Dr. Nancy Monteiro-Riviere's office is a study in contrasts. While the walls in her office in the College of Veterinary Medicine (CVM) bloom with her children's colorful drawings and love notes, the desk and bookshelves are full of files ominously labeled "Jet Fuels," "Gulf War," and "Chemical Warfare."

Monteiro-Riviere is based in the CVM's Center for Chemical Toxicology Research and Pharmacokinetics, one of the country's top university centers focused on drug delivery through the skin. Her work spotlights absorption of pesticides, industrial chemicals, and pharmaceuticals, as well as the resulting physical effects on the skin itself. The research has become increasingly important in recent years in helping the U.S. military develop antidotes and treatments for soldiers exposed to chemical warfare agents.

 Monteiro-Riviere has been getting under people’s skin as a researcher and teacher at NC State since 1984. As an investigative dermatologist and toxicologist, she uses in vitro models to mimic human skin—cell cultures, flow-through diffusion cells, and flaps of pig skin (a system she and husband Dr. James Riviere developed in 1984). Live pigs provide the most human-like in vivo model, but Monteiro-Riviere is an advocate of replacing, reducing, and refining the use of animals for research where possible. To that end, she leads a team including technicians Al Inman and Lauren Gast in developing a new kind of artificial skin with all the layers and internal structure of living human skin.

"Commercially available 3-D skin culture models have no homogeneous basement membranes or complete barrier—which we need for testing blistering agents—nor do they have melanocytes, Merkel cells, Langerhans cells, dermis, or vascular system," she explains. "And because the product lots vary greatly, it is difficult to use them to reproduce results and standardize among laboratories, let alone extrapolate to humans." Part of the reason lies in the techniques used to culture the skin cells.

Working with industrial engineering professors Ola Harrysson and Denis Cormier and textile chemist Marian McCord, Monteiro-Riviere has designed a biologically and functionally complete skin organ system using advanced tissue engineering techniques. The team has conducted a promising pilot test using piezo-electric "ink-jet" printer technology to spray cells layer by layer onto novel thermo-reversible hydrogel scaffolds to create an anatomically intact and fully functional epidermis and dermis. This skin could be used in percutaneous (through the skin) absorption research or as grafts for burn patients.

With some refinements since the pilot test, the “printer” is ready again to start laying down cells in gels. "The control inherent to the ink-jet technology, coupled with the use of optimized gels allowing incorporation of appropriate substrates, lipids, and growth factors, should allow production of a human-skin-equivalent system," says Monteiro-Riviere. "The ability to mass-produce artificial skin will not only reduce or replace the use of animal skin in research, but also make it easier to screen large numbers of compounds, including those toxic or lethal agents that we could not ethically study in animals."

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