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  • richardmitnick 2:39 pm on September 2, 2014 Permalink | Reply
    Tags: , Autism, Medicine,   

    From Princeton: “Early cerebellum injury hinders neural development, possible root of autism, theory suggests” 

    Princeton University
    Princeton University

    September 2, 2014
    Morgan Kelly, Office of Communications

    A brain region largely known for coordinating motor control has a largely overlooked role in childhood development that could reveal information crucial to understanding the onset of autism, according to Princeton University researchers.

    The cerebellum — an area located in the lower rear of the brain — is known to process external and internal information such as sensory cues that influence the development of other brain regions, the researchers report in the journal Neuron. Based on a review of existing research, the researchers offer a new theory that an injury to the cerebellum during early life potentially disrupts this process and leads to what they call “developmental diaschisis,” which is when a loss of function in one part of the brain leads to problems in another region.

    cere
    Drawing of the human brain, showing cerebellum and pons

    The researchers specifically apply their theory to autism, though they note that it could help understand other childhood neurological conditions. Conditions within the autism spectrum present “longstanding puzzles” related to cognitive and behavioral disruptions that their ideas could help resolve, they wrote. Under their theory, cerebellar injury causes disruptions in how other areas of the brain develop an ability to interpret external stimuli and organize internal processes, explained first author Sam Wang, an associate professor of molecular biology and the Princeton Neuroscience Institute (PNI).

    wang
    Princeton University researchers offer a new theory that an early-life injury to the cerebellum disrupts the brain’s processing of external and internal information and leads to “developmental diaschisis,” wherein a loss of function in one brain region leads to problems in another. Applied to autism, cerebellar injury could hinder how other areas of the brain interpret external stimuli and organize internal processes. Based on a review of existing research, the researchers found that a cerebellar injury at birth can make a person 36 times more likely to score highly on autism screening tests, and is the largest un-inherited risk (above).

    “It is well known that the cerebellum is an information processor. Our neocortex [the largest part of the brain, responsible for much higher processing] does not receive information unfiltered. There are critical steps that have to happen between when external information is detected by our brain and when it reaches the neural cortex,” said Wang, who worked with doctoral student Alexander Kloth and postdoctoral research associate Aleksandra Badura, both in PNI.

    “At some point, you learn that smiling is nice because Mom smiles at you. We have all these associations we make in early life because we don’t arrive knowing that a smile is nice,” Wang said. “In autism, something in that process goes wrong and one thing could be that sensory information is not processed correctly in the cerebellum.”

    Mustafa Sahin, a neurologist at Boston’s Children Hospital and associate professor of neurology at Harvard Medical School, said that Wang and his co-authors build upon known links between cerebellar damage and autism to suggest that the cerebellum is essential to healthy neural development. Numerous studies — including from his own lab — support their theory, said Sahin, who is familiar with the work but was not involved in it.

    “The association between cerebellar deficits and autism has been around for a while,” Sahin said. “What Sam Wang and colleagues do in this perspective article is to synthesize these two themes and hypothesize that in a critical period of development, cerebellar dysfunction may disrupt the maturation of distant neocortical circuits, leading to cognitive and behavioral symptoms including autism.”

    Traditionally, the cerebellum has been studied in relation to motor movement and coordination in adults. Recent studies, however, strongly suggest that it also influences childhood cognition, Wang said. Several studies also have found a correlation between cerebellar injury and the development of a disorder in the autism spectrum, the researchers report. For instance, the researchers cite a 2007 paper in the journal Pediatrics that found that individuals who experienced cerebellum damage at birth were 40 times more likely to score highly on autism screening tests. They also reference studies in 2004 and 2005 that found that the cerebellum is the most frequently disrupted brain region in people with autism.

    “What we realized from looking at the literature is that these two problems — autism and cerebellar injury — might be related to each other” via the cerebellum’s influence on wider neural development, Wang said. “We hope to get people and scientists thinking differently about the cerebellum or about autism so that the whole field can move forward.”

    The researchers conclude by suggesting methods for testing their theory. First, by inactivating brain-cell electrical activity, it should be possible to pinpoint the developmental stage in which injury to one part of the brain affects the maturation of another. A second, more advanced method is to reconstruct the neural connections between the cerebellum and other brain regions; the federal BRAIN Initiative announced in 2013 aims to map the activity of all the brain’s neurons. Finally, mouse brains can be used to disable and restore brain-region function to observe the “upstream” effect in other areas.

    The paper, The cerebellum, sensitive periods, and autism,” was published Aug. 6 in Neuron. The work was supported by grants from the National Institutes of Health (grant nos. R01 NS045193 and F31 MH098651), the Nancy Lurie Marks Family Foundation, and the Sutherland Cook Fund.

    See the full article here.

    About Princeton: Overview

    Princeton University is a vibrant community of scholarship and learning that stands in the nation’s service and in the service of all nations. Chartered in 1746, Princeton is the fourth-oldest college in the United States. Princeton is an independent, coeducational, nondenominational institution that provides undergraduate and graduate instruction in the humanities, social sciences, natural sciences and engineering.

    As a world-renowned research university, Princeton seeks to achieve the highest levels of distinction in the discovery and transmission of knowledge and understanding. At the same time, Princeton is distinctive among research universities in its commitment to undergraduate teaching.

    Today, more than 1,100 faculty members instruct approximately 5,200 undergraduate students and 2,600 graduate students. The University’s generous financial aid program ensures that talented students from all economic backgrounds can afford a Princeton education.

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  • richardmitnick 2:05 pm on September 2, 2014 Permalink | Reply
    Tags: , , , Medicine   

    From Carnegie Mellon: “Acoustic Tweezers” 

    Carnegie Mellon University logo
    Carnegie Mellon university

    Carnegie Mellon University President Subra Suresh and researchers from MIT and Pennsylvania State University have devised a new way to separate cells by exposing them to sound waves as they flow through a tiny channel.

    five
    [l-r] Tony Huang, Ming Dao, Subra Suresh, Peng Li, Zhangli Peng

    Their device could be used to detect the extremely rare tumor cells that circulate in cancer patients’ blood, helping doctors predict whether a tumor is going to spread.

    no

    “The method we describe in this paper is a step forward in the detection and isolation of circulating tumor cells in the body,” Dr. Suresh said. “It has the potential to offer a safe and effective new tool for cancer researchers, clinicians and patients.”

    The research is published online in the Proceedings of the National Academy of Sciences (PNAS).

    The paper describes a process that could dramatically alter the way scientists on the leading edge of cell research, disease diagnostics and therapeutics conduct their work. The technology demonstrated can be used to separate rare circulating cancer cells from white blood cells. The researchers have filed for a patent on the device.

    The method used by President Suresh and his co-authors shows unique promise. It causes the least disturbance and damage to the cells being separated of any process developed so far.

    Their approach adopts a method that researchers sometimes call “acoustic tweezers.”

    “Acoustic pressure is very mild and much smaller in terms of forces and disturbance to the cell,” said Ming Dao, a principal research scientist in MIT’s Department of Materials Science and Engineering and one of the senior authors of the paper.

    Dao said this is a gentler method to existing cell-sorting technologies, which require tagging the cells using chemicals or exposing them to damaging mechanical forces.

    The team was able to accurately separate cells when the difference between cell diameters was smaller than two micrometers.

    Dao said that the next steps are to test the device using patient samples and improve the throughput to shorten the process time.

    “When blood is out of the body too long, the properties change,” Dao said.

    Tony Jun Huang, a professor of engineering science and mechanics at Penn State, is also a senior author of the paper. Lead authors are MIT postdoc Xiaoyun Ding and Zhangli Peng, a former MIT postdoc who is now an assistant professor at the University of Notre Dame.

    See the full article here.

    Carnegie Mellon University (CMU) is a global research university with more than 12,000 students, 95,000 alumni, and 5,000 faculty and staff.
    CMU has been a birthplace of innovation since its founding in 1900.
    Today, we are a global leader bringing groundbreaking ideas to market and creating successful startup businesses.
    Our award-winning faculty members are renowned for working closely with students to solve major scientific, technological and societal challenges. We put a strong emphasis on creating things—from art to robots. Our students are recruited by some of the world’s most innovative companies.
    We have campuses in Pittsburgh, Qatar and Silicon Valley, and degree-granting programs around the world, including Africa, Asia, Australia, Europe and Latin America.

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  • richardmitnick 7:16 am on August 26, 2014 Permalink | Reply
    Tags: , , Medicine, Microfluidics   

    From M.I.T.: “Sorting cells with sound waves” 


    MIT News

    August 25, 2014
    Anne Trafton | MIT News Office

    Acoustic device that separates tumor cells from blood cells could help assess cancer’s spread.

    cells
    Illustration: Christine Daniloff/MIT

    Researchers from MIT, Pennsylvania State University, and Carnegie Mellon University have devised a new way to separate cells by exposing them to sound waves as they flow through a tiny channel. Their device, about the size of a dime, could be used to detect the extremely rare tumor cells that circulate in cancer patients’ blood, helping doctors predict whether a tumor is going to spread.

    Separating cells with sound offers a gentler alternative to existing cell-sorting technologies, which require tagging the cells with chemicals or exposing them to stronger mechanical forces that may damage them.

    “Acoustic pressure is very mild and much smaller in terms of forces and disturbance to the cell. This is a most gentle way to separate cells, and there’s no artificial labeling necessary,” says Ming Dao, a principal research scientist in MIT’s Department of Materials Science and Engineering and one of the senior authors of the paper, which appears this week in the Proceedings of the National Academy of Sciences.

    Subra Suresh, president of Carnegie Mellon, the Vannevar Bush Professor of Engineering Emeritus, and a former dean of engineering at MIT, and Tony Jun Huang, a professor of engineering science and mechanics at Penn State, are also senior authors of the paper. Lead authors are MIT postdoc Xiaoyun Ding and Zhangli Peng, a former MIT postdoc who is now an assistant professor at the University of Notre Dame.

    The researchers have filed for a patent on the device, the technology of which they have demonstrated can be used to separate rare circulating cancer cells from white blood cells.

    To sort cells using sound waves, scientists have previously built microfluidic devices with two acoustic transducers, which produce sound waves on either side of a microchannel. When the two waves meet, they combine to form a standing wave (a wave that remains in constant position). This wave produces a pressure node, or line of low pressure, running parallel to the direction of cell flow. Cells that encounter this node are pushed to the side of the channel; the distance of cell movement depends on their size and other properties such as compressibility.

    However, these existing devices are inefficient: Because there is only one pressure node, cells can be pushed aside only short distances.

    The new device overcomes that obstacle by tilting the sound waves so they run across the microchannel at an angle — meaning that each cell encounters several pressure nodes as it flows through the channel. Each time it encounters a node, the pressure guides the cell a little further off center, making it easier to capture cells of different sizes by the time they reach the end of the channel.

    This simple modification dramatically boosts the efficiency of such devices, says Taher Saif, a professor of mechanical science and engineering at the University of Illinois at Urbana-Champaign. “That is just enough to make cells of different sizes and properties separate from each other without causing any damage or harm to them,” says Saif, who was not involved in this work.

    In this study, the researchers first tested the system with plastic beads, finding that it could separate beads with diameters of 9.9 and 7.3 microns (thousandths of a millimeter) with about 97 percent accuracy. They also devised a computer simulation that can predict a cell’s trajectory through the channel based on its size, density, and compressibility, as well as the angle of the sound waves, allowing them to customize the device to separate different types of cells.

    To test whether the device could be useful for detecting circulating tumor cells, the researchers tried to separate breast cancer cells known as MCF-7 cells from white blood cells. These two cell types differ in size (20 microns in diameter for MCF-7 and 12 microns for white blood cells), as well as density and compressibility. The device successfully recovered about 71 percent of the cancer cells; the researchers plan to test it with blood samples from cancer patients to see how well it can detect circulating tumor cells in clinical settings. Such cells are very rare: A 1-milliliter sample of blood may contain only a few tumor cells.

    “If you can detect these rare circulating tumor cells, it’s a good way to study cancer biology and diagnose whether the primary cancer has moved to a new site to generate metastatic tumors,” Dao says. “This method is a step forward for detection of circulating tumor cells in the body. It has the potential to offer a safe and effective new tool for cancer researchers, clinicians and patients,” Suresh says.

    The research was funded by the National Institutes of Health and the National Science Foundation.

    See the full article, with video, here.

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  • richardmitnick 6:38 am on August 26, 2014 Permalink | Reply
    Tags: , Gerontology, Medicine   

    From Brown: “Care improves with culture change” 

    Brown University
    Brown University

    August 25, 2014
    David Orenstein 401-863-1862

    If a nursing home makes an extensive investment in “culture change” it will see improvements in quality of care, according to a new study led by Brown University gerontology researchers.

    home
    Benefits of cultural change Creating warm residential-style common areas is one of many cultural changes that improve quality of care. Opportunities for residents to make choices, schedules that are less restrictive, and care decisions informed by front line staff are all part of cultural change. Photo: Wayne Dion for Tockwotton Home

    Culture change is a rethinking of nursing home operations and structure to allow a more residential lifestyle for residents, more resident choice in schedules and activities, and more front-line staff input into care management. Residents, for example, may become able to decide when to go to lunch and nurse’s aides may get a seat at the table in designing care processes. Across the country nursing homes are at various stages of implementing such changes, ranging from not at all to extensively.

    In the new study, a research team led by Susan Miller, professor of health services policy and practice at the Brown University School of Public Health, focused on homes that had recently accomplished some degree of implementation. Miller’s goal was not only to measure whether culture change introduction produced improvements in care quality but to do so for nursing homes that had implemented a similar extent of culture change practice by 2009-10.

    “What’s unique about this paper is that we stratified by the amount of implementation,” said Miller, senior author of the research published online in the Journal of the American Geriatrics Society.

    The study’s results come from surveys of directors of nursing at 824 homes in which Miller and her team assessed the degree of culture change implementation as of 2009-10. The researchers considered nursing homes that introduced culture change between 2005 and 2010, excluding homes that either had not adopted change or were especially early adopters.

    In their analysis Miller and her colleagues separated out the top quartile of implementers from the bottom three quartiles. For each group they looked at whether the list of 13 quality measures improved or worsened in the year after culture change introduction, compared to similar nursing homes that had not yet introduced it. They controlled for factors such as the homes’ occupancy rates, their mix of medical cases, and the degree of county-level competition.

    Degrees of quality improvement

    Upon introduction of culture change, the homes that implemented culture change most extensively produced statistically significant improvements in the percent of residents on bladder training programs, the percent of residents who required restraints, the proportion of residents with feeding tubes, and the percent with pressure ulcers. They also showed a nearly significant reduction in resident hospitalizations. No quality indicator became significantly worse.

    Among homes that implemented less culture change, the only significant improvement occurred in the number of Medicare/Medicaid health-related and quality of life survey deficiencies. (Miller said some nursing home administrators stated in interviews that they implemented those practices targeted by state surveyors.) Urinary tract infections and hospitalizations got slightly worse.

    No degree of culture change significantly improved other quality indicators such as the percent of residents with advanced directives or the proportion on antipscychotic medications. Falls did not get better, but they also did not get worse as some elder care observers had feared they would under culture change, Miller noted.

    The results help affirm that culture change can be effective in homes where the staff has embraced its patient-centered, flatter-management philosophy, Miller said.

    “It seems to be a valid notion to improve quality with adoption when you really adopt the philosophy and are doing a lot,” she said.

    In addition to Miller, the paper’s other authors are Michael Lepore, Julie Lima, Renee Shield, and Denise Tyler.

    The Retirement Research Foundation (grant 2008-086) and the National Institute on Aging (grant 1P01AG027296) funded the study.

    See the full article here.

    Welcome to Brown

    Rhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interiorRhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interior

    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

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  • richardmitnick 4:07 pm on August 25, 2014 Permalink | Reply
    Tags: , , , Medicine, University of Chicago   

    From Argonne Lab: “Gut bacteria that protect against food allergies identified” 

    News from Argonne National Laboratory

    August 25, 2014
    This story was first reported by the University of Chicago Medicine and Biological Sciences.

    The presence of Clostridia, a common class of gut bacteria, protects against food allergies, a new study in mice finds. By inducing immune responses that prevent food allergens from entering the bloodstream, Clostridia minimize allergen exposure and prevent sensitization – a key step in the development of food allergies. The discovery points toward probiotic therapies for this so-far untreatable condition, report scientists from the University of Chicago, Aug. 25 in the Proceedings of the National Academy of Sciences.

    clos
    One variety of many of Clostridia

    “From a basic science perspective, what is fascinating with this research is the fine-scale machinations that the host microbiome exhibits with its host,” said Dionysios Antonopoulos of the Institute for Genomics and Systems Biology at Argonne National Laboratory and a co-author for the study. “Specific populations of microorganisms serve specific functions in mediating how the host’s immune system senses and interacts with its environment. As with this study, understanding how specific populations of the microbial community are impacted by antibiotics or diet provides a guide on what therapeutic strategies need to be developed to restore a healthy state.”

    Although the causes of food allergy – a sometimes deadly immune response to certain foods – are unknown, studies have hinted that modern hygienic or dietary practices may play a role by disturbing the body’s natural bacterial composition. In recent years, food allergy rates among children have risen sharply – increasing approximately 50 percent between 1997 and 2011 – and studies have shown a correlation to antibiotic and antimicrobial use.

    “Environmental stimuli such as antibiotic overuse, high fat diets, caesarean birth, removal of common pathogens and even formula feeding have affected the microbiota with which we’ve co-evolved,” said study senior author Cathryn Nagler, PhD, Bunning Food Allergy Professor at the University of Chicago. “Our results suggest this could contribute to the increasing susceptibility to food allergies.”

    To test how gut bacteria affect food allergies, Nagler and her team investigated the response to food allergens in mice. They exposed germ-free mice (born and raised in sterile conditions to have no resident microorganisms) and mice treated with antibiotics as newborns (which significantly reduces gut bacteria) to peanut allergens. Both groups of mice displayed a strong immunological response, producing significantly higher levels of antibodies against peanut allergens than mice with normal gut bacteria.

    This sensitization to food allergens could be reversed, however, by reintroducing a mix of Clostridia bacteria back into the mice. Reintroduction of another major group of intestinal bacteria, Bacteroides, failed to alleviate sensitization, indicating that Clostridia have a unique, protective role against food allergens.

    Closing the door

    To identify this protective mechanism, Nagler and her team studied cellular and molecular immune responses to bacteria in the gut. Genetic analysis revealed that Clostridia caused innate immune cells to produce high levels of interleukin-22 (IL-22), a signaling molecule known to decrease the permeability of the intestinal lining.

    Antibiotic-treated mice were either given IL-22 or were colonized with Clostridia. When exposed to peanut allergens, mice in both conditions showed reduced allergen levels in their blood, compared to controls. Allergen levels significantly increased, however, after the mice were given antibodies that neutralized IL-22, indicating that Clostridia-induced IL-22 prevents allergens from entering the bloodstream.

    “We’ve identified a bacterial population that protects against food allergen sensitization,” Nagler said. “The first step in getting sensitized to a food allergen is for it to get into your blood and be presented to your immune system. The presence of these bacteria regulates that process.” She cautions, however, that these findings likely apply at a population level, and that the cause-and-effect relationship in individuals requires further study.

    While complex and largely undetermined factors such as genetics greatly affect whether individuals develop food allergies and how they manifest, the identification of a bacteria-induced barrier-protective response represents a new paradigm for preventing sensitization to food. Clostridia bacteria are common in humans and represent a clear target for potential therapeutics that prevent or treat food allergies. Nagler and her team are working to develop and test compositions that could be used for probiotic therapy and have filed a provisional patent.

    “It’s exciting because we know what the bacteria are; we have a way to intervene,” Nagler said. “There are of course no guarantees, but this is absolutely testable as a therapeutic against a disease for which there’s nothing. As a mom, I can imagine how frightening it must be to worry every time your child takes a bite of food.”

    “Food allergies affect 15 million Americans, including one in 13 children, who live with this potentially life-threatening disease that currently has no cure,” said Mary Jane Marchisotto, senior vice president of research at Food Allergy Research & Education. “We have been pleased to support the research that has been conducted by Dr. Nagler and her colleagues at the University of Chicago.”

    The study, Commensal bacteria protect against food allergen sensitization, was supported by Food Allergy Research & Education (FARE) and the University of Chicago Digestive Diseases Research Core Center. Gene sequencing was conducted at the Next-Generation Sequencing Core at Argonne National Labortory. Additional authors include Andrew T. Stefka, Taylor Feehley, Prabhanshu Tripathi, Ju Qiu, Kathy D. McCoy, Sarkis K. Mazmanian, Melissa Y. Tjota, Goo-Young Seo, Severine Cao, Betty R. Theriault, Dionysios A. Antonopoulos, Liang Zhou, Eugene B. Chang and Yang-Xin Fu.

    Food Allergy Research & Education (FARE) is a 501(c)(3) nonprofit organization that seeks to find a cure for food allergies while keeping affected individuals safe and included. FARE does this by investing in world-class research that advances the treatment and understanding of the disease, providing evidence-based education and resources, undertaking advocacy at all levels of government and increasing awareness of food allergy as a serious public health issue.

    The University of Chicago Medicine and Biological Sciences is one of the nation’s leading academic medical institutions. It comprises the Pritzker School of Medicine, a top medical school in the nation; the University of Chicago Biological Sciences Division; and the University of Chicago Medical Center, which recently opened the Center for Care and Discovery, a $700 million specialty medical facility. Twelve Nobel Prize winners in physiology or medicine have been affiliated with the University of Chicago Medicine.

    See the full article here.

    Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation’s first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America’s scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science. For more visit http://www.anl.gov.

    The Advanced Photon Source at Argonne National Laboratory is one of five national synchrotron radiation light sources supported by the U.S. Department of Energy’s Office of Science to carry out applied and basic research to understand, predict, and ultimately control matter and energy at the electronic, atomic, and molecular levels, provide the foundations for new energy technologies, and support DOE missions in energy, environment, and national security. To learn more about the Office of Science X-ray user facilities, visit http://science.energy.gov/user-facilities/basic-energy-sciences/.

    Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science

    Argonne Lab Campus

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  • richardmitnick 3:28 pm on August 23, 2014 Permalink | Reply
    Tags: , Diabetes, Electrical Engineering, , Medicine   

    From Princeton: “Laser device may end pin pricks, improve quality of life for diabetics” 

    Princeton University
    Princeton University

    August 20, 2014
    John Sullivan, Office of Engineering Communications

    Princeton University researchers have developed a way to use a laser to measure people’s blood sugar, and, with more work to shrink the laser system to a portable size, the technique could allow diabetics to check their condition without pricking themselves to draw blood.

    “We are working hard to turn engineering solutions into useful tools for people to use in their daily lives,” said Claire Gmachl, the Eugene Higgins Professor of Electrical Engineering and the project’s senior researcher. “With this work we hope to improve the lives of many diabetes sufferers who depend on frequent blood glucose monitoring.”

    In an article published June 23 in the journal Biomedical Optics Express, the researchers describe how they measured blood sugar by directing their specialized laser at a person’s palm. The laser passes through the skin cells, without causing damage, and is partially absorbed by the sugar molecules in the patient’s body. The researchers use the amount of absorption to measure the level of blood sugar.

    Sabbir Liakat, the paper’s lead author, said the team was pleasantly surprised at the accuracy of the method. Glucose monitors are required to produce a blood-sugar reading within 20 percent of the patient’s actual level; even an early version of the system met that standard. The current version is 84 percent accurate, Liakat said.

    “It works now but we are still trying to improve it,” said Liakat, a graduate student in electrical engineering.

    team
    A new system developed by Princeton researchers uses a laser to allow diabetics to check their blood sugar without pricking their skin. Members of the research team included, from left, Sabbir Liakat, a graduate student in electrical engineering; Claire Gmachl, the Eugene Higgins Professor of Electrical Engineering; and Kevin Bors, who graduated in 2013 with a degree in electrical engineering. (Photos by Frank Wojciechowski for the Office of Engineering Communications)

    When the team first started, the laser was an experimental setup that filled up a moderate-sized workbench. It also needed an elaborate cooling system to work. Gmachl said the researchers have solved the cooling problem, so the laser works at room temperature. The next step is to shrink it.

    “This summer, we are working to get the system on a mobile platform to take it places such as clinics to get more measurements,” Liakat said. “We are looking for a larger dataset of measurements to work with.”

    The key to the system is the infrared laser’s frequency. What our eyes perceive as color is created by light’s frequency (the number of light waves that pass a point in a certain time). Red is the lowest frequency of light that humans normally can see, and infrared’s frequency is below that level. Current medical devices often use the “near-infrared,” which is just beyond what the eye can see. This frequency is not blocked by water, so it can be used in the body, which is largely made up of water. But it does interact with many acids and chemicals in the skin, so it makes it impractical to use for detecting blood sugar.

    Mid-infrared light, however, is not as much affected by these other chemicals, so it works well for blood sugar. But mid-infrared light is difficult to harness with standard lasers. It also requires relatively high power and stability to penetrate the skin and scatter off bodily fluid. (The target is not the blood but fluid called dermal interstitial fluid, which has a strong correlation with blood sugar.)

    The breakthrough came from the use of a new type of device that is particularly adept at producing mid-infrared frequencies — a quantum cascade laser.

    device
    The new monitor uses a laser, instead of blood sample, to read blood sugar levels. The laser is directed at the person’s palm, passes through skin cells and is partially absorbed by sugar molecules, allowing researchers to calculate the level of blood sugar.

    In many lasers, the frequency of the beam depends on the material that makes up the laser — a helium-neon laser, for example, produces a certain frequency band of light. But in a quantum cascade laser, in which electrons pass through a “cascade” of semiconductor layers, the beam can be set to one of a number of different frequencies. The ability to specify the frequency allowed the researchers to produce a laser in the mid-infrared region. Recent improvements in quantum cascade lasers also provided for increased power and stability needed to penetrate the skin.

    To conduct their experiment, the researchers used the laser to measure the blood sugar of three healthy people before and after they each ate 20 jellybeans, which raise blood sugar levels. The researchers also checked the measurements with a finger-prick test. They conducted the measurements repeatedly over several weeks.

    The researchers said their results indicated that the laser measurements readings produced average errors somewhat larger than the standard blood sugar monitors, but remained within the clinical requirement for accuracy.

    “Because the quantum cascade laser can be designed to emit light across a very wide wavelength range, its usability is not just for glucose detection, but could conceivably be used for other medical sensing and monitoring applications,” Gmachl said.

    Besides Liakat and Gmachl, researchers included Kevin Bors, Class of 2013, Laura Xu, Class of 2015, and Callie Woods, Class of 2014, who worked on the project as undergraduate students majoring in electrical engineering; and Jessica Doyle, a teacher at Hunterdon Regional Central High School.

    Support for the research was provided in part by the Wendy and Eric Schmidt Foundation, the National Science Foundation, Daylight Solutions Inc., and Opto-Knowledge Systems. The research involving human subjects was conducted according to regulations set by the Princeton University Institutional Review Board.

    See the full article here.

    About Princeton: Overview

    Princeton University is a vibrant community of scholarship and learning that stands in the nation’s service and in the service of all nations. Chartered in 1746, Princeton is the fourth-oldest college in the United States. Princeton is an independent, coeducational, nondenominational institution that provides undergraduate and graduate instruction in the humanities, social sciences, natural sciences and engineering.

    As a world-renowned research university, Princeton seeks to achieve the highest levels of distinction in the discovery and transmission of knowledge and understanding. At the same time, Princeton is distinctive among research universities in its commitment to undergraduate teaching.

    Today, more than 1,100 faculty members instruct approximately 5,200 undergraduate students and 2,600 graduate students. The University’s generous financial aid program ensures that talented students from all economic backgrounds can afford a Princeton education.

    Princeton Shield
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  • richardmitnick 2:15 pm on August 23, 2014 Permalink | Reply
    Tags: , , Medicine, NASA ISS   

    From NASA: “Microgravity Research Breaks Down How to Build Better Bones “ 

    NASA

    NASA

    August 22, 2014
    By Jessica Nimon
    International Space Station Program Science Office
    NASA’s Johnson Space Center

    iss
    ISS

    As the saying goes, sticks and stones may break your bones—especially if you have a weak skeleton. This is not only a concern for the elderly who can suffer from osteoporosis. Inactivity from injury, illness, or malnutrition from anorexia or dietary challenges also can lead to bone breakdown in otherwise healthy people. Another cause of bone loss is living in microgravity. While most people may never experience life in space, the benefits of studying bone loss aboard the International Space Station has the potential to touch all of our lives here on the ground.

    Bone loss occurs at an accelerated rate in space because of the lack of normal weight-bearing activities in the microgravity environment. Using nutrition and specific exercises, the crew aboard the space station can mitigate concerns. This accelerated aspect of bone loss in spaceflight provides an opportunity for researchers to identify the mechanisms that control bones at a cellular level. With that goal in mind, researchers looked at rodents flown aboard space shuttle missions to the space station in a series of experiments called the Commercial Biomedical Testing Module (CBTM) investigations.

    bones
    Micro-computed tomography bone density imaging shows ground mice (G) with highly connected, dense spongy bone structure, flight mice (F) with less connectivity and flight mice treated with a myostatin inhibitor (F+D) on STS-118 that appear to have bone structure unaffected by microgravity.
    Image Credit: Ted Bateman

    For the CBTM studies, the rodents lived in a habitat designed for spaceflight—the Animal Enclosure Module (AEM)—developed by NASA’s Ames Research Center in Moffett Field, California. The data from this series of investigations factored into research related to pharmaceuticals for use on Earth to mitigate bone loss, such as Prolia.

    “We contributed to preclinical trials of pharmaceuticals to show how well they work to improve bone and/or muscle loss that results from disuse,” said Virginia Ferguson, Ph.D., CBTM principal investigator at BioServe Space Technologies, University of Colorado, Boulder.

    Bone remodeling—the natural breakdown and rebuilding of bone—occurs in a balanced fashion in healthy bone so that the rate of rebuilding, known as formation, equals the rate of breakdown and absorption, known as resorption. This cycle of breakdown and buildup helps us to maintain skeletal strength and repair injuries like fractures so we can continue to enjoy normal mobility. When this natural process is out of balance, our bones and health may suffer.

    The CBTM studies were collaborative in nature toward a better understanding of bone health in the science community. CBTM, CBTM 2, and CBTM 3 took place aboard the space shuttles on missions STS-108, STS-118 and STS-135, respectively. Ferguson and her colleagues Louis Stodieck, Ph.D., of Bioserve, and Ted Bateman, Ph.D., of University of North Carolina, Chapel Hill, and their teams then analyzed the data on the ground.

    “This [was] an amazing group effort,” said Ferguson. “Many researchers across countless disciplines have benefited from access to the tissues that we collected from mice on STS-108, 118 and 135.”

    group
    Researchers for the Commercial Biomedical Testing Module (CBTM) investigation conducting ground work related to the STS-135 investigation.
    Image Credit: Bioserve

    The first flight launched in 2001 and looked at using Osteoprotegrin (OPG), while in 2011 researchers flew a sclerostin antibody treatment. OPG and the sclerostin antibody are used as drugs to mitigate bone loss and are based on naturally occurring molecules in the body. The 2007 flight studied myostatin, a preclinical therapy for treating muscle loss. All three therapeutics, which were in preclinical development with Amgen during the time of their flights, had positive impacts on maintaining bone strength.

    “In all three cases all three drugs had tremendous beneficial effects to the bone, and this is even despite the one for STS-118 being the one for muscle therapeutic—meaning it has both bone and muscle effects,” said Ferguson. “For the myostatin inhibitor, it was surprising. We thought it would have bone effects—it’s a naturally occurring pathway in bone metabolism—but we never anticipated that the bone effects would be as beneficial as they were in this particular model.”

    Ferguson elaborated that the therapies studied in the CBTM investigations are favored for pharmaceutical development because they work with the body’s existing methods of breaking down and building up bone. These processes are a necessary part of bone health as we grow and age. The use of a drug such as OPG can turn the natural signaling pathways on or off, encouraging the bone either toward or away from resorption of its cells.

    “It’s cool because you can turn back normal bone function after you stop trying to arrest resorption,” said Ferguson. For instance, she continued, “You try to stop bone removal in an astronaut during flight, and when they come back you allow that bone removal to proceed as normal by altering that pathway a little further with another therapeutic. You try to get their bones back to a normal state of remodeling.”

    Getting therapies from the lab to the medicine cabinet takes time, as did the progression of these studies—which spanned a decade in orbit as the space station was under construction. This duration enabled advances in the ways researchers conducted their microgravity investigations, including enhancements to the available tools for analysis.

    “Some of our imaging techniques improved dramatically for small animal imaging between the first flight and our third flight,” said Ferguson. “We were able to collect a tremendous amount of data on the third flight through technologies that were not even available on the first one. That was thrilling for us to be able to add to our repertoire that way.”

    Now that the station is complete, this research can continue for longer test runs than the shuttle missions would allow, thereby increasing data collection and the potential for discovery.

    “We did these investigations on space shuttle flights because that was what was available to us at the time. The [AEM] hardware that they flew the mice in previously had been limited to being approved for use for about the duration of a space shuttle flight,” said Ferguson. The three shuttle flights for the studies lasted 11 to 12 days each. “[Ames engineers have] since made modifications to the hardware that will enable mice to fly for longer periods of time [up to three months]. We are really excited about the potential that these longer periods of time afford us.”

    With the space station’s upcoming Rodent Research Facility, the AEM concept was modified to enable the next generation of studies planned for operations in orbit, such as Rodent Research-1 (RR-1). The RR-1 mission will validate the capabilities of the new rodent research hardware and feature a commercial study. One of CBTM’s investigators, Stodieck, will conduct this research, which is facilitated by CASIS in cooperation with Bioserve and industry partners. The investigation is planned to launch with the fourth SpaceX commercial resupply mission in 2014 and make use of the various partnerships that enable research aboard the orbiting laboratory. These relationships continue to push the envelope of science in space, seeking answers to propel exploration and benefit people on Earth.

    “One thing that can’t be ignored is the tie to the commercialization of space and the integration of these industries,” said Ferguson. “The biotech and pharmaceutical companies are using spaceflight as a medium to study their drugs and do the preclinical work that’s really important for FDA approval.”

    See the full article here.

    The National Aeronautics and Space Administration (NASA) is the agency of the United States government that is responsible for the nation’s civilian space program and for aeronautics and aerospace research.

    President Dwight D. Eisenhower established the National Aeronautics and Space Administration (NASA) in 1958 with a distinctly civilian (rather than military) orientation encouraging peaceful applications in space science. The National Aeronautics and Space Act was passed on July 29, 1958, disestablishing NASA’s predecessor, the National Advisory Committee for Aeronautics (NACA). The new agency became operational on October 1, 1958.

    Since that time, most U.S. space exploration efforts have been led by NASA, including the Apollo moon-landing missions, the Skylab space station, and later the Space Shuttle. Currently, NASA is supporting the International Space Station and is overseeing the development of the Orion Multi-Purpose Crew Vehicle and Commercial Crew vehicles. The agency is also responsible for the Launch Services Program (LSP) which provides oversight of launch operations and countdown management for unmanned NASA launches. Most recently, NASA announced a new Space Launch System that it said would take the agency’s astronauts farther into space than ever before and lay the cornerstone for future human space exploration efforts by the U.S.

    NASA science is focused on better understanding Earth through the Earth Observing System, advancing heliophysics through the efforts of the Science Mission Directorate’s Heliophysics Research Program, exploring bodies throughout the Solar System with advanced robotic missions such as New Horizons, and researching astrophysics topics, such as the Big Bang, through the Great Observatories [Hubble,
    Chandra, Spitzer ]and associated programs. NASA shares data with various national and international organizations such as from the Greenhouse Gases Observing Satellite.

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  • richardmitnick 11:20 am on August 19, 2014 Permalink | Reply
    Tags: , , , , Medicine   

    From Astrobiology: “Study Reveals Immune System is Dazed and Confused During Spaceflight” 

    Astrobiology Magazine

    Astrobiology Magazine

    Aug 19, 2014
    No Writer Credit

    There is nothing like a head cold to make us feel a little dazed. We get things like colds and the flu because of changes in our immune system. Researchers have a good idea what causes immune system changes on Earth—think stress, inadequate sleep and improper nutrition.

    But the results of two NASA collaborative investigations—Validation of Procedures for Monitoring Crewmember Immune Function (Integrated Immune) and Clinical Nutrition Assessment of ISS Astronauts, SMO-016E (Clinical Nutrition Assessment)—recently published in the Journal of Interferon & Cytokine Research suggest that spaceflight may temporarily alter the immune system of crew members flying long duration missions aboard the International Space Station. This is of concern as NASA looks ahead to six-month and multiple-year missions to asteroids, the moon and Mars because something as simple as a cold or the flu can be risky business in space.

    ISS
    ISS

    Data generated early in NASA’s Integrated Immune study indicated that the distribution of immune cells in the blood of crew members aboard the space station is relatively unchanged during flight. However, they also revealed that some cell function is significantly lower than normal, or depressed, and some cell activity is heightened. In a sense, the immune systems of crew members are confused.

    ak
    European Space Agency astronaut Andre Kuipers, Expedition 30 flight engineer, prepares vials in the Columbus laboratory of the International Space Station for venous blood sample draws during an immune system investigation. Image Credit: NASA

    When cell activity is depressed, the immune system is not generating appropriate responses to threats. This may also lead to the asymptomatic viral shedding observed in some crew members, which means latent, or dormant, viruses in the body reawaken, but without symptoms of illness. When activity heightens, the immune system reacts excessively, resulting in things like increased allergy symptoms and persistent rashes, which have been reported by some crew members.

    “Prior to the Integrated Immune study, little immune system in-flight data had been collected,” said Brian Crucian, Ph.D. and NASA biological studies and immunology expert. “Previous post-flight studies were not enough to make any determination about spaceflight’s effect on the immune system. This in-flight data provided the information we needed to determine that immune dysregulation does occur and actually persists during long-duration spaceflight.”

    Recently, in a collaboration between NASA’s Integrated Immune and Clinical Nutrition Assessment flight studies, researchers examined the blood plasma of 28 crew members before, during and after their missions. They were measuring for the concentration of cytokines – the proteins that regulate immunity. Cytokines recruit immune cells to the infected or injured body site, facilitate cell-to-cell communication, and signal immune cells to activate and mount a defense against invaders. This process is usually referred to as inflammation. The data indicated that, like the changes in cell function indicated in the Integrated Immune study, crew members also have changes in blood cytokines that persist during flight. This gives researchers an idea of what areas of a crew member’s immune system may be confused during flight.

    ah
    Japan Aerospace Exploration Agency astronaut Akihiko Hoshide, Expedition 32 flight engineer, poses for a photo after undergoing a generic blood draw in the European Laboratory/Columbus Orbital Facility. International Space Station crew members routinely perform blood draws for investigations. Image Credit: NASA

    According to Crucian, the immune system is likely being altered by many factors associated with the overall spaceflight environment. “Things like radiation, microbes, stress, microgravity, altered sleep cycles and isolation could all have an effect on crew member immune systems,” said Crucian. “If this situation persisted for longer deep space missions, it could possibly increase risk of infection, hypersensitivity, or autoimmune issues for exploration astronauts.”

    Despite these immune system changes, it has yet to be determined whether these alterations increase crew risk for medical issues during spaceflight. According to Crucian, further investigations are required to precisely assess whether there is increased clinical risk to crew members on longer duration missions.

    NASA Human Research Program Chief Scientist Mark Shelhamer says continued study of the immune system is critical. “These studies tell us that this is an important issue and that we are measuring the right things,” said Shelhamer. “They also tell us there is no place during spaceflight where we see stabilization of the immune system. This is critical as we pursue longer duration missions and why we are studying this further during the upcoming one-year mission.”

    Once these investigations are complete, Crucian expects the agency will have a decision point for establishing countermeasures that it must then decide how to implement. If deemed necessary, countermeasures for immunity could include new types of radiation shielding, nutritional supplementation, pharmaceuticals and more.

    Studies of how space flight affects the immune system may provide benefits to Earth-based medicine. This includes information on how stress causes immune system changes in healthy adults, changes that may precede disease.

    In the end, NASA may just shift the immune system during spaceflight from dazed to unfazed.

    See the full article here.
    Astrobiology Magazine is a NASA-sponsored online popular science magazine. Our stories profile the latest and most exciting news across the wide and interdisciplinary field of astrobiology — the study of life in the universe. In addition to original content, Astrobiology Magazine also runs content from non-NASA sources in order to provide our readers with a broad knowledge of developments in astrobiology, and from institutions both nationally and internationally. Publication of press-releases or other out-sourced content does not signify endorsement or affiliation of any kind.
    Established in the year 2000, Astrobiology Magazine now has a vast archive of stories covering a broad array of topics.

    NASA

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  • richardmitnick 11:05 am on August 19, 2014 Permalink | Reply
    Tags: , , , Medicine   

    From Brown: “Intimacy a strong motivator for PrEP HIV prevention” 

    Brown University
    Brown University

    August 19, 2014
    David Orenstein

    Men in steady same-sex relationships where both partners are HIV negative will often forgo condoms out of a desire to preserve intimacy, even if they also have sex outside the relationship. But the risk of HIV still lurks. In a new study of gay and bisexual men who reported at least one instance of condomless anal sex in the last 30 days, researchers found that the same desire for intimacy is also a strong predictor of whether men would be willing to take antiretroviral medications to prevent HIV, an emerging practice known as pre-exposure prophylaxis or PrEP.

    Earlier this year the U.S. Public Health Service recommended that people at high risk of getting HIV use PrEP, including gay or bisexual men who have condomless anal sex. But as the recommendation becomes clinical practice, many people are wondering whether men will make PrEP part of their daily lives and what will keep them motivated to adhere to it strictly, which is required if the medication is to have its protective effect.

    The new study, published in the Annals of Behavioral Medicine, suggests that PrEP’s appeal to many men who have sex with men (MSM) in romantic relationships with HIV-negative partners is the perception that it can allow them to remain intimate with their partners while still having some protection from HIV.

    kg
    Kristi Gamarel
    “Sex doesn’t happen in a vacuum — interpersonal and relationship context really matter.”

    “In this sample of men who are in a relationship with a perceived HIV-negative man, we found that intimacy motivation was the strongest predictor [of adopting PrEP],” said Kristi Gamarel, a psychiatry and human behavior postdoctoral researcher in the Warren Alpert Medical School of Brown University. She was at the City University of New York with senior author and principal investigator for the NIH-funded project, Sarit Golub, when she performed the research. “Sex doesn’t happen in a vacuum — interpersonal and relationship context really matter. Many HIV infections are occurring between people who are in a primary relationship.”

    The study is based on extensive interviews with 164 HIV-negative MSMs who were in steady same-sex relationships and who had condomless anal sex at least once in the prior 30 days. The researchers found in a multivariate statistical analysis that those who rated intimacy highly as a reason why they sometimes engage in condomless sex also were 55 percent more likely to say they would adopt PrEP if it were available for free (likely a hypothetical condition for many, but not necessarily all, recipients).

    In basic analyses reported in the paper, there were several other factors in the study that also predicted a greater likelihood of adopting PrEP: older age, higher perception of HIV risk, sex (either protected or not) with partners outside the main relationship, and having less than a bachelor’s degree level of education. But upon controlling for possible overlap among factors, desire for intimacy, low education levels and to a lesser extent older age survived as the strongest predictors of using PrEP.

    Relationships matter

    An important implication of the study’s findings are that as physicians and counselors discuss PrEP with MSM in steady relationships, Gamarel said, they should consider that a desire for intimacy in the relationship appears to be a prime motivation.

    “For people who are disseminating PrEP or talking to patients about PrEP, I think it’s important to think about their relationships,” Gamarel said. “Something that’s being supported and endorsed right now by the World Health Organization is couples voluntary testing and counseling. That may be a way to disseminate PrEP and to allow couples to have a discussion about whether PrEP is good for their relationship and how they can support each other using PrEP.”

    Gamarel cautioned that the study results cannot be taken as evidence that PrEP will reduce condom use. The men in this study were already forgoing condoms at times without being on PrEP, Gamarel notes. The study simply sought to ascertain whether these men would adopt PrEP and to determine why. Condoms remain uniquely important to gay men’s sexual health, she noted, both because they reduce the risk of HIV transmission and because they can block other sexually transmitted infections that PrEP does not.

    The National Institute of Mental Health funded the study (grant: R01MH095565 to Golub).

    See the full article here.

    Welcome to Brown

    Rhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interiorRhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interior

    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

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  • richardmitnick 7:47 pm on August 18, 2014 Permalink | Reply
    Tags: , , Medicine,   

    From M.I.T.: “Engineering new bone growth” 


    MIT News

    August 18, 2014
    Anne Trafton | MIT News Office

    Coated tissue scaffolds help the body grow new bone to repair injuries or congenital defects.

    MIT chemical engineers have devised a new implantable tissue scaffold coated with bone growth factors that are released slowly over a few weeks. When applied to bone injuries or defects, this coated scaffold induces the body to rapidly form new bone that looks and behaves just like the original tissue.

    bone
    Pictured is a scanning electron micrograph of a porous, nanostructured poly(lactic-co-glycolic acid) (PLGA) membrane. The membrane is coated with a polyelectrolyte (PEM) multilayer coating that releases growth factors to promote bone repair. Image courtesy of Nasim Hyder and Nisarg J. Shah

    This type of coated scaffold could offer a dramatic improvement over the current standard for treating bone injuries, which involves transplanting bone from another part of the patient’s body — a painful process that does not always supply enough bone. Patients with severe bone injuries, such as soldiers wounded in battle; people who suffer from congenital bone defects, such as craniomaxillofacial disorders; and patients in need of bone augmentation prior to insertion of dental implants could benefit from the new tissue scaffold, the researchers say.

    “It’s been a truly challenging medical problem, and we have tried to provide one way to address that problem,” says Nisarg Shah, a recent PhD recipient and lead author of the paper, which appears in the Proceedings of the National Academy of Sciences this week.

    Paula Hammond, the David H. Koch Professor in Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Department of Chemical Engineering, is the paper’s senior author. Other authors are postdocs Nasim Hyder and Mohiuddin Quadir, graduate student Noémie-Manuelle Dorval Courchesne, Howard Seeherman of Restituo, Myron Nevins of the Harvard School of Dental Medicine, and Myron Spector of Brigham and Women’s Hospital.

    Stimulating bone growth

    Two of the most important bone growth factors are platelet-derived growth factor (PDGF) and bone morphogenetic protein 2 (BMP-2). As part of the natural wound-healing cascade, PDGF is one of the first factors released immediately following a bone injury, such as a fracture. After PDGF appears, other factors, including BMP-2, help to create the right environment for bone regeneration by recruiting cells that can produce bone and forming a supportive structure, including blood vessels.

    Efforts to treat bone injury with these growth factors have been hindered by the inability to effectively deliver them in a controlled manner. When very large quantities of growth factors are delivered too quickly, they are rapidly cleared from the treatment site — so they have reduced impact on tissue repair, and can also induce unwanted side effects.

    “You want the growth factor to be released very slowly and with nanogram or microgram quantities, not milligram quantities,” Hammond says. “You want to recruit these native adult stem cells we have in our bone marrow to go to the site of injury and then generate bone around the scaffold, and you want to generate a vascular system to go with it.”

    This process takes time, so ideally the growth factors would be released slowly over several days or weeks. To achieve this, the MIT team created a very thin, porous scaffold sheet coated with layers of PDGF and BMP. Using a technique called layer-by-layer assembly, they first coated the sheet with about 40 layers of BMP-2; on top of that are another 40 layers of PDGF. This allowed PDGF to be released more quickly, along with a more sustained BMP-2 release, mimicking aspects of natural healing.

    “This is a major advantage for tissue engineering for bones because the release of the signaling proteins has to be slow and it has to be scheduled,” says Nicholas Kotov, a professor of chemical engineering at the University of Michigan who was not part of the research team.

    The scaffold sheet is about 0.1 millimeter thick; once the growth-factor coatings are applied, scaffolds can be cut from the sheet on demand, and in the appropriate size for implantation into a bone injury or defect.

    Effective repair

    The researchers tested the scaffold in rats with a skull defect large enough — 8 millimeters in diameter — that it could not heal on its own. After the scaffold was implanted, growth factors were released at different rates. PDGF, released during the first few days after implantation, helped initiate the wound-healing cascade and mobilize different precursor cells to the site of the wound. These cells are responsible for forming new tissue, including blood vessels, supportive vascular structures, and bone.

    BMP, released more slowly, then induced some of these immature cells to become osteoblasts, which produce bone. When both growth factors were used together, these cells generated a layer of bone, as soon as two weeks after surgery, that was indistinguishable from natural bone in its appearance and mechanical properties, the researchers say.

    “Using this combination allows us to not only have accelerated proliferation first, but also facilitates laying down some vascular tissue, which provides a route for both the stem cells and the precursor osteoblasts and other players to get in and do their jobs. You end up with a very uniform healed system,” Hammond says.

    Another advantage of this approach is that the scaffold is biodegradable and breaks down inside the body within a few weeks. The scaffold material, a polymer called PLGA, is widely used in medical treatment and can be tuned to disintegrate at a specific rate so the researchers can design it to last only as long as needed.

    Hammond’s team has filed a patent based on this work and now aims to begin testing the system in larger animals in hopes of eventually moving it into clinical trials.

    This study was funded by the National Institutes of Health.

    See the full article here.

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