Development of a Gene-Activated Scaffold Incorporating multifunctional cell penetrating peptides for pSDF1 alpha delivery for enhanced angiogenesis in tissue engineering applications R Power.pdf (2.59 MB)
Download file

Development of a gene-activated scaffold incorporating multifunctional cell-penetrating peptides for pSDF-1α delivery for enhanced angiogenesis in tissue engineering applications

Download (2.59 MB)
Non-viral gene delivery has become a popular approach in tissue engineering, as it permits the transient delivery of a therapeutic gene, in order to stimulate tissue repair. However, the efficacy of non-viral delivery vectors remains an issue. Our lab has created gene-activated scaffolds by incorporating various non-viral delivery vectors, including the glycosaminoglycan-binding enhanced transduction (GET) peptide into collagen-based scaffolds with proven osteogenic potential. A modification to the GET peptide (FLR) by substitution of arginine residues with histidine (FLH) has been designed to enhance plasmid DNA (pDNA) delivery. In this study, we complexed pDNA with combinations of FLR and FLH peptides, termed GET* nanoparticles. We sought to enhance our gene-activated scaffold platform by incorporating GET* nanoparticles into collagen-nanohydroxyapatite scaffolds with proven osteogenic capacity. GET* N/P 8 was shown to be the most effective formulation for delivery to MSCs in 2D. Furthermore, GET* N/P 8 nanoparticles incorporated into collagen-nanohydroxyapatite (coll-nHA) scaffolds at a 1:1 ratio of collagen:nanohydroxyapatite was shown to be the optimal gene-activated scaffold. pDNA encoding stromal-derived factor 1α (pSDF-1α), an angiogenic chemokine which plays a role in BMP mediated differentiation of MSCs, was then delivered to MSCs using our optimised gene-activated scaffold platform, with the aim of significantly increasing angiogenesis as an important precursor to bone repair. The GET* N/P 8 coll-nHA scaffolds successfully delivered pSDF-1α to MSCs, resulting in a significant, sustained increase in SDF-1α protein production and an enhanced angiogenic effect, a key precursor in the early stages of bone repair.

Funding

Health Research Board (HRB) in Ireland under grant numbers ILP-POR-2017-032 and ILP-POR-2019-023

Centre for Advanced Materials and Bioengineering Research (AMBER) under grant number SFI/12/RC/2278

European Research Council under the European Community’s Horizon 2020 Research and Innovation Program under ERC grant agreement no. 788,753 (ReCaP)

European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement 227845

Medical Research Council (grant number MR/K022682/1)

Engineering and Physical Sciences Research Council

Biotechnology and Biological Sciences Research Council

History

Comments

The original article is available at https://www.mdpi.com/

Published Citation

Power RN, Cavanagh BL, Dixon JE, Curtin CM, O'Brien FJ. Development of a gene-activated scaffold incorporating multifunctional cell-penetrating peptides for pSDF-1α delivery for enhanced angiogenesis in tissue engineering applications. Int J Mol Sci. 2022 ;23(3):1460

Publication Date

27 January 2022

PubMed ID

35163379

Department/Unit

  • Amber (Advanced Material & Bioengineering Research) Centre
  • Anatomy and Regenerative Medicine
  • Tissue Engineering Research Group (TERG)

Research Area

  • Immunity, Infection and Inflammation
  • Biomaterials and Regenerative Medicine
  • Chemistry and Pharmaceutical Sciences

Publisher

MDPI

Version

  • Published Version (Version of Record)