Nature has an extraordinary knack for producing composite materials that are simultaneously light and strong, porous and rigid – like mollusk shells or bone. But producing such materials in a lab or factory – particularly using environmentally friendly materials and processes – is extremely challenging. Researchers in the Soft Materials Laboratory of EPFL in Switzerland turned to nature for a solution. They have pioneered a 3D printable ink that contains Sporosarcina pasteurii: a bacterium which, when exposed to a urea-containing solution, triggers a mineralization process that produces calcium carbonate (CaCO₃). The upshot is that the researchers can use their ink – dubbed BactoInk – to 3D-print virtually any shape, which will then gradually mineralize over the course of a few days.

“3D printing is gaining increasing importance in general, but the number of materials that can be 3D printed is limited for the simple reason that inks must fulfil certain flow conditions,” explains lab head Esther Amstad. “For example, they must behave like a solid when at rest, but still be extrudable through a 3D printing nozzle – sort of like ketchup.”

Amstad explains that 3D printing inks containing small mineral particles have previously been used to meet some of these flow criteria, but that the resulting structures tend to be soft, or to shrink upon drying, leading to cracking and loss of control over the shape of the final product. “So, we came up with a simple trick: instead of printing minerals, we printed a polymeric scaffold using our BactoInk, which is then mineralized in a second, separate step. After about four days, the mineralization process triggered by the bacteria in the scaffold leads to a final product with a mineral content of over 90%.” The result is a strong and resilient bio-composite, which can be produced using a standard 3D printer and natural materials, and without the extreme temperatures often required for manufacturing ceramics. Final products no longer contain living bacteria, as they are submerged in ethanol at the end of the mineralization process.

A paper on the study was recently published in the journal Materials Today.

Source: https://actu.epfl.ch/

 As any weekend warrior understands, cartilage injuries to joints such as knees, shoulders, and hips can prove extremely painful and debilitating. In addition, conditions that cause cartilage degeneration, like arthritis and temporomandibular joint disorder (TMJ), affect 350 million people in the world and cost the US public health system more than $303 billion every year. Patients suffering from these conditions experience increased pain and discomfort over time.

However, an exciting study led by faculty at The Forsyth Institute suggests new strategies for making cartilage cells with huge implications in regenerative medicine for future cartilage injuries and degeneration treatments. In a paper, entitled “GATA3 mediates nonclassical β-catenin signaling in skeletal cell fate determination and ectopic chondrogenesis,” co-first authors Takamitsu Maruyama and Daigaku Hasegawa, and senior author Wei Hsu, describe two breakthrough discoveries, including a new understanding of a multifaced protein called β-catenin. Dr. Hsu is a senior scientist at the Forsyth Insitute and a Professor of Developmental Biology at Harvard University. He is also an affiliate faculty member of the Harvard Stem Cell Institute.

“The goal of this study,” said Dr. Maruyama of Forsyth, “was to figure out how to regenerate cartilage. We wanted to determine how to control cell fate, to cause the somatic cell to become cartilage instead of bone.”

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Researchers at The University of Toledo have developed an experimental vaccine that shows significant promise in preventing rheumatoid arthritis, a painful autoimmune disease that cannot currently be cured. The findings, detailed in a paper published in the journal Proceedings of the National Academy of Sciences, represent a major breakthrough in the study of rheumatoid arthritis and autoimmune diseases in general.
One of the most common autoimmune diseases, rheumatoid arthritis occurs when the body’s immune system attacks and breaks down healthy tissue — most notably the lining of joints in the hands, wrists, ankles and knees. Some estimates suggest rheumatoid arthritis affects as much as 1% of the global population.

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A Band-Aid® adhesive bandage is an effective treatment for stopping external bleeding from skin wounds, but an equally viable option for internal bleeding does not yet exist. Surgical glues are often used inside the body instead of traditional wound closure techniques like stitches, staples, and clips because they reduce the patient’s time in the hospital and lower the risk of secondary injury/damage at the wound site. An effective surgical glue needs to be strong, flexible, non-toxic, and able to accommodate movement, yet there are no adhesives currently available that have all of those properties. Researchers at the Wyss Institute (Harvard University) have developed a new super-strong hydrogel adhesive inspired by the glue secreted by a common slug that is biocompatible, flexible, and can stick to dynamically moving tissues even in the presence of blood.

The hydrogel itself is a hybrid of two different types of polymers: a seaweed extract called alginate that is used to thicken food, and polyacrylamide, which is the main material in soft contact lenses. When these relatively weak polymers become entangled with each other, they create a molecular network that demonstrates unprecedented toughness and resilience for hydrogel materials – on par with the body’s natural cartilage. When combined with an adhesive layer containing positively-charged polymer molecules (chitosan), the resulting hybrid material is able to bind to tissues stronger than any other available adhesive, stretch up to 20 times its initial length, and attach to wet tissue surfaces undergoing dynamic movement (e.g., a beating heart).

Studies of the hydrogel adhesive demonstrated that it is capable of withstanding three times the amount of tension that disrupts the best current medical adhesives, maintaining its stability and adhesion when implanted into rats for two weeks, and sealing a hole in a pig heart that was subjected to tens of thousands of cycles of pumping. Additionally, it caused no tissue damage or adhesions to surrounding tissues when applied to a liver hemorrhage in mice.

The hydrogel adhesive has numerous potential applications in the medical field, either as a patch that can be cut to desired sizes and applied to many tissues including bone, cartilage, tendon, or pleura, or as an injectable solution for deeper injuries. It can also be used to attach medical devices to their target structures, such as an actuator to support heart function. While the current iteration is designed to be a permanent structure, it could be made to biodegrade over time as the body heals from injury.

Source: https://wyss.harvard.edu/

Emily Whitehead was diagnosed with acute lymphoblastic leukemia (ALL) when she was just five years old. Acute lymphoblastic leukemia is a type of cancer of the blood and bone marrow that affects white blood cells, and is most common in children ages three to five. Whitehead needed chemotherapy, but after two years, it was unsuccessful. Her health was rapidly declining, and the local hospital told them to go home and enjoy the days they had left with her. But Whitehead’s parents refused to give up on their daughter and turned to the Children’s Hospital of Philadelphia (CHOP) for help.. There, they learned about a clinical trial that had just started involving CAR T-cell therapy, which genetically alters a patient’s white blood cells to fight cancer cells. Whitehead’s doctor, Dr. Grub, says this therapy is a game-changer for blood cancers and is a great option for those who relapsed and don’t have their cancer under control. In 2012, Whitehead became the first pediatric patient in the world to receive this type of therapy. Today, she is 17 years old and just celebrated being ten years cancer-free!

“I’m feeling great. I’m really healthy. I’m driving now, I got my driver’s license in January.”

Not all patients who receive CAR T for relapsed ALL reach the same outcome as Emily. Currently, more than 90% of patients who receive CAR T-cell therapy for relapsed ALL go into remission; approximately 50% of those patients will remain cancer free. Researchers are continuing to advance the field so that more patients never relapse. Because CHOP is the pediatric oncology program with the most CAR T experience — having to date treated more than 440 patients, who have come to CHOP from across the globe — the program remains poised to further improve those outcomes.

In addition, Dr. Grupp says there has been a change in thinking surrounding enrollment in clinical trials for cancer patients. Rather than waiting until a patient is nearly out of options to consider experimental treatment options, oncologists are recognizing patients who might qualify for CAR T-cell therapy and other clinical trials earlier in the process. While CAR T-cell therapy is good for blood cancers, doctors and researchers will be spending the next five to ten years trying to figure out how to make this work for other types of cancers such as breast cancer and lung cancer.

Source: https://www.chop.edu/

Researchers have used sound waves to turn stem cells into bone cells, in a tissue engineering advance that could one day help patients regrow bone lost to cancer or degenerative disease. The innovative stem cell treatment from RMIT researchers in Australia offers a smart way forward for overcoming some of the field’s biggest challenges, through the precision power of high-frequency sound waves.

Tissue engineering is an emerging field that aims to rebuild bone and muscle by harnessing the human body’s natural ability to heal itself. A key challenge in regrowing bone is the need for large amounts of bone cells that will thrive and flourish once implanted in the target area. To date, experimental processes to change adult stem cells into bone cells have used complicated and expensive equipment and have struggled with mass production, making widespread clinical application unrealistic. Additionally, the few clinical trials attempting to regrow bone have largely used stem cells extracted from a patient’s bone marrow – a highly painful procedure.

In a new study published in the journal Small, the RMIT research team showed stem cells treated with high-frequency sound waves turned into bone cells quickly and efficiently. Importantly, the treatment was effective on multiple types of cells including fat-derived stem cells, which are far less painful to extract from a patient. Co-lead researcher Dr Amy Gelmi said the new approach was faster and simpler than other methods.

A magnified image showing adult stem cells in the process of turning into bone cells after treatment with high-frequency sound waves. Green colouring shows the presence of collagen, which the cells produce as they become bone cells

“The sound waves cut the treatment time usually required to get stem cells to begin to turn into bone cells by several days,” said Gelmi, a Vice-Chancellor’s Research Fellow at RMIT. “This method also doesn’t require any special ‘bone-inducing’ drugs and it’s very easy to apply to the stem cells. “Our study found this new approach has strong potential to be used for treating the stem cells, before we either coat them onto an implant or inject them directly into the body for tissue engineering.”

The high-frequency sound waves used in the stem cell treatment were generated on a low-cost microchip device developed by RMIT. Co-lead researcher Distinguished Professor Leslie Yeo and his team have spent over a decade researching the interaction of sound waves at frequencies above 10 MHz with different materials. The sound wave-generating device they developed can be used to precisely manipulate cells, fluids or materials. “We can use the sound waves to apply just the right amount of pressure in the right places to the stem cells, to trigger the change process,” Yeo said. “Our device is cheap and simple to use, so could easily be upscaled for treating large numbers of cells simultaneously – vital for effective tissue engineering.”

Source: https://www.rmit.edu.au/

An international team led by uOttawa Faculty of Medicine researchers have published findings that could contribute to future therapeutics for muscle degeneration due to old age, and diseases such as cancer and muscular dystrophy. In a study appearing in the Journal of Cell Biology, which publishes peer-reviewed research on cellular structure and function, the authors said their work demonstrates the importance of the enzyme GCN5 in maintaining the expression of key structural proteins in skeletal muscle. Those are the muscles attached to bone that breathing, posture and locomotion all rely on.

“We found that if you delete GCN5 expression from muscle it will no longer be able to handle extreme physical stress,” says Dr. Keir Menzies, a molecular biologist at the Faculty of Medicine’s Biochemistry, Microbiology and Immunology department and cross-appointed as an associate professor at the Interdisciplinary School of Health Sciences.

Over the span of roughly five years, the uOttawa-led international collaboration painstakingly experimented with a muscle-specific mouse “knockout” of GCN5, a well-studied enzyme which regulates multiple cellular processes such as metabolism and inflammation. Through a series of manipulations, scientists produce lab mice in which specific genes are disrupted, or knocked out, to unveil animal models of human disease and better understand how genes work.

In this case, multiple experiments were done to examine the role the GCN5 enzyme plays in muscle fiber. What they found with this line of muscle-specific mouse knockouts was a notable decline in muscle health during physical stress, such as downhill treadmill running, a type of exercise known by athletes to cause micro-tears in muscle fibres to stimulate muscle growth. The lab animals’ muscle fibers became dramatically weaker as they scurried downhill, like those of old mice, while wild-type mice were not similarly impacted. 

Dr. Menzies, the senior author of the study, says the findings are akin to what is observed in advanced aging, or myopathies and muscular dystrophy, a group of genetic diseases that result in progressive weakness and loss of muscle mass. It was supported by human data, including an observed negative correlation between muscle fiber diameter and Yin Yang 1, a highly multifunctional protein that is pivotal to a slew of cellular processes and found by the Menzies lab to be a target of GCN5. Ultimately, the team’s research found that GCN5 boosts the expression of key structural muscle proteins, notably dystrophin, and a lack of it will reduce them.

Source: https://rupress.org/
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https://www.thebrighterside.news

Research headed by scientists at the National Institute of Dental and Craniofacial Research (NIDCR) has shown how blocking the function of the blood clotting protein, fibrin, prevents bone loss from periodontal (gum) disease in mice. Drawing on animal and human data, the study—headed by NIDCR investigators Niki Moutsopoulos, DDS, PhD, and Thomas Bugge, PhD, found that build-up of fibrin triggers an overactive immune response that damages the gums and underlying bone. The results suggest that suppressing abnormal fibrin activity could hold promise for preventing or treating periodontal disease, as well as other inflammatory disorders—including arthritis and multiple sclerosis—that are marked by fibrin buildup.

”Severe periodontal disease can lead to tooth loss and remains a barrier to productivity and quality of life for far too many Americans, especially those lacking adequate access to dental care,” said NIDCR director Rena D’Souza, DDS, PhD. “By providing the most comprehensive picture yet of the underlying mechanisms of periodontal disease, this study brings us closer to more effective methods for prevention and treatment.”

Periodontal disease is a bacterial infection of the tissues supporting the teeth. The condition affects nearly half of people in the United States who are over the age 30, and 70% of those who are 65 years and older. In its early stages, periodontal disease causes redness and swelling (inflammation) of the gums. In advanced stages, called periodontitis, the underlying bone becomes damaged, leading to tooth loss. While scientists have known that periodontitis is driven in part by an exaggerated immune cell response, until now, it was unclear what triggered the response, and how it caused tissue and bone damage.

Moutsopoulos, Bugge, and colleagues reported their findings in Science, in a paper titled, “Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier.”

Source: https://www.genengnews.com/

Researchers have identified a subpopulation of mesenchymal stem cells (MSCs) that boost the healing of bone fractures and show an ability to differentiate into various cell types.

Their findings are published in the journal Bone Reports in a paper titled, “Bone marrow CD73⁺ mesenchymal stem cells display increased stemness in vitro and promote fracture healing in vivo,” and led by researchers from the University of Tsukuba (Japan), in collaboration with the University of Bonn, Germany.

“MSCs are multipotent and considered to be of great potential for regenerative medicine,” the researchers wrote. “We could show recently (Breitbach, Kimura, et al. 2018) that a subpopulation of MSCs, as well as sinusoidal endothelial cells (sECs) in the bone marrow (BM) of CD73-EGFP reporter mice, could be labeled in vivo. We took advantage of this model to explore the plasticity and osteogenic potential of CD73-EGFP+ MSCs in vitro and their role in the regenerative response upon bone lesion in vivo.”

“The generation of the callus is critically dependent on the recruitment of MSCs from the surrounding tissue and the bone marrow,” explained Kenichi Kimura, PhD, lead author and assistant professor at the University of Tsukuba. “Therefore, fracture healing models are helpful for exploring the cellular dynamics of MSC migration and differentiation during tissue regeneration.”

The new finding of the subpopulation of MSCs paves the way for new regenerative medicine and the treatment of fractures to be made.

“Our study underscores the heterogeneity of BM-MSCs and their differential response and mobilization upon bone fracture. We found that the CD73+ subpopulation of BM- MSCs contributes to the regeneration process of bone fracture healing by promoting callus formation and that also the BM sEC fraction participates in the neovascularization process during bone repair,” concluded the researchers.

Source: https://www.genengnews.com/

An international research team led by Monash University has uncovered a new technique that could speed up recovery from bone replacements by altering the shape and nucleus of individual stem cells. The research collaboration involving Monash University, the Melbourne Centre for Nanofabrication, CSIRO, the Max Planck Institute for Medical Research and the Swiss Federal Institute of Technology in Lausanne, developed micropillar arrays using UV nanoimprint lithography that essentially ‘trick’ the cells to become bone. Nanoimprint lithography allows for the creation of microscale patterns with low cost, high throughput and high resolution.

When implanted into the body as part of a bone replacement procedure, such as a hip or knee, researchers found these pillars – which are 10 times smaller than the width of a human hair – changed the shape, nucleus and genetic material inside stem cells. Not only was the research team able to define the topography of the pillar sizes and the effects it had on stem cells, but they discovered four times as much bone could be produced compared to current methods.

Novel micropillars, 10 times smaller than the width of a human hair, can change the size, shape and nucleus of individual stem cells and ‘trick’ them to become bone

“What this means is, with further testing, we can speed up the process of locking bone replacements with surrounding tissue, in addition to reducing the risks of infection,” Associate Professor Jessica Frith from Monash University’s Department of Materials Science and Engineering said. “We’ve also been able to determine what form these pillar structures take and what size they need to be in order to facilitate the changes to each stem cell, and select one that works best for the application.”

Researchers are now advancing this study into animal model testing to see how they perform on medical implants. Engineers, scientists and medical professionals have known for some time that cells can take complex mechanical cues from the microenvironment, which in turn influences their development.

However, Dr Victor Cadarso from Monash University’s Department of Mechanical and Aerospace Engineering says their results point to a previously undefined mechanism where ‘mechanotransductory signalling’ can be harnessed using microtopographies for future clinical settings. “Harnessing surface microtopography instead of biological factor supplementation to direct cell fate has far-reaching ramifications for smart cell cultureware in stem cell technologies and cell therapy, as well as for the design of smart implant materials with enhanced osteo-inductive capacity,” Dr Cadarso said.

The findings were published in Advanced Science.

Source: https://www.monash.edu/