Fabrication of biofunctional stents with endothelial progenitor cell specificity for vascular re-endothelialization

Abstract

Endothelial progenitor cells (EPCs) have been identified as a crucial factor for re-endothelialization after stenting, resulting in the prevention of stent thrombosis and neointimal hyperplasia. Because EPCs can be introduced by antibody–antigen interactions, the suitable choice of antibody and the biocompatible surface modification technology including antibody immobilization are essential for developing an EPC-capturing stent. In this study, we fabricated a biofunctional stent with EPC specificity by grafting a hydrophilic polymer and consecutively immobilizing the antibody against vascular endothelial cadherin (VE-cadherin) which is one of the specific EPC surface markers. The surface of a stainless steel stent was sequentially modified by acid-treatment, silanization and covalent attachment of polymers not only to improve biocompatibility but also to introduce functional groups on the stent surface. The surface-modified stent immobilized anti-VE-cadherin antibodies, and the EPCs were remarkably captured whereas THP-1s, human acute monocytic leukemia cells, were not adsorbed on the stent. Furthermore, we confirmed that the recruited EPCs developed the endothelial cell layers on the antibody-conjugated stent. These positive in vitro results will encourage the extensive application of biofunctional surface modification technology for a variety of medical devices.