Bioactive coronary stent coating based on layer-by-layer technology for siRNA release

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  • S. Hossfeld, NMI – Natural and Medical Sciences Institute at the University of Tuebingen, Tyskland
  • A. Nolte, Clinical Research Laboratory, Department of Thoracic, Cardiac, and Vascular Surgery, University Hospital of Tuebingen, Tyskland
  • H. Hartmann, NMI – Natural and Medical Sciences Institute at the University of Tuebingen, Tyskland
  • M. Recke, Clinical Research Laboratory, Department of Thoracic, Cardiac, and Vascular Surgery, University Hospital of Tuebingen, Tyskland
  • M. Schaller, Clinical Research Laboratory, Department of Dermatology, University Hospital of Tuebingen, Tyskland
  • T. Walker, Clinical Research Laboratory, Department of Thoracic, Cardiac, and Vascular Surgery, University Hospital of Tuebingen, Tyskland
  • Jørgen Kjems
  • B. Schlosshauer, NMI – Natural and Medical Sciences Institute at the University of Tuebingen, Tyskland
  • D. Stoll, NMI – Natural and Medical Sciences Institute at the University of Tuebingen, Tyskland
  • H.-P. Wendel, Clinical Research Laboratory, Department of Thoracic, Cardiac, and Vascular Surgery, University Hospital of Tuebingen, Tyskland
  • R. Krastev, NMI – Natural and Medical Sciences Institute at the University of Tuebingen, Tyskland
One procedure to treat stenotic coronary arteries is the percutaneous transluminal coronary angioplasty (PTCA). In recent years, drug-eluting stents (DESs) have demonstrated elaborate ways to improve outcomes of intravascular interventions. To enhance DESs, the idea has evolved to design stents that elute specific small interfering RNA (siRNA) for better vascular wall regeneration. Layer-by-layer (LbL) technology offers the possibility of incorporating siRNA nanoplexes (NPs) to achieve bioactive medical implant coatings. The LbL technique was used to achieve hyaluronic acid/chitosan (HA/Chi) films with incorporated Chi-siRNA NPs. The multilayer growth was monitored by quartz crystal microbalance. The coating on the stents and its thickness were analyzed using fluorescence and scanning electron microscopy. All stents showed a homogeneous coating, and the polyelectrolyte multilayers (PEMs) were not disrupted after ethylene oxide sterilization or expansion. The in vitro uptake of fluorescent-labeled NPs from PEMs in primary human endothelial cells (ECs) was analyzed by flow cytometry for 2, 6 and 9 days. Furthermore, stents coated with HA/Chi and Chi-siRNA NPs were expanded into porcine arteries and showed ex vivo delivery of NPs. The films showed no critical results in terms of hemocompatibility. This study demonstrates that Chi-siRNA NPs can be incorporated into PEMs consisting of HA and Chi. We conclude that the NPs were delivered to ECs under in vitro conditions. Furthermore, under ex vivo conditions, NPs were transferred into porcine artery walls. Due to their good hemocompatibility, they might make an innovative tool for achieving bioactive coatings for coronary stents
OriginalsprogEngelsk
TidsskriftActa Biomaterialia
Vol/bind9
Nummer5
Sider (fra-til)6741-6752
Antal sider12
ISSN1742-7061
DOI
StatusUdgivet - maj 2013

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