Chip, Chip Hurray!

By Anna Lynn Spitzer

Irvine, December 11, 2012 -- Multidisciplinary research and Dr. Steven George fit together like a hand and glove. The UCI engineering professor also is a medical doctor by training – so he has a firm grasp of both worlds.
Last July, George received a prestigious $1 million NIH grant, one of only 17 awarded nationally by the interdisciplinary Tissue Chip for Drug Screening Initiative, which is focused on improving the process for predicting drug safety in humans.
George, director of UCI’s Edwards Lifesciences Center for Advanced Cardiovascular Technology, is an authority in tissue engineering. 

He has assembled an eight-member multidisciplinary team that is building three-dimensional perfused artificial tissue chips that  will mimic the physiology and biology of cardiac and cancer tissues. These engineered microsystems will be used for testing the safety and efficacy of cancer drugs before they are tested in people, and one day they could even replace human clinical trials.

George (left) gathered an eight-member team that includes Hughes (center) and Lee, as well as experts in several other fields. (Photo: Paul Kennedy)

More than 30 percent of promising pharmaceutical treatments, while successful in animal testing, prove toxic in humans. Because the project’s cell-based artificial tissue chips will mimic the response in human organs, they will indicate more accurately potential toxicity in new drugs, vaccines and biologic agents.

Biomedical engineering professor and project participant Abe Lee, who is microfabricating the chips, says the development of new drugs has been cost-prohibitive.

“This holds great potential for the drugs to be tested in automated tissue chips at a fraction of the cost of animal testing, and consequently enhances the ability to predict the efficacy for the next pipeline of new drugs,” he says.
Ultimately, George hopes to combine cancer and cardiac tissue on a single chip. Cardiac side effects often doom new cancer therapies, so “if they’re on the same platform you could see if a certain concentration of an anti-cancer drug is able to kill the cancer without damaging the heart tissue.”
The chips are significantly larger than silicon computer chips – approximately 2 inches by 2 inches. They are made from a polymer called PDMS (poly-dimethyl-siloxide), in which human cells can thrive.
Cardiac cells encased in liquid protein are injected by pipette into micro-compartments on the artificial tissue. The protein is activated with an enzyme, causing it to gel. Tiny micro-channels carry oxygen, sugars and food to the cells; waste products are removed by other fluidic lines, mimicking the body’s circulation.

Drugs can be introduced into the tissue, and researchers can watch and measure the cardiac cells’ reactions. Optical imaging shows the cells expanding and contracting, and can even document arrhythmias.

Molecular biologist Chris Hughes is charged with growing the blood vessels on the chips. “Working with engineers gives us access to enabling technologies – solutions to problems that basic scientists could not otherwise solve,” he says.

“This collaboration allows us to think bigger and not be constrained by what is currently possible; engineers help us to make our ‘thought experiments’ real, enhancing our ability to answer some of the toughest questions in biology.”
George echoes the sentiment. “I think most people will tell you that true breakthroughs happen at the interface of disciplines,” he says. “There are all kinds of examples where [experts from different fields] bring their own expertise to bear on some problem that hasn’t been solved and together they see ways to solve it.”

All three researchers agree that the sophistication of their project demands a multidisciplinary approach. “The difficulty of this project cannot be overstated,” Lee says. “It not only needs cutting-edge microfluidic technology, but knowledge of how to engineer physiological tissue, and how tissues create and synthesize vessels at the molecular scale.

“More importantly, it needs a true cross-fertilization of knowledge [from all] the labs.”

Of the 17 NIH grant awardees, 10 are constructing artificial tissue chips representing separate human organ systems. The other seven awardees are developing stem cells and progenitor cells that could populate the tissue chips. The eventual goal, George says, is a single platform that simulates all 10 systems.
“I think we have the potential to identify organ interactions in human cells that can’t currently be examined,” George says. “This could change our potential to officially identify drugs that are safe and efficacious.”