TSP-2 gene silencing in human aortic endothelial cells via siRNA delivered from an electrospun polyester graft material

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.