Sep.16, 2013

When it comes to responding to chemical, or biological attacks, whether it's the Ebola virus or Sarin and Ricin, doctors need to have effective antidotes ready. To accelerate the development of new therapies, Wake Forest Baptist Medical Center's Institute for Regenerative Medicine is leading a unique $24 million project funded by the U.S. Department of Defense to develop a "body on a chip" that will be used to develop these countermeasures. And Wake Forest Baptist's one-of-a-kind 3-D printer will be used to print the organoids onto the chip.

The goal is to build a tiny human organs and placed on a chip to see how they react to harmful agents during testing and develop potential therapies. This approach has the potential to reduce the need for testing in animals, which is expensive, slow, and has results that aren't always applicable to people.

"What we are trying to do is create small tissues and organs, on a very miniature scale, a mircochip scale," said Dr. Anthony Atala, M.D., institute director and lead investigator on the project. "Miniature lab-engineered, organ-like hearts, lungs, livers and blood vessels – linked together with a circulating blood substitute – will be used both to predict the effects of chemical and biologic agents and to test the effectiveness of potential treatments."

Dr. Atala has been working on growing and regenerating tissues and organs for years. In a 2011 Ted Talk, Dr. Atala demonstrated an early-stage experiment that could someday solve the organ-donor problem: a 3D printer that uses living cells to output a transplantable kidney. Atala said that he and his team were actively designing a printer prototype that would engineer laboratory-grown organs.

The "body on a chip" concept is based on similar accomplishments in the electronics industry. Rather than miniaturizing electronics on a chip, however, researchers are miniaturizing human organs, monitoring devices and laboratory processes.

Wake Forest Baptist's 3D printer will be used to print the tiny organ-like structures that mimic the function of the heart, liver, lung and blood vessels. Placed on a 2-inch (5cm) chip, these structures will be connected to a system of fluid channels and sensors to provide on-line monitoring of individual organs and the overall organ system.

The circulating blood substitute will keep the cells alive and can be used to introduce chemical or biologic agents, as well as potential therapies, into the system. Hollow channels will automatically guide the toxins or therapies that are being evaluated from one tissue to the next and sensors will measure real-time temperature, oxygen levels, PH and other factors.

"If successful, the platforms established under the eX Vivo Capabilities for Evaluation and Licensure (X.C.E.L.) program would significantly decrease the time and cost needed to develop medical countermeasures which would have a direct and positive affect on the ability of the United States government to respond to a chemical or biological attack," said Dr. Clint Florence, acting branch chief of vaccines within the Translational Medical Division at DTRA. "A long-term goal of this research is to explore the potential for this technology to reduce the overall burden of in vivo testing in the development and management of products for human use by accurately predicting human safety, efficacy and pharmacokinetics of candidate Medical Countermeasures (MCMs)."

Wake Forest Baptist will lead the project. Other partners include Brigham and Women's Hospital, University of Michigan, the U.S. Army Edgewood Chemical Biological Center, Morgan State University and the Johns Hopkins Bloomberg School of Public Health.

This will be one of the first efforts to combine several organs in the same device to model the human response to chemical toxins or biologic agents. It is hoped that the system can also identify pre-symptomatic "biomarkers" of exposure and assess the effectiveness of treatment.

 


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