title: The (PrS/HGF-pDNA) multilayer films for gene-eluting stent coating: Gene-protecting, anticoagulation, antibacterial properties, and in vivo antirestenosis evaluation.
abstract: Vascular gene-eluting stents (GES) is a promising strategy for treatment of cardiovascular disease. Very recently, we have proved that the (protamine sulfate/plasmid DNA encoding hepatocyte growth factor) (PrS/HGF-pDNA) multilayer can serve as a powerful tool for enhancing competitiveness of endothelial cell over smooth muscle cell, which opens perspectives for the regulation of intercellular competitiveness in the field of interventional therapy. However, before the gene multilayer films could be used in vascular stents for real clinical application, the preservation of gene bioactivity during the industrial sterilization and the hemocompatibility of film should be taken into account. Actually, both are long been ignored issues in the field of gene coating for GES. In this study, we demonstrate that the (PrS/HGF-pDNA) multilayer film exhibits the good gene-protecting abilities, which is confirmed by using the industrial sterilizations (gamma irradiation and ethylene oxide) and a routine storage condition (dry state at 4°C for 30 days). Furthermore, hemocompatible measurements (such as platelet adhesion and whole blood coagulation) and antibacterial assays (bacteria adhesion and growth inhibition) indicate the good anticoagulation and antibacterial properties of the (PrS/HGF-pDNA) multilayer film. The in vivo preliminary data of angiography and histological analysis suggest that the (PrS/HGF-pDNA) multilayer coated stent can reduce the in-stent restenosis. This work reveals that the (PrS/HGF-pDNA) multilayer film could be a promising candidate as coating for GES, which is of great potential in future clinic application.
authors.affiliation: Department of Polymer Science and Engineering, MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Zhejiang University, Hangzhou, 310027, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chang
authors.forename: Ke-feng
authors.initials: KF
authors.lastname: Ren
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.forename: Jin-lei
authors.initials: JL
authors.lastname: Wang
authors.forename: Bai-liang
authors.initials: BL
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000494:pharmacology; D054855:Drug-Eluting Stents; D018014:Gene Transfer Techniques; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D017228:Hepatocyte Growth Factor; D008297:Male; D008422:Materials Testing; D010957:Plasmids / Q000737:chemistry / Q000494:pharmacology; D011479:Protamines / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits
chemical_list: D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D020099:Coated Materials, Biocompatible; D011479:Protamines; D017228:Hepatocyte Growth Factor; D004247:DNA
keywords: gene-eluting stent coating; hepatocyte growth factor; in-stent restenosis; industry sterilization; layer-by-layer assembly