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Cell-controlled and spatially arrayed gene delivery from fibrin hydrogels

Paper ID Volume ID Publish Year Pages File Format Full-Text
9210 620 2009 10 PDF Available
Title
Cell-controlled and spatially arrayed gene delivery from fibrin hydrogels
Abstract

We investigated fibrin-mediated gene transfer by embedding pDNA within the hydrogel during polymerization and using two modes of gene transfection with cells placed either on the surface (2D transfection) or within the hydrogel (3D transfection). Using this model, we found that cell transfection depended strongly on the local cell–pDNA microenvironment as defined by the 2D vs. 3D context, target cell type and density, as well as fibrinogen and pDNA concentrations. When cells were embedded within the fibrin matrix lipofectamine-induced cell death decreased significantly, especially at low target cell density. Addition of fibrinolytic inhibitors decreased gene transfer in a dose-dependent manner, suggesting that fibrin degradation may be necessary for efficient gene transfer. We also provided proof-of-concept that fibrin-mediated gene transfer can be used for spatially localized gene delivery, which is required in cell-transfection microarrays. When lipoplex-containing hydrogels were spotted in an array format gene transfer was strictly confined to pDNA-containing fibrin spots with no cross-contamination between neighboring sites. Collectively, our data suggest that fibrin may be used as a biomaterial to deliver genes in an efficient, cell-controlled and spatially localized manner for potential applications in vitro or in vivo.

Keywords
Fibrin hydrogels; Fibrinolysis; Matrix-mediated transfection; Cell-controlled gene delivery; Transfection microarrays
First Page Preview
Cell-controlled and spatially arrayed gene delivery from fibrin hydrogels
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 22, August 2009, Pages 3790–3799
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering