The gut-on-a-chip mimics complex 3D features of the intestine in a miniaturized form. Here, blue and red liquid is pumped through the device to help visualize the upper and lower microchannels. Image: Wyss Institute for Biologically Inspired Engineering at Harvard University

Researchers at the Wyss Institute for Biologically
Inspired Engineering at Harvard
University have created a
gut-on-a-chip microdevice lined by living human cells that mimics the
structure, physiology, and mechanics of the human intestine—even supporting the
growth of living microbes within its luminal space. As a more accurate
alternative to conventional cell culture and animal models, the microdevice
could help researchers gain new insights into intestinal disorders, such as
Crohn’s disease and ulcerative colitis, and also evaluate the safety and
efficacy of potential treatments. The research findings appear online in Lab on a Chip.

Building on the Wyss Institute’s breakthrough
“Organ-on-Chip” technology that uses microfabrication techniques to
build living organ mimics, the gut-on-a-chip is a silicon polymer device about
the size of a computer memory stick. Wyss Founding Director, Donald Ingber, MD,
PhD, led the research team, which included Postdoctoral Fellow, Hyun Jung Kim,
PhD; Technology Development Fellow, Dan Huh, PhD; and Senior Staff Scientist,
Geraldine Hamilton, PhD. Ingber is also the Judah Folkman Professor of Vascular
Biology at Harvard Medical School and the Vascular Biology Program at
Children’s Hospital Boston, and Professor of Bioengineering at Harvard’s School
of Engineering and Applied Sciences.

The new device mimics complex 3D features of the
intestine in a miniaturized form. Inside a central chamber, a single layer of
human intestinal epithelial cells grows on a flexible, porous membrane,
recreating the intestinal barrier. The membrane attaches to side walls that
stretch and recoil with the aid of an attached vacuum controller. This cyclic
mechanical deformation mimics the wave-like peristaltic motions that move food
along the digestive tract. The design also recapitulates the intestinal
tissue-tissue interface, which allows fluids to flow above and below the
intestinal cell layer, mimicking the luminal microenvironment on one side of
the device and the flow of blood through capillary vessels on the other.

In addition, the researchers were able to grow and
sustain common intestinal microbes on the surface of the cultured intestinal
cells, thereby simulating some of the physiological features important to
understanding many diseases. These combined capabilities suggest that
gut-on-a-chip has the potential to become a valuable in vitro diagnostic tool to better understand the cause and
progression of a variety of intestinal disorders and to help develop safe and
effective new therapeutics, as well as probiotics. The gut-on-a-chip could also
be used to test the metabolism and oral absorption of drugs and nutrients.

“Because the models most often available to us today
do not recapitulate human disease, we can’t fully understand the mechanisms
behind many intestinal disorders, which means that the drugs and therapies we
validate in animal models often fail to be effective when tested in
humans,” said Ingber. “Having better, more accurate in vitro disease models, such as the
gut-on-a-chip, can therefore significantly accelerate our ability to develop
effective new drugs that will help people who suffer from these
disorders.”

Gut-on-a-chip represents the most recent advance in the
Wyss Institute’s portfolio of engineered organ models. The platform technology
was first reported on in Science in June 2010, where a living, breathing, human
lung-on-a-chip was described. That same year, the Wyss received funding from
the National Institutes of Health and the U.S. Food and Drug Administration to
develop a heart-lung micromachine to test the safety and efficacy of inhaled
drugs on the integrated heart and lung function. In September 2011, the Wyss
was awarded a four-year grant from the Defense Advanced Research Projects
Agency to develop a spleen-on-a-chip to treat sepsis, a commonly fatal
bloodstream infection.

Wyss Institute for Biologically Inspired Engineering at Harvard University