Local and sustained gene delivery in silica-collagen nanocomposites

Local delivery of biomolecules from hydrogels is highly challenging because of their rapid diffusion and degradation. Gene therapy represents an alternative that allows for the prolonged production of proteins by transfected cells. In this study, we have developed nanocomposites consisting of DNA-polyethylenimine-silica nanoparticle complexes coencapsulated with fibroblasts within collagen hydrogels. Through the modulation of the particle size and polyethylenimine molecular weight, it was possible to achieve "in-gel" transfection permitting the sustained production of biomolecules from hydrogels over 1 week. Alternative configurations consisting of particle addition to cellularized gels and cell culture in the presence of complex-containing hydrogels were also investigated. These studies demonstrated that particle encapsulation limits DNA and silica dissemination outside the collagen hydrogels. They also show the key role of cell proliferation within collagen hydrogels on the transfection efficiency. Such nanocomposites therefore constitute promising materials for the development of novel gene delivery systems to promote tissue repair.