DNA nanoparticles encapsulated in 3D tissue-engineered scaffolds enhance osteogenic differentiation of mesenchymal stem cells

In this study, we enhanced the expression of a plasmid DNA in mesenchymal stem cells (MSC) by the combination of three‐dimensional (3D) tissue‐engineered scaffold and nonviral gene carrier. To function as an enhanced delivery of plasmid DNA, acetic anhydride was reacted with polyethylenimine (PEI) t...

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Published in:Journal of biomedical materials research. Part A 2008-04, Vol.85A (1), p.47-60
Main Authors: Hosseinkhani, Hossein, Hosseinkhani, Mohsen, Gabrielson, Nathan P., Pack, Daniel W., Khademhosseini, Ali, Kobayashi, Hisatoshi
Format: Article
Language:English
Subjects:
Acetylation
Animals
Biocompatible Materials - chemistry
Cell Differentiation - physiology
DNA
DNA nanoparticles
enhanced gene expression
Male
Mesenchymal Stromal Cells - cytology
Nanoparticles
Osteogenesis - physiology
osteogenic differentiation
plasmid DNA
Polyethyleneimine - chemistry
Rats
Rats, Inbred F344
scaffold
Swine
Tissue Scaffolds
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Summary:In this study, we enhanced the expression of a plasmid DNA in mesenchymal stem cells (MSC) by the combination of three‐dimensional (3D) tissue‐engineered scaffold and nonviral gene carrier. To function as an enhanced delivery of plasmid DNA, acetic anhydride was reacted with polyethylenimine (PEI) to acetylate 80% of the primary and 20% of the secondary amines (PEI‐Ac80). This acetylated PEI has been demonstrated to show enhanced gene‐delivery efficiency over unmodified PEI. Collagen sponges reinforced by incorporating of poly(glycolic acid) (PGA) fibers were used as the scaffold material. DNA nanoparticles formed through simple mixing of plasmid DNA encoding bone morphogenetic protein‐2 (BMP‐2) and PEI‐Ac80 solutions were encapsulated within these scaffolds. MSC were seeded into each scaffold and cultured for several weeks. Within these scaffolds, the level of BMP‐2 expression by transfected MSC was significantly enhanced compared to MSC transfected by DNA nanoparticles in solution (in 2D tissue culture plates). Homogeneous bone formation was histologically observed throughout the sponges seeded with transfected MSC by using DNA nanoparticles after subcutaneous implantation into the back of rats. The level of alkaline phosphatase activity and osteocalcin content at the implanted sites of sponges seeded with transfected MSC by using DNA nanoparticles were significantly higher when compared with those seeded with other agents. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
ISSN:1549-3296
1552-4965
DOI:10.1002/jbm.a.31327