The characteristics and in vivo suppression of neointimal formation with sirolimus-eluting polymeric stents.
Drug-eluting stents have emerged as a predominant percutaneous strategy in patients with coronary artery disease. However, hypersensitivity reactions caused by their nonerodable polymer coatings and bare-metal stents may result in serious clinical sequelae. In this report, a new biodegradable sirolimus-eluting stent, made from chitosan-based strips fixed by an epoxy compound, coated with a hydrophobic heparin was developed. Due to the covalent crosslinks formed in the stent matrix, the fabricated stent had a shape-memory property to memorize its permanent shape. The shape-memory ability and mechanical strength of the stent could be enhanced by increasing its degree of crosslinking. The cytocompatibility of the stent was demonstrated in vitro. The heparin coating on the stent effectively reduced platelet adhesion; additionally, it acted as a diffusion barrier and led to a nearly linear sustained-release profile of sirolimus. Cell-cycle analysis demonstrated that the released sirolimus could inhibit smooth muscle cell proliferation by inducing cell-cycle arrest in G(1) phase. When compared to the unloaded stent, neointimal formation was significantly suppressed after implantation of the sirolimus-eluting stent in rabbit infrarenal abdominal aortas. These findings suggested that the developed sirolimus-eluting polymeric stent can be a potential alternative for treatment of atherosclerosis.
Chen
Mei-Chin
MC
Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
Chang
Yen
Y
Liu
Chin-Tang
CT
Lai
Wei-Yun
WY
Peng
Shu-Fen
SF
Hung
Yi-Wen
YW
Tsai
Hung-Wen
HW
Sung
Hsing-Wen
HW
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology; D019245:Compressive Strength / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D054855:Drug-Eluting Stents; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D010973:Platelet Adhesiveness / Q000187:drug effects; D011108:Polymers / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D020123:Sirolimus / Q000494:pharmacology*; D013997:Time Factors; D017539:Tunica Intima / Q000166:cytology / Q000187:drug effects*
D003432:Cross-Linking Reagents; D011108:Polymers; D048271:Chitosan; D020123:Sirolimus