An Efficient, Non-viral Dendritic Vector for Gene Delivery in Tissue Engineering

Overview

Journal Gene Ther

Date 2017 Sep 15

PMID 28905887

Citations 4

Authors

D P Walsh

A Heise

F J OBrien

S-A Cryan

Affiliations

Soon will be listed here.

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 (Superfect) 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.

Citing Articles

Optimizing the Delivery of mRNA to Mesenchymal Stem Cells for Tissue Engineering Applications.

McCormick K, Moreno Herrero J, Haas H, Fattah S, Heise A, OBrien F Mol Pharm. 2024; 21(4):1662-1676.

PMID: 38504417 PMC: 10988554. DOI: 10.1021/acs.molpharmaceut.3c00898.

Dendritic Polymers in Tissue Engineering: Contributions of PAMAM, PPI PEG and PEI to Injury Restoration and Bioactive Scaffold Evolution.

Arkas M, Vardavoulias M, Kythreoti G, Giannakoudakis D Pharmaceutics. 2023; 15(2).

PMID: 36839847 PMC: 9966633. DOI: 10.3390/pharmaceutics15020524.

Soft-Nanoparticle Functionalization of Natural Hydrogels for Tissue Engineering Applications.

Elkhoury K, Russell C, Sanchez-Gonzalez L, Mostafavi A, Williams T, Kahn C Adv Healthc Mater. 2019; 8(18):e1900506.

PMID: 31402589 PMC: 6752977. DOI: 10.1002/adhm.201900506.

Injectable Biodegradable Chitosan-Alginate 3D Porous Gel Scaffold for mRNA Vaccine Delivery.

Yan J, Chen R, Zhang H, Bryers J Macromol Biosci. 2018; 19(2):e1800242.

PMID: 30444317 PMC: 6611697. DOI: 10.1002/mabi.201800242.

References

OBrien F, Harley B, V Yannas I, Gibson L . Influence of freezing rate on pore structure in freeze-dried collagen-GAG scaffolds. Biomaterials. 2003; 25(6):1077-86. DOI: 10.1016/s0142-9612(03)00630-6. View

Kern S, Eichler H, Stoeve J, Kluter H, Bieback K . Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006; 24(5):1294-301. DOI: 10.1634/stemcells.2005-0342. View

de Jong G, Telenius A, Vanderbyl S, Meitz A, Drayer J . Efficient in-vitro transfer of a 60-Mb mammalian artificial chromosome into murine and hamster cells using cationic lipids and dendrimers. Chromosome Res. 2001; 9(6):475-85. DOI: 10.1023/a:1011680529073. View

OBrien F, Harley B, Yannas I, Gibson L . The effect of pore size on cell adhesion in collagen-GAG scaffolds. Biomaterials. 2004; 26(4):433-41. DOI: 10.1016/j.biomaterials.2004.02.052. View

Hortensius R, Becraft J, Pack D, Harley B . The effect of glycosaminoglycan content on polyethylenimine-based gene delivery within three-dimensional collagen-GAG scaffolds. Biomater Sci. 2015; 3(4):645-54. PMC: 4469389. DOI: 10.1039/C5BM00033E. View

OLeary C, Cavanagh B, Unger R, Kirkpatrick C, ODea S, OBrien F . The development of a tissue-engineered tracheobronchial epithelial model using a bilayered collagen-hyaluronate scaffold. Biomaterials. 2016; 85:111-27. DOI: 10.1016/j.biomaterials.2016.01.065. View

Robbins P, Ghivizzani S . Viral vectors for gene therapy. Pharmacol Ther. 1998; 80(1):35-47. View

Endo M, Kuroda S, Kondo H, Maruoka Y, Ohya K, Kasugai S . Bone regeneration by modified gene-activated matrix: effectiveness in segmental tibial defects in rats. Tissue Eng. 2006; 12(3):489-97. DOI: 10.1089/ten.2006.12.489. View

Jones C, Campbell R, Franks Z, Gibson C, Thiagarajan G, Vieira-de-Abreu A . Cationic PAMAM dendrimers disrupt key platelet functions. Mol Pharm. 2012; 9(6):1599-611. PMC: 3367133. DOI: 10.1021/mp2006054. View

10.

Santos J, Oramas E, Pego A, Granja P, Tomas H . Osteogenic differentiation of mesenchymal stem cells using PAMAM dendrimers as gene delivery vectors. J Control Release. 2008; 134(2):141-8. DOI: 10.1016/j.jconrel.2008.11.007. View

11.

Shi S, Dan B, Liu F, Lin L, Fu Z, Jing G . Synthesis and characterization of a novel cationic polymer gene delivery vector. Int J Mol Med. 2010; 26(4):491-500. DOI: 10.3892/ijmm_00000490. View

12.

Seow Y, Wood M . Biological gene delivery vehicles: beyond viral vectors. Mol Ther. 2009; 17(5):767-77. PMC: 2835126. DOI: 10.1038/mt.2009.41. View

13.

Quinlan E, Thompson E, Matsiko A, OBrien F, Lopez-Noriega A . Long-term controlled delivery of rhBMP-2 from collagen-hydroxyapatite scaffolds for superior bone tissue regeneration. J Control Release. 2015; 207:112-9. DOI: 10.1016/j.jconrel.2015.03.028. View

14.

Banerjee P, Reichardt W, Weissleder R, Bogdanov Jr A . Novel hyperbranched dendron for gene transfer in vitro and in vivo. Bioconjug Chem. 2004; 15(5):960-8. DOI: 10.1021/bc0342128. View

15.

Cunniffe G, Dickson G, Partap S, Stanton K, OBrien F . Development and characterisation of a collagen nano-hydroxyapatite composite scaffold for bone tissue engineering. J Mater Sci Mater Med. 2010; 21(8):2293-8. DOI: 10.1007/s10856-009-3964-1. View

16.

Castano I, Curtin C, Shaw G, Murphy J, Duffy G, OBrien F . A novel collagen-nanohydroxyapatite microRNA-activated scaffold for tissue engineering applications capable of efficient delivery of both miR-mimics and antagomiRs to human mesenchymal stem cells. J Control Release. 2015; 200:42-51. DOI: 10.1016/j.jconrel.2014.12.034. View

17.

Li C, Liu H, Sun Y, Wang H, Guo F, Rao S . PAMAM nanoparticles promote acute lung injury by inducing autophagic cell death through the Akt-TSC2-mTOR signaling pathway. J Mol Cell Biol. 2009; 1(1):37-45. DOI: 10.1093/jmcb/mjp002. View

18.

Brougham C, Levingstone T, Jockenhoevel S, Flanagan T, OBrien F . Incorporation of fibrin into a collagen-glycosaminoglycan matrix results in a scaffold with improved mechanical properties and enhanced capacity to resist cell-mediated contraction. Acta Biomater. 2015; 26:205-14. DOI: 10.1016/j.actbio.2015.08.022. View

19.

Rejman J, Oberle V, Zuhorn I, Hoekstra D . Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem J. 2003; 377(Pt 1):159-69. PMC: 1223843. DOI: 10.1042/BJ20031253. View

20.

Georgiou T, Phylactou L, Patrickios C . Synthesis, characterization, and evaluation as transfection reagents of ampholytic star copolymers: effect of star architecture. Biomacromolecules. 2006; 7(12):3505-12. DOI: 10.1021/bm060657y. View