Gene silencing in human aortic smooth muscle cells induced by PEI–siRNA complexes released from dip-coated electrospun poly(ethylene terephthalate) grafts

Abstract

An excessive tissue response to prosthetic arterial graft material leads to intimal hyperplasia (IH), the leading cause of late graft failure. Seroma and abnormal capsule formation may also occur after prosthetic material implantation. The matricellular protein Thrombospondin-2 (TSP-2) has shown to be upregulated in response to biomaterial implantation. This study evaluates the uptake and release of small interfering RNA (siRNA) from unmodified and surface functionalized electrospun PET graft materials. ePET graft materials were synthesized using electrospinning technology. Subsets of the ePET materials were then chemically modified to create surface functional groups. Unmodified and surface-modified ePET grafts were dip-coated in siRNAs alone or siRNAs complexed with transfection reagents polyethyleneimine (PEI) or Lipofectamine RNAiMax. Further, control and TSP-2 siRNA-PEI complex treated ePET samples were placed onto a confluent layer of human aortic smooth muscle cells (AoSMCs). Complexation of all siRNAs with PEI led to a significant increase in adsorption to unmodified ePET. TSP-2 siRNA-PEI released from unmodified-ePET silenced TSP-2 in AoSMC. Regardless of the siRNA-PEI complex evaluated, AoSMC migrated into the ePET. siRNA-PEI complexes delivered to AoSMC from dip-coated ePET can result in gene knock-down. This methodology for siRNA delivery may improve the tissue response to vascular and other prosthetics.

Matricellular proteins in drug delivery: Therapeutic targets, active agents, and therapeutic localization

“…A reduced FBR would also be advantageous for vascular grafts, where adverse remodeling after implantation can lead to neointimal hyperplasia and restenosis. One potential solution, a vascular graft coated in gene delivery vehicles for TSP-2 siRNA, showed the ability to transfect adhered aortic smooth muscle cells and knockdown TSP-2 (67). …”

Technologies for controlled, local delivery of siRNA

“…Another approach that has been tested for the delivery of siRNA formulations from vascular stents was via adsorption of siRNA complexes onto electrospun polyethylene terephthalate (PET) 177 . This study showed effective (>50%) silencing in aortic smooth muscle cells when 2–6 μg of PEI-complexed siRNA was adsorbed onto PET grafts.…”

Gene Silencing via PDA/ERK2‐siRNA‐Mediated Electrospun Fibers for Peritendinous Antiadhesion

“…[10,11] Among these systems, nanoparticles, formed by the electrostatic self-assembly of siRNA and loaded in electrospun fibers, are potentially promising for the provision of advanced sustainable gene silencing, but complex techniques of electrospinning are usually also required. [8,13] Moreover, certain types of nanoparticle, such as polyethylenimine (PEI), polyamidoamine dendrimers, polylysine, and chitosan, were shown to suffer from low efficiency and/or toxicity issues when incorporated into scaffolds. [8,13] Moreover, certain types of nanoparticle, such as polyethylenimine (PEI), polyamidoamine dendrimers, polylysine, and chitosan, were shown to suffer from low efficiency and/or toxicity issues when incorporated into scaffolds.…”