title: RNA-Eluting Surfaces for the Modulation of Gene Expression as A Novel Stent Concept.
abstract: Presently, a new era of drug-eluting stents is continuing to improve late adverse effects such as thrombosis after coronary stent implantation in atherosclerotic vessels. The application of gene expression-modulating stents releasing specific small interfering RNAs (siRNAs) or messenger RNAs (mRNAs) to the vascular wall might have the potential to improve the regeneration of the vessel wall and to inhibit adverse effects as a new promising therapeutic strategy. Different poly (lactic-co-glycolic acid) (PLGA) resomers for their ability as an siRNA delivery carrier against intercellular adhesion molecule (ICAM)-1 with a depot effect were tested. Biodegradability, hemocompatibility, and high cell viability were found in all PLGAs. We generated PLGA coatings with incorporated siRNA that were able to transfect EA.hy926 and human vascular endothelial cells. Transfected EA.hy926 showed significant siICAM-1 knockdown. Furthermore, co-transfection of siRNA and enhanced green fluorescent protein (eGFP) mRNA led to the expression of eGFP as well as to the siRNA transfection. Using our PLGA and siRNA multilayers, we reached high transfection efficiencies in EA.hy926 cells until day six and long-lasting transfection until day 20. Our results indicate that siRNA and mRNA nanoparticles incorporated in PLGA films have the potential for the modulation of gene expression after stent implantation to achieve accelerated regeneration of endothelial cells and to reduce the risk of restenosis.
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany. olivia.koenig@gmx.de.
authors.forename: Olivia
authors.initials: O
authors.lastname: Koenig
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany. diane.zengerle@icloud.com.
authors.forename: Diane
authors.initials: D
authors.lastname: Zengerle
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany. nadja.perle@gmx.de.
authors.forename: Nadja
authors.initials: N
authors.lastname: Perle
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany. susanne.hossfeld@nexgo.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Hossfeld
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany. b.neumann.71@web.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumann
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany. behring.andi@googlemail.com.
authors.forename: Andreas
authors.initials: A
authors.lastname: Behring
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany. meltem.avci.adali@gmail.com.
authors.forename: Meltem
authors.initials: M
authors.lastname: Avci-Adali
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany. tobias.walker@med.uni-tuebingen.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Walker
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany. christian.schlensak@med.uni-tuebingen.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Schlensak
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany. hans-peter.wendel@med.uni-tuebingen.de.
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Wendel
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany. andrea.nolte-karayel@gmx.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Nolte
keywords: PLGA films; atherosclerosis; drug eluting stents; gene delivery; gene knockdown; local transfection; mRNA; siICAM-1