Gene-activated and cell-migration guiding PEG matrices based on three dimensional patterning of RGD peptides and DNA complexes

Essential to the design of genetic bioreactors used in the human body is a consideration of how the properties of biomaterials can combine to envelope, spatially guide, reprogramme by gene transfer, and then release cells. In order to approach this goal, poly(ethylene glycol) (PEG) matrices with modulated structural features and defined spatial patterns of bioactive signals have been designed and produced. In particular, within such PEG matrices, both an adhesive RGD peptide gradient, to directionally attract NIH3T3 cells, and a designed spatial distribution of immobilized poly(ethylenimine) (PEI)/DNA complexes, to obtain a localized transfection, have been realized. These bioactive biomaterials have been designed bearing in mind that cells following an RGD gradient migrate through the matrix, in which they find the bound DNA and become transfected. Both cell migration and transfection have been monitored by fluorescence microscopy. Results show that this system is able to envelope cells, spatially guide them towards the immobilized gene complexes and locally transfect them. Therefore, the system, acting as a genetic bioreactor potentially useful for the regulation of biology at a distance, could be used to directly control cell trafficking and activation in the human body, and has many potential biomedical applications.