Fibronectin-Assisted Coating of Low-Molecular-Weight Fucoidan Creates a Biomimetic Interface for Endothelialization of Cobalt-Chromium Stents

Abstract

Incomplete or delayed endothelialization after stent implantation compromises vascular healing and increases the risk of restenosis and late thrombosis. To address this limitation, Cobalt-Chromium (Co-Cr) stents were modified with a biomimetic coating combining Low-Molecular-Weight Fucoidan (LMWF), a sulfated polysaccharide with glycocalyx-mimetic properties, and fibronectin, to promote endothelial repair while preserving vascular homeostasis. The morphology, chemical composition, wettability and stability of the coating were characterized using complementary physicochemical approaches. The behavior of human endothelial cells cultured on this dual fibronectin-LMWF-coated stent was then assessed. Our results showed that fibronectin-LMWF-based coating achieved a ten-fold higher surface density on the stent than LMWF alone (0.29 ± 0.04 vs 0.03 ± 0.01 µg/mm2) and retained 0.27 ± 0.03 µg/mm2 of the coating after 168 h, compared with 0.01 ± 0.01 µg/mm2 for LMWF alone. Although wettability remained similar to that of uncoated stents, the combined coating markedly enhanced endothelial cell adhesion, spreading, lamellipodia formation, proliferation, and MMP-2 secretion. These effects were accompanied by enhanced F-actin organization and redistribution of membrane-associated VE-cadherin, integrins β1 and α6, and syndecans-1 and -4, without major changes in their total expression. Importantly, the coating induced these responses without detectable cytotoxicity or significant inflammatory activation. Overall, the fibronectin-LMWF-based coating provides a stable biomimetic interface that enhances endothelialization through coordinated remodeling of adhesion, cytoskeletal, and glycocalyx-associated structures, while maintaining endothelial homeostasis on Co-Cr stent. This strategy offers a promising platform for next-generation glycocalyx-like stent coatings designed to improve vascular healing and limit restenosis.