Peer Reviewed
1
Document Type
Article
Publication Date
1-11-2017
Keywords
Gene Activated, Superfect, DNA Delivery, Nanoparticle, Collagen Scaffold, Mesenchymal Stem Cells
Funder/Sponsor
This study was undertaken as part of the Translational Research in Nanomedical Devices (TREND) research group, School of Pharmacy, RCSI, facilitated via a Science Foundation Ireland Investigators Program 13/IA/1840. The authors would like to thank Brenton Cavanagh, RCSI, Ireland, for his assistance in obtaining TEM & Live/Dead images.
Abstract
Recent developments within the field of tissue engineering (TE) have shown that biomaterial scaffold systems can be augmented via the incorporation of gene therapeutics. The objective of this study was to assess the potential of the activated polyamidoamine dendrimer (dPAMAM) transfection reagent (SuperfectTM) as a gene delivery system to mesenchymal stem cells (MSCs) in both monolayer and 3D culture on collagen based scaffolds. dPAMAM-pDNA polyplexes at a mass ratio (M:R) 10:1 (dPAMAM : pDNA) (1 ug pDNA) were capable of facilitating prolonged reporter gene expression in monolayer MSCs which was superior to that facilitated using polyethylenimine (PEI)-pDNA polyplexes (2 ug pDNA). When dPAMAM-pDNA polyplexes (1 ug pDNA) were soak loaded onto a collagen-chondroitin sulphate (CS) scaffold prolonged transgene expression was facilitated which was higher than that obtained for a PEI-pDNA polyplex (2 ug pDNA) loaded scaffold. Transgene expression was dependent on the composite nature of the collagen scaffold with varying expression profiles obtained from a suite of collagen constructs including a collagen alone, collagen-CS, collagen-hydroxyapatite, collagen-nanohydroxyapatite and collagen-hyaluronic acid scaffold. Therefore, the dPAMAM vector described herein represents a biocompatible, effective gene delivery vector for TE applications which, via matching with a particular composite scaffold type, can be tailored for regeneration of various tissue defects.
Disciplines
Anatomy
Citation
Walsh DP, Heise A, O'Brien FJ, Cryan SA. An efficient, non-viral dendritic vector for gene delivery in tissue engineering. Gene Therapy. 2017;24(11):681-691.
PubMed ID
28905887
Link to this item at
https://epubs.rcsi.ie/anatart/118/
DOI Link
10.1038/gt.2017.58
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.
Comments
This article is also available at https://www.nature.com/articles/gt201758
DOI: 10.1038/gt.2017.58