Kaipel, M, Schützenberger, S, Hofmann, AT et al. (4 more authors) (2014) Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model. International Orthopaedics, 38 (12). pp. 2607-2613. ISSN 0341-2695
Abstract
Purpose: Treatment of large-segmental bone defects still is a challenge in clinical routine. Application of gene-activated matrices (GAMs) based on fibrin, bone morphogenic protein (BMP) 2/7 plasmids and nonviral transfection reagents (cationic polymers) could be an innovative treatment strategy to overcome this problem. The aim of this study was to determine the therapeutic efficacy of fibrin GAMs with or without additional transfection reagents for BMP2 and 7 plasmid codelivery in a femur nonunion rat model. Methods: In this experimental study, a critical-sized femoral defect was created in 27 rats. At four weeks after the surgery, animals were separated into four groups and underwent a second operation. Fibrin clots containing BMP2/7 plasmids with and without cationic polymer were implanted into the femoral defect. Fibrin clots containing recombinant human (rh) BMP2 served as positive and clots without supplement as negative controls. Results: At eight weeks, animals that received GAMs containing the cationic polymer and BMP2/7 plasmids showed decreased bone volume compared with animals treated with GAMs and BMP2/7 only. Application of BMP2/7 plasmids in fibrin GAMs without cationic polymer led to variable results. Animals that received rhBMP2 protein showed increased bone volume, and osseous unions were achieved in two of six animals. Conclusions: Cationic polymers decrease therapeutic efficiency of fibrin GAM-based BMP2/7 plasmid codelivery in bone regeneration. Nonviral gene transfer of BMP2/7 plasmids needs alternative promoters (e.g. by sonoporation, electroporation) to produce beneficial clinical effects.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © SICOT aisbl 2014. This is an author produced version of a paper published in International Orthopaedics. The final publication is available at Springer via http://dx.doi.org/10.1007/s00264-014-2499-3. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | BMP2/7 plasmids, Gene therapy, Gene activated matrix, Fibrin, Nonunion, Cationic polymers |
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: | 20 May 2016 15:30 |
Last Modified: | 26 Jan 2018 09:48 |
Published Version: | http://dx.doi.org/10.1007/s00264-014-2499-3 |
Status: | Published |
Publisher: | Springer Verlag |
Identification Number: | 10.1007/s00264-014-2499-3 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:96604 |