Lego-inspired bone and soft tissue repair with tiny, 3D-printed bricks
Tiny, 3D-printed bricks have been designed to heal broken bones – and could one day lead to lab-made organs for human transplant. Inspired by Lego blocks, the small, hollow bricks serve as scaffolding onto which both hard and soft tissue can regrow better than today's standard regeneration methods, according to new research published July 23, 2020, in Advanced Materials. Each brick is 1.5 millimeters cubed, or roughly the size of a small flea. Orthopedic surgeons typically repair more complex bone fractures by implanting metal rods or plates to stabilize the bone and then inserting bio-compatible scaffolding materials packed with powders or pastes that promote healing. A unique advantage of this new scaffolding system is that its hollow blocks can be filled with small amounts of gel containing various growth factors that are precisely placed closest to where they are needed. The study found growth factor-filled blocks placed near repaired rat bones led to about three times more blood vessel growth than conventional scaffolding material. The small devices are modular and can be assembled to fit into almost any space. When piecing together block segments containing four layers of four-bricks-by-four bricks, the researchers estimate more than 29,000 different configurations can be created. The researchers said they believe their 3D-printed technology could be used to heal bones that have to be cut out for cancer treatment, for spinal fusion procedures and to build up weakened jaw bones ahead of a dental implant. And, by changing the composition of the technology's 3D-printed materials, they envision it also could be used to build or repair soft tissues. With significantly more research, they hope the modular microcage approach could even be used to make organs for transplant.
Mutant zebrafish reveals a turning point in spine's evolution
A chance mutation that led to spinal defects in a zebrafish has opened a little window into man’s past. Durham, N.C.-based Duke University researchers found that embryos of the mutant fish have a single-letter change in their DNA that alters the way they build the bones and other structures that make up their spine, leaving them with a shorter body and a tortured looking spine that contains clefts dividing their vertebrae in half. The mutant fish are named spondo, short for spondylos, which is Greek for spine, and a reference to dispondyly, a condition in which each vertebra has two bony arches instead of one. The mutant fish spine looked a lot like fossil specimens of ancestral fish whose style of spine mostly has gone out of fashion. The tiny mutation showed that both recipes for spine development are still to be found in the fish genome. While the zebrafish has become a laboratory workhorse for all sorts of interesting studies, its usefulness as a model of human spine development has been in doubt because they grow their backbones differently. But not anymore. The research team's new paper, which appears July 20, 2020, in Current Biology, shows that the difference between the way bony fish, also known as teleosts, and land animals grow their spines comes down to signaling from the notochord, which was revealed by this single-letter change in the DNA. And that, in turn, gives them the insight to study human spinal defects with these fast-growing, translucent fish, because the spondo mutants are sensitive to factors known to cause congenital scoliosis in human children. "Overall, what this study means is that notochord signals are key to establishing the spine. These signals have changed over evolutionary time and account for differences that exist in spine patterning strategies across vertebrates," the researchers said. "So, we are all fish after all."
Newly discovered cells act as a warning signal for rheumatoid arthritis flares
For people with rheumatoid arthritis, life is a little like sailing. On clear days with no symptoms, everything works exactly as it should; when a storm rolls in and symptoms flare up, even simple tasks become painfully difficult. But while literal storms are easy to forecast, arthritis flares tend to strike with no rhyme or reason. Now, new research suggests that life with the disease may become a little more predictable in the future. In a paper appearing July 16, 2020, in the New England Journal of Medicine, researchers from the lab of Robert Darnell, of New York-based Rockefeller University, have identified a new type of cell whose presence in the bloodstream dramatically increases in the week leading up to a flare-up. These cells could be used as a warning sign for flares. In addition, the newly discovered cells may hold a key to understanding the root causes of rheumatoid arthritis, perhaps offering a way to prevent the flares from taking place at all. Over a period of four years, patients mailed their blood samples to the lab and reported their symptoms, noting when flares occurred. Later, the researchers analyzed blood collected the weeks before symptoms worsened. About two weeks before a flare, lab members saw increased activity from B cells, which create antibodies, a common trait of autoimmune disorders. But things got more interesting in the samples collected a week later, in the days just prior to a flare. There, the scientists noticed a signature for a cell that didn't match any known cell type. The cells normally were present in low levels in the blood, then spiked in the week before a flare, and all but disappeared during the flare itself. They named their new discovery PRIME cells. And PRIME cells didn't look anything like what's normally found in the bloodstream. Darnell believes that PRIME cells may be precursors to synovial fibroblasts, which are known to play a role in causing rheumatoid arthritis symptoms. If doctors easily can test for the presence of PRIME cells in the blood one day, they may be able to provide patients with forecasts of oncoming flares to make symptoms less disruptive. Moreover, if it turns out that PRIME cells are indeed causing the flares, their discovery may open the door to developing therapies that nip inflammation in the bud.