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Development of a Gene-Activated Scaffold Incorporating Multifunctional Cell-Penetrating Peptides for pSDF-1α Delivery for Enhanced Angiogenesis in Tissue Engineering Applications

Power, Rachael N.; Cavanagh, Brenton L.; Dixon, James E.; Curtin, Caroline M.; O’Brien, Fergal J.

Development of a Gene-Activated Scaffold Incorporating Multifunctional Cell-Penetrating Peptides for pSDF-1α Delivery for Enhanced Angiogenesis in Tissue Engineering Applications Thumbnail


Authors

Rachael N. Power

Brenton L. Cavanagh

JAMES DIXON JAMES.DIXON@NOTTINGHAM.AC.UK
Associate Professor

Caroline M. Curtin

Fergal J. O’Brien



Abstract

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.

Citation

Power, R. N., Cavanagh, B. L., Dixon, J. E., Curtin, C. M., & O’Brien, F. J. (2022). Development of a Gene-Activated Scaffold Incorporating Multifunctional Cell-Penetrating Peptides for pSDF-1α Delivery for Enhanced Angiogenesis in Tissue Engineering Applications. International Journal of Molecular Sciences, 23(3), Article 1460. https://doi.org/10.3390/ijms23031460

Journal Article Type Article
Acceptance Date Jan 21, 2022
Online Publication Date Jan 27, 2022
Publication Date Feb 1, 2022
Deposit Date Jun 13, 2022
Publicly Available Date Jun 14, 2022
Journal International Journal of Molecular Sciences
Print ISSN 1661-6596
Electronic ISSN 1422-0067
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 23
Issue 3
Article Number 1460
DOI https://doi.org/10.3390/ijms23031460
Keywords Inorganic Chemistry; Organic Chemistry; Physical and Theoretical Chemistry; Computer Science Applications; Spectroscopy; Molecular Biology; General Medicine; Catalysis
Public URL https://nottingham-repository.worktribe.com/output/7351547
Publisher URL https://www.mdpi.com/1422-0067/23/3/1460

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