title: 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 knockdown. This methodology for siRNA delivery may improve the tissue response to vascular and other prosthetics.
authors.affiliation: Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Surgery, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Christoph S
authors.initials: CS
authors.lastname: Nabzdyk
authors.affiliation: Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Maggie C
authors.initials: MC
authors.lastname: Chun
authors.affiliation: Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Hunter S
authors.initials: HS
authors.lastname: Oliver-Allen
authors.affiliation: BioSurfaces, Inc., Ashland, MA, USA.
authors.forename: Saif G
authors.initials: SG
authors.lastname: Pathan
authors.affiliation: BioSurfaces, Inc., Ashland, MA, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Phaneuf
authors.affiliation: Harvard School of Engineering and Applied Sciences, Cambridge, MA, USA; Department of Engineering Chemistry, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Jin-Oh
authors.initials: JO
authors.lastname: You
authors.affiliation: Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: lpradhan@bidmc.harvard.edu.
authors.forename: Leena K
authors.initials: LK
authors.lastname: Pradhan-Nabzdyk
authors.affiliation: Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: flogerfo@bidmc.harvard.edu.
authors.forename: Frank W
authors.initials: FW
authors.lastname: LoGerfo
mesh_terms: D000327:Adsorption; D001011:Aorta / Q000166:cytology*; D002448:Cell Adhesion / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects*; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011093:Polyethylene Terephthalates; D011094:Polyethyleneimine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D015203:Reproducibility of Results; D014162:Transfection
chemical_list: D020099:Coated Materials, Biocompatible; D011093:Polyethylene Terephthalates; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D011094:Polyethyleneimine
keywords: Human aortic smooth muscle cells; Polyester; Silencing RNA; Thrombospondin-2; Transfection reagents