Design and fabrication of 3D porous scaffolds to facilitate cell-based gene therapy.
Biomaterials capable of efficient gene delivery by embedded cells provide a fundamental tool for the treatment of acquired or hereditary diseases. A major obstacle is maintaining adequate nutrient and oxygen diffusion to cells within the biomaterial. In this study, we combined the solid free-form fabrication and porogen leaching techniques to fabricate three-dimensional scaffolds, with bimodal pore size distribution, for cell-based gene delivery. The objective of this study was to design micro-/macroporous scaffolds to improve cell viability and drug delivery. Murine bone marrow-derived mesenchymal stromal cells (MSCs) genetically engineered to secrete erythropoietin (EPO) were seeded onto poly-L-lactide (PLLA) scaffolds with different microporosities. Over a period of 2 weeks in culture, an increase in cell proliferation and metabolic activity was observed with increasing scaffold microporosity. The concentration of EPO detected in supernatants also increased with increasing microporosity level. Our study shows that these constructs can promote cell viability and release of therapeutic proteins, and clearly demonstrates their capacity for a dual role as scaffolds for tissue regeneration and as delivery systems for soluble gene products.
El-Ayoubi
Rouwayda
R
Industrial Materials Institute, National Research Council of Canada, Boucherville, Quebec, Canada.
Eliopoulos
Nicoletta
N
Diraddo
Robert
R
Galipeau
Jacques
J
Yousefi
Azizeh-Mitra
AM
D000818:Animals; D049109:Cell Proliferation; D004548:Elasticity; D004921:Erythropoietin / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D016062:Porosity; D017154:Stromal Cells / Q000166:cytology / Q000648:ultrastructure; D054457:Tissue Scaffolds / Q000737:chemistry*; D014057:Tomography, X-Ray Computed; D014783:Viscosity
D004921:Erythropoietin