Hydroxybutyl Chitosan Polymer-Mediated CD 133 Antibody Coating of Metallic Stents to Reduce Restenosis in a Porcine Model of Atherosclerosis

摘要

Antibody-coated stents to capture circulating endothelial progenitor cells (EPCs) for re-endothelialization appear to be a novel therapeutic option for the treatment of atherosclerotic disease. Hydroxybutyl chitosan (HBC), a linear polysaccharide made from shrimps and other crustacean shells, is biocompatible, nontoxic, and hydrophilic, making it ideal for biomedical applications. In this study, HBC was explored for the immobilization of anti-CD 133 antibodies. We demonstrated that CD 133 antibodies mediated by HBC were successfully coated on cobalt chromium alloy discs and metal stents. The coating was homogeneous and smooth as shown by electronic microscopy analysis. Balloon expansion of coated stents did not cause cracking or peeling. The HBC discs promoted CD 133+ EPCs and human umbilical vein endothelial cell growth in vitro. The CD 133 antibody-coated but not bare discs bound CDI33+ EPCs in vitro. Implantation of CDI33 antibody-coated stents significantly inhibited intinnal hyperplasia and reduced restenosis compared with implantation of bare stents in a porcine model of atherosclerosis. These findings suggest HBC is a valuable anchoring agent that can be applied for bioactive coating of stents and that CD 133 antibody-coated stents might be a potential therapeutic alternative for the treatment of atherosclerotic disease.