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An efficient, non-viral dendritic vector for gene delivery in tissue engineering.

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journal contribution
posted on 22.11.2019 by David P. Walsh, Andreas Heise, Fergal J. O'Brien, Sally-Ann Cryan

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.

Funding

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.

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This article is also available at https://www.nature.com/articles/gt201758 DOI: 10.1038/gt.2017.58

Published 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.

Publication Date

01/11/2017

Publisher

Nature Publishing Group

PubMed ID

28905887

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