Hayden1, P.J., Petrali22, J.P., Stolper1, G., Hamilton2, T.A., Jackson Jr1, G.R., Wertz3, P.W., Ito4, S., Smith2, W.J., and Klausner1, M. 1MatTek Corp., 200 Homer Avenue, Ashland, MA 01721, USA. 2US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, USA. 3University of Iowa, Iowa City, IA, USA. 4Harvard Medical School, Boston, MA, USA.

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) activity and development of preventive/therapeutic approaches for sulfur mustard pathology. Bis-(beta-chloroethyl) sulfide (Sulfur Mustard) is a potent skin vesicant previously used for chemical warfare. Progress in determination of the mechanistic basis of sulfur mustard pathology, and development of prophylactic and/or therapeutic countermeasures to sulfur mustard exposure has been hampered by lack of physiologically relevant models of human skin. The current work evaluated a newly developed tissue engineered full-thickness human skin model in a completely in vitro approach to investigation of sulfur mustard-induced dermal pathology. The model was first characterized with regard to overall morphology, lipid composition, basement membrane (BM) composition and ultrastructural features that are important targets of SM pathologic activity. Well-developed basement membrane ultrastructural features were observed at the dermal–epidermal junction (DEJ), thus demonstrating successful resolution of a primary deficiency of models previously evaluated for sulfur mustard studies. Studies were then conducted to evaluate histopathological effects of sulfur mustard on the model. Good replication of in vivo effects was observed, including apoptosis of basal keratinocytes (KC) and microblister formation at the dermal-epidermal junction. Tissue engineered skin models with well-developed basement membrane structures thus appear to be useful tools for in vitro mechanistic studies of sulfur mustard vesicant activity and development of preventive/ therapeutic approaches for sulfur mustard pathology.


Acantholysis, Acyl glucosylated ceramide, Alpha-6 integrin, Anchoring fibrils, Apoptosis, Apoptotic cells, Basement membrane, Basement membrane zone, Ceramides, Chemical warfare, Cholesterol, Cholesterol esters, Collagen IV, Collagen VII, Dermal/epidermal junction, EFT-400, EpiDerm-FT, EpiDermFT, Free fatty acids, Glucosphingolipid, Hemidesmosomes, Histopathology, Lamina densa, Laminin, Lipid analysis, Microblister formation, Phospholipids, Pyknotic nuclei, Skin vesicant, Tonofilaments, Triglycerides, Vapor cups, Vesicating (blistering) chemical

Materials Tested

Bis-(beta-chloroethyl) sulfide, Sulfur mustard

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