TSP-2 gene silencing in human aortic endothelial cells via siRNA delivered from an electrospun polyester graft material
Published on Apr 1, 2014 in NEBEC (Northeast Bioengineering Conference)
· DOI :10.1109/NEBEC.2014.6972915
Intimal hyperplasia (IH) remains one of the primary causes of prosthetic vascular graft failure. The goal of this study is to engineer a vascular graft material that has the ability to knock down genes associated with IH by local delivery of a select siRNA moiety to cells surrounding the implant. Thrombospondin-2 (TSP-2), previously shown to have increased expression during graft implantation, is a logical candidate for knock down. TSP-2 siRNA, alone and when complexed with the transfection reagent polyethyleneimine (PEI), was incorporated into an electrospun poly(ethylene terephthalate) vascular graft material (ePET) via a simple dip-coating technique. TSP-2 siRNA complexed with PEI had the greatest attachment to the graft material. HAoECs showed attachment and continued proliferation. TSP-2 siRNA was internalized by human aortic endothelial cells (HAoECs) seeded on the dip-coated graft and displayed success in down-regulating TSP-2 gene expression as compared to controls after 3 days of culture. In vivo data verified transfection of a vessel wall when ePET graft was used as a surrounding sleeve. This proof of principal study demonstrates the potential of using an electrospun ePET graft to locally deliver siRNA in order to target genes associated with IH.