Soft hydrophilic interfaces boost endothelial selectivity of bioactive peptides for long-term vascular graft patency

The surface modification of bioactive molecules is thought to aid endothelial cell adhesion, which is crucial for achieving rapid endothelialization of vascular grafts and thus ensuring long-term patency. However, conventional hydrophilic coatings possess inherent limitations in resisting nonspecific adsorption, making it difficult to maintain selectivity for endothelial cells in complex blood environments. As a result, the deposition of nonspecific proteins and cells on the surface may trigger neointimal hyperplasia and luminal stenosis, ultimately leading to graft failure. This study proposed a soft hydrophilic coating that combines a low elastic modulus with high hydrophilicity and site-specifically grafted the endothelial cell-selective YIGSR peptide via click chemistry. The coating featured a dual physical-chemical antifouling mechanism. Compared to traditional hard hydrophilic coatings, the soft hydrophilic coating showed improved resistance to protein and non-target cell adhesion (such as fibroblasts, smooth muscle cells, and inflammatory cells) in complex biological environments, while maintaining the selective pro-adhesive function of YIGSR peptides for endothelial cells. By specifically interacting with integrin receptors on the endothelial cell surface, the coating facilitated firm endothelial attachment and upregulated vinculin expression, thereby contributing to the formation of a functional endothelium. Notably, in rat and rabbit in vivo small vascular graft replacement models, this coating significantly promoted rapid and functional endothelialization and ensured long-term patency of the grafts. This study provided a new strategy to address the rapid loss of in vivo bioactivity in existing coatings and offered valuable insights for the design of next-generation cardiovascular implants.