Highly versatile cell-penetrating peptide loaded scaffold for efficient and localised gene delivery to multiple cell types: From development to application in tissue engineering
| Autor: | Gang Chen, Irene Mencía Castaño, Fergal J. O'Brien, Lia Blokpoel Ferreras, Rosanne M. Raftery, Kevin M. Shakesheff, James E. Dixon, David P. Walsh, Gizem Osman, Mark Lemoine |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Genetic enhancement Biophysics Bone Morphogenetic Protein 2 Neovascularization Physiologic Bioengineering Cell-Penetrating Peptides 02 engineering and technology Gene delivery Viral vector Rats Sprague-Dawley Biomaterials 03 medical and health sciences Tissue engineering Osteogenesis Animals Rats Wistar Bone regeneration Cells Cultured 030304 developmental biology 0303 health sciences Tissue Engineering Tissue Scaffolds Chemistry Gene Transfer Techniques DNA Genetic Therapy Transfection 021001 nanoscience & nanotechnology Cell biology Mechanics of Materials Ceramics and Composites Cell-penetrating peptide Collagen Stem cell 0210 nano-technology |
| Zdroj: | Biomaterials. 216:119277 |
| ISSN: | 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2019.119277 |
| Popis: | Gene therapy has recently come of age with seven viral vector-based therapies gaining regulatory approval in recent years. In tissue engineering, non-viral vectors are preferred over viral vectors, however, lower transfection efficiencies and difficulties with delivery remain major limitations hampering clinical translation. This study describes the development of a novel multi-domain cell-penetrating peptide, GET, designed to enhance cell interaction and intracellular translocation of nucleic acids; combined with a series of porous collagen-based scaffolds with proven regenerative potential for different indications. GET was capable of transfecting cell types from all three germ layers, including stem cells, with an efficiency comparable to Lipofectamine® 3000, without inducing cytotoxicity. When implanted in vivo, GET gene-activated scaffolds allowed for host cell infiltration, transfection localized to the implantation site and sustained, but transient, changes in gene expression – demonstrating both the efficacy and safety of the approach. Finally, GET carrying osteogenic (pBMP-2) and angiogenic (pVEGF) genes were incorporated into collagen-hydroxyapatite scaffolds and with a single 2 μg dose of therapeutic pDNA, induced complete repair of critical-sized bone defects within 4 weeks. GET represents an exciting development in gene therapy and by combining it with a scaffold-based delivery system offers tissue engineering solutions for a myriad of regenerative indications. |
| Databáze: | OpenAIRE |
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