Tag Archives: Harvard University School of Engineering and Applied Sciences (SEAS)

A nano fabrication technique used to create next generation heart valve

I am going to have take the researchers’ word that these somehow lead to healthy heart valve tissue,

In rotary jet spinning technology, a rotating nozzle extrudes a solution of extracellular matrix (ECM) into nanofibers that wrap themselves around heart valve-shaped mandrels. By using a series of mandrels with different sizes, the manufacturing process becomes fully scalable and is able to provide JetValves for all age groups and heart sizes. Credit: Wyss Institute at Harvard University

From a May 18, 2017 news item on ScienceDaily,

The human heart beats approximately 35 million times every year, effectively pumping blood into the circulation via four different heart valves. Unfortunately, in over four million people each year, these delicate tissues malfunction due to birth defects, age-related deteriorations, and infections, causing cardiac valve disease.

Today, clinicians use either artificial prostheses or fixed animal and cadaver-sourced tissues to replace defective valves. While these prostheses can restore the function of the heart for a while, they are associated with adverse comorbidity and wear down and need to be replaced during invasive and expensive surgeries. Moreover, in children, implanted heart valve prostheses need to be replaced even more often as they cannot grow with the child.

A team lead by Kevin Kit Parker, Ph.D. at Harvard University’s Wyss Institute for Biologically Inspired Engineering recently developed a nanofiber fabrication technique to rapidly manufacture heart valves with regenerative and growth potential. In a paper published in Biomaterials, Andrew Capulli, Ph.D. and colleagues fabricated a valve-shaped nanofiber network that mimics the mechanical and chemical properties of the native valve extracellular matrix (ECM). To achieve this, the team used the Parker lab’s proprietary rotary jet spinning technology — in which a rotating nozzle extrudes an ECM solution into nanofibers that wrap themselves around heart valve-shaped mandrels. “Our setup is like a very fast cotton candy machine that can spin a range of synthetic and natural occurring materials. In this study, we used a combination of synthetic polymers and ECM proteins to fabricate biocompatible JetValves that are hemodynamically competent upon implantation and support cell migration and re-population in vitro. Importantly, we can make human-sized JetValves in minutes — much faster than possible for other regenerative prostheses,” said Parker.

A May 18,2017 Wyss Institute for Biologically Inspired Engineering news release (also on EurekAlert), which originated the news item, expands on the theme of Jetvalves,

To further develop and test the clinical potential of JetValves, Parker’s team collaborated with the translational team of Simon P. Hoerstrup, M.D., Ph.D., at the University of Zurich in Switzerland, which is a partner institution with the Wyss Institute. As a leader in regenerative heart prostheses, Hoerstrup and his team in Zurich have previously developed regenerative, tissue-engineered heart valves to replace mechanical and fixed-tissue heart valves. In Hoerstrup’s approach, human cells directly deposit a regenerative layer of complex ECM on biodegradable scaffolds shaped as heart valves and vessels. The living cells are then eliminated from the scaffolds resulting in an “off-the-shelf” human matrix-based prostheses ready for implantation.

In the paper, the cross-disciplinary team successfully implanted JetValves in sheep using a minimally invasive technique and demonstrated that the valves functioned properly in the circulation and regenerated new tissue. “In our previous studies, the cell-derived ECM-coated scaffolds could recruit cells from the receiving animal’s heart and support cell proliferation, matrix remodeling, tissue regeneration, and even animal growth. While these valves are safe and effective, their manufacturing remains complex and expensive as human cells must be cultured for a long time under heavily regulated conditions. The JetValve’s much faster manufacturing process can be a game-changer in this respect. If we can replicate these results in humans, this technology could have invaluable benefits in minimizing the number of pediatric re-operations,” said Hoerstrup.

In support of these translational efforts, the Wyss Institute for Biologically Inspired Engineering and the University of Zurich announced today a cross-institutional team effort to generate a functional heart valve replacement with the capacity for repair, regeneration, and growth. The team is also working towards a GMP-grade version of their customizable, scalable, and cost-effective manufacturing process that would enable deployment to a large patient population. In addition, the new heart valve would be compatible with minimally invasive procedures to serve both pediatric and adult patients.

The project will be led jointly by Parker and Hoerstrup. Parker is a Core Faculty member of the Wyss Institute and the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). Hoerstrup is Chair and Director of the University of Zurich’s Institute for Regenerative Medicine (IREM), Co-Director of the recently founded Wyss Translational Center Zurich and a Wyss Institute Associate Faculty member.

Since JetValves can be manufactured in all desired shapes and sizes, and take seconds to minutes to produce, the team’s goal is to provide customized, ready-to-use, regenerative heart valves much faster and at much lower cost than currently possible.

“Achieving the goal of minimally invasive, low-cost regenerating heart valves could have tremendous impact on patients’ lives across age-, social- and geographical boundaries. Once again, our collaborative team structure that combines unique and leading expertise in bioengineering, regenerative medicine, surgical innovation and business development across the Wyss Institute and our partner institutions, makes it possible for us to advance technology development in ways not possible in a conventional academic laboratory,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at SEAS.

This scanning electron microscopy image shows how extracellular matrix (ECM) nanofibers generated with JetValve technology are arranged in parallel networks with physical properties comparable to those found in native heart tissue. Credit: Wyss Institute at Harvard University

Here’s a link to and a citation for the paper,

JetValve: Rapid manufacturing of biohybrid scaffolds for biomimetic heart valve replacement by Andrew K. Capulli, Maximillian Y. Emmert, Francesco S. Pasqualini, b, Debora Kehl, Etem Caliskan, Johan U. Lind, Sean P. Sheehy, Sung Jin Park, Seungkuk Ahn, Benedikt Webe, Josue A. Goss. Biomaterials Volume 133, July 2017, Pages 229–241  https://doi.org/10.1016/j.biomaterials.2017.04.033

This paper is behind a paywall.

Graphene like water

This is graphene research from Harvard University and Raytheon according to a Feb. 11, 2016 news item on phys.org (Note: Links have been removed),

It’s one atom thick [i.e., two-dimensional], stronger than steel, harder than diamond and one of the most conductive materials on earth.

But, several challenges must be overcome before graphene products are brought to market. Scientists are still trying to understand the basic physics of this unique material. Also, it’s very challenging to make and even harder to make without impurities.

In a new paper published in Science, researchers at the [sic] Harvard and Raytheon BBN Technology have advanced our understanding of graphene’s basic properties, observing for the first time electrons in a metal behaving like a fluid.

A Feb. 11, 2016 Harvard University press release by Leah Burrows (also on EurekAlert), which originated the news item, provides more detail,

In order to make this observation, the team improved methods to create ultra-clean graphene and developed a new way measure its thermal conductivity. This research could lead to novel thermoelectric devices as well as provide a model system to explore exotic phenomena like black holes and high-energy plasmas.

An electron super highway

In ordinary, three-dimensional metals, electrons hardly interact with each other. But graphene’s two-dimensional, honeycomb structure acts like an electron superhighway in which all the particles have to travel in the same lane. The electrons in graphene act like massless relativistic objects, some with positive charge and some with negative charge. They move at incredible speed — 1/300 of the speed of light — and have been predicted to collide with each other ten trillion times a second at room temperature.  These intense interactions between charge particles have never been observed in an ordinary metal before.

The team created an ultra-clean sample by sandwiching the one-atom thick graphene sheet between tens of layers of an electrically insulating perfect transparent crystal with a similar atomic structure of graphene.

“If you have a material that’s one atom thick, it’s going to be really affected by its environment,” said Jesse Crossno, a graduate student in the Kim Lab [Philip Kim, professor of physics and applied physics] and first author of the paper.  “If the graphene is on top of something that’s rough and disordered, it’s going to interfere with how the electrons move. It’s really important to create graphene with no interference from its environment.”

The technique was developed by Kim and his collaborators at Columbia University before he moved to Harvard in 2014 and now have been perfected in his lab at SEAS [Harvard School of Engineering and Applied Sciences].

Next, the team set up a kind of thermal soup of positively charged and negatively charged particles on the surface of the graphene, and observed how those particles flowed as thermal and electric currents.

What they observed flew in the face of everything they knew about metals.

A black hole on a chip

Most of our world — how water flows or how a curve ball curves —  is described by classical physics. Very small things, like electrons, are described by quantum mechanics while very large and very fast things, like galaxies, are described by relativistic physics, pioneered by Albert Einstein.

Combining these laws of physics is notoriously difficult but there are extreme examples where they overlap. High-energy systems like supernovas and black holes can be described by linking classical theories of hydrodynamics with Einstein’s theories of relativity.

But it’s difficult to run an experiment on a black hole. Enter graphene.

When the strongly interacting particles in graphene were driven by an electric field, they behaved not like individual particles but like a fluid that could be described by hydrodynamics.

“Instead of watching how a single particle was affected by an electric or thermal force, we could see the conserved energy as it flowed across many particles, like a wave through water,” said Crossno.

“Physics we discovered by studying black holes and string theory, we’re seeing in graphene,” said Andrew Lucas, co-author and graduate student with Subir Sachdev, the Herchel Smith Professor of Physics at Harvard. “This is the first model system of relativistic hydrodynamics in a metal.”

Moving forward, a small chip of graphene could be used to model the fluid-like behavior of other high-energy systems.

Industrial implications

So we now know that strongly interacting electrons in graphene behave like a liquid — how does that advance the industrial applications of graphene?

First, in order to observe the hydrodynamic system, the team needed to develop a precise way to measure how well electrons in the system carry heat.  It’s very difficult to do, said co-PI Kin Chung Fong, scientist with Raytheon BBN Technology.

Materials conduct heat in two ways: through vibrations in the atomic structure or lattice; and carried by the electrons themselves.

“We needed to find a clever way to ignore the heat transfer from the lattice and focus only on how much heat is carried by the electrons,” Fong said.

To do so, the team turned to noise. At finite temperature, the electrons move about randomly:  the higher the temperature, the noisier the electrons. By measuring the temperature of the electrons to three decimal points, the team was able to precisely measure the thermal conductivity of the electrons.

“This work provides a new way to control the rate of heat transduction in graphene’s electron system, and as such will be key for energy and sensing-related applications,” said Leonid Levitov, professor of physics at MIT [Massachusetts Institute of Technology].

“Converting thermal energy into electric currents and vice versa is notoriously hard with ordinary materials,” said Lucas. “But in principle, with a clean sample of graphene there may be no limit to how good a device you could make.”

Here’s a link to and a citation for the paper,

Observation of the Dirac fluid and the breakdown of the Wiedemann-Franz law in graphene by Jesse Crossno, Jing K. Shi, Ke Wang, Xiaomeng Liu, Achim Harzheim, Andrew Lucas, Subir Sachdev, Philip Kim, Takashi Taniguchi, Kenji Watanabe, Thomas A. Ohki, Kin Chung Fong.Science  11 Feb 2016: pp. DOI: 10.1126/science.aad0343

This paper is behind a paywall.

Here’s an image illustrating the research,

Caption: In a new paper published in Science, researchers at the Harvard and Raytheon BBN Technology have advanced our understanding of graphene's basic properties, observing for the first time electrons in a metal behaving like a fluid. Credit: Peter Allen/Harvard SEAS

Caption: In a new paper published in Science, researchers at the Harvard and Raytheon BBN Technology have advanced our understanding of graphene’s basic properties, observing for the first time electrons in a metal behaving like a fluid. Credit: Peter Allen/Harvard SEAS

Origami and our pop-up future

They should have declared Jan. 25, 2016 ‘L. Mahadevan Day’ at Harvard University. The researcher was listed as an author on two major papers. I covered the first piece of research, 4D printed hydrogels, in this Jan. 26, 2016 posting. Now for Mahadevan’s other work, from a Jan. 27, 2016 news item on Nanotechnology Now,

What if you could make any object out of a flat sheet of paper?

That future is on the horizon thanks to new research by L. Mahadevan, the Lola England de Valpine Professor of Applied Mathematics, Organismic and Evolutionary Biology, and Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). He is also a core faculty member of the Wyss Institute for Biologically Inspired Engineering, and member of the Kavli Institute for Bionano Science and Technology, at Harvard University.

Mahadevan and his team have characterized a fundamental origami fold, or tessellation, that could be used as a building block to create almost any three-dimensional shape, from nanostructures to buildings. …

A Jan. 26, 2016 Harvard University news release by Leah Burrows, which originated the news item, provides more detail about the specific fold the team has been investigating,

The folding pattern, known as the Miura-ori, is a periodic way to tile the plane using the simplest mountain-valley fold in origami. It was used as a decorative item in clothing at least as long ago as the 15th century. A folded Miura can be packed into a flat, compact shape and unfolded in one continuous motion, making it ideal for packing rigid structures like solar panels.  It also occurs in nature in a variety of situations, such as in insect wings and certain leaves.

“Could this simple folding pattern serve as a template for more complicated shapes, such as saddles, spheres, cylinders, and helices?” asked Mahadevan.

“We found an incredible amount of flexibility hidden inside the geometry of the Miura-ori,” said Levi Dudte, graduate student in the Mahadevan lab and first author of the paper. “As it turns out, this fold is capable of creating many more shapes than we imagined.”

Think surgical stents that can be packed flat and pop-up into three-dimensional structures once inside the body or dining room tables that can lean flat against the wall until they are ready to be used.

“The collapsibility, transportability and deployability of Miura-ori folded objects makes it a potentially attractive design for everything from space-bound payloads to small-space living to laparoscopic surgery and soft robotics,” said Dudte.

Here’s a .gif demonstrating the fold,

This spiral folds rigidly from flat pattern through the target surface and onto the flat-folded plane (Image courtesy of Mahadevan Lab) Harvard University

This spiral folds rigidly from flat pattern through the target surface and onto the flat-folded plane (Image courtesy of Mahadevan Lab) Harvard University

The news release offers some details about the research,

To explore the potential of the tessellation, the team developed an algorithm that can create certain shapes using the Miura-ori fold, repeated with small variations. Given the specifications of the target shape, the program lays out the folds needed to create the design, which can then be laser printed for folding.

The program takes into account several factors, including the stiffness of the folded material and the trade-off between the accuracy of the pattern and the effort associated with creating finer folds – an important characterization because, as of now, these shapes are all folded by hand.

“Essentially, we would like to be able to tailor any shape by using an appropriate folding pattern,” said Mahadevan. “Starting with the basic mountain-valley fold, our algorithm determines how to vary it by gently tweaking it from one location to the other to make a vase, a hat, a saddle, or to stitch them together to make more and more complex structures.”

“This is a step in the direction of being able to solve the inverse problem – given a functional shape, how can we design the folds on a sheet to achieve it,” Dudte said.

“The really exciting thing about this fold is it is completely scalable,” said Mahadevan. “You can do this with graphene, which is one atom thick, or you can do it on the architectural scale.”

Co-authors on the study include Etienne Vouga, currently at the University of Texas at Austin, and Tomohiro Tachi from the University of Tokyo. …

Here’s a link to and a citation for the paper,

Programming curvature using origami tessellations by Levi H. Dudte, Etienne Vouga, Tomohiro Tachi, & L. Mahadevan. Nature Materials (2016) doi:10.1038/nmat4540 Published online 25 January 2016

This paper is behind a paywall.