The heart-on-a-chip consists of a network of microchannels printed on a layer of polymer. Heart cells are placed within these microchannels to manipulate and observe their behavior.(Image courtesy N. Hanacek/NIST)
GAITHERSBURG, Md.—Researchers at the National Institute of Standards and Technology (NIST) have reportedly taken a major step forward in drug development by developing a tool for building a system known as heart-on-a-chip (HoC). The technology seeks to address the limitations of conventional cardiovascular drug development, which relies heavily on animal testing, according to a release from NIST.
By replicating humanlike models for studying cardiovascular diseases, the HoC system holds the promise of helping to replace animal testing, shortening drug development timelines, and reducing costs. The NIST team’s results were published in Lab on a Chip.
The HoC is a device that mimics the intricate interactions of cells within the heart on a small chip and is part of the larger organ-on-a-chip (OoC) suite. The actual design of the heart-on-a-chip varies, but it is typically a small, transparent or semi-transparent chip consisting of a network of microchannels printed on a layer of polymer. These microchannels are intricately designed to imitate the blood vessels found in the human heart. Researchers place human heart cells within these microchannels to manipulate and observe their behavior. Researchers can independently stimulate them or observe their behavior under different conditions, such as the introduction of a drug, according to the release.
“The heart-on-a-chip is designed to mimic the conditions of a real heart,” said NIST researcher Darwin Reyes, who led the development of this HoC system. “We can manipulate the environment to change stem cells into heart cells and make them contract and relax, as they do in a body to produce a heartbeat,” he said in the release.
The “heart” of the organ-on-a-chip system lies in microfluidics, essentially a miniature plumbing system in which researchers can precisely control and manipulate tiny amounts of liquids. Researchers use microfluidics to create advanced models of organs and tissues on small chips in the lab.
The organ-on-a-chip suite, which includes heart-on-a-chip, helps ensure safer, faster, and more precise drug development. (Image courtesy N. Hanacek/NIST)
The concept of “organ-on-a-chip” extends beyond just the heart. Researchers can create chips that mimic the conditions of various organs, and these chips can even be interconnected to form a multi-organ system. For example, a heart-on-a-chip could be connected to a liver-on-a-chip to simulate how the heart and liver interact in response to certain drugs or medical conditions. This approach is said to provide a more comprehensive understanding of how different organs function together in the human body.
Rethinking animal testing
In traditional drug development, animals are often used as test subjects. However, animal physiology does not perfectly match human physiology. A drug may pass a test on an animal subject but may then fail in human testing. This not only delays the drug testing process but also puts human test subjects at risk of adverse effects from the drug. There is also ongoing debate about the ethical considerations of animal testing.
“The ultimate goal is to, if possible, be able to skip the animal testing altogether,” said Reyes. “This would also shorten the time it takes to test drugs, which would hopefully make the medications cost less.”
In 2022, President Joe Biden signed into law the FDA Modernization Act 2.0. The bill essentially revises the Federal Food, Drug, and Cosmetics Act of 1938, which mandated animal testing for every new drug development protocol. For the past century, the mandate was intended to ensure certain quality and safety standards for drugs and medical devices. But recent advancements in science have begun to offer increasingly viable alternatives to animal testing, including organ-on-a-chip systems, the release said.
Global collaboration for standardizing organ-on-a-chip technology
Developing this new technology is not done in a vacuum. Researchers across the world are working on similar microfluidic devices to usher in a new era of drug development. However, to make this a reality, there’s a need for standardization—establishing consistent guidelines and rules for these technologies. This not only helps in gaining regulatory approvals but also ensures better acceptance in the scientific, industrial, and medical communities. The National Institute of Standards and Technology is an active participant, along with scientific organizations across the globe, in developing standards for this technology.
“The more collaborative research there is outside of what is currently being done and where we’re heading, the better this technology is going to be,” said Reyes.
Expanding horizons beyond cardiovascular focus
While heart-on-a-chip is focused on cardiovascular drug development, the organ-on-a-chip capabilities extend beyond a specific organ. The system can be applied to various cell types, including those relevant to cancer research, according to NIST.
“We are in the test phase of understanding how we can track the movement and aggressiveness of cancer cells in real time,” said Reyes. “Our hope is, in the future, with more testing, the system may be able to provide measurements of cancer cell aggressiveness that could help with diagnosis.”
This new technology, underpinned by rigorous standards, is said to mark an important step toward a future where drug development is characterized by precision, efficiency, and heightened ethical considerations.
Source: NIST.gov
Paper: Derrick Butler and Darwin R. Reyes. Heart-on-a-Chip System: Disease Modeling and Drug Screening Applications. Lab on a Chip. Published online Feb. 6, 2024. DOI: 10.1039/D3LC00829K