Researchers have developed a much needed alternative to bone grafts that could help alleviate the long-term hospitalization, disability, and considerable costs to the health system associated with non-healing fractures. Roughly 100,000 broken bones every year in the United States fail to heal properly, resulting in nonunion fractures, and more than 2 million bone grafts are performed around the world annually in attempts to treat these challenging injuries. Harvesting fresh bone from patients, however, is often painful and donated grafts from tissue banks frequently fail to integrate. Now, Maxim Bez and colleagues devised a two-step gene therapy method coupled with FDA-approved ultrasound and microbubbles that completely healed nonunion fractures in pigs within eight weeks of treatment. First, researchers placed a collagen scaffold at the site of the break to provide a welcoming niche for bone progenitor cells. Next, they injected microbubbles mixed with genetic material for a bone growth factor. Pulses of sound from an ultrasound wand promoted uptake of the growth factor DNA by progenitor cells, which stimulated bone growth. Unlike other gene therapies that rely on viral vectors to deliver their cargo - risky because viruses can permanently integrate into the genome and later promote cancer or set off lethal immune responses - the ultrasound and microbubbles didn't appreciably trigger inflammation, and expression of the introduced gene was undetectable after 10 days. The technique was proven to be minimally invasive, safe, and promoted total bone healing, with comparable strength to gold-standard graft procedures. Bez et al. say that with further development, their system has the potential to be used in many different tissue engineering applications.