Bubbles to mend broken bones that won’t heal
ABLAST of tiny bubbles to repair fractures that won’t heal has been developed by US scientists. The pioneering technique uses the bubbles to deliver bone-healing genes directly into cells inside broken bones.
This is thought to trigger the damaged bones to regenerate themselves and avoids the need for invasive bone-graft surgery.
In a recent study on pigs, published in the journal Science Translational Medicine, all fractures treated with the bubbles were completely healed within eight weeks. Human trials are expected to follow and, if successful, the treatment could be available in as little as five years.
Most fractures heal naturally, with the help of a splint or cast to keep the bone in place.
But around 5% of cases are ‘nonunion’ injuries, where a bone doesn’t properly fuse, leaving a gap between the two broken ends. Without surgery, patients face a possible lifetime of constant pain and immobility.
The severity of the injury and bone loss are factors; so, too, is being a smoker.
Non-union fractures are treated with surgery, which involves inserting a bone graft harvested from another part of the body (such as the pelvis or hip) to bridge the gap between the two broken bones.
But patients can be left with nerve damage and severe pain from where the graft was taken. There is also a risk the graft fails, so surgery needs to be repeated.
The new procedure provides a safe and minimally invasive alternative to bone-graft surgery.
First, a collagen scaffold is put into the gap between the fractured bones — this takes around half an hour. At the moment it is done as an operation, but the researchers hope that in future they will be able to inject the scaffold.
Collagen is a naturally occurring protein which gives structure to skin and muscle. Over two weeks, the collagen scaffold encourages the release of stem cells (which are capable of turning into bone, cartilage and tendon) by sending out signals that it needs healing.
In a follow-up ten-minute procedure, the fracture is injected with fluid filled with ‘microbubbles’ — gas bubbles coated with fat. These contain genetic material called plasmid, which is a short strand of DNA known to promote bone growth.
The DNA is unable to enter the cells on its own because it cannot penetrate the cell’s outer membrane. But ultrasound is used to oscillate, or wobble, the microbubbles, which tear tiny holes in the membrane of the cells, allowing the DNA to enter. Once inside, the genetic material instructs the stem cells to become new bone cells.
In the recent study at Cedars-Sinai Medical Centre in Los Angeles, the treatment was given to 18 pigs, and it completely healed fractures in all of them within eight weeks.
Those animals not treated with the ultrasound or microbubbles did not completely heal.
Commenting on the technique, Amir Qureshi, a consultant knee surgeon and limb reconstruction specialist, said: ‘Non-union treatments can be invasive, complex and take a long time to heal the bone.
‘Any research, both in terms of successful outcomes and speeding up the healing process, has to be very welcome.’
MEANWHILE, microbubbles may also help diagnose cancer, without a biopsy or surgery.
Researchers at Stanford University injected microbubbles into women with suspected ovarian and breast tumours and then used ultrasound to see where they had clustered; they were designed to bind to a receptor called KDR which is found only on tumour blood vessels.
The scientists checked the diagnosis by the microbubbles against results from biopsies from the patients, and found that they were very accurate, according to a report in the Journal of Clinical Oncology.
More studies are planned.