Development of a mammalian neurosensory full‐thickness skin equivalent and its application to screen sensitizing stimuli

Abstract

Human skin equivalents (HSEs) are an increasingly popular research tool due to limitations associated with animal testing for dermatological research. They recapitulate many aspects of skin structure and function, however, many only contain two basic cell types to model dermal and epidermal compartments, which limits their application. We describe advances in the field skin tissue modeling to produce a construct containing sensory-like neurons that is responsive to known noxious stimuli.Through incorporation of mammalian sensory-like neurons, we were able to recapitulate aspects of the neuroinflammatory response including secretion of substance P and a range of pro-inflammatory cytokines in response to a well-characterized neurosensitizing agent: capsaicin. We observed that neuronal cell bodies reside in the upper dermal compartment with neurites extending toward the keratinocytes of the stratum basale where they exist in close proximity to one another. These data suggest that we are able to model aspects of the neuroinflammatory response that occurs during exposure to dermatological stimuli including therapeutics and cosmetics. We propose that this skin construct can be considered a platform technology with a wide range of applications including screening of actives, therapeutics, modeling of inflammatory skin diseases, and fundamental approaches to probe underlying cell and molecular mechanisms.

First Advanced Bilayer Scaffolds for Tailored Skin Tissue Engineering Produced via Electrospinning and Melt Electrowriting

“…Finally, compared with Alvetex, the MEW design is more porous with better interconnectivity enabling much easier fibroblast penetration, and has better reproducibility. [20,21,25,49]…”

“…[21] Porous scaffolds can be fabricated from either biological material such as collagen, elastin, or hyaluronic acid (either individually or in combination), or from synthetic materials such as polystyrene or poly(𝜖-caprolactone) (PCL). [22][23][24][25] There are several available techniques for creating such scaffolds including electrospinning, [26,27] 3D bioprinting, [28] selfassembly, [29] phase separation, [30] particulate leaching, [31] melt extrusion [32] and gas foaming. [24,33] The scaffold architecture aims to mimic dermal organization as closely as possible, however this is often far from being achieved for many of the techniques.…”

Impact of the Physical Cellular Microenvironment on the Structure and Function of a Model Hepatocyte Cell Line for Drug Toxicity Applications

“…In this study, we describe the enhancement of HepG2 function for drug toxicity screening through 3D culture and probe underlying changes at both gene and protein levels. We utilise a porous, inert, polystyrene scaffold, Alvetex ® (Beltsville, MD, USA), that is routinely used in a wide array of tissue engineering applications [17][18][19][20][21][22][23][24][25][26][27]. This study utilises the mid-pore-size variant, Alvetex ® Strata (average 15 µm), which provides 3D growth cues whilst preventing infiltration, promoting a close cell-cell contact reminiscent of native hepatocytes.…”