4.6 Article

Delivery of Bioactive Gene Particles via Gelatin-Collagen-PEG-Based Electrospun Matrices

Journal

PHARMACEUTICALS
Volume 14, Issue 7, Pages -

Publisher

MDPI
DOI: 10.3390/ph14070666

Keywords

electrospun matrices; gelatin; collagen; gene delivery; plasmid DNA; Bone Morphogenetic Protein

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This study investigated the delivery of gene complexes via electrospun mats with different compositions to cells, finding that a high fraction of collagen in the mats can affect fiber quality and reduce transfection efficiency, while double-layered mats containing collagen without complexes as a first layer and gelatin-collagen-PEG with complexes as a second layer successfully induced GFP expression in cells.
The fabrication of fiber mats via electrospinning has been adopted in the last decades to produce high quality scaffolds for tissue engineering. However, an effective combination of electrospinning methods with gene delivery therapies remains a challenge. In this study, we describe how the delivery of gene complexes via electrospun mats that contain different volumes of gelatin (Gel), collagen (Col), and polyethylene glycol (PEG) can affect gene expression by transfected cells. Non-viral complexes were formulated by using lipid modified polyethylenimine (PEI) polymer and plasmid DNAs (pDNA) like the reporter Green Fluorescent Protein (GFP) and the therapeutically relevant Bone Morphogenetic Protein-2 (BMP-2) and electrospuned after being mixed with different volumes of Gel-Col-PEG mats and delivered to human myoblast (C2C12) and mouse osteoblast cells (MC3T3). The entrapment of GFP complexes via different homogeneous electrospun fiber mats revealed that a high fraction of collagen in the mats affected the quality of the fibers and led to reduced transfection efficiency on target cells. On the other hand, the fabrication of double-layered mats that contained collagen without complexes as a first layer and gelatin-collagen-PEG with complexes as a second layer successfully induced GFP expression and ALP activity in C2C12 cells. We conclude that this study has established the advantage of formulating multilayered bioactive collagen-based mats for gene delivery applications.

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