@article {19118,
	title = {In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs},
	journal = {Sci Transl Med},
	volume = {9},
	number = {390},
	year = {2017},
	note = {Bez, Maxim Sheyn, Dmitriy Tawackoli, Wafa Avalos, Pablo Shapiro, Galina Giaconi, Joseph C Da, Xiaoyu David, Shiran Ben Gavrity, Jayne Awad, Hani A Bae, Hyun W Ley, Eric J Kremen, Thomas J Gazit, Zulma Ferrara, Katherine W Pelled, Gadi Gazit, Dan eng P30 AR069655/AR/NIAMS NIH HHS/ P50 AR054041/AR/NIAMS NIH HHS/ R01 CA112356/CA/NCI NIH HHS/ Sci Transl Med. 2017 May 17;9(390). pii: eaal3128. doi: 10.1126/scitranslmed.aal3128.[["fid":"22192","view_mode":"default","type":"media","attributes":"height":"100","width":"100","class":"wysiwyg-placeholder media-element file-default"]]},
	type = {Journal Article},
	abstract = {More than 2 million bone-grafting procedures are performed each year using autografts or allografts. However, both options carry disadvantages, and there remains a clear medical need for the development of new therapies for massive bone loss and fracture nonunions. We hypothesized that localized ultrasound-mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells would induce efficient bone regeneration and fracture repair. To test this hypothesis, we surgically created a critical-sized bone fracture in the tibiae of Yucatan mini-pigs, a clinically relevant large animal model. A collagen scaffold was implanted in the fracture to facilitate recruitment of endogenous mesenchymal stem/progenitor cells (MSCs) into the fracture site. Two weeks later, transcutaneous ultrasound-mediated reporter gene delivery successfully transfected 40\% of cells at the fracture site, and flow cytometry showed that 80\% of the transfected cells expressed MSC markers. Human bone morphogenetic protein-6 (BMP-6) plasmid DNA was delivered using ultrasound in the same animal model, leading to transient expression and secretion of BMP-6 localized to the fracture area. Micro-computed tomography and biomechanical analyses showed that ultrasound-mediated BMP-6 gene delivery led to complete radiographic and functional fracture healing in all animals 6 weeks after treatment, whereas nonunion was evident in control animals. Collectively, these findings demonstrate that ultrasound-mediated gene delivery to endogenous mesenchymal progenitor cells can effectively treat nonhealing bone fractures in large animals, thereby addressing a major orthopedic unmet need and offering new possibilities for clinical translation.},
	issn = {1946-6242 (Electronic) 1946-6234 (Linking)},
	doi = {10.1126/scitranslmed.aal3128},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/28515335},
	author = {Bez, M. and Sheyn, D. and Tawackoli, W. and Avalos, P. and Shapiro, G. and Giaconi, J. C. and Da, X. and David, S. B. and Gavrity, J. and Awad, H. A. and Bae, H. W. and Ley, E. J. and Kremen, T. J. and Gazit, Z. and Ferrara, K. W. and Pelled, G. and Gazit, D.}
}
