Disease Biophysics Group

Cambridge, MA, United States

Disease Biophysics Group

Cambridge, MA, United States
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Ahn S.,Sogang University | Deravi L.F.,Disease Biophysics Group | Park S.-J.,Disease Biophysics Group | Dabiri B.E.,Disease Biophysics Group | And 3 more authors.
Advanced Materials | Year: 2015

Spontaneous, highly ordered large-scale fibronectin networks driven by electrostatic polymer patterns are fabricated, and these precisely controlled protein connections are demonstrated. It is examined whether this scheme, universal to various fibrillar extracellular matrix proteins beyond fibronectin, collagen, and laminin, can be self-organized. These data reveal a novel bottom-up method to form anisotropic, free-standing protein networks to be used as flexible, transferrable substrates for cardiac and neuronal tissue engineering. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


News Article | October 10, 2016
Site: www.cemag.us

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. The research is published in Macromolecular Materials and Engineering. 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,” says 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,” says 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,” says 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.


Mosadegh B.,Wyss Institute for Biologically Inspired Engineering | Mosadegh B.,Harvard University | Dabiri B.E.,Wyss Institute for Biologically Inspired Engineering | Dabiri B.E.,Disease Biophysics Group | And 9 more authors.
Advanced Healthcare Materials | Year: 2014

In vitro models of ischemia have not historically recapitulated the cellular interactions and gradients of molecules that occur in a 3D tissue. This work demonstrates a paper-based 3D culture system that mimics some of the interactions that occur among populations of cells in the heart during ischemia. Multiple layers of paper containing cells, suspended in hydrogels, are stacked to form a layered 3D model of a tissue. Mass transport of oxygen and glucose into this 3D system can be modulated to induce an ischemic environment in the bottom layers of the stack. This ischemic stress induces cardiomyocytes at the bottom of the stack to secrete chemokines which subsequently trigger fibroblasts residing in adjacent layers to migrate toward the ischemic region. This work demonstrates the usefulness of patterned, stacked paper for performing in vitro mechanistic studies of cellular motility and viability within a model of the laminar ventricle tissue of the heart. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


News Article | October 25, 2016
Site: www.gizmag.com

Researchers at Harvard have developed new materials that allow them to 3D print a heart-on-a-chip, with integrated sensors to simplify data collection(Credit: Johan Lind, Michael Rosnach, Disease Biophysics Group/Lori K. Sanders, Lewis Lab/Harvard University) Microphysiological systems, or organs-on-chips, are emerging as a way for scientists to study the effect that drugs, cosmetics and diseases may have on the human body, without needing to test on animals. The problem is, manufacturing and retrieving data from them can be a costly and time-consuming process. Now researchers at Harvard have developed new materials to enable them to 3D print the devices, including the integrated sensors to easily gather data from them over time. At around the size of a USB stick, organs-on-chips use living human cells to mimic the functions of organs like the lungs, intestines, placenta and heart, as well as emulate and study afflictions like heart disease. But as promising as the technology is, making the chips is a delicate, complicated process, and microscopes and high-speed cameras are needed to collect data from them. "Our approach was to address these two challenges simultaneously via digital manufacturing," says Travis Busbee, co-author of the paper. "By developing new printable inks for multi-material 3D printing, we were able to automate the fabrication process while increasing the complexity of the devices." In all, the Harvard team developed six custom 3D-printable materials that could replicate the structure of human heart tissue, with soft strain sensors embedded inside. These are printable in one continuous and automated process and separate wells in the chip host different tissues. "We are pushing the boundaries of three-dimensional printing by developing and integrating multiple functional materials within printed devices," says Jennifer Lewis, another of the paper's co-authors. "This study is a powerful demonstration of how our platform can be used to create fully functional, instrumented chips for drug screening and disease modeling." The incorporated sensors allow the researchers to study the tissue over time, particularly how their contractile stress changes, and how long-term exposure to toxins may affect the organs. "Researchers are often left working in the dark when it comes to gradual changes that occur during cardiac tissue development and maturation because there has been a lack of easy, non-invasive ways to measure the tissue functional performance," says Johan Ulrik Lind, first author of the study and postdoctoral fellow at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). "These integrated sensors allow researchers to continuously collect data while tissues mature and improve their contractility. Similarly, they will enable studies of gradual effects of chronic exposure to toxins." The research was published in the journal, Nature Materials, and a time-lapse of the 3D printing process can be seen in the video below.


News Article | March 1, 2017
Site: phys.org

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." 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 . Credit: Leila Deravi/Harvard University Explore further: Techniques offer better, tunable production of nanofibers for bulletproof vests, cellular scaffolding More information: Leila F. Deravi et al. Design and Fabrication of Fibrous Nanomaterials Using Pull Spinning, Macromolecular Materials and Engineering (2017). DOI: 10.1002/mame.201600404


News Article | March 1, 2017
Site: www.eurekalert.org

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. 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."


News Article | March 1, 2017
Site: www.rdmag.com

A new lightweight, portable nanofiber fabrication device may revolutionize several different fields. The material—developed by Harvard University researchers— could be used for everything from dressing wounds on a battlefield or creating engineered tissue to improving bullet proof vests or creating fashion-forward customizable fabrics. The Disease Biophysics Group at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) recently announced the development of a hand-held device that can quickly produce nanofibers with precise control over fiber orientation. By regulating fiber alignment and deposition, scientists can build nanofiber scaffolds that mimic highly aligned tissue in the body or design 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,” Nina Sinatra, a graduate student in the Disease Biophysics Group and co-first author of the paper, said in a statement. “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 nanofibers have been made using centrifugal force, capillary force, electric field, stretching, blowing, melting and evaporation. Rotary Jet-Spinning (RJS) and Immersion Rotary Jet-Spinning (iRJS) both dissolve polymers and proteins in a liquid solution and use centrifugal force or precipitation to elongate and solidify polymer jets into nanoscale fibers, making these methods ideal for producing large amounts of materials including DNA, nylon and even Kevlar. However, before the Harvard experiment they have not been particularly portable. 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 then travels in a spiral trajectory and solidifies before detaching from the bristle and moves toward a collector. This is different from other processes that involve multiple manufacturing variables, while pull spinning requires only one processing parameter—solution viscosity—to regulate nanofiber diameter. Minimal process parameters translate to ease use and flexibility at the bench— and one day in the field. Pull spinning works with a range of different polymers and proteins and the researchers were able to demonstrate 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,” Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics and director of the Disease Biophysics Group, said in a statement. “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.” The study was published in Macromolecular Materials and Engineering.

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