Magnetic field and hydrogels could be used to grow new cartilage

Using a magnetic field and hydrogels, a team of researchers in the Perelman School of Medicine at the University of Pennsylvania have demonstrated a new possible way to rebuild complex body tissues, which could result in more lasting fixes to common injuries, such as cartilage degeneration. This research was published in Advanced Materials. In humans, tissues like cartilage can often break down, causing joint instability or pain. Often, the breakdown isn't in total, but covers an area, forming a hole. Current fixes are to fill those holes in with synthetic or biologic materials, which can work but often wear away because they are not the same exact material as what was there before. It's similar to fixing a pothole in a road by filling it with gravel and making a tar patch: the hole will be smoothed out but eventually wear away with use because it's not the same material and can't bond the same way. The researchers sought to find a way to fix the potholes by repaving them instead of filling them in. With that in mind, the research team found that if they added a magnetic liquid to a three-dimensional hydrogel solution, cells, and other non-magnetic objects including drug delivery microcapsules, could be arranged into specific patterns that mimicked natural tissue using an external magnetic field. After brief contact with the magnetic field, the hydrogel solution (and the objects in it) was exposed to ultraviolet light in a process called "photo crosslinking" to lock everything in place, and the magnetic solution subsequently was diffused out. After this, the engineered tissues maintained the necessary cellular gradient. With this magneto-patterning technique, the team was able to recreate articular cartilage, the tissue that covers the ends of bones. While the technique was restricted to in vitro studies, it's the first step toward potential longer-lasting, more efficient fixes in living subjects.

COVID-19 pandemic has dramatic impact on osteoporosis management, finds new global study

A new study published prior to World Osteoporosis Day found that the COVID-19 pandemic, which has severely affected management of non-communicable diseases, is markedly impacting the management of osteoporosis as judged by access to online FRAX fracture risk assessments. Globally, usage of the Fracture Risk Assessment Tool (FRAX) website was on average 58% lower in April than in February 2020. FRAX is used to generate 10-year probabilities of fracture at the hip or major skeletal sites using clinical risk factors, with or without bone mineral density (BMD) values. FRAX calculators are available for 66 countries, representing well over 80% of the global population, and the tool is accessed by at least 228 countries/territories worldwide. Widely adopted within clinical guidelines for osteoporosis, FRAX is a key component in the initiation of targeted treatment to reduce the future burden of fractures. "The findings of this study reveal that, since the pandemic was officially declared by the WHO on March 11, there has been a dramatic drop in FRAX usage, averaging 58% but ranging up to 96%, with two-thirds of the 66 countries/territories evaluated showing reductions by at least 50%," the researchers said. There was no significant relationship between the reduction in FRAX usage and measures of disease burden such as COVID-attributed deaths per million of the population. The researchers estimated that approximately 175,000 patients were likely excluded from fracture risk assessment in April 2020, suggesting that over a three-month period more than 0.5 million patients would be excluded from assessment, and a significant portion of those from necessary treatment. The researchers said they expect that FRAX, which can be undertaken remotely via telemedicine and has been shown to have a predictive value for fractures that is comparable to the use of bone density values alone, may be able to play a significant role in addressing this enormous backlog in assessments for osteoporosis.

Casting call: Why immobilizing helps in healing

By far, the most common injuries seen in emergency rooms in the U.S. are those affecting extremities. Immobilization is the most common treatment, and yet, until recently, it was unknown exactly why this technique worked to advance healing. In a study published in the Journal of Clinical Investigation, Benjamin Levi, now associate professor of surgery and plastic surgery at UT Southwestern, discovered the mechanism by which immobilization alters an injured extremity and the cells in the injured area. This finding could eventually help doctors optimize healing in patients with extremity injuries. Levi and his team at the University of Michigan, where he worked before joining UT Southwestern, found that immobilizing extremities by casting or splinting after injury alters the way stem cells interact with their extracellular environment, switching their fate from becoming debilitating bone to benign fat. Up to now, it's been unclear why some wounds heal abnormally, often with detrimental consequences. To help clarify this issue, Levi and his colleagues worked with a mouse model of heterotopic ossification (HO) in which bone grows in nonskeletal tissues such as muscles and tendons after injuries. Affected mice were either fitted with immobilizers – which acted like tiny casts to keep their joints stable – exercised on a treadmill, or were given range-of-motion exercises similar to what many human patients receive after joint surgery. The mice that exercised or received range-of-motion exercises developed HO – but the immobilized animals did not. Rather, the immobilized animals developed bubbles of fat within the affected areas instead of bone. Delving deeper, the researchers harvested mesenchymal stem cells (MSCs) – cell types that play a key role in healing – from the site. When the researchers examined which genes were active in these cells, they found increased expression in molecular pathways relating to how the cells attach to surfaces and interact with the extracellular matrix, a network of proteins and other molecules outside cells that nurture them and provide physical support. Genetic manipulation or use of small molecules to inactivate these molecular pathways stifled HO from developing in the mobilized mice. "The take-home message is that when we immobilize joints, we are changing the entire environment of a wound on both the tissue level and the cellular level," Levi said. "We could harness this knowledge to aid in healing, either by altering our mobilization protocols or targeting specific genes that affect how cells interact with the extracellular matrix using small molecules that are already in clinical pipelines."

Osteoarthritis biomarker could help 300 million people worldwide

Using new state-of-the-art imaging techniques to identify signs of osteoarthritis (OA), University of Southern Australia (UniSA) scientists are learning more about changes at the molecular level which indicate the severity of cartilage damage. A study using mass spectrometry imaging (MSI) has mapped complex sugars on OA cartilage, showing different sugars are associated with damaged tissue compared to healthy tissue. The finding will potentially help overcome one of the main challenges of osteoarthritis research – identifying why cartilage degrades at different rates in the body. Existing OA biomarkers are still largely focused on bodily fluids which are neither reliable nor sensitive enough to map all the changes in cartilage damage. By understanding the biomolecular structure at the tissue level and how the joint tissues interact in the early stages of osteoarthritis, UniSA researchers say any molecular changes could be targeted to help slow the progression of the disease with appropriate medication or treatment. In a recent paper published in the International Journal of Molecular Sciences, the researchers explored how advances in mass spectrometry imaging (MSI) to detect OA are promising. To date, diagnosing osteoarthritis has relied heavily on X-rays or MRI, but these provide limited information and don't detect biomolecular changes that signal cartilage and bone abnormalities, the researchers said. By contrast, alternative imaging methods such as MSI can identify specific molecules and organic compounds in the tissue section. MSI has already demonstrated its strengths in identifying biomarkers for different types of cancer, and UniSA researchers are hopeful it can achieve the same for early diagnosis of osteoarthritis.