Stories about: Wyss Institute

The design world’s eyes are on organs-on-chips

Organs-on-chips Museum of Modern Art MoMA London Design Museum exhibit Wyss Institute Vascular Biology
Organs-on-chips on display in New York City’s Museum of Modern Art. (Photo: Wyss Institute at Harvard University)

[Update 5/18/15: According to a Wyss Institute press release, the Design Museum in London has selected the organs-on-chips as the winner of their 2015 Designs of the Year exhibition’s Product category.]

If you’re in New York City in the next few months, pop into the Museum of Modern Art (MoMA) and stop by the “This Is For Everyone: Design For The Common Good” exhibit. There—alongside displays dedicated to the “@” symbol, the pin icon from Google Maps and bricks made from living mushroom roots—you’ll find three small silicone blocks mounted on a wall panel.

Those blocks are actually three of the organs-on-chips developed in the lab of Donald Ingber, MD, PhD, founding director of the Wyss Institute for Biologically Inspired Engineering and a scientist in Boston Children’s Hospital’s Vascular Biology Program.

Earlier this month, MoMA announced its plans to include the chips as part of their exploration of contemporary design in the digital age. In the museum’s eyes, organs-on-chips are more than a way to model disease in a complex, living system—they’re also art.

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A simpler way to measure complex biochemical interactions

DNA nanoswitches electrophoresis Wesley Wong PCMM Wyss Institute
Do you really need complex high-end analytical equipment to study molecular interactions, or will an electrophoresis gel do the trick?

Life teems with interactions. Proteins bind. Bonds form between atoms, and break. Enzymes cut. Drugs attach to cell receptors. DNA hybridizes. Those interactions make the processes of life work, and capturing them has led to many medical advances.

“Determining which molecules interact, and measuring the strength of these interactions is fundamental for many areas of research, from drug discovery to understanding the mechanisms underlying disease,” says Wesley P. Wong, PhD, a biophysicist with Boston Children’s Hospital’s Program in Cellular and Molecular Medicine (PCMM), Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering.

Technologies abound for studying molecular-level interactions quantitatively. But most are complex and expensive, requiring dedicated instruments and specific training on how to prep samples and run the experiments.

Wong and his team, including graduate student Mounir Koussa and postdoctoral fellows Ken Halvorsen, PhD (now at the RNA Institute) and Andrew Ward, PhD, have created an alternative method that democratizes the process. Using electrophoresis gels, found in just about any biomedical laboratory, they’ve developed what they call DNA nanoswitches. These switches let researchers make interaction measurements without complex instruments, at a cost of pennies per sample.

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A biospleen is born

biospleen sepsis Wyss Institute Donald Ingber
The Wyss Institute’s biospleen. (Photos courtesy Wyss Institute)

On a Friday morning a few years ago, a childhood friend of mine walked into his doctor’s office, saying his hip hurt. The pain was pretty severe, and had been getting worse for several days.

By Saturday morning, he was in intensive care, fighting for his life against an overwhelming case of sepsis. He survived, but at a cost: he’s now a quadruple amputee.

It’s people like him—and the other million-plus Americans who develop sepsis every year—that Donald Ingber, MD, PhD, and his team had in mind while developing the biospleen, a device that filters sepsis-causing pathogens from the blood. Announced to the world in September, the biospleen grew out of the organs-on-chips technology that Ingber’s team at the Wyss Institute for Biomedically Inspired Engineering launched commercially this past summer.

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The backstory behind organs-on-chips

Organs-on-chips drug testing drug discovery mechanobiology microfluidics Wyss Institute Vascular Biology Program
(Credit: Wyss Institute)

With the launch this summer of Emulate Inc., organs-on-chips—a disease-modeling platform we’ve covered several times on Vector—made the jump from academic to commercial development.

Though developed at the Wyss Institute for Biologically Inspired Engineering, the chips’ story actually began more than 20 years ago in Boston Children’s Hospital’s Vascular Biology Program (VBP). It’s a story that brings together characters from multiple fields and emerges from one fundamental concept: that mechanical forces are critical to the function and fate of cells, tissues and organs.

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Capturing complexity: Modeling bone marrow on a chip

Bone marrow on a chip organs on chips Wyss Institute Donald Ingber
Microscopic view of the engineered bone with an opening exposing the internal trabecular bony network, overlaid with colored images of blood cells and a supportive vascular network that fill the open spaces in the bone marrow-on-a-chip. (James Weaver, Harvard's Wyss Institute)

We’ve had a lung on a chip, and a gut on a chip. Now researchers at the Wyss Institute for Biologically Inspired Engineering have added another tissue to their list of “organs-on-chips”— devices that mimic in vitro tissues’ in vivo structure and function for pharmaceutical discovery and testing. In a paper published in Nature Methods, a team led by Donald Ingber, MD, PhD, (a member of Boston Children’s Hospital’s Vascular Biology Program and founding director of the Wyss), announced that they have developed “bone marrow-on-a-chip.”

The sheer complexity of the new device sets it apart from the Wyss’s previous organs, reflecting the greater natural complexity of bone marrow.

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The solution to keeping IV lines clear and infection-free? Make them slippery

A slippery coating inspired by the surface of a pitcher plant could help keep IV lines free of bacteria and blood clots. (kleo_marlo/Flickr)

Pick up a piece of IV tubing (should you happen to have one nearby) and run your hand down the length of it. The surface feels pretty smooth, yes?

From the perspective of bacteria and platelets, that same surface is pockmarked with nooks and crannies where they can stick, aggregate and start to form blood clots (in the case of platelets) or hard-to-combat biofilms (in the case of bacteria).

That’s a problem for hospital care. Contaminated central lines (IV lines threaded into deep veins for long periods of time) cause upwards of 41,000 costly and potentially fatal central line-associated bloodstream infections (CLABSIs) in pediatric and adult patients in U.S. hospitals every year. And blood clots can preclude patients, including premature babies, from receiving new lung-protecting treatments because they can’t tolerate anticoagulants.

Both problems may have a single solution. Clinicians in Boston Children’s Department of Newborn Medicine and engineers at Harvard’s Wyss Institute for Biologically Inspired Engineering have collaborated to develop a coating, inspired by pitcher plants, that makes the surfaces of clinical-grade plastics so slippery that platelets and bacteria can’t get a toehold.

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A Goldilocks approach to leaky blood vessels: Not too stiff, but not too loose

Just like Goldilocks wouldn’t eat porridge that was too hot or too cold, blood vessels won't grow properly in tissues that are too stiff or too loose. (Project Gutenberg/Wikimedia Commons)
In the tale Goldilocks and the Three Bears, Goldilocks tries all of the bears’ porridge, chairs and beds, finding that only the little bear’s things were just right. Everything else was a little off for her…too hot or too cold, too hard or too soft and so on.

Similarly, for everything to work as it should in the body, things need to be just right. Blood pressure shouldn’t be too high or too low; organs can’t be too big or too small, etc.

Donald Ingber, MD, PhD, and his lab in Boston Children’s Vascular Biology Program take this “just right” approach when thinking about how organs and tissues are structured. Recently, he and a member of his research staff, Akiko Mammoto, MD, PhD, discovered that by changing the stiffness of the surrounding tissues—not too loose and not too tight— they could keep blood vessels from leaking. Their finding could have real consequences for people with sepsis or other diseases featuring leaky vessels.

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Building a body, one organ chip at a time

It may not look like it, but it's a lung, just in chip form.

They don’t look like much sitting in your hand. A few pieces of clear plastic, each smaller than an Altoids tin, with channels visible inside and holes for plugging tubing into them.

But fill them with cells and treat those cells the right way, and they turn into something amazing: tiny hearts, lungs, guts, kidneys.

They’re “organs on chips,” and they represent what’s probably the most comprehensive effort to date to physically model the functions of whole organs for drug development and disease research.

Developed by a team of biologists and engineers led by Donald Ingber, MD, PhD, a member of Boston Children’s Hospital’s Vascular Biology Program and director of the Wyss Institute for Biologically Inspired Engineering at Harvard, they’re the building blocks for an ambitious project to create an artificial multi-organ system—essentially, a whole body on a chip.

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Putting the squeeze on blood clots to stop a stroke

Blood should flow through an artery like water through a hose. The stress of a blockage can encourage clots to form, potentially resulting in a heart attack or stroke. Donald Ingber thinks the same forces could be used to help dissolve clots. (Beth Kingery/Flickr)

Grab a garden hose. Put your thumb over the end, but not all the way, and turn the water on. What happens? The water coming out of the hose gets squeezed as it tries to push past your thumb, putting a lot of force on the molecules in the water and making a big spray.

Now do the same thing with an artery: Partially block it with a clot and let blood flow through it. In this case, the force you’ve created in the artery could be lethal—creating fertile ground for blood clots that could lead to a stroke or heart attack.

But what if that combination of force and pressure could be used to stop something like a stroke instead? What if it could release a clot-dissolving drug on the spot? Donald Ingber, MD, PhD, a member of Boston Children’s Hospital’s Vascular Biology Program, had wondered that for many years. To find out, Ingber, who also directs the Wyss Institute for Biologically Inspired Engineering at Harvard, had his team start with a simple question: How do clots form?

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