, June 21, 2010, by Anuradha Menon  —  Twenty-seven stroke victims are alive and well today because of a new tool that vacuums clots out of blood vessels in the brain. Known as the Penumbra System of Continuous Aspiration Thrombectomy, the technology has been assessed at the Seaman MR Research Centre at Canada’s University of Calgary. If used within a few hours of a stroke, it can restore blood flow to the brain, thus reversing the effects of the stroke and preventing any permanent brain damage.

Medical technology firm Penumbra designed the tool. The process involves going in through the patient’s groin, and threading a tiny catheter into a blood vessel. That catheter goes up to the neck, at which point an even smaller catheter emerges from it and goes into the brain, whereupon it vacuums out the blood clot. “It requires years of training to be able to do this,” said Dr. Mayank Goyal, director of the Seaman Centre. “It places enormous demands on the interventionalist, on the imaging specialists, and on the emergency team that gets the patient to a designated stroke care facility. Teamwork is key for success.” The Penumbra System is intended for use on ischemic strokes, which involve blood clots in the brain, and constitute 80% of all strokes. Currently, such clots are treated with the drug t-PA, which has to be administered within three hours of the event. The new system involves less of a risk of bleeding, and may still work after more than three hours.

(Source: Gizmag)

The scaffolding used to attract stem cells and grow replacement teeth in place.

 (Source: Columbia University Medical Center)




Researchers at Columbia University Medical Center in New York City have developed a method of growing dental implants in place using stem cells. The process can result in a fully formed replacement tooth in less than nine weeks from initial implantation. Unlike current dental implants, these teeth conform to changes that occur to the jaw bone over time, limiting the need for costly and time consuming adjustments or replacement implants., July 21, 2010, by Janice Karin  —  Dr. Jeremy Mao and his colleagues at the Columbia’s Tissue Engineering and Regenerative Medicine Laboratory attach a scaffold infused with a growth factor to the empty tooth socket. Stem cells hone in on the scaffold, eventually forming a tooth of the correct shape and size to fit the individual patient’s mouth. In addition to forming a more naturally compatible tooth, this method eliminates the need to harvest stem cells or grow the implant in a petri dish or other laboratory environment then implanting it fully formed. This process also regenerates periodontal ligaments and alveolar bone, neither of which is possible with traditional dental implants, and makes for a much more effective and natural tooth replacement.

Dr. Mao’s procedure results in a fully formed tooth in approximately nine weeks. This is a significant time improvement over regular implants which can take as long as eighteen months from initial patient visit to a fully healed implanted tooth. A regular implant can also require visits to a long series of different types of dentists, adding complexity and expense to the mix. The new process is simpler, more natural, more efficient, probably longer lasting, and likely to be less expensive than traditional implants.

Although animal models have been successful, the new implant method has not yet been tried in human mouths. Although general use by dentists is still in the future, Columbia is actively looking to start the approval process and commercial development of the new implants.

TFOT has previously reported on a knee replacement technique using similar scaffolding that coaxes cartilage and bone regrowth. TFOT has also previously reported on other dental research and advancements including an herbal lollipop designed to help prevent cavities, the use of spectroscopy to discover early stages of tooth decay, and a study showing daily tooth brushing improves the health of patients confined to hospital beds.

Read more about the new tooth implant process in this Columbia University Medical Center press release and more about Dr. Mao’s previous stem cell research in this CUMC newsletter article

Columbia University Medical Center, July 21, 2010  —  When news media reported last year that Jeremy Mao’s research team had created a breast implant from stem cells, few noted that Dr. Mao is a dentist. Though Dr. Mao (who has a D.D.S. and a Ph.D.) spends less time treating patients, his career as a tissue engineer exemplifies a growing trend in dental research, particularly at the College of Dental Medicine. Research increasingly shows that oral health is entwined with general health and that dental research can bring benefits to a wide array of medical fields. Dr. Mao, who recently joined the College of Dental Medicine from the University of Illinois at Chicago, took a break from his busy schedule to talk with InVivo.

What connection does your stem cell work have to dentistry?

A lot, actually. My lab got into that mostly by serendipity, because the same stem cells that we used previously to make the bone and cartilage in an engineered temporomandibular joint (TMJ) can also make adipose tissue. When we were trying to engineer the joint, we also turned these human stem cells into fat cells. People asked us, ‘why make fat cells? most people are trying to get rid of their fat cells!’ But for patients with soft tissue defects resulting from congenital disorders, trauma or tumor surgery, engineered fat tissue from stem cells has the potential to provide a replacement. Breast cancer defects can potentially be fixed from the patient’s own stem cells instead of synthetic implants.

Earlier research has used fat cells leftover from liposuction to make soft tissue implants, but these quickly shrink because the cells have limited lifespan. Implants made from stem cell-derived fat cells are long lasting, because stem cells in the implant keep replenishing the supply.

So what does this have to do with dentistry? Dentistry is much more than just the teeth. A great deal of reconstructive and plastic surgery is performed in the craniofacial region. The soft tissue and hard tissue defects that result from oral surgery or craniofacial surgery can potentially be corrected using stem cells.

The bioengineered TMJ your team created a few years ago also got a lot of media attention. How much of a health issue is this type of disease?

About 10 million people in the United States have TMJ problems and in the most severe cases they can hardly talk or chew, and must rely on a liquid diet.

Today, surgeons use bone grafts harvested from the hip or rib to repair a badly diseased TMJ. The downside is you create a secondary trauma site. Why should a patient have to sacrifice a perfectly normal rib? Sometimes metal and synthetic materials are used, but none of these, including the bone graft, are satisfactory. They break, they chip, they wear out. And they don’t work that well.

The goal of tissue engineering is to enable tissue and organ replacements to be ‘grown’ by the patient, and look and function as nature’s originals. In our lab we’ve used human stem cells and put them through steps that nature uses to grow a TMJ that has the same shape and dimensions as the original structure. Also, TMJ is a prototype for larger joints such as the knee or hip. We recently engineered a part of a human-shaped knee joint from human stem cells. We want to grow functional joints from stem cells in patients with arthritis and trauma.

Dental researchers today seem to be less confined to strictly dental issues. How did that come about?

Earlier dental research has solved some of the ‘easier’ problems in dentistry, and in the process the practice of dentistry has changed. In the 1930s and 40s cavities and tooth decay were so prevalent that most people lost some or many teeth by their teens or early 20s. That’s not the case anymore in the United States, largely because of dental research. Dentists saw that people living in areas with naturally high levels of fluoride in the water didn’t get many cavities. Based on that research, most regions started to add fluoride to drinking water. Now some people reach their 20s and beyond without any tooth decay.
But there are so many other issues that are harder to deal with, like TMJ diseases. Dental professionals realized that if we want to provide effective treatment for these individuals, we can’t do it without research and so are using modern tools like molecular biology, stem cells, and tissue engineering to advance the field.

In addition, a lot of dental research has ramifications that go far beyond dentistry. For example, gum disease may trigger cardiovascular disease. Many craniofacial disfigurations are associated with defects in other regions of the body. A cut inside the mouth heals without scarring, just like a fetal wound, whereas a cut in the skin scars. Research on macromolecules in oral mucosa may provide clues to scarless skin healing. One scientific connection between dentistry and medicine is that the same stem cells that develop into the bulk of the teeth can also develop into bone, cartilage, fat, tendons, ligaments, and even cells that form internal organs.

—Susan Conova, by Anni Shaer  —   research team led by Levitt Shuichi Takayama at the University of Michigan has developed a new technology for growing lung cells outside the body. The scientists developed a tiny device, named “lung on a chip”, which causes the cells on it to act as if they would were they inside the body. Using this device, the team researched the effects of pulmonary diseases such as cystic fibrosis and asthma on lung cells, and found that some of the symptoms of these diseases may be causing further damage to the lungs. The team believe that in time, the chip may help scientists find a cure for lung illnesses.

When the airways in the lungs are blocked by thick fluids, breathing causes hissing sounds named “crackles”. In some pulmonary diseases such as cystic fibrosis, these crackles are rather common, since the body suffers from a deficiency in the protein which makes these fluids less gluey. When people who suffer from a pulmonary disease inhale, the plugs “explode”, causing the crackling sound. Until now, these sounds were considered as symptoms of the disease. However, the latest experiments conducted by the University of Michigan scientists imply that the crackles themselves damage the lung. If the plugs rupture, they cause a stress wave, similar to an explosion, damaging the surrounding cells.

In order to see the crackles’ progression, the researchers created the “lung on a chip”. Two rubber sheets were connected, with a groove carved across them. A porous polyester sheet was placed between the grooved sides, causing the rubber sheets to attach and creating two chambers, which were then filled with a nourishing liquid. When the lung cells began to grow, the top chamber was emptied to simulate an airway. This caused the cells to develop further than they do in a Petri dish. The cells began acting in a lung-like way in terms of protein secretion, tissue connections, and overall function. The device is exactly the size of the smallest airway branches in human lungs.

When the cell development was complete, the researchers ran the control part of the experiment. The team observed that liquid followed by air passing through the channels did not damage the cells. The team then turned on a “microfabricated plug generator”, which is a vial of liquid attached to the cell culture chamber on the chip and pumped air through it. Drops of liquid from the vial entered the simulated airways of the chip and due to the pressure, burst, creating “crackles”. Testing revealed that at least 24% of the lung cells die as a result of the bursts. The more frequent the plug bursts were, the more damage the surrounding cells suffered. Further research is necessary in order to fully understand the crackles’ effects and in order to explore more research possibilities of the “lung on a chip”. The chip’s developers hope their device will lead to the development of new treatments for respiratory diseases.

TFOT recently covered the use of artificial body parts in research, including a bionic eye capable of restoring the eye sight of people who suffer from age-related blindness, developed by the Boston Retinal Implant Project. Another related TFOT story focused on the creation of an artificial arm by the German company Festo. We have also covered a “blood test on a chip” device. The micro-sized laboratory is capable of analyzing minute blood samples, and was developed in Caltech (California Institute of Technology).

More information regarding the lung on a chip can be found on the University of Michigan News Service webpage.

Clemson University, US Dept of Defense, by Asaf Peer  —  A biosensor developed in Clemson University, South Carolina, funded by the U.S. Department of Defense, will be able to transmit information regarding blood lactate and glucose levels of a wounded soldier or of other injured patients. The biochip will be implanted in the patient’s body for a short time and will wirelessly transmit the levels of lactate and glucose to the medical staff.

The biochip, sized 2mm x 4mm x 0.5mm, is a dual sensing element coated with hydrogels to prevent it from being rejected by human tissue. The sensor has the ability to transmit life saving readings to the medical personnel. The implantation of the chip will only be temporary, although long term biochip implants are also being tested and may be used as a precaution in some cases. 

Blood glucose and lactate levels are very important for medical staff in the first stages of dealing with a trauma patient. These measurements can imply what the oxygen level in the patients’ blood is and can indicate the overall metabolic state of the patient. The blood lactate level is sometimes used to determine whether or not a trauma patient can survive surgery. Getting these measurements in real time can help the medics in a hospital or out in the field make decisions much faster and by doing so will help save lives. 

The chip has undergone some tests and the developers assume it will be tested on humans within five years. Although the main use of the biochip is aiding with trauma injuries, it may be useful in diabetes care, transplant organ care and intensive care. After the sensor will be clinically approved it will be easier to develop similar sensors to measure levels of other molecules’ in the blood. 

TFOT recently reported about other biochips, including the nanocytometer and the “lab on a chip”. The main difference between these technologies is that this biochip is implanted in a patient’s body where as the others are used externally to analyze one’s blood samples.

More information on the implantable biochip can be found on the Clemson website.

Gravity: The force that helps stars ignite, planets stay together and objects orbit is one of the most pervasive yet weakest in the cosmos

Scientists have fine-tuned just about every equation and model to describe and predict gravity, yet its source within matter remains a complete and utter mystery.

Some think infinitesimal particles called gravitons exude the force in all matter, but whether or not they could ever be detected is questionable.

Still, a massive hunt is on for major shake-ups in the universe called gravitational waves. If detected (perhaps from a merger of black holes), Albert Einstein’s concept that the universe has a “fabric” of spacetime would be on solid ground.

Caption: Artist depiction of gravity waves around merging black holes. Credit: NASA

The New York Times, July 21, 2010, by Dennis Overbye  —   It’s hard to imagine a more fundamental and ubiquitous aspect of life on the Earth than gravity, from the moment you first took a step and fell on your diapered bottom to the slow terminal sagging of flesh and dreams.

But what if it’s all an illusion, a sort of cosmic frill, or a side effect of something else going on at deeper levels of reality?

So says Erik Verlinde, 48, a respected string theorist and professor of physics at the University of Amsterdam, whose contention that gravity is indeed an illusion has caused a continuing ruckus among physicists, or at least among those who profess to understand it. Reversing the logic of 300 years of science, he argued in a recent paper, titled “On the Origin of Gravity and the Laws of Newton,” that gravity is a consequence of the venerable laws of thermodynamics, which describe the behavior of heat and gases.

“For me gravity doesn’t exist,” said Dr. Verlinde, who was recently in the United States to explain himself. Not that he can’t fall down, but Dr. Verlinde is among a number of physicists who say that science has been looking at gravity the wrong way and that there is something more basic, from which gravity “emerges,” the way stock markets emerge from the collective behavior of individual investors or that elasticity emerges from the mechanics of atoms.

Looking at gravity from this angle, they say, could shed light on some of the vexing cosmic issues of the day, like the dark energy, a kind of anti-gravity that seems to be speeding up the expansion of the universe, or the dark matter that is supposedly needed to hold galaxies together.

Dr. Verlinde’s argument turns on something you could call the “bad hair day” theory of gravity.

It goes something like this: your hair frizzles in the heat and humidity, because there are more ways for your hair to be curled than to be straight, and nature likes options. So it takes a force to pull hair straight and eliminate nature’s options. Forget curved space or the spooky attraction at a distance described by Isaac Newton’s equations well enough to let us navigate the rings of Saturn, the force we call gravity is simply a byproduct of nature’s propensity to maximize disorder.

Some of the best physicists in the world say they don’t understand Dr. Verlinde’s paper, and many are outright skeptical. But some of those very same physicists say he has provided a fresh perspective on some of the deepest questions in science, namely why space, time and gravity exist at all — even if he has not yet answered them.

“Some people have said it can’t be right, others that it’s right and we already knew it — that it’s right and profound, right and trivial,” Andrew Strominger, a string theorist at Harvard said.

“What you have to say,” he went on, “is that it has inspired a lot of interesting discussions. It’s just a very interesting collection of ideas that touch on things we most profoundly do not understand about our universe. That’s why I liked it.”

Dr. Verlinde is not an obvious candidate to go off the deep end. He and his brother Herman, a Princeton professor, are celebrated twins known more for their mastery of the mathematics of hard-core string theory than for philosophic flights.

Born in Woudenberg, in the Netherlands, in 1962, the brothers got early inspiration from a pair of 1970s television shows about particle physics and black holes. “I was completely captured,” Dr. Verlinde recalled. He and his brother obtained Ph.D’s from the University of Utrecht together in 1988 and then went to Princeton, Erik to the Institute for Advanced Study and Herman to the university. After bouncing back and forth across the ocean, they got tenure at Princeton. And, they married and divorced sisters. Erik left Princeton for Amsterdam to be near his children.

He made his first big splash as a graduate student when he invented Verlinde Algebra and the Verlinde formula, which are important in string theory, the so-called theory of everything, which posits that the world is made of tiny wriggling strings.

You might wonder why a string theorist is interested in Newton’s equations. After all Newton was overturned a century ago by Einstein, who explained gravity as warps in the geometry of space-time, and who some theorists think could be overturned in turn by string theorists.

Over the last 30 years gravity has been “undressed,” in Dr. Verlinde’s words, as a fundamental force.

This disrobing began in the 1970s with the discovery by Jacob Bekenstein of the Hebrew University of Jerusalem and Stephen Hawking of Cambridge University, among others, of a mysterious connection between black holes and thermodynamics, culminating in Dr. Hawking’s discovery in 1974 that when quantum effects are taken into account black holes would glow and eventually explode.

In a provocative calculation in 1995, Ted Jacobson, a theorist from the University of Maryland, showed that given a few of these holographic ideas, Einstein’s equations of general relativity are just a another way of stating the laws of thermodynamics.

Those exploding black holes (at least in theory — none has ever been observed) lit up a new strangeness of nature. Black holes, in effect, are holograms — like the 3-D images you see on bank cards. All the information about what has been lost inside them is encoded on their surfaces. Physicists have been wondering ever since how this “holographic principle” — that we are all maybe just shadows on a distant wall — applies to the universe and where it came from.

In one striking example of a holographic universe, Juan Maldacena of the Institute for Advanced Study constructed a mathematical model of a “soup can” universe, where what happened inside the can, including gravity, is encoded in the label on the outside of the can, where there was no gravity, as well as one less spatial dimension. If dimensions don’t matter and gravity doesn’t matter, how real can they be?

Lee Smolin, a quantum gravity theorist at the Perimeter Institute for Theoretical Physics, called Dr. Jacobson’s paper “one of the most important papers of the last 20 years.”

But it received little attention at first, said Thanu Padmanabhan of the Inter-University Center for Astronomy and Astrophysics in Pune, India, who has taken up the subject of “emergent gravity” in several papers over the last few years. Dr. Padmanabhan said that the connection to thermodynamics went deeper that just Einstein’s equations to other theories of gravity. “Gravity,” he said recently in a talk at the Perimeter Institute, “is the thermodynamic limit of the statistical mechanics of “atoms of space-time.”

Dr. Verlinde said he had read Dr. Jacobson’s paper many times over the years but that nobody seemed to have gotten the message. People were still talking about gravity as a fundamental force. “Clearly we have to take these analogies seriously, but somehow no one does,” he complained.

His paper, posted to the physics archive in January, resembles Dr. Jacobson’s in many ways, but Dr. Verlinde bristles when people say he has added nothing new to Dr. Jacobson’s analysis. What is new, he said, is the idea that differences in entropy can be the driving mechanism behind gravity, that gravity is, as he puts it an “entropic force.”

That inspiration came to him courtesy of a thief.

As he was about to go home from a vacation in the south of France last summer, a thief broke into his room and stole his laptop, his keys, his passport, everything. “I had to stay a week longer,” he said, “I got this idea.”

Up the beach, his brother got a series of e-mail messages first saying that he had to stay longer, then that he had a new idea and finally, on the third day, that he knew how to derive Newton’s laws from first principles, at which point Herman recalled thinking, “What’s going on here? What has he been drinking?”

When they talked the next day it all made more sense, at least to Herman. “It’s interesting,” Herman said, “how having to change plans can lead to different thoughts.”

Think of the universe as a box of scrabble letters. There is only one way to have the letters arranged to spell out the Gettysburg Address, but an astronomical number of ways to have them spell nonsense. Shake the box and it will tend toward nonsense, disorder will increase and information will be lost as the letters shuffle toward their most probable configurations. Could this be gravity?

As a metaphor for how this would work, Dr. Verlinde used the example of a polymer — a strand of DNA, say, a noodle or a hair — curling up.

“It took me two months to understand polymers,” he said.

The resulting paper, as Dr. Verlinde himself admits, is a little vague.

“This is not the basis of a theory,” Dr. Verlinde explained. “I don’t pretend this to be a theory. People should read the words I am saying opposed to the details of equations.”

Dr. Padmanabhan said that he could see little difference between Dr. Verlinde’s and Dr. Jacobson’s papers and that the new element of an entropic force lacked mathematical rigor. “I doubt whether these ideas will stand the test of time,” he wrote in an e-mail message from India. Dr. Jacobson said he couldn’t make sense of it.

John Schwarz of the California Institute of Technology, one of the fathers of string theory, said the paper was “very provocative.” Dr. Smolin called it, “very interesting and also very incomplete.”

At a workshop in Texas in the spring, Raphael Bousso of the University of California, Berkeley, was asked to lead a discussion on the paper.

“The end result was that everyone else didn’t understand it either, including people who initially thought that did make some sense to them,” he said in an e-mail message.

“In any case, Erik’s paper has drawn attention to what is genuinely a deep and important question, and that’s a good thing,” Dr. Bousso went on, “I just don’t think we know any better how this actually works after Erik’s paper. There are a lot of follow-up papers, but unlike Erik, they don’t even understand the problem.”

The Verlinde brothers are now trying to recast these ideas in more technical terms of string theory, and Erik has been on the road a bit, traveling in May to the Perimeter Institute and Stony Brook University on Long Island, stumping for the end of gravity. Michael Douglas, a professor at Stony Brook, described Dr. Verlinde’s work as “a set of ideas that resonates with the community, adding, “everyone is waiting to see if this can be made more precise.”

Until then the jury of Dr. Verlinde’s peers will still be out.

Over lunch in New York, Dr. Verlinde ruminated over his experiences of the last six months. He said he had simply surrendered to his intuition. “When this idea came to me, I was really excited and euphoric even,” Dr. Verlinde said. “It’s not often you get a chance to say something new about Newton’s laws. I don’t see immediately that I am wrong. That’s enough to go ahead.”

He said friends had encouraged him to stick his neck out and that he had no regrets. “If I am proven wrong, something has been learned anyway. Ignoring it would have been the worst thing.”

The next day Dr. Verlinde gave a more technical talk to a bunch of physicists in the city. He recalled that someone had told him the other day that the unfolding story of gravity was like the emperor’s new clothes.

“We’ve known for a long time gravity doesn’t exist,” Dr. Verlinde said, “It’s time to yell it.”

AFLOAT The astrophysicist Stephen Hawking goes weightless in a special jet

Zero Gravity Corp, via Associated Press

ZERO GRAVITY Dr. Erik Verlinde says, “For me gravity doesn’t exist.” In a recent paper he expounded on his theory.

Kirsten Luce for The New York Times