Research ArticleBone Regeneration

In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs

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Science Translational Medicine  17 May 2017:
Vol. 9, Issue 390, eaal3128
DOI: 10.1126/scitranslmed.aal3128

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Bubbles and BMP-6 for bone repair

Treatments for bone nonunions (fractures that fail to heal) include surgery and bone grafting. As an alternative to viral gene delivery, Bez et al. developed a two-step therapy. First, endogenous mesenchymal stem/progenitor cells were recruited to the bone nonunion by implanting a collagen sponge in the defect site. Two weeks later, bone morphogenetic protein-6 (BMP-6) plasmid DNA and microbubbles were injected into nonunions, and ultrasound was applied to oscillate the microbubbles, which helped the recruited progenitors take up the BMP-6. This therapy led to transient BMP-6 secretion, bone regeneration, and fracture healing over 6 weeks in critical-sized tibial nonunions in mini-pigs.