Pore-forming bioinks to enable spatio-temporally defined gene delivery in bioprinted tissues
| Autor: | Helen O. McCarthy, Daniel J. Kelly, Tomas Gonzalez-Fernandez, Nicholas Dunne, Pierluca Pitacco, Christopher Hobbs, Gráinne M. Cunniffe, Swetha Rathan, Fiona E. Freeman, Fergal J. O'Brien, Valeria Nicolosi |
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| Rok vydání: | 2019 |
| Předmět: |
Alginates
Swine Pharmaceutical Science Bone Morphogenetic Protein 2 02 engineering and technology Gene delivery Methylcellulose 03 medical and health sciences Transforming Growth Factor beta3 Tissue engineering Animals 030304 developmental biology 0303 health sciences Tissue Engineering Chemistry Regeneration (biology) Bioprinting Gene Transfer Techniques Hydrogels Mesenchymal Stem Cells SOX9 Transcription Factor Transfection DNA 021001 nanoscience & nanotechnology Chondrogenesis Cell biology Self-healing hydrogels Printing Three-Dimensional Ink Stem cell 0210 nano-technology Porosity Biofabrication Plasmids |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 301 |
| ISSN: | 1873-4995 |
| Popis: | The regeneration of complex tissues and organs remains a major clinical challenge. With a view towards bioprinting such tissues, we developed a new class of pore-forming bioink to spatially and temporally control the presentation of therapeutic genes within bioprinted tissues. By blending sacrificial and stable hydrogels, we were able to produce bioinks whose porosity increased with time following printing. When combined with amphipathic peptide-based plasmid DNA delivery, these bioinks supported enhanced non-viral gene transfer to stem cells in vitro. By modulating the porosity of these bioinks, it was possible to direct either rapid and transient (pore-forming bioinks), or slower and more sustained (solid bioinks) transfection of host or transplanted cells in vivo. To demonstrate the utility of these bioinks for the bioprinting of spatially complex tissues, they were next used to zonally position stem cells and plasmids encoding for either osteogenic (BMP2) or chondrogenic (combination of TGF-β3, BMP2 and SOX9) genes within networks of 3D printed thermoplastic fibers to produce mechanically reinforced, gene activated constructs. In vivo, these bioprinted tissues supported the development of a vascularised, bony tissue overlaid by a layer of stable cartilage. When combined with multiple-tool biofabrication strategies, these gene activated bioinks can enable the bioprinting of a wide range of spatially complex tissues. |
| Databáze: | OpenAIRE |
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