Tag Archives: Josue A. Goss

A nano fabrication technique used to create next generation heart valve

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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.

Portable nanofibre fabrication device (point-of-use manufacturing)

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A portable nanofiber fabrication device is quite an achievement although it seems it’s not quite ready for prime time yet. From a March 1, 2017 news item on Nanowerk (Note: A link has been removed),

Harvard researchers have developed a lightweight, portable nanofiber fabrication device that could one day be used to dress wounds on a battlefield or dress shoppers in customizable fabrics. The research was published recently in Macromolecular Materials and Engineering (“Design and Fabrication of Fibrous Nanomaterials Using Pull Spinning”)

A schematic of the pull spinning apparatus with a side view illustration of a fiber being pulled from the polymer reservoir. The pull spinning system consists of a rotating bristle that dips and pulls a polymer jet in a spiral trajectory (Leila Deravi/Harvard University)

A March 1, 2017 Harvard University news release (also on EurekAlert) by Leah Burrow,, which originated the news item, describes the current process for nanofiber fabrication and explains how this technique is an improvement,

There are many ways to make nanofibers. These versatile materials — whose target applications include everything from tissue engineering to bullet proof vests — have been made using centrifugal force, capillary force, electric field, stretching, blowing, melting, and evaporation.

Each of these fabrication methods has pros and cons. For example, Rotary Jet-Spinning (RJS) and Immersion Rotary Jet-Spinning (iRJS) are novel manufacturing techniques developed in the Disease Biophysics Group at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering. Both RJS and iRJS dissolve polymers and proteins in a liquid solution and use centrifugal force or precipitation to elongate and solidify polymer jets into nanoscale fibers. These methods are great for producing large amounts of a range of materials – including DNA, nylon, and even Kevlar – but until now they haven’t been particularly portable.

The Disease Biophysics Group recently announced the development of a hand-held device that can quickly produce nanofibers with precise control over fiber orientation. Regulating fiber alignment and deposition is crucial when building nanofiber scaffolds that mimic highly aligned tissue in the body or designing point-of-use garments that fit a specific shape.

“Our main goal for this research was to make a portable machine that you could use to achieve controllable deposition of nanofibers,” said Nina Sinatra, a graduate student in the Disease Biophysics Group and co-first author of the paper. “In order to develop this kind of point-and-shoot device, we needed a technique that could produce highly aligned fibers with a reasonably high throughput.”

The new fabrication method, called pull spinning, uses a high-speed rotating bristle that dips into a polymer or protein reservoir and pulls a droplet from solution into a jet. The fiber travels in a spiral trajectory and solidifies before detaching from the bristle and moving toward a collector. Unlike other processes, which involve multiple manufacturing variables, pull spinning requires only one processing parameter — solution viscosity — to regulate nanofiber diameter. Minimal process parameters translate to ease of use and flexibility at the bench and, one day, in the field.

Pull spinning works with a range of different polymers and proteins. The researchers demonstrated proof-of-concept applications using polycaprolactone and gelatin fibers to direct muscle tissue growth and function on bioscaffolds, and nylon and polyurethane fibers for point-of-wear apparel.

“This simple, proof-of-concept study demonstrates the utility of this system for point-of-use manufacturing,” said Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics and director of the Disease Biophysics Group. “Future applications for directed production of customizable nanotextiles could extend to spray-on sportswear that gradually heats or cools an athlete’s body, sterile bandages deposited directly onto a wound, and fabrics with locally varying mechanical properties.”

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

Design and Fabrication of Fibrous Nanomaterials Using Pull Spinning by Leila F. Deravi, Nina R. Sinatra, Christophe O. Chantre, Alexander P. Nesmith, Hongyan Yuan, Sahm K. Deravi, Josue A. Goss, Luke A. MacQueen, Mohammad R. Badrossamy, Grant M. Gonzalez, Michael D. Phillips, and Kevin Kit Parker. Macromolecular Materials and Engineering DOI: 10.1002/mame.201600404 Version of Record online: 17 JAN 2017

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Stronger more robust nanofibers for everything from bulletproof vests to cellular scaffolds (tissue engineering)

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This work on a new technique for producing nanofibers comes from Harvard University’s School of Engineering and Applied Sciences and the Wyss Institute for Biologically Inspired Engineering (also at Harvard University). From an Oct. 10, 2016 news item on phys.org,

Fibrous materials—known for their toughness, durability and pliability—are used in everything from bulletproof vests to tires, filtration systems and cellular scaffolds for tissue engineering and regenerative medicine.

The properties of these materials are such that the smaller the fibers are, the stronger and tougher they become. But making certain fibers very small has been an engineering challenge.

Now, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering at Harvard have developed a new method to make and collect nanofibers and control their size and morphology. This could lead to stronger, more durable bulletproof vests and armor and more robust cellular scaffolding for tissue repair.

An Oct. 7, 2016 Harvard University press release by Leah Burrows, which originated the news item, describes the research in more detail (Note: A link has been removed),

Nanofibers are smaller than one micrometer in diameter.  Most nanofiber production platforms rely on dissolving polymers in a solution, which then evaporates as the fiber forms.

Rotary Jet-Spinning (RJS), the technique developed by Kit Parker’s Disease Biophysics Group, works likes a cotton candy machine. Parker is Tarr Family Professor of Bioengineering and Applied Physics at SEAS and a Core Member of the Wyss Institute. A liquid polymer solution is loaded into a reservoir and pushed out through a tiny opening by centrifugal force as the device spins. As the solution leaves the reservoir, the solvent evaporates and the polymers solidify and elongate into small, thin fibers.

“This advance is important because it allows us to manufacture ballistic protection that is much lighter, more flexible and more functional than what is available today,” said Parker, who in addition to his Harvard role is a lieutenant colonel in the United States Army Reserve and was motivated by his own combat experiences in Afghanistan. “Not only could it save lives but for the warfighter, it also could help reduce the repetitive injury motions that soldiers, sailors, marines and airmen have suffered over the last 15 years of the war on terror.”

“Rotary Jet-Spinning is great for most polymer fibers you want to make,” said Grant Gonzalez, a graduate student at SEAS and first author of the paper.  “However, some fibers require a solvent that doesn’t evaporate easily. Para-aramid, the polymer used in Kevlar® for example, is dissolved in sulfuric acid, which doesn’t evaporate off. The solution just splashes against the walls of the device without forming fibers.”

Nanofibers are smaller than one micrometer in diameter.  Most nanofiber production platforms rely on dissolving polymers in a solution, which then evaporates as the fiber forms.

Rotary Jet-Spinning (RJS), the technique developed by Kit Parker’s Disease Biophysics Group, works likes a cotton candy machine. Parker is Tarr Family Professor of Bioengineering and Applied Physics at SEAS and a Core Member of the Wyss Institute. A liquid polymer solution is loaded into a reservoir and pushed out through a tiny opening by centrifugal force as the device spins. As the solution leaves the reservoir, the solvent evaporates and the polymers solidify and elongate into small, thin fibers.

“This advance is important because it allows us to manufacture ballistic protection that is much lighter, more flexible and more functional than what is available today,” said Parker, who in addition to his Harvard role is a lieutenant colonel in the United States Army Reserve and was motivated by his own combat experiences in Afghanistan. “Not only could it save lives but for the warfighter, it also could help reduce the repetitive injury motions that soldiers, sailors, marines and airmen have suffered over the last 15 years of the war on terror.”

“Rotary Jet-Spinning is great for most polymer fibers you want to make,” said Grant Gonzalez, a graduate student at SEAS and first author of the paper.  “However, some fibers require a solvent that doesn’t evaporate easily. Para-aramid, the polymer used in Kevlar® for example, is dissolved in sulfuric acid, which doesn’t evaporate off. The solution just splashes against the walls of the device without forming fibers.”

Other methods, such as electrospinning, which uses an electric field to pull the polymer into a thin fiber, also have poor results with Kevlar and other polymers such as alginate used for tissue scaffolding and DNA.

The Harvard team overcame these challenges by developing a wet-spinning platform, which uses the same principles as the RJS system but relies on precipitation rather than evaporation to separate the solvent from the polymer.

In this system, called immersion Rotary Jet-Spinning (iRJS), when the polymer solution shoots out of the reservoir, it first passes through an area of open air, where the polymers elongate and the chains align. Then the solution hits a liquid bath that removes the solvent and precipitates the polymers to form solid fibers. Since the bath is also spinning — like water in a salad spinner — the nanofibers follow the stream of the vortex and wrap around a rotating collector at the base of the device.

Using this system, the team produced Nylon, DNA, alginate and ballistic resistant para-aramid nanofibers. The team could tune the fiber’s diameter by changing the solution concentration, the rotational speed and the distance the polymer traveled from the reservoir to the bath.

“By being able to modulate fiber strength, we can create a cellular scaffold that can mimic skeleton muscle and native tissues,” said Gonzalez.  “This platform could enable us to create a wound dressing out of alginate material or seed and mature cells on scaffolding for tissue engineering.”

Because the fibers were collected by a spinning vortex, the system also produced well-aligned sheets of nanofibers, which is important for scaffolding and ballistic resistant materials.

This is the ‘candy floss’ technique at work,

Rotary Jet-Spinning (RJS) works likes a cotton candy machine. A liquid polymer solution is loaded into a reservoir and pushed out through a tiny opening by centrifugal force as the device spins. As the solution leaves the reservoir, the solvent evaporates and the polymers solidify and elongate into small, thin fibers. Courtesy: Harvard University

Rotary Jet-Spinning (RJS) works likes a cotton candy machine. A liquid polymer solution is loaded into a reservoir and pushed out through a tiny opening by centrifugal force as the device spins. As the solution leaves the reservoir, the solvent evaporates and the polymers solidify and elongate into small, thin fibers. Courtesy: Harvard University

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

Production of Synthetic, Para-Aramid and Biopolymer Nanofibers by Immersion Rotary Jet-Spinning by Grant M. Gonzalez, Luke A. MacQueen, Johan U. Lind, Stacey A. Fitzgibbons, Christophe O. Chantre, Isabelle Huggler, Holly M. Golecki, Josue A. Goss, Kevin Kit Parker. Macromolecular Materials and Engineering DOI: 10.1002/mame.201600365 Version of Record online: 7 OCT 2016

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.