, whereas intact human epidermis is up to 100 μm thick. Our established mathematical model of epidermal homeostasis predicted that the undulatory pattern of the papillary layer beneath the epidermis is a key determinant of epidermal thickness. Here, we tested this prediction by seeding human keratinocytes on polyester textiles with various fiber-structural patterns in culture dishes exposed to air, aiming to develop a more physiologically realistic epidermal model using passaged keratinocytes. Textile substrate with fiber thickness and inter-fiber distance matching the computer predictions afforded a three-dimensional epidermal-equivalent model with thick stratum corneum and intercellular lamellar lipid structure. The basal layer structure was similar to that of human papillary layer. Cells located around the textile fibers were proliferating, as indicated by BrdU and YAP (Yes-associated protein) staining and expression of melanoma-associated chondroitin sulfate proteoglycan. Filaggrin, loricrin, claudin 1 and ZO-1 were all appropriately expressed. Silencing of transcriptional coactivator YAP with siRNA disturbed construction of the three-dimensional structure. Measurement of trans-epidermal water loss (TEWL) indicated that the model has excellent barrier function. Our results support the idea that mathematical modeling of complex biological processes can have predictive ability and practical value.
Highlights
Experimental models of human epidermis are useful research tools for basic studies of skin biology and functional mechanisms, as well as for the development of transdermally administrable medicines and safety testing of cosmetics and other products[1]
Based on the computational predictions of the improved simulation model, we examined whether a full-thickness three-dimensional epidermal-equivalent model that included stratum corneum and intercellular lamellar lipid structure, which are essential for skin barrier function, could be obtained by seeding passaged human keratinocytes on an undulating surface consisting of polyester textile with an appropriate fiber pattern in culture dishes exposed to air
The living layer of epidermis and the stratum corneum in the epidermal model were thickest when we used textile substrate having an undulation pattern whose spatial scale was comparable to that predicted to be most effective by the computer simulation
Summary
Experimental models of human epidermis are useful research tools for basic studies of skin biology and functional mechanisms, as well as for the development of transdermally administrable medicines and safety testing of cosmetics and other products[1]. When we applied sinusoidal modulation of the basement membrane shape and systematically changed the amplitude and wavelength, we found that formation of a thick and stable epidermal structure required basement membrane undulations with large amplitude and short wavelength[6] This result indicated that the undulatory pattern of the papillary layer, which lies at the top of the dermis immediately below the epidermis, is critical for constructing an epidermal model with physiological thickness. Based on the computational predictions of the improved simulation model, we examined whether a full-thickness three-dimensional epidermal-equivalent model that included stratum corneum and intercellular lamellar lipid structure, which are essential for skin barrier function, could be obtained by seeding passaged human keratinocytes on an undulating surface consisting of polyester textile with an appropriate fiber pattern in culture dishes exposed to air. They support the idea that mathematical modeling of complex biological processes can have predictive ability and practical value
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