Metal-phenolic networks assisted construction of multi-layered endothelium-mimetic polyelectrolyte coating with...

During cardiovascular-stent endothelialization, application of an endothelium-mimetic coating is desirable to establish a conducive microenvironment that promotes endothelialization, thereby reducing the risks of in-stent thrombosis and restenosis. In this study, we construct an endothelium-mimetic coating on vascular stents assisted by metal-phenolic networks (MPNs). The functional components are integrated through a layer-by-layer self-assembly technique with positively charged polyethyleneimine, negatively charged hyaluronic acid (HA), and MPNs composed of epigallocatechin gallate and Cu as a sandwiched assisting interlayer. Vasoactive nitric oxide (NO) released by Cu catalysis along with the glycocalyx major component HA modification on the surface, endow vascular stents with protective functionalities similar to that of natural endothelial cells. The presence of cation-anion electrolytes and polyphenols enhances the loading, stability, and uniformity of the coating through various interactions such as electrostatic adsorption, hydrogen bonding, π-π stacking, and covalent crosslinking of phenol-aldehyde-amine. Systematic in-vitro and in-vivo studies demonstrate that this coating significantly reduces platelet adhesion and activation and thrombus formation, selectively promotes endothelial cells proliferation and regulates the behaviour of smooth muscle cells, and mitigates inflammatory responses by the synergistic effects of NO catalytic release and glycocalyx functionalization. In-vivo stent implantation experiment reveals that, compared to bare stents, this coating accelerates stent endothelialization and inhibits intimal hyperplasia of vessels. Three months after implantation, the lumen loss rate of the coated stent is only one-third of that of the bare stent. Overall, the MPNs-assisted construction of multi-layered endothelium-mimetic polyelectrolyte coatings with a dual-modality strategy integrating contact therapy via glycocalyx functionalization and gas therapy via NO generation provides innovative insights for the development of next-generation stents. The proposed method can serve as a universal surface-modification strategy to enhance the biocompatibility of implantable cardiovascular devices.