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Blasting tiny bubbles at broken pig bones makes them heal on their own

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Bubble bubble oink and trouble

Image of a healed pig tibia undergoing torsion-strength testing after being treated with gene therapy for bone regeneration
M. Bez et al. Science Translational Medicine. (2017)

Scientists have healed severe bone fractures in pigs by blasting tiny bubbles with ultrasound in the animals’ bones. The technique encourages the pigs’ bodies to regenerate themselves, and could one day be used to help humans — especially the elderly — heal dangerous bone injuries.

Broken bones are common: you wrap an arm or wrist in a cast and the bone eventually heals on its own. But sometimes, people have “nonunion fractures,” meaning bones fail to produce new bone tissue and don’t heal properly. There are about 100,000 cases of this in the United States every year. One solution is bone grafts, or bone transplants using donated marrow, but this procedure is invasive and there is a risk that the body will reject the marrow. Another solution is to use viruses to deliver “bone morphogenetic proteins” (BMPs) that encourage the body’s own stem cells to create more bone marrow. But using a virus can have negative side effects like inflammation.

In a study published today in Science Translational Medicine, scientists healed a 0.4-inch fracture in pigs in eight weeks without invasive surgery. “Going from something invasive to something like this that potentially could be an outpatient procedure has been the holy grail in orthopedics,” says Edward Schwarz, director of the University of Rochester’s Center for Musculoskeletal Research, who was not involved with the study. He adds that, though these nonunion fractures aren’t the most common health problem, they’re a serious one. “People are shocked when I tell them that the life expectancy with a nonunion fracture is shorter than with pancreatic cancer,” he says. “We’re like horses. If we can’t get up and walk again, then we’re done.”

In the study, the researchers first caused a 0.4-inch fracture in the shins of 18 minipigs. Then, they inserted a biodegradable scaffolds into the broken shins, says co-author Gadi Pelled, a professor of surgery at Cedars-Sinai Medical Center. The scaffold helped support bone stem cells in the area. The scientists let the stem cells migrate and populate over the scaffold for two weeks — but that was’t enough. The stem cells had to be triggered to actually heal the injury. So the scientists injected microbubbles mixed with bone morphogenetic proteins. Immediately after the injection, they applied ultrasound, which stimulated the BMPs to enter into the stem cells and activate them.

Cartoon schematic explaining ultrasound delivery method for gene therapy
M. Bez et al. Science Translational Medicine. (2017)

The stem cells then turned into bone cells and healed the fracture after eight weeks. This method doesn’t have the side effects associated with using viruses, and the fact that it uses the body’s own stem cells means there’s no risk of rejection, says co-author Zulma Gazit, also at Cedars-Sinai. This ultrasound and microbubbles combo has already been approved by the Food and Drug Administration and is often used in radiology, so the new technique could be readily approved for use in humans.

Next, says Pelled, the team is studying whether the same technology can also work with tissues like ligaments; they gathering more comprehensive information. “Before we move forward into humans, we need to determine that this technology is safe,” says Pelled. They’re hopeful that a clinical trial is on the way.