Nomikou, N, Feichtinger, GA orcid.org/0000-0002-7724-3006, Saha, S et al. (4 more authors) (2018) Ultrasound‐responsive gene‐activated matrices for osteogenic gene therapy using matrix‐assisted sonoporation. Journal of Tissue Engineering and Regenerative Medicine, 12 (1). e250-e260. ISSN 1932-6254
Abstract
Gene‐activated matrix (GAM)‐based therapeutics for tissue regeneration are limited by efficacy, the lack of spatiotemporal control and availability of target cells, all of which impact negatively on their translation to the clinic. Here, an advanced ultrasound‐responsive GAM is described containing target cells that facilitates matrix‐assisted sonoporation (MAS) to induce osteogenic differentiation. Ultrasound‐responsive GAMs consisting of fibrin/collagen hybrid‐matrices containing microbubbles, bone morphogenetic protein BMP2/7 coexpression plasmids together with C2C12 cells were treated with ultrasound either in vitro or following parenteral intramuscular implantation in vivo. Using direct measurement for alkaline phosphatase activity, von Kossa staining and immunohistochemical analysis for osteocalcin expression, MAS‐stimulated osteogenic differentiation was confirmed in the GAMs in vitro 7 days after treatment with ultrasound. At day 30 post‐treatment with ultrasound, ectopic osteogenic differentiation was confirmed in vivo using X‐ray microcomputed tomography and histological analysis. Osteogenic differentiation was indicated by the presence of ectopic bone structures in all animals treated with MAS. In addition, bone volumes in this group were statistically greater than those in the control groups. This novel approach of incorporating a MAS capability into GAMs could be exploited to facilitate ex vivo gene transfer with subsequent surgical implantation or alternatively provide a minimally invasive means of stimulating in situ transgene delivery for osteoinductive gene‐based therapies.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 John Wiley & Sons, Ltd. This is the peer reviewed version of the following article: Nomikou, N., Feichtinger, G. A., Saha, S., Nuernberger, S., Heimel, P., Redl, H., and McHale, A. P. (2018) Ultrasound‐responsive gene‐activated matrices for osteogenic gene therapy using matrix‐assisted sonoporation. J Tissue Eng Regen Med, 12: e250–e260., which has been published in final form at https://doi.org/10.1002/term.2406. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Osteogenesis, gene, matrix, sonoporation, ultrasound, regeneration |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) > Oral Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 17 Jan 2017 12:47 |
Last Modified: | 19 Mar 2018 11:39 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/term.2406 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:110662 |