Peer-Reviewed Journal Details
Mandatory Fields
Tierney, EG;Duffy, GP;Hibbitts, AJ;Cryan, SA;O'Brien, FJ
2012
March
Journal Of Controlled Release
The development of non-viral gene-activated matrices for bone regeneration using polyethyleneimine (PEI) and collagen-based scaffolds
Published
Altmetric: 1WOS: 46 ()
Optional Fields
MESENCHYMAL STEM-CELLS MARROW STROMAL CELLS IN-VIVO PROTON SPONGE GROWTH-FACTOR PLASMID DNA DELIVERY TRANSFECTION HYDROXYAPATITE EXPRESSION
158
304
311
The healing potential of scaffolds for tissue engineering can be enhanced by combining them with genes to produce gene-activated matrices (GAMs) for tissue regeneration. We examined the potential of using polyethyleneimine (PEI) as a vector for transfection of mesenchymal stem cells (MSCs) in monolayer culture and in 3D collagen-based GAMs. PEI-pDNA polyplexes were fabricated at a range of N/P ratios and their optimal transfection parameters (N/P 7 ratio, 2 mu g dose) and transfection efficiencies (30 +/- 8%) determined in monolayer culture. The polyplexes were then loaded onto collagen, collagen-glycosaminoglycan and collagen-nanohydroxyapatite scaffolds where gene expression was observed up to 21 days with a polyplex dose as low as 2 mu g. Transient expression profiles indicated that the GAMs act as a polyplex depot system whereby infiltrating cells become transfected over time as they migrate throughout the scaffold. The collagen-nHa GAM exhibited the most prolonged and elevated levels of transgene expression. This research has thus demonstrated that PEI is a highly efficient pDNA transfection agent for both MSC monolayer cultures and in the 3D GAM environment. By combining therapeutic gene therapy with highly engineered scaffolds, it is proposed that these GAMs might have immense capability to promote tissue regeneration. (C) 2011 Elsevier B.V. All rights reserved.
0168-3659
10.1016/j.jconrel.2011.11.026
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