Tag Archives: University of Pittsburgh

Replacement cartilage grown on laboratory chip

Most of us don’t think too much about cartilage (soft, flexible connective tissue found in the body) unless it’s damaged in which case it’s importance becomes immediately apparent. There is no substitute for cartilage although scientists are working on that problem and it seems that one team may have made a significant breakthrough according to an April 27, 2014 news item on ScienceDaily,

In a significant step toward reducing the heavy toll of osteoarthritis around the world, scientists have created the first example of living human cartilage grown on a laboratory chip. The researchers ultimately aim to use their innovative 3-D printing approach to create replacement cartilage for patients with osteoarthritis or soldiers with battlefield injuries.

“Osteoarthritis has a severe impact on quality of life, and there is an urgent need to understand the origin of the disease and develop effective treatments” said Rocky Tuan, Ph.D., director of the Center for Cellular and Molecular Engineering at the University of Pittsburgh School of Medicine, member of the American Association of Anatomists and the study’s senior investigator. “We hope that the methods we’re developing will really make a difference, both in the study of the disease and, ultimately, in treatments for people with cartilage degeneration or joint injuries.”

Osteoarthritis is marked by a gradual disintegration of cartilage, a flexible tissue that provides padding where bones come together in a joint. Causing severe pain and loss of mobility in joints such as knees and fingers, osteoarthritis is one of the leading causes of physical disability in the United States. It is estimated that up to 1 in 2 Americans will develop some form of the disease in their lifetime.

Although some treatments can help relieve arthritis symptoms, there is no cure. Many patients with severe arthritis ultimately require a joint replacement.

An April 27,2014 Experimental Biology (EB) 2014 news release provides more insight,

Tuan said artificial cartilage built using a patient’s own stem cells could offer enormous therapeutic potential. “Ideally we would like to be able to regenerate this tissue so people can avoid having to get a joint replacement, which is a pretty drastic procedure and is unfortunately something that some patients have to go through multiple times,” said Tuan.

In addition to offering relief for people with osteoarthritis, Tuan said replacement cartilage could also be a game-changer for people with debilitating joint injuries, such as soldiers with battlefield injuries. “We really want these technologies to help wounded warriors return to service or pursue a meaningful post-combat life,” said Tuan, who co-directs the Armed Forces Institute of Regenerative Medicine, a national consortium focused on developing regenerative therapies for injured soldiers. “We are on a mission.”

Creating artificial cartilage requires three main elements: stem cells, biological factors to make the cells grow into cartilage, and a scaffold to give the tissue its shape. Tuan’s 3-D printing approach achieves all three by extruding thin layers of stem cells embedded in a solution that retains its shape and provides growth factors. “We essentially speed up the development process by giving the cells everything they need, while creating a scaffold to give the tissue the exact shape and structure that we want,” said Tuan.

The ultimate vision is to give doctors a tool they can thread through a catheter to print new cartilage right where it’s needed in the patient’s body. Although other researchers have experimented with 3-D printing approaches for cartilage, Tuan’s method represents a significant step forward because it uses visible light, while others have required UV light, which can be harmful to living cells.

In another significant step, Tuan has successfully used the 3-D printing method to produce the first “tissue-on-a-chip” replica of the bone-cartilage interface. Housing 96 blocks of living human tissue 4 millimeters across by 8 millimeters deep, the chip could serve as a test-bed for researchers to learn about how osteoarthritis develops and develop new drugs. “With more testing, I think we’ll be able to use our platform to simulate osteoarthritis, which would be extremely useful since scientists really know very little about how the disease develops,” said Tuan.

As a next step, the team is working to combine their 3-D printing method with a nanofiber spinning technique they developed previously. They hope combining the two methods will provide a more robust scaffold and allow them to create artificial cartilage that even more closely resembles natural cartilage.

Rocky Tuan presented the research during the Experimental Biology 2014 meeting on Sunday, April 27 [2014].

I haven’t been able to find any papers published on this work but you can find Rocky Tuan’s faculty page (along with a list of publications) here and you may have more luck with the EB 2014 conference website than I did.

Using magnets to attract nanoparticles containing anesthesia

An April 11, 2014 news item on ScienceDaily, researchers describe a technique that would require far less anesthesia to numb the pain of various surgical procedures,

A technique using anesthesia-containing nanoparticles — drawn to the targeted area of the body by magnets — could one day provide a useful alternative to nerve block for local anesthesia in patients, suggests an experimental study in the April issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

“We have established proof of principle that it is possible to produce ankle block in the rat by intravenous injection of magnetic nanoparticles associated with ropivacaine and magnet application at the ankle,” write Dr Venkat R.R. Mantha and colleagues of University of Pittsburgh School of Medicine. With further study, the nano-anesthesia technique might allow more potent doses of local anesthetics to be delivered safely during local anesthesia in humans.

The April 11, 2014 Walters Kluwer news release, which originated the news item, preliminary research,

The experimental pilot study evaluated the use of magnet-directed nanoparticles containing the local anesthetic drug ropivacaine (MNP/Ropiv) to produce anesthesia of the limbs.  The researchers engineered nanoparticle complexes containing small amounts of ropivacaine and the iron oxide mineral magnetite.  The MNP/Ropiv complexes were injected into the veins (intravenously, or IV) of anesthetized rats.

The researchers then placed magnets around the ankle of the right paw for 15, 30, or 60 minutes.  The goal was to use the magnets to draw the nanoparticles to ankle. Once there, the particles would release the anesthetic, numbing the nerves around the ankle.

Sensation in the right paw was assessed by comparing the right paw to the left paw, which was not affected. Other groups of rats received standard nerve block, with ropivacaine injected directly into the ankle; or IV injection of ropivacaine alone, not incorporated into nanoparticles.

Injection of MNP/Ropiv complexes followed by magnet application produced significant nerve block in the right ankle, similar to a standard nerve block.  The left ankle was unaffected.

The ankle block produced by MNP/Ropiv injection was greatest when the magnet was applied for 30 minutes—likely reflecting the time of maximum ropivacaine release.  High ropivacaine concentrations were found in right ankles of the MNP/Ropiv group, suggesting “sequestration of the drug locally by the magnet.”
 
In rats receiving MNP/Ropiv, the nanoparticles contained a total of 14 milligrams of ropivacaine—a dose high enough to cause potentially fatal toxic effects.  Yet none of the animals in the MNP/Ropiv group had apparent adverse effects of ropivacaine.  This was similar to the findings in rats receiving 1 milligram of plain ropivacaine.  Thus the safe dose of ropivacaine combined with nanoparticles could be at least 14 times higher, compared to IV ropivacaine alone.

Magnet-directed nanoparticles have previously been used for targeted delivery of chemotherapy drugs.  The new study suggests that a similar technique could be used to attract local anesthetic-containing nanoparticles to specific areas, as an alternative to local anesthetic block—like that used for foot and ankle surgery, for example.

Additional animal experiments would be needed before the MNP/Ropiv technique can be tested in humans.  But if it proved safe, the magnet-directed approach could provide a useful new alternative for regional anesthesia—delivering high concentrations of local anesthetics directly to the desired area, without increasing toxic effects.

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

Nanoanesthesia: A Novel, Intravenous Approach to Ankle Block in the Rat by Magnet-Directed Concentration of Ropivacaine-Associated Nanoparticles by Venkat R. R. Mantha, Harsha K. Nair, Raman Venkataramanan, Yuan Yue Gao, Krzysztof Matyjaszewski, Hongchen Dong, Wenwen Li, Doug Landsittel, Elan Cohen, William R. Lariviere. Anesthesia & Analgesia: doi: 10.1213/ANE.0000000000000175

This paper is open access.

‘Zero-dimensional’ carbon nanotubes

They never say (at least not in the news releases I read) but I get the impression that the carbon nanotube researchers are pretty competitive with the graphene researchers since graphene has largely replaced carbon nanotubes as the basis for magic materials that will transform electronics and make everything thinner, lighter, and stronger. I exaggerate the claims but not by much. At any rate, members of the carbon nanotube research community from the University of Pittsburgh have announced the smallest, thinnest carbon nanotubes yet in a Dec. 9, 2013 University of Pittsburgh news release (also on EurekAlert but dated Dec. 10, 2013),

Synthetic, man-made cells and ultrathin electronics built from a new form of “zero-dimensional” carbon nanotube may be possible through research at the University of Pittsburgh Swanson School of Engineering. The research, ““Zero-Dimensional” Single-Walled Carbon Nanotubes,” was published in the journal Angewandte Chemie.

“Since its discovery, carbon nanotubes have held the promise to revolutionize the field of electronics, material science and even medicine,” says Dr. Little [Steven R. Little, PhD, associate professor]. “Zero-dimensional carbon nanotubes present the possibility to build ultrathin, superfast electronic devices, far superior to the best existing ones and it could be possible to build strong and ultralight cars, bridges, and airplanes.”

One of the most difficult hurdles is processing the carbon nanotubes into smaller forms. However, previous research at Pitt has managed to cut the carbon nanotubes into the smallest dimensions ever to overcome this problem.

“We have confirmed that these shorter nanotubes are more dispersible and potentially easier to process for industrial as well as biomedical application, and could even constitute the building blocks for the creation of synthetic cells,” says Dr. Gottardi.

The organization of the atoms within nanotubes makes them particularly interesting materials to work with. However, they are barely soluble, making industrial processing difficult. One aspect of the team’s research will focus on creating more soluble and therefore more usable carbon nanotubes. These shorter nanotubes have the same dimensions as many proteins that compose the basic machinery of living cells, presenting the potential for cell or protein-level biomedical imaging, protein or nucleic acid vaccination carriers, drug delivery vehicles, or even components of synthetic cells.

Overall, the project is aimed at developing and working with these more dispersible carbon nanotubes with the aim of making them easier to process. The creation of the smaller nanotubes is the first step toward reaching this goal.

For the curious, here’s a link to and a citation for the paper,

“Zero-Dimensional” Single-Walled Carbon Nanotubes by Dr. Kaladhar Kamalasanan, Dr. Riccardo Gottard, Dr. Susheng Tan, Dr. Yanan Chen, Dr. Bhaskar Godugu, Dr. Sam Rothstein, Dr. Anna C. Balazs, Dr. Alexander Star, Dr. Steven R. Little. Angewandte Chemie Volume 125, Issue 43, pages 11518–11522, October 18, 2013 Article first published online: 5 SEP 2013 DOI: 10.1002/ange.201305526

Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This article is behind a paywall.

Squishy wonderfulness: new possibilities for hydrogels

i have two items for this posting about hydrogels and biomimicry (aka biomimetics). One concerns the use of light to transform hydrogels and the other concerns the potential for using hydrogels in ‘soft’ robotics. First, researchers at the University of Pittsburgh have found a way to make hydrogels change their shapes, from an Aug. 1, 2013 news item on Nanowerk,

Some animals—like the octopus and cuttlefish—transform their shape based on environment, fending off attackers or threats in the wild. For decades, researchers have worked toward mimicking similar biological responses in non-living organisms, as it would have significant implications in the medical arena.

Now, researchers at the University of Pittsburgh have demonstrated such a biomimetic response using hydrogels—a material that constitutes most contact lenses and microfluidic or fluid-controlled technologies.

The Aug. 1, 2013 University of Pittsburgh news release, which originated the news item, offers this description from the paper’s lead authorl,

“Imagine an apartment with a particular arrangement of rooms all in one location,” said lead author Anna Balazs, Pitt Distinguished Professor of Chemical and Petroleum Engineering in the Swanson School of Engineering. “Now, consider the possibility of being able to shine a particular configuration of lights on this structure and thereby completely changing not only the entire layout, but also the location of the apartment. This is what we’ve demonstrated with hydrogels.”

The news release goes on to provide more specific details about the work,

Together with Olga Kuksenok, research associate professor in the Swanson School, Balazs experimented with a newer type of hydrogel containing spirobenzopyran molecules. Such materials had been previously shown to form distinct 2-D patterns on initially flat surfaces when introduced to varying displays of light and are hydrophilic (“liking” water) in the dark but become hydrophobic (“disliking” water) under blue light illumination. Therefore, Balazs and Kuksenok anticipated that light could be a useful stimulus for tailoring the gel’s shape.

Using computer modeling, the Pitt team demonstrated that the gels “ran away” when exposed to the light, exhibiting direct, sustained motion. The team also factored in heat—combining the light and local variations in temperature to further control the samples’ motions. Controlling a material with light and temperature could be applicable, Balazs said, in terms of regulating the movement of a microscopic “conveyor belt” or “elevator” in a microfluidic device.

“This theoretical modeling points toward a new way of configuring the gels into any shape, while simultaneously driving the gels to move due to the presence of light,” said Kuksenok.

“Consider, for example, that you could take one sheet of hydrogel and, with the appropriate use of light, fashion it into a lens-shaped object, which could be used in optical applications”, added Balazs.

The team also demonstrated that the gels could undergo dynamic reconfiguration, meaning that, with a different combination of lights, the gel could be used for another purpose. Reconfigurable systems are particularly useful because they are reusable, leading to a significant reduction in cost.

“You don’t need to construct a new device for every new application,” said Balazs. “By swiping light over the system in different directions, you can further control the movements of a system, further regulating the flow of materials.”

Balazs said this type of dynamic reconfiguration in response to external cues is particularly advantageous in the realm of functional materials. Such processes, she said, would have a dramatic effect on manufacturing and sustainability, since the same sample could be used and reused for multiple applications.

The team will now study the effect of embedding microscopic fibers into the gel to further control the shape and response of the material to other stimuli.

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

Modeling the Photoinduced Reconfiguration and Directed Motion of Polymer Gels by Olga Kuksenok and Anna C. Balazs. Article first published online: 31 JUL 2013, Adv. Funct. Mater.. doi: 10.1002/adfm.201203876

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall. However, there is a video of Anna Balazs’s June 27, 2013 talk (Reconfigurable assemblies of active, auto-chemotactic gels) on these gels at the Isaac Newton Institute for Mathematical Sciences.

Meanwhile, researchers at North Carolina State University are pursuing a different line of query involving hydrogels. From an Aug. 2, 2013 North Carolina State University news release (also on EurekAlert),

Researchers from North Carolina State University have developed a new technique for creating devices out of a water-based hydrogel material that can be patterned, folded and used to manipulate objects. The technique holds promise for use in “soft robotics” and biomedical applications.

“This work brings us one step closer to developing new soft robotics technologies that mimic biological systems and can work in aqueous environments,” says Dr. Michael Dickey, an assistant professor of chemical and biomolecular engineering at NC State and co-author of a paper describing the work.

“In the nearer term, the technique may have applications for drug delivery or tissue scaffolding and directing cell growth in three dimensions, for example,” says Dr. Orlin Velev, INVISTA Professor of Chemical and Biomolecular Engineering at NC State, the second senior author of the paper.

The technique they’ve developed uses hydrogels, which are water-based gels composed of water and a small fraction of polymer molecules. Hydrogels are elastic, translucent and – in theory – biocompatible. The researchers found a way to modify and pattern sections of hydrogel electrically by using a copper electrode to inject positively charged copper ions into the material. Those ions bond with negatively charged sites on the polymer network in the hydrogel, essentially linking the polymer molecules to each other and making the material stiffer and more resilient. The researchers can target specific areas with the electrodes to create a framework of stiffened material within the hydrogel. The resulting patterns of ions are stable for months in water.

“The bonds between the biopolymer molecules and the copper ions also pull the molecular strands closer together, causing the hydrogel to bend or flex,” Velev says. “And the more copper ions we inject into the hydrogel by flowing current through the electrodes, the further it bends.”

The researchers were able to take advantage of the increased stiffness and bending behavior in patterned sections to make the hydrogel manipulate objects. For example, the researchers created a V-shaped segment of hydrogel. When copper ions were injected into the bottom of the V, the hydrogel flexed – closing on an object as if the hydrogel were a pair of soft tweezers. By injecting ions into the back side of the hydrogel, the tweezers opened – releasing the object.

The researchers also created a chemically actuated “grabber” out of an X-shaped segment of hydrogel with a patterned framework on the back of the X. When the hydrogel was immersed in ethanol, the non-patterned hydrogel shrank. But because the patterned framework was stiffer than the surrounding hydrogel, the X closed like the petals of a flower, grasping an object. When the X-shaped structure was placed in water, the hydrogel expanded, allowing the “petals” to unfold and release the object. Video of the hydrogels in action is available here.

“We are currently planning to use this technique to develop motile, biologically compatible microdevices,” Velev says.

“It’s also worth noting that this technique works with ions other than copper, such as calcium, which are biologically relevant,” Dickey says.

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

Reversible patterning and actuation of hydrogels by electrically assisted ionoprinting by Etienne Palleau, Daniel Morales, Michael D. Dickey & Orlin D. Velev. Nature Communications 4, Article number: 2257 doi:10.1038/ncomms3257 Published 02 August 2013

This article is behind a paywall.

Connecting the dots in quantum computing—the secret is in the spins

The Feb. 26, 2013 University of Pittsburgh news release puts it a lot better than I can,

Recent research offers a new spin on using nanoscale semiconductor structures to build faster computers and electronics. Literally.

University of Pittsburgh and Delft University of Technology researchers reveal in the Feb. 17 [2013]online issue of Nature Nanotechnology a new method that better preserves the units necessary to power lightning-fast electronics, known as qubits (pronounced CUE-bits). Hole spins, rather than electron spins, can keep quantum bits in the same physical state up to 10 times longer than before, the report finds.

“Previously, our group and others have used electron spins, but the problem was that they interacted with spins of nuclei, and therefore it was difficult to preserve the alignment and control of electron spins,” said Sergey Frolov, assistant professor in the Department of Physics and Astronomy within Pitt’s Kenneth P. Dietrich School of Arts and Sciences, who did the work as a postdoctoral fellow at Delft University of Technology in the Netherlands.

Whereas normal computing bits hold mathematical values of zero or one, quantum bits live in a hazy superposition of both states. It is this quality, said Frolov, which allows them to perform multiple calculations at once, offering exponential speed over classical computers. However, maintaining the qubit’s state long enough to perform computation remains a long-standing challenge for physicists.

“To create a viable quantum computer, the demonstration of long-lived quantum bits, or qubits, is necessary,” said Frolov. “With our work, we have gotten one step closer.”

Thankfully, an explanation of the hole spins vs. electron spins issue follows,

The holes within hole spins, Frolov explained, are literally empty spaces left when electrons are taken out. Using extremely thin filaments called InSb (indium antimonide) nanowires, the researchers created a transistor-like device that could transform the electrons into holes. They then precisely placed one hole in a nanoscale box called “a quantum dot” and controlled the spin of that hole using electric fields. This approach- featuring nanoscale size and a higher density of devices on an electronic chip-is far more advantageous than magnetic control, which has been typically employed until now, said Frolov.

“Our research shows that holes, or empty spaces, can make better spin qubits than electrons for future quantum computers.”

“Spins are the smallest magnets in our universe. Our vision for a quantum computer is to connect thousands of spins, and now we know how to control a single spin,” said Frolov. “In the future, we’d like to scale up this concept to include multiple qubits.”

This graphic displays spin qubits within a nanowire. [downloaded from http://www.news.pitt.edu/connecting-quantum-dots]

This graphic displays spin qubits within a nanowire. [downloaded from http://www.news.pitt.edu/connecting-quantum-dots]

From the news release,

Coauthors of the paper include Leo Kouwenhoven, Stevan Nadj-Perge, Vlad Pribiag, Johan van den Berg, and Ilse van Weperen of Delft University of Technology; and Sebastien Plissard and Erik Bakkers from Eindhoven University of Technology in the Netherlands.

The paper, “Electrical control over single hole spins in nanowire quantum dots,” appeared online Feb. 17 in Nature Nanotechnology. The research was supported by the Dutch Organization for Fundamental Research on Matter, the Netherlands Organization for Scientific Research, and the European Research Council.

According to the scientists we’re going to be waiting a bit longer for a quantum computer but this work is promising. Their paper is behind a paywall.

A gel that communicates

A Jan. 8, 2013 news item on ScienceDaily highlights some work with oscillating gels being done at the University of Pittsburgh,

Self-moving gels can give synthetic materials the ability to “act alive” and mimic primitive biological communication, University of Pittsburgh researchers have found.

Anna Balazs, principal investigator of the study [published in the Jan. 8 print edition of the Proceedings of the National Academy of Sciences] and Distinguished Professor of Chemical and Petroleum Engineering in Pitt’s Swanson School of Engineering, has long studied the properties of the Belousov-Zhabotinsky (BZ) gel, a material first fabricated in the late 1990s and shown to pulsate in the absence of any external stimuli.

The Jan. 8, 2013 University of Pittsburgh news release, which originated the news item, provides some history about the project and more details about the latest results,

In a previous study, the Pitt team noticed that long pieces of gel attached to a surface by one end “bent” toward one another, almost as if they were trying to communicate by sending signals. This hint that “chatter” might be taking place led the team to detach the fixed ends of the gels and allow them to move freely.

Balazs and her team developed a 3-D gel model to test the effects of the chemical signaling and light on the material. They found that when the gel pieces were moved far apart, they would automatically come back together, exhibiting autochemotaxis—the ability to both emit and sense a chemical, and move in response to that signal.

“This study demonstrates the ability of a synthetic material to actually ‘talk to itself’ and follow out a given action or command, similar to such biological species as amoeba and termites,” said Balazs. “Imagine a LEGO® set that could by itself unsnap its parts and then put itself back together again in different shapes but also allow you to control those shapes through chemical reaction and light.”

Here’s a link to the online version of the article,

Reconfigurable assemblies of active, autochemotactic gels” by Pratyush Dayal, Olga Kuksenok, and Anna C. Balazs. Published online before print December 27, 2012, doi: 10.1073/pnas.1213432110 PNAS [Proceedings of the National Academy of Sciences]  December 27, 2012 201213432

This article is behind a paywall.