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Artificial Intestine Will Help CALS Scientists Engineer Disease-Fighting Gut Bacteria

By Stacey Shackford


CALS professor John March is attempting to transform bacteria in our gut into disease-fighting machines. Now, thanks to two members of his research team, he has a powerful new tool to help: an artificial intestine.

The three-dimensional hydrogel scaffolds developed by Jiajie Yu and Jong Hwan Sung, PhD ’09, will allow scientists to grow cells under realistic physiological conditions, an important breakthrough. Previously, scientists had to rely on two-dimensional cultures or live animal models.

“We knew the flat models weren’t accurate. Cells behave differently in different three-dimensional environments,” says March, an assistant professor of biological and environmental engineering. “This will enable us to better study drug absorptions and interactions between epithelia and bacteria in the intestine.”

Yu and Sung used laser ablation to create a hard plastic mold, then covered it with a softer “sacrificial” mold made from calcium alginate that could be dissolved, leaving a collagen scaffold upon which live cells could be grown. In this way, they avoided damaging the delicate shapes during separation of the molds.

They tested the model by seeding it with human colon carcinoma cells. After being cultured for three weeks, it was covered with finger-like structures mimicking the intestinal villi.

All this was done on a tiny scale, about 1mm high and 200 microns across, visible under a scanning electron microscope. March says scientists had previously managed to fabricate models as small as 1 or 2 microns, but slightly larger sizes—especially those with tricky aspect ratios or curvature—have eluded them.

The technique used to make the models can be applied to create other micro-sized environments, in research disciplines such as tissue engineering, pharmaceutical sciences, and cell biology. And it does not use expensive or complicated equipment required by most microfabrication methods; it can be carried out on a common lab bench or a sterilized biosafety cabinet.

“I think we’ll eventually be able to understand the 3D physical environment of the gastrointestinal tract and other parts of the body much more effectively than we do now,” March says.