Bioactive coatings of endovascular stents based on polyelectrolyte multilayers.
Layer-by-layer self-assembly of two polysaccharides, hyaluronan (HA) and chitosan (CH), was employed to engineer bioactive coatings for endovascular stents. A polyethyleneimine (PEI) primer layer was adsorbed on the metallic surface to initiate the sequential adsorption of the weak polyelectrolytes. The multilayer growth was monitored using a radiolabeled HA and shown to be linear as a function of the number of layers. The chemical structure, interfacial properties, and morphology of the self-assembled multilayer were investigated by time-of-flight secondary ions mass spectrometry (ToF-SIMS), contact angle measurements, and atomic force microscopy (AFM), respectively. Multilayer-coated NiTi disks presented enhanced antifouling properties, compared to unmodified NiTi disks, as demonstrated by a decrease of platelet adhesion in an in vitro assay (38% reduction; p = 0.036). An ex vivo assay on a porcine model indicated that the coating did not prevent fouling by neutrophils. To assess whether the multilayers may be exploited as in situ drug delivery systems, the nitric-oxide-donor sodium nitroprusside (SNP) was incorporated within the multilayer. SNP-doped multilayers were shown to further reduce platelet adhesion, compared to standard multilayers (40% reduction). When NiTi wires coated with a multilayer containing a fluorescently labeled HA were placed in intimate contact with the vascular wall, the polysaccharide translocated on the porcine aortic samples, as shown by confocal microscopy observation of a treated artery. The enhanced thromboresistance of the self-assembled multilayer together with the antiinflammatory and wound healing properties of hyaluronan and chitosan are expected to reduce the neointimal hyperplasia associated with stent implantation.
Thierry
Benjamin
B
Department of Biomedical Engineering, Mc Gill University, 3775 University Street, Montreal, Qc, H3A 2B4, Canada.
Winnik
Françoise M
FM
Merhi
Yahye
Y
Silver
Jim
J
Tabrizian
Maryam
M
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001807:Blood Vessel Prosthesis / Q000009:adverse effects; D002686:Chitin / Q000031:analogs & derivatives* / Q000494:pharmacology; D048271:Chitosan; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D009599:Nitroprusside / Q000008:administration & dosage; D010973:Platelet Adhesiveness / Q000187:drug effects; D011094:Polyethyleneimine; D011134:Polysaccharides / Q000494:pharmacology*; D015607:Stents / Q000009:adverse effects; D013499:Surface Properties; D013552:Swine; D014665:Vasodilator Agents / Q000008:administration & dosage
D020099:Coated Materials, Biocompatible; D011134:Polysaccharides; D014665:Vasodilator Agents; D002686:Chitin; D009599:Nitroprusside; D011094:Polyethyleneimine; D006820:Hyaluronic Acid; D048271:Chitosan