Creating 3-D tissue and its potential for regeneration

Bioprinting technique may provide potential for tissue repair and regenerative medicine

Researchers are one step closer to embedding vascular networks into thick human tissues, which could result in tissue repair and regeneration — and ultimately even replacement of whole organs.

A team at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School for Engineering and Applied Sciences (SEAS) has invented a method for 3-D bioprinting thick vascularized tissue constructs. The vasculature network enables fluids, nutrients, and cell growth factors to be perfused uniformly throughout the tissue.

The advance was reported Monday in the journal Proceedings of the National Academy of Sciences.

“This latest work extends the capabilities of our multi-material bioprinting platform to thick human tissues, bringing us one step closer to creating architectures for tissue repair and regeneration,” says the study’s senior author, Jennifer A. Lewis, who is a Wyss core faculty member and the Hansjörg Wyss Professor of Biologically Inspired Engineering at SEAS.

Printing Vascular Tissue

Printing vessel vasculature is essential for sustaining functional living tissues. Until now, bioengineers have had difficulty building thick tissues, lacking a method to embed vascular networks. Credit: Lewis Lab/ Wyss Institute at Harvard University

In the study, Lewis and her team showed that their 3-D printed, vascularized tissues could thrive and function as living tissue architectures for upwards of six weeks.

To date, scaling up human tissues built of a variety of cell types has been limited by an inability to embed life-sustaining vascular networks. Building on their earlier work, Lewis and her team have now increased the tissue thickness threshold nearly tenfold, setting the stage for future advances in tissue engineering and repair. The method combines vascular plumbing with living cells and an extracellular matrix, enabling the structures to function as living tissues.

As an example of what can be done with the technology, Lewis’ team printed 1-centimeter-thick tissue containing human bone marrow stem cells surrounded by connective tissue. By pumping bone growth factors through supporting vasculature lined with the same endothelial cells found in human blood vessels, the scientists induced the cells to develop into bone cells over the course of one month, according to the study.

“This research will help to establish the fundamental scientific understanding required for bioprinting of vascularized living tissues,” said Zhijian Pei, National Science Foundation program director for the Directorate for Engineering Division of Civil, Mechanical, and Manufacturing Innovation, which funded the project. “Research such as this enables broader use of 3-D human tissues for drug safety and toxicity screening and, ultimately, for tissue repair and regeneration.”

Lewis’ novel 3-D bioprinting method uses a customizable, printed silicone mold to house the printed tissue structure. Inside this mold, layers of vascular channels made of pluronic (a material that liquefies at refrigerator temperature) and living stem cells are interdigitated like locking fingers. A cellular matrix is poured around this structure, and solidifies. The entire device is then refrigerated until the pluronic turns to liquid and is sucked out by a vacuum. This creates channels through which liquid containing endothelial cells, oxygen, nutrients, and growth factors — basically, simulated blood — can flow.

The bioprinted material can be used to create living tissue cultures as well as to drive directed tissue growth such as differentiating stem cells. To achieve a variety of tissue shapes, thicknesses, and composition, the shape of the printed silicone chip can be customized and the printable cellular material can be tuned to include a wide variety of cell types. In other words, this new method creates a fully controllable, living 3-D tissue environment, researchers say.

“Having the vasculature prefabricated within the tissue allows enhanced cell functionality at the deep core of the tissue, and gives us the ability to modulate those cell functions through the use of perfusable substances such as growth factors,” said David Kolesky, a graduate researcher at the Wyss Institute and SEAS and one of the study’s first authors.

“Jennifer and her team are shifting the paradigm in the field of tissue engineering based on their unique bioprinting approach,” said Wyss Institute Director Donald Ingber. “Their ability to build living 3-D vascularized tissues from the bottom up provides a potential way to form macroscale functional tissue replacements that can be surgically connected to the body’s own blood vessels to provide immediate perfusion of these artificial tissues, and thus, greatly increase their likelihood of survival. This would overcome many of the problems that held back tissue engineering from clinical success in the past.”

Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the vascular biology program at Boston Children’s Hospital, and professor of bioengineering at SEAS. In addition to Lewis and Kolesky, other team members on the new study include co-first authors Kimberly Homan, research associate at the Wyss Institute, and Mark Skylar-Scott, postdoctoral fellow at the Wyss Institute.

The work was supported by the National Science Foundation and the Wyss Institute for Biologically Inspired Engineering at Harvard University.

Adapted from a Wyss Institute press release written by Kat J. McAlpine, Wyss Institute Communications.

ORIGINAL: Harvard Gazzette

March 8, 2016

This new material pulls clean drinking water straight out of the air

Daniel Taeger/Shutterstock.com

This could solve a lot of problems.

One of the ways of sourcing drinking water in areas afflicted by drought is by harvesting it from the air, and now a new material developed by scientists in the US could make this tricky feat easier than ever.

Researchers at Harvard University have taken inspiration from a variety of water-collecting traits in different natural species to develop what could be an unrivalled composite system for harvesting and transporting atmospheric H20.

"Everybody is excited about bio-inspired materials research," said chemical biologist Joanna Aizenberg from Harvard's Wyss Institute for Biologically Inspired Engineering. "However, so far, we tend to mimic one inspirational natural system at a time."

Instead, the team's system combines elements from three distinct plant and animal species to create a material that they claim outperforms other synthetic surfaces designed to trap condensation.

According to the researchers, the major challenges in harvesting water from the air lie in controlling the size, speed, and direction of water droplets as they form and flow on a surface. At the core of their solution to this problem, the researchers copy the external bumps of Namib desert beetles, which help the insect to collect water droplets on its shell.

Aizenberg Lab/Harvard SEAS

Scientists already knew that the bumps' hydrophilic (water-attracting) tops and hydrophobic (water-repelling) surroundings helped them collect water, but Aizenberg's team realised that the convex shape of the protrusions themselves might also be able to harvest water too.

Using modelling, the team found that this natural water-trapping mechanism could be enhanced by mimicking the geometry and slopes of cactus spines, which help drive collected droplets down the slopes.

By combining this further with a nano-coating designed to emulate the slippery surfaces of pitcher plants, the material facilitates greater droplet formation as the water beads downwards.

"We experimentally found that the geometry of bumps alone could facilitate condensation," said one of the researchers, Kyoo-Chul Park. "By 

• optimising that bump shape through detailed theoretical modelling and 
• combining it with the asymmetry of cactus spines and 
• the nearly friction-free coatings of pitcher plants, 

we were able to design a material that can collect and transport a greater volume of water in a short time compared to other surfaces."

The tandem effect of the system – together with a technology developed by the researchers called Slippery Liquid-Infused Porous Surfaces – helps the material collect water in ways that could otherwise prove impossible.

"Bumps that are rationally designed to integrate these mechanisms are able to grow and transport large droplets even against gravity and overcome the effect of an unfavourable temperature gradient," the authors write in their paper, published in Nature.

Not only could this technique help to harvest water from the air in areas affected by water shortages, but it could also be of use to enhance condensation in industrial machinery.

"Thermal power plants, for example, rely on condensers to quickly convert steam to liquid water," said one of the team, Philseok Kim. "This design could help speed up that process and even allow for operation at a higher temperature, significantly improving the overall energy efficiency."

With about 1.2 billion people around the world living with water scarcity and two-thirds of the global population experiencing water shortages on a monthly basis, the potential of technology like this could make a huge difference to so many lives.

ORIGINAL: Science Alert

PETER DOCKRILL

7 MAR 2016

http://www.seas.harvard.edu/news/2016/02/pulling-water-from-thin-air

Pulling water from thin air

INSPIRED BY A DESERT BEETLE, CACTUS AND PITCHER PLANT, RESEARCHERS DESIGN A NEW MATERIAL TO COLLECT WATER DROPLETS

February 24, 2016

By Leah Burrows

An array of slippery asymmetric bumps shows a significantly greater volume of water collected at the bottom of the surface compared to the flat slippery surfaces. (Courtesy of the Aizenberg Lab/Harvard SEAS)

Organisms such as cacti and desert beetles can survive in arid environments because they’ve evolved mechanisms to collect water from thin air. The Namib desert beetle, for example, collects water droplets on the bumps of its shell while V-shaped cactus spines guide droplets to the plant’s body.  

As the planet grows drier, researchers are looking to nature for more effective ways to pull water from air. Now, a team of researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering at Harvard University have drawn inspiration from these organisms to develop a better way to promote and transport condensed water droplets.

“Everybody is excited about bioinspired materials research,” said Joanna Aizenberg, the Amy Smith Berylson Professor of Materials Science at SEAS and core faculty member of the Wyss Institute. “However, so far, we tend to mimic one inspirational natural system at a time. Our research shows that a complex bio-inspired approach, in which we marry multiple biological species to come up with non-trivial designs for highly efficient materials with unprecedented properties, is a new, promising direction in biomimetics.”

The new system, described in Nature, is inspired by 

• the bumpy shell of desert beetles, 
• the asymmetric structure of cactus spines and 
• slippery surfaces of pitcher plants. 

The material harnesses the power of these natural systems, plus Slippery Liquid-Infused Porous Surfaces technology (SLIPS) developed in Aizenberg’s lab, to collect and direct the flow of condensed water droplets.

This approach is promising not only for harvesting water but also for industrial heat exchangers.

“Thermal power plants, for example, rely on condensers to quickly convert steam to liquid water,” said Philseok Kim, co-author of the paper and co-founder and vice president of technology at SEAS spin-off SLIPS Technologies, Inc. “This design could help speed up that process and even allow for operation at a higher temperature, significantly improving the overall energy efficiency.”   

The major challenges in harvesting atmospheric water are controlling the size of the droplets, speed in which they form and the direction in which they flow.  

For years, researchers focused on the hybrid chemistry of the beetle’s bumps — a hydrophilic top with hydrophobic surroundings — to explain how the beetle attracted water.  However, Aizenberg and her team took inspiration from a different possibility – that convex bumps themselves also might be able to harvest water.

Time lapse of droplets growing faster on the apex of the bumps compared to a flat region with the same height. (Courtesy of the Aizenberg Lab/Harvard SEAS)

“We experimentally found that the geometry of bumps alone could facilitate condensation,” said Kyoo-Chul Park, a postdoctoral researcher and the first author of the paper.  “By optimizing that bump shape through detailed theoretical modeling and combining it with the asymmetry of cactus spines and the nearly friction-free coatings of pitcher plants, we were able to design a material that can collect and transport a greater volume of water in a short time compared to other surfaces.”

 

Inspired by a cactus spine, asymmetric topography guides the droplet off the bump. (Courtesy of the Aizenberg Lab/Harvard SEAS)

“Without one of those parameters, the whole system would not work synergistically to promote both the growth and accelerated directional transport of even small, fast condensing droplets,” said Park.

“This research is an exciting first step towards developing a passive system that can efficiently collect water and guide it to a reservoir,” said Kim.

This research was supported by the Department of Energy.

Robotic insect mimics Nature's extreme moves

An international team of Seoul National University and Harvard researchers looked to water strider insects to develop robots that jump off water’s surface

(SEOUL and BOSTON) — The concept of walking on water might sound supernatural, but in fact it is a quite natural phenomenon. Many small living creatures leverage water's surface tension to maneuver themselves around. One of the most complex maneuvers, jumping on water, is achieved by a species of semi-aquatic insects called water striders that not only skim along water's surface but also generate enough upward thrust with their legs to launch themselves airborne from it.

In this video, watch how novel robotic insects developed by a team of Seoul National University and Harvard scientists can jump directly off water's surface. The robots emulate the natural locomotion of water strider insects, which skim on and jump off the surface of water. Credit: Wyss Institute at Harvard University

Now, emulating this natural form of water-based locomotion, an international team of scientists from Seoul National University, Korea (SNU), Harvard’s Wyss Institute for Biologically Inspired Engineering, and the Harvard John A. Paulson School of Engineering and Applied Sciences, has unveiled a novel robotic insect that can jump off of water's surface. In doing so, they have revealed new insights into the natural mechanics that allow water striders to jump from rigid ground or fluid water with the same amount of power and height. The work is reported in the July 31 issue of Science.

"Water's surface needs to be pressed at the right speed for an adequate amount of time, up to a certain depth, in order to achieve jumping," said the study's co–senior author Kyu Jin Cho, Associate Professor in the Department of Mechanical and Aerospace Engineering and Director of the Biorobotics Laboratory at Seoul National University. "The water strider is capable of doing all these things flawlessly."

The water strider, whose legs have slightly curved tips, employs a rotational leg movement to aid it its takeoff from the water’s surface, discovered co–senior author Ho–Young Kim who is Professor in SNU's Department of Mechanical and Aerospace Engineering and Director of SNU's Micro Fluid Mechanics Lab. Kim, a former Wyss Institute Visiting Scholar, worked with the study’s co–first author Eunjin Yang, a graduate researcher at SNU's Micro Fluid Mechanics lab, to collect water striders and take extensive videos of their movements to analyze the mechanics that enable the insects to skim on and jump off water's surface.

It took the team several trial and error attempts to fully understand the mechanics of the water strider, using robotic prototypes to test and shape their hypotheses.

"If you apply as much force as quickly as possible on water, the limbs will break through the surface and you won’t get anywhere," said Robert Wood, Ph.D., who is a co–author on the study, a Wyss Institute Core Faculty member, the Charles River Professor of Engineering and Applied Sciences at the Harvard Paulson School, and founder of the Harvard Microrobotics Lab.

But by studying water striders in comparison to iterative prototypes of their robotic insect, the SNU and Harvard team discovered that the best way to jump off of water is to maintain leg contact on the water for as long as possible during the jump motion.

"Using its legs to push down on water, the natural water strider exerts the maximum amount of force just below the threshold that would break the water’s surface," said the study's co-first author Je-Sung Koh, Ph.D., who was pursuing his doctoral degree at SNU during the majority of this research and is now a Postdoctoral Fellow at the Wyss Institute and the Harvard Paulson School.

Mimicking these mechanics, the robotic insect built by the team can exert up to 16 times its own body weight on the water's surface without breaking through, and can do so without complicated controls. Many natural organisms such as the water strider can perform extreme styles of locomotion – such as flying, floating, swimming, or jumping on water – with great ease despite a lack of complex cognitive skills.

From left, Seoul National University (SNU) professors Ho-Young Kim, Ph.D., and Kyu Jin Cho, Ph.D., observe the semi-aquatic jumping robotic insects developed by an SNU and Harvard team. Credit: Seoul National University.

"This is due to their natural morphology," said Cho. "It is a form of embodied or physical intelligence, and we can learn from this kind of physical intelligence to build robots that are similarly capable of performing extreme maneuvers without highly–complex controls or artificial intelligence."

The robotic insect was built using a "torque reversal catapult mechanism" inspired by the way a flea jumps, which allows this kind of extreme locomotion without intelligent control. It was first reported by Cho, Wood and Koh in 2013 in the International Conference on Intelligent Robots and Systems.

For the robotic insect to jump off water, the lightweight catapult mechanism uses a burst of momentum coupled with limited thrust to propel the robot off the water without breaking the water's surface. An automatic triggering mechanism, built from composite materials and actuators, was employed to activate the catapult.

To produce the body of the robotic insect, "pop-up" manufacturing was used to create folded composite structures that self-assemble much like the foldable components that "pop–up" in 3D books. Devised by engineers at the Harvard Paulson School and the Wyss Institute, this ingenious layering and folding process enables the rapid fabrication of microrobots and a broad range of electromechanical devices.

"The resulting robotic insects can achieve the same momentum and height that could be generated during a rapid jump on firm ground – but instead can do so on water – by spreading out the jumping thrust over a longer amount of time and in sustaining prolonged contact with the water's surface," said Wood.

"This international collaboration of biologists and roboticists has not only looked into nature to develop a novel, semi–aquatic bioinspired robot that performs a new extreme form of robotic locomotion, but has also provided us with new insights on the natural mechanics at play in water striders," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D.

Additional co–authors of the study include Gwang–Pil Jung, a Ph.D. candidate in SNU's Biorobotics Laboratory; Sun–Pill Jung, an M.S. candidate in SNU's Biorobotics Laboratory; Jae Hak Son, who earned his Ph.D. in SNU's Laboratory of Behavioral Ecology and Evolution; Sang–Im Lee, Ph.D., who is Research Associate Professor at SNU's Institute of Advanced Machines and Design and Adjunct Research Professor at the SNU's Laboratory of Behavioral Ecology and Evolution; and Piotr Jablonski, Ph.D., who is Professor in SNU's Laboratory of Behavioral Ecology and Evolution.

This work was supported by the National Research Foundation of Korea, Bio–Mimetic Robot Research Center funding from the Defense Acquisition Program Administration, and the Wyss Institute for Biologically Inspired Engineering at Harvard University.

IMAGE AND VIDEO AVAILABLE

###

PRESS CONTACTS

Seoul National University College of Engineering

Kyu Jin Cho, kjcho@snu.ac.kr, +82 10-5616-1703

Wyss Institute for Biologically Inspired Engineering at Harvard University

Kat J. McAlpine, katherine.mcalpine@wyss.harvard.edu, +1 617-432-8266

Harvard University John A. Paulson School of Engineering and Applies Sciences

Leah Burrows, lburrows@seas.harvard.edu, +1 617-496-1351

The Seoul National University College of Engineering (SNU CE) (http://eng.snu.ac.kr/english/index.php) aims to foster leaders in global industry and society. In CE, professors from all over the world are applying their passion for education and research. Graduates of the college are taking on important roles in society as the CEOs of conglomerates, founders of venture businesses, and prominent engineers, contributing to the country's industrial development. Globalization is the trend of a new era, and engineering in particular is a field of boundless competition and cooperation. The role of engineers is crucial to our 21st century knowledge and information society, and engineers contribute to the continuous development of Korea toward a central role on the world stage. CE, which provides enhanced curricula in a variety of major fields, has now become the environment in which future global leaders are cultivated.

The Wyss Institute for Biologically Inspired Engineering at Harvard University (http://wyss.harvard.edu) uses Nature's design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing that are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and formation of new start–ups. The Wyss Institute creates transformative technological breakthroughs by engaging in high risk research, and crosses disciplinary and institutional barriers, working as an alliance that includes Harvard's Schools of Medicine, Engineering, Arts & Sciences and Design, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, Dana–Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, and Charité – Universitätsmedizin Berlin, University of Zurich and Massachusetts Institute of Technology.

The Harvard University John A. Paulson School of Engineering and Applied Sciences (http://seas.harvard.edu) serves as the connector and integrator of Harvard's teaching and research efforts in engineering, applied sciences, and technology. Through collaboration with researchers from all parts of Harvard, other universities, and corporate and foundational partners, we bring discovery and innovation directly to bear on improving human life and society.

ORIGINAL: Wyss Institute

Jul 30, 2015

The Best Design of the Year (Maybe Ever?)

Every year, the Design Museum in London picks a single object and names it the best design of the year. It’s pretty bad sometimes! But this year, the museum picked a winner: A chip that replaces animal test subjects with a complex package of human cells.

It’s called a lung-on-a-chip--a name that is very literally true, lest you think this is simply a computer chip programmed to mimic a lung. It comes from Harvard’s Wyss Institute for Biologically Inspired Engineering, which explains in a great video how it works.

This clear, simple-looking brick of plastic actually contains complex human cells, arranged in a simplified version of the way a lung works: Along the central channels, there’s a lining of human lung cells separated from a lining of capillary blood cells by a porous membrane, just like the air sacs in your lung:

On each side, channels create the flexing movement that an air sac does while you breathe.

In other words, it’s all of the biological complexity of your lungs distilled onto a computer chip.

Scientists can, for example, introduce bacteria to the channels to mimic an infection—and white blood cells in the capillary channel will attack. Or, they can introduce the chemicals you breathe in regularly to mimic air pollution and its affect on your lungs. Or test new medications.

“Bio-inspired micro-devices that mimic whole human organs, such as the lung on a chip, could potentially replace animal testing and bring new therapies to patients faster and at lower cost in the future,” the design team explains in their video. Other labs are working on organs like the heart and even spleen, and Wyss’ ultimate goal is to build ten different organs and link them to create a whole body.

Who do we have to thank for bringing news of the chip to the design world? That would be Paola Antonelli, MoMA’s Senior Curator of Architecture & Design, as Dezeen points out today in its announcement as the award’s media partner. Antonelli not only nominated the chip, she already added it to MoMA’s permanent collection in March, writing on MoMA’s blog:

Esoteric or specialized, perhaps, but universally remarkable in their balance of form, function, and vision, investigations like the Wyss Institute’s Human Organs-on-Chips demonstrate new, radical intersections of synthetic biology and design.

In the past, the Design Museum’s pick have ranged from anodyne at best—a lightbulb, in 2011—to downright tone-deaf, like the jury’s choice of a Zaha Hadid building in Azerbaijan built by a dictatorial regime and named for a president known for his human rights abuses. This year, the jury really turned it around, selecting an object that is not only a brilliant piece of design, but also has the power to end the barbaric practice of animal testing while helping human patients.

Antonelli deserves a lot of credit for caring what’s happening in science, medicine, and technology, and forcing the rest of the design world to broaden insular, myopic field of view to include objects that aren’t just lightbulbs and billion-dollar museums, great though they are. Design—while it won’t save the world—can certainly change it for good.

Contact the author at kelsey@Gizmodo.com.

ORIGINAL: Gizmodo

Kelsey Campbell-Dollaghan
6/23/15