Biomimetic Cu2+/Zn2+ bimetallic surface with glycocalyx-mimicking polymer for selective vascular cell regulation and enhanced hemocompatibility

The vascular endothelium represents the ideal hemocompatible interface, exhibiting unique capabilities to prevent thrombus formation while maintaining vascular homeostasis. To emulate these properties, we have developed a biomimetic surface combining two critical endothelial components: biologically active metal ions that regulate vascular function, and synthetic glycosaminoglycan analogs that replicate the endothelial glycocalyx's antithrombogenic properties. Here, a bimetallic Cu 2+ /Zn 2+ composite coating was developed on polyvinyl chloride (PVC) substrates through dopamine-assisted immobilization, with the surface metal composition being controlled by adjustment of the Cu 2+ /Zn 2+ feeding ratio. The Cu 2+ -rich surface (PC 5 Z 1 ) demonstrated enhanced nitric oxide (NO) catalytic release, effectively suppressing human umbilical vein smooth muscle cell (HUVSMC) proliferation, while the Zn 2+ -enriched surface (PC 1 Z 4 ) promoted human umbilical vein endothelial cell (HUVEC) growth. The optimal Cu 2+ /Zn 2+ (1:1, PC 1 Z 1 ) surface was further functionalized with glycosaminoglycan analog poly(SS- co -OEGMA) (PSO), creating a multifunctional coating that synergistically combines metal ion regulation with glycocalyx-mimicking chemistry. The resulting PC 1 Z 1 -PSO surface achieved a HUVEC/HUVSMC ratio of 2.4 in co-culture, demonstrating its dual capability in promoting endothelialization while inhibiting smooth muscle cell proliferation. Furthermore, platelet adhesion and clotting time assays showed the excellent hemocompatibility of the PC 1 Z 1 -PSO surface. These results demonstrate that strategic integration of bioactive metal ions with glycocalyx-mimicking polymers can effectively mimic key endothelial functions, offering a promising strategy for optimizing the hemocompatibility of blood-contacting materials.