Researchers have developed tiny bubbles used as an alternative to bone grafts that could help alleviate the long-term hospitalisation, disability, and considerable costs to the health system associated with non-healing fractures.
More than two million challenging bone grafts are performed around the world each year in attempts to treat broken bones that fail to heal properly and nonunion fractures occur.
Harvesting fresh bone from patients, however, is often painful and donated grafts from tissue banks frequently fail to integrate. Now, Maxim Bez and colleagues have 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 micro-bubbles 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.
Source: American Association for the Advancement of Science.
Reference: Maxim Bez and others. In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs. Science Translational Medicine, 2017; 9 (390): eaal3128 DOI: 10.1126/scitranslmed.aal3128