Scientists grow cartilage to reconstruct nose

Made from a probe of the nasal septum: white, glossy cartilage was made in the laboratory.
Credit: Department of Biomedicine at the University of Basel

Scientists at the University of Basel report first ever successful nose reconstruction surgery using cartilage grown in the laboratory. Cartilage cells were extracted from the patient's nasal septum, multiplied and expanded onto a collagen membrane. The so-called engineered cartilage was then shaped according to the defect and implanted. The results will be published in the current edition of the academic journal The Lancet.

A research team from the University of Basel in Switzerland has reported that nasal reconstruction using engineered cartilage is possible. They used a method called tissue engineering where cartilage is grown from patients' own cells. This new technique was applied on five patients, aged 76 to 88 years, with severe defects on their nose after skin cancer surgery. One year after the reconstruction, all five patients were satisfied with their ability to breathe as well as with the cosmetic appearance of their nose. None of them reported any side effects.

Cells from the nasal septum

The type of non-melanoma skin cancer investigated in this study is most common on the nose, specifically the alar wing of the nose, because of its cumulative exposure to sunlight. To remove the tumor completely, surgeons often have to cut away parts of cartilage as well. Usually, grafts for reconstruction are taken from the nasal septum, the ear or the ribs and used to functionally reconstruct the nose. However, this procedure is very invasive, painful and can, due to the additional surgery, lead to complications at the site of the excision.

Together with colleagues from the University Hospital, the research team from the Department of Biomedicine at the University of Basel has now developed an alternative approach using engineered cartilage tissue grown from cells of the patients' nasal septum. 

They extracted a small biopsy, isolated the cartilage cells (chondrocytes) and multiplied them. The expanded cells were seeded onto a collagen membrane and cultured for two additional weeks, generating cartilage 40 times the size of the original biopsy. The engineered grafts were then shaped according to the defect on the nostril and implanted.

New possibilities for facial reconstruction

According to Ivan Martin, Professor for Tissue Engineering at the Department of Biomedicine at the University and University Hospital of Basel, "The engineered cartilage had clinical results comparable to the current standard surgery. This new technique could help the body to accept the new tissue better and to improve the stability and functionality of the nostril. Our success is based on the long-standing, effective integration in Basel between our experimental group at the Department of Biomedicine and the surgical disciplines at the University Hospital. The method opens the way to using engineered cartilage for more challenging reconstructions in facial surgery such as the complete nose, eyelid or ear."

The same engineered grafts are currently being tested in a parallel study for articular cartilage repair in the knee. Despite the optimistic perspectives, the use of these procedures in the clinical practice is still rather distant. "We need rigorous assessment of efficacy on larger cohorts of patients and the development of business models and manufacturing paradigms that will guarantee cost-effectiveness," says Martin.

Source: University of Basel

New technology allows medical professionals to step into their patients' shoes

Transports is a piece of technology that uses a low cost Raspberry Pi computer system, and allows users to recreate symptoms including dizziness and speech problems, along with wearable technology which creates a 6Hz tremor in the participant’s right hand. Credit: Image courtesy of University of Royal Holloway London

A pioneering piece of technology will allow users to experience the world through the eyes of a person with Young-Onset Parkinson's disease -- which could revolutionise the way carers and medical staff treat people with the degenerative condition.

Analogue, a theatre company set up by alumni of Royal Holloway, University of London has designed Transports -- a piece of technology which uses a low cost Raspberry Pi computer system, and allows users to recreate symptoms including dizziness and speech problems, along with wearable technology which creates a 6Hz tremor in the participant's right hand.
Young-Onset Parkinson's is a form of the neurological condition which affects people aged under 50. Symptoms of the disease include tremors, slowed movement and falls, and with no cure currently available, how care and treatment are managed can make a significant difference to a patient's quality of life.

The revolutionary project has been designed in collaboration with neuroscience specialist, Professor Narender Ramnani from the Department of Psychology at Royal Holloway, along with carers, researchers and people with the disease, at Parkinson's UK to ensure it is as effective and realistic as possible.

Liam Jarvis, Co-director of Analogue and Drama PhD Student at Royal Holloway, said: "Our principal interest is to work out how we can improve and facilitate communication and empathy by using simple technologies to immerse participants in the remote embodied experiences of others. Using inexpensive Raspberry Pi technology, we hope to expand the project to place participants inside different virtual subjects as an aid to better understand the experience of others."

The technology will now be tested with BSc psychology students at Royal Holloway and carers at Parkinson's UK to see how it can help medical practitioners better understand their patients and in the long term improve the treatment of the disease.

Anna Farrer, User Involvement Advisor at Parkinson's UK, said:"We know that people with Parkinson's feel that better public awareness about the condition would mean that they face less discrimination and have a better quality of life. Projects such as Transports have an important role educating the public, raising awareness -- and we hope, changing attitudes."

Source: University of Royal Holloway London

CASIS research set for launch aboard SpaceX mission to space station

The Bone Densitometer developed by Techshot, Inc. will enable X-ray testing for research studies aboard the International Space Station. Credit: CASIS

This fall marks another commercial cargo flight to the International Space Station. In September, SpaceX's Dragon spacecraft is scheduled to blast off to the orbital laboratory carrying supplies and investigations as part of the company's fourth contracted mission to the complex.

Included in the cargo will be the third suite of research investigations sponsored by the Center for the Advancement of Science in Space (CASIS). With the role of managing the U.S. National Laboratory on the space station, CASIS is responsible for brokering and facilitating research investigations on the station with clear Earth applications and benefits.

The latest collection of CASIS-sponsored research, termed Advancing Research Knowledge (ARK)-2, centers heavily on life sciences. Studies include those focused on drug development, disease understanding and validation testing. Each investigation will use the unique conditions aboard the space station to advance researchers' understanding in those areas of study.

Additionally, CASIS and NASA have partnered with Techshot Inc., of Greenville, Indiana, to develop a new hardware device capable of assisting with research that may improve understandings of muscle wasting and diseases like osteoporosis.

The CASIS-sponsored hardware and life science investigations destined for the space station's national laboratory include the Bone Densitometer, which will be the first X-ray machine installed on the space station. A joint project between CASIS, NASA and Techshot, the facility will be instrumental in conducting rodent research on station. The Bone 

Densitometer will allow astronauts to examine bone density of model organisms in space through the use of Dual-Energy X-ray Absorptiometry (DEXA) technology. In short, researchers will be able to assess bone density loss by measuring energy levels absorbed by bones via the device.

The Rodent Research-1 investigation kicks off a series of NASA and CASIS-sponsored investigations focused on rodent research aboard the space station. The study will be the first to use the Bone Densitometer in an effort to help scientists examine the effects of long duration spaceflight. There are numerous applications to these investigations including studying bone loss, muscle atrophy and cardiovascular anomalies. However, the primary focus of this inaugural mission will be to assess the operational capabilities of the new hardware designed for these investigations.

The Drug Metabolism study will assist researchers in the area of drug development and human biology. This investigation is led by a scientist from the U.S. Department of Veteran Affairs, Dr. Timothy Hammond, who is looking to study yeast cells in microgravity. The goal of this investigation is to explore the changes in these cells in space to improve drug development for various diseases, including cancer therapeutics.

The Protein Crystal Optimization study is an investigation aiming to leverage the unique location of the space station to examine the internal structure of three medically important proteins. The space environment should allow researchers to grow the selected protein crystals to an optimal size and quality to allow for closer examination via neutron diffraction. This protein crystal growth in microgravity may reveal new characteristics that are masked by gravity on Earth. By studying these three proteins, medically relevant to salmonella infection, peptic ulcer disease, and biomarkers for heart attack and liver disease, researchers can apply insights towards improved treatments.

A New Era In Commercial Use of the Space Station

The space station's national laboratory affords researchers the ability to conduct experiments in a distinctive environment with factors and variables that are near impossible to replicate on the ground. With access to our nation's only orbiting laboratory, CASIS works with new and non-traditional users to take advantage of this resource. A great example of novel commercial research heading to station is the Cobra Puma Golf investigation.

The Cobra Puma Golf-electroplating investigation, also launching aboard SpaceX, is a materials science investigation sponsored by CASIS in collaboration with COBRA PUMA Golf (CPG). The CPG research and development team will examine the impacts of microgravity on electroplating -- the process of coating a metallic surface using an electric current. The study will test a variety of coating substances on materials used in golf equipment manufacturing. The insight gained from this investigation will aid CPG in identifying improved material development techniques.

CPG's project is another example of a commercial user leveraging the capabilities of the ISS National Lab to advance ground research. Through brokering research investigations with commercial companies, CASIS hopes to demonstrate the space station is not only a test-bed for groundbreaking research and development, but a unique laboratory that can help differentiate investigations initiatives from ground-based studies.

The mission is another milestone for the space community, showcasing how commercial endeavors can work hand-in-hand with research goals. The studies of ARK-2 exemplify the diverse possibilities for the space station and users of the research platform. From commercial launch providers that transport investigations to space, to commercial researchers looking to use the national laboratory, science in space is good for life on Earth.

Source: NASA

Roman Gladiators ate a mostly vegetarian diet and drank a tonic of ashes after training

Anthropology unlocks clues about Roman gladiators' eating habits. Credit: OEAI, Pietsch

Roman gladiators ate a mostly vegetarian diet and drank ashes after training as a tonic. These are the findings of anthropological investigations carried out on bones of warriors found during excavations in the ancient city of Ephesos.

Historic sources report that gladiators had their own diet. This comprised beans and grains. Contemporary reports referred to them as "hordearii" ("barley eaters").

In a study by the Department of Forensic Medicine at the MedUni Vienna in cooperation with the Department of Anthropology at the Institute of Forensic Medicine at the University of Bern, bones were examined from a gladiator cemetery uncovered in 1993 which dates back to the 2nd or 3rd century BC in the then Roman city of Ephesos (now in modern-day Turkey). At the time, Ephesos was the capital of the Roman province of Asia and had over 200,000 inhabitants.

Using spectroscopy, stable isotope ratios (carbon, nitrogen and sulphur) were investigated in the collagen of the bones, along with the ratio of strontium to calcium in the bone mineral.

The result shows that gladiators mostly ate a vegetarian diet. There is virtually no difference in terms of nutrition from the local "normal population." Meals consisted primarily of grain and meat-free meals. The word "barley eater" relates in this case to the fact that gladiators were probably given grain of an inferior quality.

Build-up drink following physical exertion

The difference between gladiators and the normal population is highly significant in terms of the amount of strontium measured in their bones. This leads to the conclusion that the gladiators had a higher intake of minerals from a strontium-rich source of calcium. The ash drink quoted in literature probably really did exist. "Plant ashes were evidently consumed to fortify the body after physical exertion and to promote better bone healing," explains study leader Fabian Kanz from the Department of Forensic Medicine at the MedUni Vienna. "Things were similar then to what we do today -- we take magnesium and calcium (in the form of effervescent tablets, for example) following physical exertion." Calcium is essential for bone building and usually occurs primarily in milk products.

A further research project is looking at the migration of gladiators, who often came from different parts of the Roman Empire to Ephesos. The researchers are hoping that comparison of the bone data from gladiators with that of the local fauna will yield a number of differences.

Source: Medical University of Vienna

New natural supplement relieves canine arthritis

Portrait old dog

Arthritis pain in dogs can be relieved, with no side effects, by a new product based on medicinal plants and dietary supplements that was developed at the University of Montreal's Faculty of Veterinary Medicine. "While acupuncture and electrical stimulation are two approaches that have been shown to have positive effects on dogs, until now a few studies have investigated a plant-based approach to therapy," explained Professor Éric Troncy, senior author of the study. His findings were published in Research in Veterinary Science.

Troncy and his team worked with 32 dogs (and their owners!) who had been diagnosed with arthritis by X-ray and orthopaedic exam, and who all weighed more than 20 kilograms. By drawing on existing rodent studies and working with Pierre Haddad of the university's Department of Pharmacology, Troncy developed two formulas for his trial. These formulas are not currently commercially available.

The first formula, composed of curcumin, devil's claw, black current, Indian frankincense (Salai), willow bark, pineapple bromelaine and camomile, was developed to treat arthritis-induced inflammation. The second included the same ingredients, plus dietary supplements such as omega 3, chondroitin sulfate and glutamine, and was formulated in the hope that it would promote the regeneration of articulations.

Half the dogs received the first formula for four weeks and then the second formula for another four weeks. The other half, acting as the control, received a placebo. The outcomes were tested using three methods. Firstly, the dogs were filmed as they walked at a consistent speed over a special platform that captures the strength of each paw. Secondly, a special electronic collar recorded the dogs' daily activities. And finally, the owners were asked to provide their own evaluations of their dog's behaviour.

The researchers were able to identify an improvement by the fourth week of the trial. "After the eight week course, on average, the strength of the dogs receiving treatment had improved to the equivalent of a kilo of extra strength per paw, which is moreover. None of these dogs saw their health decline, unlike 35.8% of the dogs who were given the placebo," said Maxim Moreau, who was first author of the study.

The improvements were also reflected in the dogs' daily lives. The collars revealed that the dogs receiving treatment maintained their physical activity, and in fact the group average increased from six hours of daily activity to eight. Meanwhile, the dogs receiving the placebo were progressively less active. "In some cases, we recorded the dogs to ensure that the collar was recording actual physical activity rather than movements such as scratching," Troncy explained.

Nonetheless, the ratings from the owners were more mixed. "This third evaluation was more subjective and the contrast between the test group and the control group less stark," Troncy said. "We suspect that the owner may have forgotten what the animal's behaviour was like before it developed arthritis."

The findings raise the possibility of offering a new form of treatment to human beings. "The model of evaluation that we have used is the best for predicting the efficacy of anti-arthritis treatments. We can therefore consider that clinical trials on humans would have a good chance of having positive outcomes," Troncy said.

About this study: This study was funded in part by a grant from ArthroLab Inc., an ongoing New Opportunities Fund grant (#9483) and a Leader Opportunity Fund grant (#24601) from the Canada Foundation for Innovation for the pain/function equipment, a Discovery Grant (#327158-2008; #441651-2013) from the Natural Sciences and Engineering Research Council of Canada for the bio-analyses and salaries, and by the Osteoarthritis Chair of the University of Montreal Hospital Centre, Université de Montréal. Maxim Moreau received a doctoral scholarship from the Canadian Institutes of Health Research (TGF-53914) -- Strategic Training Initiative in Health Research program (MENTOR) and a doctoral scholarship from the Fonds de recherche du Québec-Santé.

Source: Universite de Montreal

Hunter-gatherer past shows our fragile bones result from inactivity since invention of farming

Hunter-gatherer bone mass compared to agriculturalist bone mass. Credit: Timothy Ryan

New research across thousands of years of human evolution shows that our skeletons have become much lighter and more fragile since the invention of agriculture -- a result of our increasingly sedentary lifestyles as we shifted from foraging to farming.

The new study, published today in the journal PNAS, shows that, while human hunter-gatherers from around 7,000 years ago had bones comparable in strength to modern orangutans, farmers from the same area over 6,000 years later had significantly lighter and weaker bones that would have been more susceptible to breaking.

Bone mass was around 20% higher in the foragers -- the equivalent to what an average person would lose after three months of weightlessness in space.

After ruling out diet differences and changes in body size as possible causes, researchers have concluded that reductions in physical activity are the root cause of degradation in human bone strength across millennia. It is a trend that is reaching dangerous levels, they say, as people do less with their bodies today than ever before.

Researchers believe the findings support the idea that exercise rather than diet is the key to preventing heightened fracture risk and conditions such as osteoporosis in later life: more exercise in early life results in a higher peak of bone strength around the age of 30, meaning the inevitable weakening of bones with age is less detrimental.

There is, in fact, no anatomical reason why a person born today could not achieve the bone strength of an orangutan or early human forager, say researchers; but even the most physically active people alive are unlikely to be loading bones with enough frequent and intense stress to allow for the increased bone strength seen in the 'peak point' of traditional hunter-gatherers and non-human primate bones.

"Contemporary humans live in a cultural and technological milieu incompatible with our evolutionary adaptations. There's seven million years of hominid evolution geared towards action and physical activity for survival, but it's only in the last say 50 to 100 years that we've been so sedentary -- dangerously so," said co-author Dr Colin Shaw from the University of Cambridge's Phenotypic Adaptability, Variation and Evolution (PAVE) Research Group.

"Sitting in a car or in front of a desk is not what we have evolved to do."

The researchers x-rayed samples of human femur bones from the archaeological record, along with femora from other primate species, focusing on the inside of the femoral head: the ball at the top of the femur which fits into the pelvis to form the hip joint, one of the most load-bearing bone connections in the body.

Two types of tissue form bone: the cortical or 'hard' bone shell coating the outside, and the trabecular or 'spongy' bone: the honeycomb-like mesh encased within cortical shell that allows flexibility but is also vulnerable to fracture.

The researchers analysed the trabecular bone from the femoral head of four distinct archaeological human populations representing mobile hunter-gatherers and sedentary agriculturalists, all found in the same area of the US state of Illinois (and likely to be genetically similar as a consequence).

The trabecular structure is very similar in all populations, with one notable exception: within the mesh, hunter-gatherers have a much higher amount of actual bone relative to air.

"Trabecular bone has much greater plasticity than other bone, changing shape and direction depending on the loads imposed on it; it can change structure from being pin or rod-like to much thicker, almost plate-like. In the hunter-gatherer bones, everything was thickened," said Shaw.

This thickening is the result of constant loading on the bone from physical activity as hunter-gatherers roamed the landscape seeking sustenance. This fierce exertion would result in minor damage that caused the bone mesh to grow back ever stronger and thicker throughout life -- building to a 'peak point' of bone strength which counter-balanced the deterioration of bones with age.

Shaw believes there are valuable lessons to be learnt from the skeletons of our prehistoric predecessors. "You can absolutely morph even your bones so that they deal with stress and strain more effectively. Hip fractures, for example, don't have to happen simply because you get older if you build your bone strength up earlier in life, so that as you age it never drops below that level where fractures can easily occur."

Other theories for humans evolving a lighter, more fragile skeleton include changes in diet or selection for a more efficient, lighter skeleton, which was never reversed.

While the initial switch to farming did cause a dip in human health due to monoculture diets that lacked variety, the populations tested were unaffected by this window in history. "Of course we need a level of calcium to maintain bone heath, but beyond that level excess calcium isn't necessary," said Shaw.

The research also counters the theory that, at some point in human evolution, our bones just became lighter -- perhaps because there wasn't enough food to support a denser skeleton. "If that was true, human skeletons would be entirely distinct from other living primates. We've shown that hunter-gatherers fall right in line with primates of a similar body size. Modern human skeletons are not systemically fragile; we are not constrained by our anatomy."

"The fact is, we're human, we can be as strong as an orangutan -- we're just not, because we are not challenging our bones with enough loading, predisposing us to have weaker bones so that, as we age, situations arise where bones are breaking when, previously, they would not have" Shaw said.

While the 7,000-year-old foragers had vastly stronger bones than the 700-year-old farmers, Shaw says that neither competes with even earlier hominids from around 150,000 years ago. 

"Something is going on in the distant past to create bone strength that outguns anything in the last 10,000 years."

The next step for Shaw's research team will be to look at how different types of loading and mobility shape bodies and bones by cross-referencing archaeological records with testing on modern ultra-marathon runners, who cover punishing distances over a range of terrains -- from the Himalayas to the Namibian desert. He hopes this future work will provide insight into the kind of mobility that gave our ancient ancestors such powerful physical strength.

Source: University of Cambridge

Making lab-grown tissues stronger

Connective tissues like cartilage are made of cross-linked bundles of collagen fibers. UC Davis biomedical engineers have discovered that reducing oxygen or adding an enzyme called LOX can make these bundles stronger. The technique can be used to strengthen both natural cartilage kept in the lab for transplant, and artificial cartilage grown in culture. Credit: Eleftherios Makris and Kyriacos Athanasiou, UC Davis

Lab-grown tissues could one day provide new treatments for injuries and damage to the joints, including articular cartilage, tendons and ligaments.

Cartilage, for example, is a hard material that caps the ends of bones and allows joints to work smoothly. UC Davis biomedical engineers, exploring ways to toughen up engineered cartilage and keep natural tissues strong outside the body, report new developments this week in the journal Proceedings of the National Academy of Sciences.

"The problem with engineered tissue is that the mechanical properties are far from those of native tissue," said Eleftherios Makris, a postdoctoral researcher at the UC Davis Department of Biomedical Engineering and first author on the paper. Makris is working under the supervision of Professor Kyriacos A. Athanasiou, a distinguished professor of biomedical engineering and orthopedic surgery, and chair of the Department of Biomedical Engineering.

While engineered cartilage has yet to be tested or approved for use in humans, a current method for treating serious joint problems is with transplants of native cartilage. But it is well known that this method is not sufficient as a long-term clinical solution, Makris said.
The major component of cartilage is a protein called collagen, which also provides strength and flexibility to the majority of our tissues, including ligaments, tendons, skin and bones. Collagen is produced by the cells and made up of long fibers that can be cross-linked together.

Engineering new cartilage

Researchers in the Athanasiou group have been maintaining native cartilage in the lab and culturing cartilage cells, or chondrocytes, to produce engineered cartilage.

"In engineered tissues the cells produce initially an immature matrix, and the maturation process makes it tougher," Makris said.

Knee joints are normally low in oxygen, so the researchers looked at the effect of depriving native or engineered cartilage of oxygen. In both cases, low oxygen led to more cross-linking and stronger material. They also found that an enzyme called lysyl oxidase, which is triggered by low oxygen levels, promoted cross-linking and made the material stronger.

"The ramifications of the work presented in the PNAS paper are tremendous with respect to tissue grafts used in surgery, as well as new tissues fabricated using the principles of tissue engineering," Athanasiou said. Grafts such as cadaveric cartilage, tendons or ligaments -- notorious for losing their mechanical characteristics in storage -- can now be treated with the processes developed at UC Davis to make them stronger and fully functional, he said.
Athanasiou also envisions that many tissue engineering methods will now be altered to take advantage of this strengthening technique.

Source: University of California - Davis