Device that mimics a human lung
How the lungs function
With every human breath, air enters the lungs, fills microscopic air sacs called alveoli, and transfers oxygen through a thin, flexible, permeable membrane of lung cells into the bloodstream. It is this membrane — a three-layered interface of lung cells, a permeable extracellular matrix, and capillary blood vessel cells — that does the lung’s heavy lifting. Also this lung-blood interface recognizes invaders such as inhaled bacteria or toxins and activates an immune response.
Device that mimics a human lung
Lung-on-a-chip [Photo credit: Felice Frankel.]
Researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University, Harvard Medical School, and Children’s Hospital Boston have created a device, about the size of a rubber eraser, which mimics a living, breathing human lung.
The device called the lung-on-a-chip microdevice has two layers of living tissues — the lining of the lung’s air sacs and the blood vessels that surround them — placed across a porous, flexible boundary. Air is delivered to the lung lining cells, a rich culture medium flows in the capillary channel to mimic blood, and cyclic mechanical stretching mimics breathing. The device was created using a novel microfabrication strategy that uses clear rubbery materials. The strategy was pioneered by Professor George Whitesides at Harvard University. As this lung device is translucent, it provides a window into the inner-workings of the human lung without having to invade a living body.
To determine how well the device replicates the natural responses of living lungs to stimuli, the researchers tested its response to inhaled living E. coli bacteria. They introduced bacteria into the air channel on the lung side of the device and at the same time flowed white blood cells through the channel on the blood vessel side. The lung cells detected the bacteria and, through the porous membrane, activated the blood vessel cells, which in turn triggered an immune response that ultimately caused the white blood cells to move to the air chamber and destroy the bacteria.
The team followed this experiment with a ‘real-world application of the device’. They introduced a variety of nano-scaled particles (a nanometer is one-billionth of a meter) into the air sac channel. Some of these particles exist in commercial products; others are found in air and water pollution. Several types of these nanoparticles entered the lung cells and caused the cells to overproduce free radicals and to induce inflammation. Many of the particles passed through the model lung into the blood channel, and the investigators discovered that mechanical breathing greatly enhanced nanoparticle absorption. Benjamin Matthews, Harvard Medical School assistant professor in the Vascular Biology Program at Children’s Hospital Boston, verified these new findings in mice.
One of the researchers Dan Huh, a Wyss technology development fellow at the Institute, said, “Most importantly, we learned from this model that the act of breathing increases nanoparticle absorption and that it also plays an important role in inducing the toxicity of these nanoparticles.”
Donald Ingber senior author on the study and founding director of Harvard’s Wyss Institute, said, “The ability of the lung-on-a-chip device to predict absorption of airborne nanoparticles and mimic the inflammatory response triggered by microbial pathogens provides proof-of-principle for the concept that organs-on-chips could replace many animal studies in the future. We really can’t understand how biology works unless we put it in the physical context of real living cells, tissues, and organs.”
Applications
The lung-on-a-chip microdevice has the potential to be a valuable tool for testing the effects of environmental toxins, absorption of aerosolized therapeutics, and the safety and efficacy of new drugs. Such a tool may help accelerate pharmaceutical development by reducing the reliance on current models, in which testing a single substance can cost more than $2 million.
Remarks by Ismagilov
Rustem Ismagilov, professor of chemistry at the University of Chicago, who specializes in biochemical microfluidic systems says, “The ability to recreate realistically both the mechanical and biological sides of the in vivo coin is an exciting innovation.” According to Ismagilov, it’s too early to predict how successful this field of research will be. Still, he says “the potential to use human cells while recapitulating the complex mechanical features and chemical microenvironments of an organ could provide a truly revolutionary paradigm shift in drug discovery.”
What next
The researchers now hope to explore the possibility to demonstrate the system’s capability to mimic gas exchange between the air sac and bloodstream, a key function of the lungs.
The Wyss Institute team is also working to build other organ models, such as a gut-on-a-chip, as well as bone marrow and even cancer models. Further, they are exploring the potential for combining organ systems. For example, Ingber is collaborating with Kevin Kit Parker, associate professor at Harvard University’s School of Engineering and Applied Sciences and another Wyss core faculty member, who has created a beating heart-on-a-chip. They hope to link the breathing lung-on-a-chip to the beating heart-on-a-chip. The engineered organ combination could be used to test inhaled drugs and to identify new and more effective therapeutics that lack adverse cardiac side effects.
Source: http://wyss.harvard.edu/viewpressrelease/36/living-breathing-human-lungonachip-a-potential-drugtesting-alternative
(The Wyss Institute for Biologically Inspired Engineering at Harvard University uses Nature’s design principles to create breakthrough technologies that will revolutionize medicine, industry, and the environment. Working as an alliance among Harvard’s Medical School, School of Engineering and Applied Sciences, and Faculty of Arts and Sciences, and in partnership with Beth Israel Deaconess Medical Center, Children’s Hospital Boston, Dana Farber Cancer Institute, University of Massachusetts Medical School, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk, fundamental research that leads to transformative change. By applying biological principles, Wyss researchers are developing innovative new engineering solutions for healthcare, manufacturing, robotics, energy, and sustainable architecture. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances and new startups.)
July 8, 2010