title: A vascular patch prepared from Thai silk fibroin and gelatin hydrogel incorporating simvastatin-micelles to recruit endothelial progenitor cells.
abstract: Delayed re-endothelialization is one of the major disadvantages in synthetic vascular grafts, especially in small-diameter grafts (inner diameter <6 mm), leading to thrombosis and stenosis of the grafts. Simvastatin, a serum cholesterol-lowering drug, has promotional effects on endothelial progenitor cell (EPC) mobilization from bone marrow and recruitment to sites of vascular injury exhibiting acceleration of re-endothelialization. In this study, we prepared double-layer vascular patches from Thai silk fibroin/gelatin with gelatin hydrogel incorporating simvastatin-micelles (SM) for sustained release of simvastatin to recruit circulation EPCs. To enhance simvastatin solubility, simvastatin was entrapped in micelles of l-lactic acid oligomer-grafted gelatin. The drug loading efficiency was at 4.1 ± 0.5 μg/mg micelles. SM had a chemoattractive effect on EPCs comparable to nonmodified simvastatin. Gelatin hydrogel incorporating SM at 100 μM of simvastatin (GSM100) could enhance in vitro EPC activities of adhesion and proliferation. In vitro results showed the initial cell adhesion of 86%, specific growth rate of 15.33×10(-3) h(-1), and population doubling time of 46.21 h. In vivo implantation of the patches incorporating SM significantly increased the recruitment of circulating EPCs. From the results of immunofluorescence staining, they demonstrated the complete re-endothelialization on the implanted patches containing SM at 2 weeks after implantation in rat carotid arteries. The gelatin hydrogel incorporating SM could be an effective inner layer of multifunctional vascular grafts to accelerate re-endothelialization in vascular tissue engineering.
authors.affiliation: 1 Biomedical Engineering Program, Faculty of Engineering, Chulalongkorn University , Bangkok, Thailand .
authors.forename: Piyanuch
authors.initials: P
authors.lastname: Thitiwuthikiat
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ii
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Michio
authors.initials: M
authors.lastname: Asahi
authors.forename: Sorada
authors.initials: S
authors.lastname: Kanokpanont
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D066026:Endothelial Progenitor Cells / Q000166:cytology* / Q000187:drug effects; D005349:Fibroins / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005780:Gelatin / Q000494:pharmacology*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D019344:Lactic Acid / Q000494:pharmacology; D008297:Male; D008823:Micelles; D011916:Rats, Inbred F344; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D008823:Micelles; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D019344:Lactic Acid; D005780:Gelatin; D005349:Fibroins; D019821:Simvastatin