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 G1 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.